Investigating the risk factors for nonadherence to analgesic medications in cancer patients: Establishing a nomogram model.

Objective: The substantial prevalence of nonadherence to analgesic medication among individuals diagnosed with cancer imposes a significant strain on both patients and healthcare resources. The objective of this study is to develop and authenticate a nomogram model for assessing nonadherence to analgesic medication in cancer patients. Methods: Clinical information, demographic data, and medication adherence records of cancer pain patients were gathered from the Affiliated Hospital of Chengde Medical University between April 2020 and March 2023. The risk factors associated with analgesic medication nonadherence in cancer patients were analyzed using the least absolute selection operator (LASSO) regression model and multivariate logistic regression. Additionally, a nomogram model was developed. The bootstrap method was employed to internally verify the model. Discrimination and accuracy of the nomogram model were evaluated using the Concordance index (C-index), area under the receiver Operating characteristic (ROC) curve (AUC), and calibration curve. The potential clinical value of the nomogram model was established through decision curve analysis (DCA) and clinical impact curve. Results: The study included a total of 450 patients, with a nonadherence rate of 43.33%. The model incorporated seven factors: age, address, smoking history, number of comorbidities, use of nonsteroidal antiinflammatory drugs (NSAIDs), use of opioids, and PHQ-8. The C-index of the model was found to be 0.93 (95% CI: 0.907-0.953), and the ROC curve demonstrated an AUC of 0.929. Furthermore, the DCA and clinical impact curves indicate that the built model can accurately predict cancer pain patients' medication adherence performance. Conclusions: A nomogram model based on 7 risk factors has been successfully developed and validated for long-term analgesic management of cancer patients.

A metasurface-based full-color circular auto-focusing Airy beam transmitter for stable high-speed underwater wireless optical communications.

Due to its unique intensity distribution, self-acceleration, and beam self-healing properties, Airy beam holds great potential for optical wireless communications in challenging channels, such as underwater environments. As a vital part of 6G wireless network, the Internet of Underwater Things requires high-stability, low-latency, and high-capacity underwater wireless optical communication (UWOC). Currently, the primary challenge of UWOC lies in the prevalent time-varying and complex channel characteristics. Conventional blue Gaussian beam-based systems face difficulties in underwater randomly perturbed links. In this work, we report a full-color circular auto-focusing Airy beams metasurface transmitter for reliable, large-capacity and long-distance UWOC links. The metasurface is designed to exhibits high polarization conversion efficiency over a wide band (440-640 nm), enabling an increased data transmission rate of 91% and reliable 4 K video transmission in wavelength division multiplexing (WDM) based UWOC data link. The successful application of this metasurface in challenging UWOC links establishes a foundation for underwater interconnection scenarios in 6G communication.

Grating-assisted hot-electron photodetectors for S- and C-band telecommunication.

Although outstanding detectivities, InGaAs photodetectors for optic fiber communication are often costly due to the need for cooling. Therefore, cryogen-free and cost-effective alternatives working in telecommunication bands are highly desired. Here, we present a design of hot-electron photodetectors (HE PDs) with attributes of room-temperature operation and strong optical absorption over S and C bands (from 1460 to 1565 nm). The designed HE PD consists of a metal-semiconductor-metal hot-electron stack integrated with a front grating. Optical simulations reveal that mode hybridizations between Fabry-Pérot resonance and grating-induced surface plasmon excitation lead to high absorption efficiencies (≥0.9) covering S and C bands. Probability-based electrical calculations clarify that device responsivity is mainly determined by working wavelength on the premise of broadband strong absorption. Moreover, through comparison studies between the grating-assisted HE PD and purely planar microcavity system that serves as a reference, we highlight the design superiorities in average absorption and average responsivity with optimized values of 0.97 and 0.73 mA W-1, respectively. The upgraded peformances of the designed device are promising for efficient photoelectric conversion in optic fiber communication systems.

High sensitivity Sagnac interferometric temperature sensor using stress region refractive index modulation.

An all-fiber temperature sensor employing intentional refractive index modulation is experimentally demonstrated. The sensor consists of four sections of polarization maintaining fiber (FPMF) sandwiched between multi-mode fiber (MMF). The stress region of two sections of polarization maintaining fibers (PMFs) is aligned and then anti-clockwise rotates one PMF in 10 deg angles while the other keeps still. Finally, the discharge proceeds. The remaining two PMFs are fusion spliced with the same method. Then the prepared FPMF-MMF structure is connected to the 3 dB coupler to construct a Sagnac loop. The temperature sensitivity reaches 1.49 nm/°C for a temperature range from 16°C to 55°C. The proposed temperature sensor with easy fabrication and good linearity in measuring temperature can be a promising candidate for various applications in environmental monitoring and industrial production.

An ultrasonic biosample disruptor with two triangular teeth on its radiation face.

Ultrasound has been used in biosample disruption such as disruption of algal cell and DNA. New structure of ultrasonic biosample disruptor (UBD) needs to be explored to increase the energy efficiency. In this study, an UBD with two triangular teeth on the bottom radiation face of the water tank has been proposed, to concentrate the acoustic energy into the slot between the two neighboring triangular teeth, in order to raise the acoustic energy utilization and fragmentation performance. The acoustic energy concentration into the slot is verified by the FEM computation, and the improvement of fragmentation performance is experimentally confirmed with spirulina and tribonema, compared to the traditional UBD which has a flat radiation face. The number proportion of fragment in the length range of 10-20 µm generated by the UBD proposed in this work is 17.08% and 10.82% more than that generated by the traditional UBD for the two samples, respectively. Besides, the UBD proposed in this work has a much smaller standard deviation of DNA fragment length (47 bp) than the traditional UBD (249 bp), with a similar mean length of fragments. Moreover, the maximum weight proportion of fragment in the range of 100-300 bp, generated by the UBD proposed in this work, is 71.4%.

Exosomes from Von Hippel-Lindau-Null Cancer Cells Promote Metastasis in Renal Cell Carcinoma.

Exosomes are extracellular vesicles that modulate essential physiological and pathological signals. Communication between cancer cells that express the von Hippel-Lindau (VHL) tumor suppressor gene and those that do not is instrumental to distant metastasis in renal cell carcinoma (RCC). In a novel metastasis model, VHL(-) cancer cells are the metastatic driver, while VHL(+) cells receive metastatic signals from VHL(-) cells and undergo aggressive transformation. This study investigates whether exosomes could be mediating metastatic crosstalk. Exosomes isolated from paired VHL(+) and VHL(-) cancer cell lines were assessed for physical, biochemical, and biological characteristics. Compared to the VHL(+) cells, VHL(-) cells produce significantly more exosomes that augment epithelial-to-mesenchymal transition (EMT) and migration of VHL(+) cells. Using a Cre-loxP exosome reporter system, the fluorescent color conversion and migration were correlated with dose-dependent delivery of VHL(-) exosomes. VHL(-) exosomes even induced a complete cascade of distant metastasis when added to VHL(+) tumor xenografts in a duck chorioallantoic membrane (dCAM) model, while VHL(+) exosomes did not. Therefore, this study supports that exosomes from VHL(-) cells could mediate critical cell-to-cell crosstalk to promote metastasis in RCC.

VHL L169P Variant Does Not Alter Cellular Hypoxia Tension in Clear Cell Renal Cell Carcinoma.

In the current era of tumor genome sequencing, single amino acid missense variants in the von Hippel-Lindau (VHL) tumor suppressor gene are frequently identified in clear cell renal carcinoma (ccRCC). Due to the incomplete knowledge of the structural architecture of VHL protein, the functional significance of many missense mutations cannot be assigned. L169P is one such missense mutation identified in the case of aggressive, metastatic ccRCC. Here, we characterized the biochemical activity, transcriptomic hypoxia signature and biological functions of the L169P variant. Lentiviral vector expressing either wildtype (WT) or L169P VHL were used to transduce two VHL-deficient human ccRCC cell lines, 786-O and RCC4. The stability of the VHL protein and the expression level of VHL, HIF1α and HIF2α were analyzed. The impact of restoring L169P or WT VHL on the hypoxia gene expression program in 786-O cells was assessed by mRNA sequencing (RNAseq) and computed hypoxic scores. The impact of restoring VHL expression on the growth of ccRCC models was assessed in cell cultures and in chorioallantoic membrane (CAM) xenografts. In the 786-O cells, the protein stability of L169P VHL was comparable to WT VHL. No obvious difference in the capability of degrading HIF1α and HIF2α was observed between WT and L169P VHL in the 786-O or RCC4 cells. The hypoxic scores were not significantly different in the 786-O cells expressing either wildtype or L169P VHL. From the cellular function perspective, both WT and L169P VHL slowed cell proliferation in vitro and in vivo. The L169P VHL variant is comparable to WT VHL in terms of protein stability, ability to degrade HIF1α factors and ability to regulate hypoxia gene expression, as well as in the suppression of ccRCC tumor cell growth. Taken together, our data indicate that the L169P VHL variant alone is unlikely to drive the oncogenesis of sporadic ccRCC.

The development of a clinical nomogram to predict medication nonadherence in patients with knee osteoarthritis.

Knee osteoarthritis (KOA) is a common bone disease in older patients. Medication adherence is of great significance in the prognosis of this disease. Therefore, this study analyzed the high-risk factors that lead to medication nonadherence in patients with KOA and constructed a nomogram risk prediction model. The basic information and clinical characteristics of inpatients diagnosed with KOA at the Department of Orthopedics, The Affiliated Hospital of Chengde Medical University, were collected from January 2020 to January 2022. The Chinese version of the eight-item Morisky scale was used to evaluate medication adherence. The Kellgren-Lawrence (KL) classification was performed in combination with the imaging data of patients. Least absolute shrinkage and selection operator regression analysis and logistic multivariate regression analysis were used to analyze high-risk factors leading to medication nonadherence, and a prediction model of the nomogram was constructed. The model was internally verified using bootstrap self-sampling. The index of concordance (C-index), area under the operating characteristic curve (AUC), decision curve, correction curve, and clinical impact curve were used to evaluate the model. A total of 236 patients with KOA were included in this study, and the non-adherence rate to medication was 55.08%. Seven influencing factors were included in the nomogram prediction: age, underlying diseases, diabetes, age-adjusted Charlson comorbidity index (aCCI), payment method, painkillers, and use of traditional Chinese medicine. The C-index and AUC was 0.935. The threshold probability of the decision curve analysis was 0.02-0.98. The nomogram model can be effectively applied to predict the risk of medication adherence in patients with KOA, which is helpful for medical workers to identify and predict the risk of individualized medication adherence in patients with KOA at an early stage of treatment, and then carry out early intervention.

An ultrasonic sweeper with micro-/nano-concentration, decorating, transmedium extraction, and localized cleaning functions.

The strategies that allow one single device to possess multiple controlled micro-/nano-manipulation functions are demanded by various fields. In this work, we have developed a probe-type ultrasonic sweeper with rich micro-/nano-manipulation functions, including concentration, decorating, transmedium extraction, and removal of micro-/nanoscale materials at the interface between a suspension film and a non-vibration substrate. The functions are implemented with a micro-manipulation probe (MMP) in contact with the substrate, which vibrates approximately linearly and perpendicularly to the substrate. Silver nanowires on the substrate can be sucked onto the vibrating MMP's tip and accumulate to form a microsheet. By moving the MMP horizontally, nanowires on its motional path can be sucked onto the MMP's tip, and controlled cleaning can be realized. If nanoparticles are mixed into the AgNW suspension uniformly, AgNWs in the accumulated microsheet can be decorated with the nanoparticles. More importantly, the accumulated nanomaterials on the MMP's tip can be transported freely in the suspension film and even extracted into air from the liquid film. To the best of our knowledge, the ultrasonic sweeper in this work possesses the richest micro-/nano-manipulation functions than any other existing acoustic manipulators. The finite element analyses indicate that the multiple manipulation functions achieved are caused by the acoustic radiation force generated by the ultrasonic field in the suspension film.

Application of IRI Visualization to Terahertz Vibrational Spectroscopy of Hydroxybenzoic Acid Isomers.

The characteristic absorption spectra of three positional isomers of hydroxybenzoic acid are measured using a terahertz time-domain spectroscopy system (THz-TDS) in the 0.6-2.0 THz region at room temperature. Significant differences in their terahertz spectra are discovered, which indicates that THz-TDS is an effective means to identify positional isomers. In order to simulate their spectra, the seven molecular clusters of 2-, 3-, and 4-hydroxybenzoic acid (2-, 3-, and 4-HA) are calculated using the DFT-D3 method. Additionally, the potential energy distribution (PED) method is used to analyze their vibration modes. The analysis indicates that the vibration modes of 2-HA are mainly out-of-plane angle bending and bond angle bend in plane. The vibration modes of 3-HA are mainly bond length stretch and dihedral angle torsion. The vibration modes of 4-HA are mainly bond angle bend in plane and dihedral angle torsion. Interaction region indicator (IRI) analysis is used to visualize the location and type of intermolecular interactions in 2-, 3-, and 4-HA crystals. The results show that the weak interaction type of 2-, 3-, and 4-HA is dominated by van der Waals (vdW) interaction. Therefore, we can confirm that terahertz spectroscopy detection technology can be used as an effective means to identify structural isomers and detect the intermolecular interactions in these crystals. In addition, it can explain the absorption mechanism of terahertz waves interacting with matter.

Early osteoarthritis diagnosis based on near-infrared spectroscopy combined with aquaphotomics.

Osteoarthritis (OA) is the most common joint disease and the leading cause of disability in elderly individuals. Despite rapid advances in imaging techniques, early OA diagnosis remains a clinical challenge. In the present study, the feasibility of early OA diagnosis was explored via near-infrared spectroscopy (NIRS) combined with aquaphotomics. Synovial fluid samples from 65 cases of OA categorized as mild, moderate, and severe according to theKellgrenandLawrence classification criteria were analyzed via NIRS. The 1st overtone of water (1300-1600 nm) was considered as the research object for an aquaphotomics model, and aquagrams of the mild, moderate, and severe OA cases were generated using 12 water absorption patterns for early OA diagnosis.The aquaphotomics results exhibited clear differences in the region of 1300-1500 nm, and the number of hydrogen bonds of different water species (1412,1424, 1482, and 1496 nm) evidently correlated with OA occurrence and development. With OA progression, the absorption intensity of water molecules without hydrogen bonds (1412 nm/1424 nm) became stronger, while the absorption intensity of water molecules with four hydrogen bonds (1482 nm/1496 nm) decreased.These results together reveal that the established accurate and rapid early OA diagnosis model based on NIRS combined with aquaphotomics is effective and feasible, and that the number of hydrogen bonds can be used as a biomarker for early OA diagnosis.

Planar hot-electron photodetection with polarity-switchable photocurrents controlled by the working wavelength.

Hot-electron photodetection is attracting increasing interests. Based on internal photoemission mechanism, hot-electron photodetectors (HE PDs) convert incident photon energy into measurable photocurrent. To obtain polarity-switchable photocurrent, one often applies electric bias to reverse the hot-electron flow. However, the employment of bias reduces the device flexibility and increasing the bias voltage degrades the detectivity of the device. Herein, we design a planar HE PD with the polarity-switchable photocurrent controlled by the working wavelength. Optical simulations show that the device exhibits two absorption peaks due to the resonances of two Tamm plasmons (TPs). Electrical calculations predict two corresponding TP-assisted responsivity peaks, but with opposite photocurrent polarities, which are determined by the hot-electron flows with opposite directions. We find that the hot-electron flows are closely related with the population differences of TP-induced hot electrons in two electrodes. We further demonstrate that the photocurrent polarity of the HE PD can be switched by altering working wavelength from one TP wavelength to the other. We believe that this approach paves a route to achieve flexible hot-electron photodetection for extensive applications.

Topological edge and corner states in honeycomb-kagome photonic crystals.

We systematically study the first- and second-order band topologies, which are tied to the pseudospin and valley degree of freedoms (DOFs), in honeycomb-kagome photonic crystals (HKPCs). We first demonstrate the quantum spin Hall phase as the first-order pseudospin-induced topology in HKPCs by observing the partial pseudospin-momentum locked edge states. By employing the topological crystalline index, we also discover the multiple corner states emerging in the hexagon-shaped supercell as the manifestation of the second-order pseudospin-induced topology in HKPCs. Next, by gapping the Dirac points, a lower band gap associated with the valley DOF emerges, in which the valley-momentum locked edge states are observed as the first-order valley-induced topology. Such HKPCs without inversion symmetry are proved to be Wannier-type second-order topological insulators, which manifested with valley-selective corner states. Additionally, we also discuss the symmetry breaking effect on pseudospin-momentum locked edge states. Our work realizes both pseudospin-induced and valley-induced topologies in a higher-order manner and thus provides more flexibility in manipulating electromagnetic waves, which may find potential applications in topological routings.

Tumor heterogeneity in VHL drives metastasis in clear cell renal cell carcinoma.

Loss of function of the von Hippel-Lindau (VHL) tumor suppressor gene is a hallmark of clear cell renal cell carcinoma (ccRCC). The importance of heterogeneity in the loss of this tumor suppressor has been under reported. To study the impact of intratumoral VHL heterogeneity observed in human ccRCC, we engineered VHL gene deletion in four RCC models, including a new primary tumor cell line derived from an aggressive metastatic case. The VHL gene-deleted (VHL-KO) cells underwent epithelial-to-mesenchymal transition (EMT) and exhibited increased motility but diminished proliferation and tumorigenicity compared to the parental VHL-expressing (VHL+) cells. Renal tumors with either VHL+ or VHL-KO cells alone exhibit minimal metastatic potential. Combined tumors displayed rampant lung metastases, highlighting a novel cooperative metastatic mechanism. The poorly proliferative VHL-KO cells stimulated the proliferation, EMT, and motility of neighboring VHL+ cells. Periostin (POSTN), a soluble protein overexpressed and secreted by VHL non-expressing (VHL-) cells, promoted metastasis by enhancing the motility of VHL-WT cells and facilitating tumor cell vascular escape. Genetic deletion or antibody blockade of POSTN dramatically suppressed lung metastases in our preclinical models. This work supports a new strategy to halt the progression of ccRCC by disrupting the critical metastatic crosstalk between heterogeneous cell populations within a tumor.

Directional Torsion Sensor Based on a Two-Core Fiber with a Helical Structure.

A fiber-optic torsion sensor based on a helical two-core fiber (HTCF) is proposed and experimentally demonstrated for simultaneously measuring torsion angle and torsion direction. The sensor consists of a segment of HTCF and two single-mode fibers (SMFs) forming a Mach-Zehnder interferometer (MZI). The helical structure is implemented by pre-twisting a 1 cm long two-core fiber (TCF). The performance of the sensor with pre-twisted angles of 180°, 360°, and 540° is experimentally analyzed. The results show that the sensor can realize the angular measurement and effectively distinguish the torsion direction. It is worth noting that the sensor has maximum sensitivity when the pre-twist angle is 180 degrees. The obtained wavelength sensitivities of torsion and temperature are 0.242 nm/(rad/m) and 32 pm/°C, respectively. The sensor has the advantages of easy fabrication, low cost, compact structure, and high sensitivity, which is expected to yield potential applications in fields where both torsion angle and direction measurements are required.

Large dynamic strain measurement via slope-assisted Brillouin optical time domain reflectometry using a frequency equalizer.

In this Letter, a method for measuring large dynamic strain via slope-assisted Brillouin optical time domain reflectometry (SA-BOTDR) is proposed. A linear artificial slope created by a frequency equalizer is used instead of the traditional slope of the Brillouin gain spectrum (BGS) as the linear response region between the Brillouin frequency shift (BFS) and signal intensity. This method makes the strain measurement range independent of the bandwidth of the BGS. The large dynamic strain with a maximum value of 3108 µÎµ and the spatial resolution of 5 m along the ∼1.94-km single-mode fiber (SMF) are obtained by means of the proposed technique. Meanwhile, a strong linear relationship is also established between the signal strength and strain at the vibration frequencies of 10.3 and 13.1 Hz. The maximum measured errors of vibration frequency are 0.5 Hz@10.3 Hz and 0.8 Hz@13.1 Hz.

Several ML Algorithms and Their Feature Vector Design for Gas Discrimination and Concentration Measurement with an Ultrasonically Catalyzed MOX Sensor.

Although gas-borne ultrasound catalysis has been developed as a new method to discriminate gas species and measure the concentration, applications of machine learning methods in gas analyses with a single metal oxide (MOX) gas sensor catalyzed by gas-borne ultrasound are still scarce. In this work, with an ultrasonically catalyzed MOX gas sensor, we explored the effectiveness of K-nearest neighbors (KNN), support vector machine (SVM), and single-hidden-layer BP-ANN (SHBP) in gas discrimination and the application of the SHBP in concentration measurement. The target gases in this work are ethanol, acetone, methanol, hydrogen, and n-butane in clean air, respectively, and the discrimination and concentration regression are implemented by two different ML models. With the properly designed feature vectors, the SHBP method has an acceptable capability of both of species discrimination and concentration regression (success rate of gas discrimination = 99.5%, relative error of concentration regression = 6.406%). The KNN and SVM methods have similar capabilities of gas discrimination as the SHBP. This work also demonstrates a method to design the feature vectors for the ultrasonically catalyzed MOX gas sensor and to choose the feature parameters.

HCC EV ECG score: An extracellular vesicle-based protein assay for detection of early-stage hepatocellular carcinoma.

BACKGROUND AND AIMS: The sensitivity of current surveillance methods for detecting early-stage hepatocellular carcinoma (HCC) is suboptimal. Extracellular vesicles (EVs) are promising circulating biomarkers for early cancer detection. In this study, we aim to develop an HCC EV-based surface protein assay for early detection of HCC. APPROACH AND RESULTS: Tissue microarray was used to evaluate four potential HCC-associated protein markers. An HCC EV surface protein assay, composed of covalent chemistry-mediated HCC EV purification and real-time immuno-polymerase chain reaction readouts, was developed and optimized for quantifying subpopulations of EVs. An HCC EV ECG score, calculated from the readouts of three HCC EV subpopulations ( E pCAM + CD63 + , C D147 + CD63 + , and G PC3 + CD63 + HCC EVs), was established for detecting early-stage HCC. A phase 2 biomarker study was conducted to evaluate the performance of ECG score in a training cohort ( n  = 106) and an independent validation cohort ( n  = 72).Overall, 99.7% of tissue microarray stained positive for at least one of the four HCC-associated protein markers (EpCAM, CD147, GPC3, and ASGPR1) that were subsequently validated in HCC EVs. In the training cohort, HCC EV ECG score demonstrated an area under the receiver operating curve (AUROC) of 0.95 (95% confidence interval [CI], 0.90-0.99) for distinguishing early-stage HCC from cirrhosis with a sensitivity of 91% and a specificity of 90%. The AUROCs of the HCC EV ECG score remained excellent in the validation cohort (0.93; 95% CI, 0.87-0.99) and in the subgroups by etiology (viral: 0.95; 95% CI, 0.90-1.00; nonviral: 0.94; 95% CI, 0.88-0.99). CONCLUSION: HCC EV ECG score demonstrated great potential for detecting early-stage HCC. It could augment current surveillance methods and improve patients' outcomes.

Bias voltage-tuned hot-electron optical sensing with planar Au-MoS2-Au junction.

Harvesting photoexcited hot electrons in metals promises a number of benefits in optical sensing. In practice, hot-electron optical sensors with tunable performance in electrical sensitivity are still absent. Herein, we propose a design to realize tunable hot-electron optical sensing. The proposed device consists of a one-dimensional grating deposited on a planar Au-MoS2-Au junction that is used for efficient hot-electron harvesting. Photoelectric simulations show that when grating-assisted plasmonic resonance is excited, bias voltage between two Au layers can be used to manipulate the magnitude and polarity of responsivity at the working wavelength. Therefore, the change in responsivity that originates from the change in refractive index of analyte in which the device is immersed can also be tuned by applied voltage. It is found that when bias voltage is 1 V, the electrical sensitivity doubled compared with that when applied voltage is absent. We believe the bias voltage-tuned strategy that is applied to planar hot-electron harvesting junctions facilitates the development of optical sensing.