Search

Avalanche photodiodes biased above the breakdown voltage are an interesting alternative to photomultiplier tubes in time-correlated single-photon counting. The characteristics and performance of a commercially available device (RCA C30921S) have been investigated. The time resolution is found to improve as the excess bias above the breakdown voltage is increased. Full width at half-maximum values down to 400 ps have been measured with the detector cooled at - 40°C, and down to 460 ps at room temperature. The best results were obtained with an active quenching circuit, suitable for operation with excess bias voltage up to 40 V; at room temperature, fast gated operation was used for attaining optimum performance. Experimental data on the statistical behavior of the avalanche current pulses in these devices are reported and discussed. [ABSTRACT FROM AUTHOR]

In order to fulfill the requirements of many applications, we recently developed a new technology aimed at combining the advantages of traditional thin and thick silicon Single Photon Avalanche Diodes (SPAD). In particular we demonstrated single-pixel detectors with a remarkable improvement in the Photon Detection Efficiency at the longer wavelengths (e.g. 40% at 800nm) while maintaining a timing jitter better than 100ps. In this paper we will analyze the factors the currently prevent the fabrication of arrays of SPADs by adopting such a Red-Enhanced (RE) technology and we will propose further modifications to the device structure that will enable the fabrication of high performance RE-SPAD arrays for photon timing applications.

Single-molecule Förster resonance energy transfer (smFRET) techniques are now widely used to address outstanding problems in biology and biophysics. In order to study freely diffusing molecules, current approaches consist in exciting a low concentration (<100 pM) sample with a single confocal spot using one or more lasers and detecting the induced single-molecule fluorescence in one or more spectrally- and/or polarization-distinct channels using single-pixel Single-Photon Avalanche Diodes (SPADs). A large enough number of single-molecule bursts must be accumulated in order to compute FRET efficiencies with sufficient statistics. As a result, the minimum timescale of observable phenomena is set by the minimum acquisition time needed for accurate measurements, typically a few minutes or more, limiting this approach mostly to equilibrium studies. Increasing smFRET analysis throughput would allow studying dynamics with shorter timescales. We recently demonstrated a new multi-spot excitation approach, employing a novel multi-pixel SPAD array, using a simplified dual-view setup in which a single 8-pixel SPAD array was used to collect FRET data from 4 independent spots. In this work we extend our results to 8 spots and use two 8-SPAD arrays to collect donor and acceptor photons and demonstrate the capabilities of this system by studying a series of doubly labeled dsDNA samples with different donor-acceptor distances ranging from low to high FRET efficiencies. Our results show that it is possible to enhance the throughput of smFRET measurements in solution by almost one order of magnitude, opening the way for studies of single-molecule dynamics with fast timescale once larger SPAD arrays become available.

In this paper we present an array of 48 Single Photon Avalanche Diodes (SPADs) specifically designed for multispot Single Molecule Analysis. The detectors have been arranged in a 12×4 square geometry with a pitch-to-diameter ratio of ten in order to minimize the collection of the light from non-conjugated excitation spots. In order to explore the trade-offs between the detectors' performance and the optical coupling with the experimental setup, SPADs with an active diameter of 25 and of 50µm have been manufactured. The use of a custom technology, specifically designed for the fabrication of the detectors, allowed us to combine a high photon detection efficiency (peak close to 50% at a wavelength of 550nm) with a low dark count rate compatible with true single molecule detection. In order to allow easy integration into the optical setup for parallel single-molecule analysis, the SPAD array has been incorporated in a compact module containing all the electronics needed for a proper operation of the detectors.

Single-molecule fluorescence spectroscopy of freely diffusing molecules in solution is a powerful tool used to investigate the properties of individual molecules. Single-Photon Avalanche Diodes (SPADs) are the detectors of choice for these applications. Recently a new type of SPAD detector was introduced, dubbed red-enhanced SPAD (RE-SPAD), with good sensitivity throughout the visible spectrum and with excellent timing performance. We report a characterization of this new detector for single-molecule fluorescence resonant energy transfer (smFRET) studies on freely diffusing molecules in a confocal geometry and alternating laser excitation (ALEX) scheme. We use a series of doubly-labeled DNA molecules with donor-to-acceptor distances covering the whole range of useful FRET values. Both intensity-based (μs-ALEX) and lifetime-based (ns-ALEX) measurements are presented and compared to identical measurements performed with standard thick SPADs. Our results demonstrate the great potential of this new detector for smFRET measurements and beyond.

Two optical configurations are commonly used in single-molecule fluorescence microscopy: point-like excitation and detection to study freely diffusing molecules, and wide field illumination and detection to study surface immobilized or slowly diffusing molecules. Both approaches have common features, but also differ in significant aspects. In particular, they use different detectors, which share some requirements but also have major technical differences. Currently, two types of detectors best fulfil the needs of each approach: single-photon-counting avalanche diodes (SPADs) for point-like detection, and electron-multiplying charge-coupled devices (EMCCDs) for wide field detection. However, there is room for improvements in both cases. The first configuration suffers from low throughput owing to the analysis of data from a single location. The second, on the other hand, is limited to relatively low frame rates and loses the benefit of single-photon-counting approaches. During the past few years, new developments in point-like and wide field detectors have started addressing some of these issues. Here, we describe our recent progresses towards increasing the throughput of single-molecule fluorescence spectroscopy in solution using parallel arrays of SPADs. We also discuss our development of large area photon-counting cameras achieving subnanosecond resolution for fluorescence lifetime imaging applications at the single-molecule level.

Single-molecule Förster resonance energy transfer (smFRET) is a powerful tool for extracting distance information between two fluorophores (a donor and acceptor dye) on a nanometer scale. This method is commonly used to monitor binding interactions or intra- and intermolecular conformations in biomolecules freely diffusing through a focal volume or immobilized on a surface. The diffusing geometry has the advantage to not interfere with the molecules and to give access to fast time scales. However, separating photon bursts from individual molecules requires low sample concentrations. This results in long acquisition time (several minutes to an hour) to obtain sufficient statistics. It also prevents studying dynamic phenomena happening on time scales larger than the burst duration and smaller than the acquisition time. Parallelization of acquisition overcomes this limit by increasing the acquisition rate using the same low concentrations required for individual molecule burst identification. In this work we present a new two-color smFRET approach using multispot excitation and detection. The donor excitation pattern is composed of 4 spots arranged in a linear pattern. The fluorescent emission of donor and acceptor dyes is then collected and refocused on two separate areas of a custom 8-pixel SPAD array. We report smFRET measurements performed on various DNA samples synthesized with various distances between the donor and acceptor fluorophores. We demonstrate that our approach provides identical FRET efficiency values to a conventional single-spot acquisition approach, but with a reduced acquisition time. Our work thus opens the way to high-throughput smFRET analysis on freely diffusing molecules.

Solution-based single-molecule fluorescence spectroscopy is a powerful new experimental approach with applications in all fields of natural sciences. Two typical geometries can be used for these experiments: point-like and widefield excitation and detection. In point-like geometries, the basic concept is to excite and collect light from a very small volume (typically femtoliter) and work in a concentration regime resulting in rare burst-like events corresponding to the transit of a single-molecule. Those events are accumulated over time to achieve proper statistical accuracy. Therefore the advantage of extreme sensitivity is somewhat counterbalanced by a very long acquisition time. One way to speed up data acquisition is parallelization. Here we will discuss a general approach to address this issue, using a multispot excitation and detection geometry that can accommodate different types of novel highly-parallel detector arrays. We will illustrate the potential of this approach with fluorescence correlation spectroscopy (FCS) and single-molecule fluorescence measurements. In widefield geometries, the same issues of background reduction and single-molecule concentration apply, but the duration of the experiment is fixed by the time scale of the process studied and the survival time of the fluorescent probe. Temporal resolution on the other hand, is limited by signal-to-noise and/or detector resolution, which calls for new detector concepts. We will briefly present our recent results in this domain.

In this letter, we report the first resonant-cavity-enhanced single-photon avalanche diode (RCE SPAD) fabricated on a reflecting silicon-on-insulator (SOI) substrate. The substrate incorporates a two-period distributed Bragg reflector fabricated using a commercially available double-SOI process. The RCE SPAD detectors have peak photon detection efficiencies ranging from 42% at 780 nm to 34% at 850 nm and time resolution of 35-ps full-width at half-maximum. Typical dark count rates of 450, 3500, and 100 000 c/s were measured at room temperature with RCE SPADs having, respectively 8-, 20-, and 50-mum diameter. [ABSTRACT FROM PUBLISHER]

One of the main drawbacks of single-photon avalanche diode arrays is optical crosstalk between adjacent detectors. In the past, this phenomenon was basically ascribed to light propagating from one detector to another through a direct optical path. Accordingly, deep trenches coated with metal were introduced as optical isolation barriers between pixels. This solution, however, was unable to completely prevent the crosstalk. In this letter, we demonstrate that a strong contribution to optical crosstalk comes from photons reflected at the bottom of the chip. These photons can bypass trenches making them less effective. [ABSTRACT FROM PUBLISHER]

We present a novel approach to high-throughput Fluorescence Correlation Spectroscopy (FCS) which enables us to obtain one order of magnitude improvement in acquisition time. Our approach utilizes a liquid crystal on silicon spatial light modulator to generate dynamically adjustable focal spots, and uses an eight-pixel monolithic single-photon avalanche photodiode array. We demonstrate the capabilities of this system by showing FCS of Rhodamine 6G under various viscosities, and by showing that, with proper calibration of each detection channel, one order of magnitude improvement in acquisition speed is obtained. More generally, our approach will allow higher throughput single-molecule studies to be performed.

Solution-based single-molecule fluorescence spectroscopy is a powerful new experimental approach with applications in all fields of natural sciences. The basic concept of this technique is to excite and collect light from a very small volume (typically femtoliter) and work in a concentration regime resulting in rare burst-like events corresponding to the transit of a single-molecule. Those events are accumulated over time to achieve proper statistical accuracy. Therefore the advantage of extreme sensitivity is somewhat counterbalanced by a very long acquisition time. One way to speed up data acquisition is parallelization. Here we will discuss a general approach to address this issue, using a multispot excitation and detection geometry that can accommodate different types of novel highly-parallel detector arrays. We will illustrate the potential of this approach with fluorescence correlation spectroscopy (FCS) and single-molecule fluorescence measurements obtained with different novel multipixel single-photon counting detectors.

Solution-based single-molecule spectroscopy and fluorescence correlation spectroscopy (FCS) are powerful techniques to access a variety of molecular properties such as size, brightness, conformation, and binding constants. However, this is limited to low concentrations, which results in long acquisition times in order to achieve good statistical accuracy. Data can be acquired more quickly by using parallelization. We present a new approach using a multispot excitation and detection geometry made possible by the combination of three powerful new technologies: (i) a liquid crystal spatial light modulator to produce multiple diffraction-limited excitation spots; (ii) a multipixel detector array matching the excitation pattern and (iii) a low-cost reconfigurable multichannel counting board. We demonstrate the capabilities of this technique by reporting FCS measurements of various calibrated samples as well as single-molecule burst measurements.

A novel microchip electrophoresis instrument based on single-photon avalanche diodes was used for the molecular characterization of mutations in disease genes. The identification of the main mutation causing cystic fibrosis, named DeltaF508, by the Amplification Refractory Mutation System was used to validate the technology. In our implemented protocol the wild-type and mutant allele-specific primers are labeled with Cy5 and Cy5.5, respectively. The protocol enables the amplification of the DNA sample in a single PCR. The genotype was deduced from the fluorescence of the amplicons run in the CE microchip. Validation on 15 DNA samples from either homozygous wild-type or heterozygous and homozygous mutated control subjects proved the complete reliability of the system, thus confirming its high diagnostic potential.

One of the main issues of Single Photon Avalanche Diode arrays is optical crosstalk. Since its intensity increases with reducing the distance between devices, this phenomenon limits the density of integration within arrays. In the past optical crosstalk was ascribed essentially to the light propagating from one detector to another through direct optical paths. Accordingly, reflecting trenches between devices were proposed to prevent it, but they proved to be not completely effective. In this paper we will present experimental evidence that a significant contribution to optical crosstalk comes from light reflected internally off the bottom of the chip, thus being impossible to eliminate it completely by means of trenches. We will also propose an optical model to predict the dependence of crosstalk on the distance between devices.

This article reports a complete characterization of single photon avalanche diodes (SPADs) at temperatures down to 120 K. We show that deep cooling of the device by means of a compact liquid-nitrogen Dewar brings several advantages, such as extremely low dark counting rates (down to 1 counts/s), better time resolution, and higher quantum efficiency in the visible range. By using a special current pick-off circuit, we achieved a time resolution of 20 ps full width at half maximum at 120 K for a 50 mum diameter SPAD. Afterpulsing effects are avoided by using a sufficiently long hold-off time (microseconds).

The four‐switch Buck‐Boost (FSBB) converter are widely used in combination with other isolated converter to extend the voltage range capability of the overall structure. When the converter operates in buck‐boost mode and boost mode, it exhibits a right half plane zero (RHPZ) in the control to output transfer function. This characteristic would cause negative impact to stability of the converter. In order to eliminate the RHPZ, a novel modulation method is proposed in this paper. The buck mode is introduced to the modulation to adjust the voltage gain, and the corresponding average state space modeling for the FSBB with the proposed modulation is established. The simulation of the converter with the proposed modulation method and traditional modulation are presented. Finally, experiment results by hardware in the loop (HIL) platform is employed to verity the correctness of theoretical analysis results. [ABSTRACT FROM AUTHOR]

Significant strides have been made in identifying tumour‐associated antigens over the past decade, revealing unique epitopes crucial for targeted cancer therapy. Among these, the New York esophageal squamous cell carcinoma (NY‐ESO‐1) protein, a cancer/testis antigen, stands out. This protein is presented on the cell surface by major histocompatibility complex class I molecules and exhibits restricted expression in germline cells and various cancers, marking it as an immune‐privileged site. Remarkably, NY‐ESO‐1 serves a dual role as both a tumour‐associated antigen and its own adjuvant, implying a potential function as a damage‐associated molecular pattern. It elicits strong humoural immune responses, with specific antibody frequencies significantly correlating with disease progression. These characteristics make NY‐ESO‐1 an appealing candidate for developing effective and specific immunotherapy, particularly for advanced stages of disease. In this review, we provide a comprehensive overview of NY‐ESO‐1 as an immunogenic tumour antigen. We then explore the diverse strategies for targeting NY‐ESO‐1, including cancer vaccination with peptides, proteins, DNA, mRNA, bacterial vectors, viral vectors, dendritic cells and artificial adjuvant vector cells, while considering the benefits and drawbacks of each strategy. Additionally, we offer an in‐depth analysis of adoptive T‐cell therapies, highlighting innovative techniques such as next‐generation NY‐ESO‐1 T‐cell products and the integration with lymph node‐targeted vaccines to address challenges and enhance therapeutic efficacy. Overall, this comprehensive review sheds light on the evolving landscape of NY‐ESO‐1 targeting and its potential implications for cancer treatment, opening avenues for future tailored directions in NY‐ESO‐1‐specific immunotherapy. Highlights: Endogenous immune response: NY‐ESO‐1 exhibited high immunogenicity, activating endogenous dendritic cells, T cells and B cells.NY‐ESO‐1‐based cancer vaccines: NY‐ESO‐1 vaccines using protein/peptide, RNA/DNA, microbial vectors and artificial adjuvant vector cells have shown promise in enhancing immune responses against tumours.NY‐ESO‐1‐specific T‐cell receptor‐engineered cells: NY‐ESO‐1‐targeted T cells, along with ongoing innovations in engineered natural killer cells and other cell therapies, have improved the efficacy of immunotherapy. [ABSTRACT FROM AUTHOR]

Single-photon avalanche diodes (SPADs) belong to a family of avalanche photodiodes (APDs) with single-photon detection capability that operate above the breakdown voltage (i.e., Geiger mode). Design and technology constraints, such as dark current, photon detection probability, and power dissipation, impose inherent device limitations on avalanche photodiodes. Moreover, after the detection of a photon, SPADs require dead time for avalanche quenching and recharge before they can detect another photon. The reduction in dead time results in higher efficiency for photon detection in high-frequency applications. In this work, an electronic interface, based on the pole-zero compensation technique for reducing dead time, was investigated. A nanosecond pulse generator was designed and fabricated to generate pulses of comparable voltage to an avalanche transistor. The quenching time constant (τq) is not affected by the compensation capacitance variation, while an increase of about 30% in the τq is related to the properties of the specific op-amp used in the design. Conversely, the recovery time was observed to be strongly influenced by the compensation capacitance. Reductions in the recovery time, from 927.3 ns down to 57.6 ns and 9.8 ns, were observed when varying the compensation capacitance in the range of 5–0.1 pF. The experimental results from an SPAD combined with an electronic interface based on an avalanche transistor are in strong accordance, providing similar output pulses to those of an illuminated SPAD. [ABSTRACT FROM AUTHOR]

We report an obvious improvement in the performance of a separated absorption charger-layer multiplication Ge/Si avalanche photodetector, achieved by passivating the sidewalls with a low-temperature remote oxygen plasma (ROP) treatment. The dangling bonds on the Ge surface can be efficiently passivated by the formation of an ideal Ge/GeO2 interface. With ROP passivation, the leakage current of the device shows a three- to fourfold decrease at 300 K, resulting in a dark current (I dark) of 3.5 × 10−6 A at 90% avalanche voltage (V br) and 3.4 × 10−7 A at punch-through voltage (V puhch-through) for the 26 μ m-diameter device. A reduction of over tenfold is demonstrated at 200 K and the passivation mechanism is revealed. In addition, a multiplication gain of 94 is obtained under 1550 nm illumination. The device with ROP passivation shows an improved gain bandwidth product of 190 GHz. The enhanced high-frequency response of the device with ROP passivation can be attributed to the alleviation of the retarding effect caused by the interface state on the sidewalls. Without using a trans-impedance amplifier, an opening eye diagram at 28 Gbps is demonstrated, indicating reliable device transmission performance. [ABSTRACT FROM AUTHOR]

We present robust pixel design methodologies for a vertical avalanche photodiode-based CMOS image sensor, taking account of three critical practical factors: (i) "guard-ring-free" pixel isolation layout, (ii) device characteristics "insensitive" to applied voltage and temperature, and (iii) stable operation subject to intense light exposure. The "guard-ring-free" pixel design is established by resolving the tradeoff relationship between electric field concentration and pixel isolation. The effectiveness of the optimization strategy is validated both by simulation and experiment. To realize insensitivity to voltage and temperature variations, a global feedback resistor is shown to effectively suppress variations in device characteristics such as photon detection efficiency and dark count rate. An in-pixel overflow transistor is also introduced to enhance the resistance to strong illumination. The robustness of the fabricated VAPD-CIS is verified by characterization of 122 different chips and through a high-temperature and intense-light-illumination operation test with 5 chips, conducted at 125 °C for 1000 h subject to 940 nm light exposure equivalent to 10 kLux. [ABSTRACT FROM AUTHOR]

Copyright of CT Theory & Applications is the property of Editorial Department of CT Theory & Applications and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Simple Summary: Endometrial endometrioid carcinoma (EEC) is generally considered to have a good prognosis. However, a subset of patients die of their disease. For this reason, it is essential to reveal and define all prognostic factors that can guide optimal treatment. Because lymphovascular space invasion (LVSI) is now related to staging, and blood vascular invasion seems to be more important than lymphovascular invasion, it could be important to encourage pathologists to distinguish between the two. The morphologic pattern of myometrial invasion may also be related to biological behavior. Myometrial invasion with an infiltrative pattern is associated with advanced-stage LVSI and recurrence. A specific pattern of myometrial invasion characterized by microcystic, elongated, and fragmented (MELF) glands is known to be associated with LVSI and lymph node metastases. This study investigated the relationship between these three closely related parameters, particularly the importance of blood vessel invasion (BVI), lymphatic vessel invasion (LVI), and MELF invasion as prognostic factors for endometrial cancer. This may be of great importance for the therapeutic approach in EEC. We studied 115 cases of EEC diagnosed on hysterectomy specimens. Double immunohistochemical staining (D2-40/CD31) was performed in all 115 cases to show LVI and BVI on the same slide. MELF pattern invasion was present in 24/115 (21%) cases. MELF-positive tumors had a higher frequency of LVI than MELF-negative tumors (58% and 23%, respectively); the frequency of BVI was twice as high in MELF-positive tumors in comparison to MELF-negative tumors (25% and 12%, respectively). These differences were significant (p ˂ 0.0001). All tumors with positive BVI also had a concomitant LVI. The presence of MELF invasion had no impact on overall survival, confirming previous studies. 5-year survival rates were almost equal in cases with negative LVSI and cases with positive isolated LVI (98% vs. 97%). However, in cases where BVI was also present, the 5-year survival rate was significantly lower, 63% (p ˂ 0.0001). Furthermore, BVI proved to be an independent prognostic factor for overall survival, disease-free survival, and recurrence in the multivariate analysis. In conclusion, MELF pattern invasion is a good predictor of lymphatic and blood vessel invasion but has no prognostic value. Our results suggest that BVI in EEC has greater clinical value than isolated LVI or myometrial invasion patterns, and the therapeutic approach should be guided by BVI presence. Therefore, we hope this study will promote the routine evaluation of BVI in the context of EEC diagnostic procedures. [ABSTRACT FROM AUTHOR]

Modern techniques for DNA and protein analysis and separation rely on measurements of LIF and face a trend toward employing progressively smaller samples. The currently employed detectors that provide the required ultrahigh sensitivity, e.g. photomultiplier tubes (PMTs), are bulky and/or costly and delicate, whereas a key issue for the development of compact and economical instruments is the availability of miniaturized, inexpensive, and ultrasensitive photodetectors. The planar epitaxial silicon single-photon avalanche diodes (SPADs) combine the typical advantages of microelectronics (miniaturization, ruggedness, low voltage, low power, low cost, etc.) with high sensitivity, even better than that of PMTs. The suitability of such SPADs to microchip CE has been here ascertained by developing a new apparatus with dual-wavelength LIF detection. The apparatus has been experimented in studies on the EOF suppression and on the coating stability and tested in rapid sizing of DNA fragments. The experimental results obtained in the separation of Cy5-labeled oligonucleotide demonstrate sensitivity better than 3 pM, which corresponds to less than 100 fluorescent molecules in the 50 pL illuminated volume.

A new integrated active quenching circuit (i-AQC) designed in a standard CMOS process is presented, capable of operating with any available single photon avalanche diode (SPAD) over wide temperature range. The circuit is suitable for attaining high photon timing resolution also with wide-area SPADs. The new i-AQC integrates the basic active-quenching loop, a patented low-side timing circuit comprising a fast pulse pick-up scheme that substantially improves time-jitter performance, and a novel active-load passive quenching mechanism (consisting of a current mirror rather than a traditional high-value resistor) greatly improves the maximum counting rate. The circuit is also suitable for portable instruments, miniaturized detector modules and SPAD-array detectors. The overall features of the circuit may open the way to new developments in diversified applications of time-correlated photon counting in life sciences and material sciences.

We present the design, fabrication, and testing of a low-cost, miniaturized detection system that utilizes chemiluminescence to measure the presence of adenosine triphosphate (ATP), the energy unit in biological systems, in water samples. The ATP–luciferin chemiluminescent solution was faced to a silicon photomultiplier (SiPM) for highly sensitive real-time detection. This system can detect ATP concentrations as low as 0.2 nM, with a sensitivity of 79.5 A/M. Additionally, it offers rapid response times and can measure the characteristic time required for reactant diffusion and mixing within the reaction volume, determined to be 0.3 ± 0.1 s. This corresponds to a diffusion velocity of approximately 44 ± 14 mm2/s. [ABSTRACT FROM AUTHOR]

Objectives: In this retrospective observational study, cases from our institution were included and the published literature reviewed to investigate the diagnosis and prognosis of cervical rhabdomyosarcoma, a rare group of tumours. Material and methods: The clinicopathological data of 12 patients with cervical rhabdomyosarcoma (RMS) treated at the West China Second University Hospital of Sichuan University from January 2006 to May 2023 were collected, and their clinicopathological characteristics, diagnoses, treatments, prognoses and pregnancy outcomes were retrospectively analysed. Results: (1) Clinical characteristics: The ages of the 12 RMS patients ranged from 15 to 50 years, with a median age of 17 years. Five of the patients were adults, and seven were adolescents. The initial symptoms were vaginal bleeding in 5 patients, vaginal tissue prolapse in 6 patients, and abdominal pain and urinary frequency in 1 patient. Two patients were considered to have "cervical polyps" and underwent polypectomy at the other hospitals, but the cervical mass recurred soon thereafter. (2) Pathological features: The maximum tumour diameter ranged from 3 to 25 cm. The twelve cases of cervical RMS consisted of embryonal rhabdomyosarcoma (ERMS) in 7 adolescents, ERMS in 3 adults, and pleomorphic rhabdomyosarcoma (PRMS) in 2 adults. Immunohistochemical results showed the expression of one or more characteristic markers of RMS. We reclassified tumour stage according to the Intergroup Rhabdomyosarcoma Study (IRS) clinical group and tumour node metastasis (TNM) classification. (3) Treatment: Eight patients underwent radical surgery (66.7%, 8/12), including all 5 of the included adults and 3 of the adolescents, 2 of whom were treated 10 years ago. Conservative surgical resection was performed on four patients (33.3%, 4/12), all of whom were adolescents. Postoperative chemotherapy was given to all patients except one, but one patient who underwent radical surgery discontinued chemotherapy on her own without receiving a full course. Two of the ERMS patients underwent preoperative chemotherapy, and the lesions were significantly reduced. (4) Prognosis: One of the 12 patients with cervical RMS was lost to follow-up. Of the remaining 11 patients, 10 (including seven adolescents and three adults) survived tumour free (90.9%, 10/11), and 1 adult patient with existing pulmonary multiple metastases (IRS stage IV, T2N0M1) at the initial diagnosis survived 9 months with progression-free disease (9.1%, 1/11). The median survival time was 91 months (5 to 213 months). Among 4 patients receiving fertility-sparing management, 1 conceived and delivered successfully (25%). Conclusions: The treatment of cervical RMS must take the patient's age and reproductive intent into account. The overall prognosis for cervical RMS in children and adolescents is good, and conservative surgical resection combined with chemotherapy is recommended to preserve fertility. The pregnancy outcome is also worth anticipating. For patients who have completed childbirth, radical surgery is preferred. Approaches to accurately assessing the patient's condition, grasping the indications and scope of surgery, and developing chemoradiotherapy regimens deserve further exploration. [ABSTRACT FROM AUTHOR]

Endometriosis is a frequent, estrogen-dependent, chronic disease, characterized by the presence of endometrial glands and stroma outside of the uterine cavity. Although it is not considered a precursor of cancer, endometriosis is associated with ovarian cancer. In this review, we summarized the evidence that clear-cell and endometrioid ovarian carcinomas (endometriosis-associated ovarian carcinoma—EAOC) may arise in endometriosis. The most frequent genomic alterations in these carcinomas are mutations in the AT-rich interaction domain containing protein 1A (ARID1A) gene, a subunit of the SWI/SNF chromatin remodeling complex, and alterations in phosphatidylinositol 3-kinase (PI3K) which frequently coexist. Recent studies have also suggested the simultaneous role of the PTEN tumor-suppressor gene in the early malignant transformation of endometriosis and the contribution of deficient MMR (mismatch repair) protein status in the pathogenesis of EAOC. In addition to activating and inactivating mutations in cancer driver genes, the complex pathogenesis of EAOC involves multiple other mechanisms such as the modulation of cancer driver genes via the transcriptional and post-translational (miRNA) modulation of cancer driver genes and the interplay with the inflammatory tissue microenvironment. This knowledge is being translated into the clinical management of endometriosis and EAOC. This includes the identification of the new biomarkers predictive of the risk of endometriosis and cancer, and it will shape the precision oncology treatment of EAOC. [ABSTRACT FROM AUTHOR]

Background: Ovarian clear cell carcinoma (OCCC) is a rare pathological histotype in ovarian cancer, while the survival rate of advanced OCCC (Stage III-IV) is substantially lower than that of the advanced serous ovarian cancer (OSC), which is the most common histotype. The goal of this study was to identify high-risk OCCC by comparing OSC and OCCC, with investigating potential risk and prognosis markers. Methods: Patients diagnosed with ovarian cancer from 2009 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) Program. Logistic and Cox regression models were used to identify risk and prognostic factors in high-risk OCCC patients. Cancer-specific survival (CSS) and overall survival (OS) were assessed using Kaplan-Meier curves. Furthermore, Cox analysis was employed to build a nomogram model. The performance evaluation results were displayed using the C-index, calibration plots, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). Immunohistochemically approach was used to identify the expression of the novel target (GPC3). Results: In the Cox analysis for advanced OCCC, age (45–65 years), tumor numbers (total number of in situ/malignant tumors for patient), T3-stage, bilateral tumors, and liver metastases could be defined as prognostic variables. Nomogram showed good predictive power and clinical practicality. Compared with OSC, liver metastases had a stronger impact on the prognosis of patients with OCCC. T3-stage, positive distant lymph nodes metastases, and lung metastases were risk factors for developing liver metastases. Chemotherapy was an independent prognostic factor for patient with advanced OCCC, but had no effect on CSS in patients with liver metastases (p = 0.0656), while surgery was significantly related with better CSS in these patients (p < 0.0001) (p = 0.0041). GPC3 expression was detected in all tissue sections, and GPC3 staining was predominantly found in the cytoplasm and membranes. Conclusion: Advanced OCCC and OCCC with liver metastases are two types of high-risk OCCC. The constructed nomogram exhibited a satisfactory survival prediction for patients with advanced OCCC. GPC3 immunohistochemistry is expected to accumulate preclinical evidence to support the inclusion of GPC3 in OCCC targeted therapy. [ABSTRACT FROM AUTHOR]

A Point-of-Care system for molecular diagnosis (PoC-MD) is described, combining GaN and CMOS chips. The device is a micro-system for fluorescence measurements, capable of analyzing both intensity and lifetime. It consists of a hybrid micro-structure based on a 32 × 32 matrix addressable GaN microLED array, with square LEDs of 50 µm edge length and 100 µm pitch, with an underneath wire bonded custom chip integrating their drivers and placed face-to-face to an array of 16 × 16 single-photon avalanche diodes (SPADs) CMOS. This approach replaces instrumentation based on lasers, bulky optical components, and discrete electronics with a full hybrid micro-system, enabling measurements on 32 × 32 spots. The reported system is suitable for long lifetime (>10 ns) fluorophores with a limit of detection ~1/4 µM. Proof-of-concept measurements of streptavidin conjugate Qdot™ 605 and Amino PEG Qdot™ 705 are demonstrated, along with the device ability to detect both fluorophores in the same measurement. [ABSTRACT FROM AUTHOR]

Focused on addressing harmonic suppression in multiphase indirect matrix converters (IMCs), this study explores spread-spectrum modulation technology through ripple analysis calculations. We introduce a current ripple spread-spectrum modulation (CR-SSM) method tailored for multiphase IMC systems. In this approach, a 3 × 6-phase IMC is modeled as a two-port network, and a small-signal model of the output side is established. The transfer function is utilized to analyze the two-port network in the complex frequency domain (s-plane). The time-domain expression of the output current ripple is derived in vector form. Subsequently, the distribution of the output ripple and locus are determined based on specified constraints. The carrier frequency is dynamically adjusted online according to the specified ripple locus. Compared to classical periodic PWM methods, this approach offers a broader range of frequency variations and achieves a more uniform output spectrum. Furthermore, CR-SSM optimizes system efficiency and enhances spread-spectrum modulation. Experimental results demonstrate that this method effectively enhances the quality of input and output waveforms in multiphase IMC systems. [ABSTRACT FROM AUTHOR]

Integrated photonics on Silicon-On-Insulator (SOI) substrates is a well developed research field that has already significantly impacted various fields, such as quantum computing, micro sensing devices, biosensing, and high-rate communications. Although quite complex circuits can be made with such technology, everything is based on a few 'building blocks' which are then combined to form more complex circuits. This review article provides a detailed examination of the state of the art of integrated photonic building blocks focusing on passive elements, covering fundamental principles and design methodologies. Key components discussed include waveguides, fiber-to-chip couplers, edges and gratings, phase shifters, splitters and switches (including y-branch, MMI, and directional couplers), as well as subwavelength grating structures and ring resonators. Additionally, this review addresses challenges and future prospects in advancing integrated photonic circuits on SOI platforms, focusing on scalability, power efficiency, and fabrication issues. The objective of this review is to equip researchers and engineers in the field with a comprehensive understanding of the current landscape and future trajectories of integrated photonic components on SOI substrates with a 220 nm thick device layer of intrinsic silicon. [ABSTRACT FROM AUTHOR]

This paper proposes a Takagi–Sugeno fuzzy system model based fault tolerant control scheme for DC–DC converters, which is robust against parameter uncertainties and achieves the output voltage of an ideal converter. The control involves estimating the duty cycle change in the form of a fault parameter required to track the output voltage, in the presence of several uncertain conditions including converter losses, variation in input voltage, and unknown and changing output load. An adaptive law is designed to estimate the fault parameter that guarantees state and parameter error convergence. The adaptive law is derived using the Lyapunov stability theorem and the required parameters are evaluated by solving a linear matrix inequalities optimization problem. The load resistance is estimated in parallel by using a Kalman filter and fed to the fault parameter estimation scheme. Furthermore, a fast and robust method to detect short and open circuit switch faults is also presented. The proposed technique offers a simple, yet effective method to regulate the output voltage under several faulty and uncertain conditions. The proposed technique is tested on a DC–DC boost converter simulation model and the demonstrated MATLAB/Simulink results show the effectiveness of the proposed algorithm. [ABSTRACT FROM AUTHOR]

Silicon Photomultipliers (SiPMs) have emerged as leading photon detectors in experimental physics since their introduction in the late 1990s. With performance characteristics superior to those of traditional photodetectors, SiPMs exhibit up to 60% photon detection efficiency, rapid signal rise times, and resistance to magnetic fields. Their solid-state construction enables mass production, compactness, and high spatial resolution, facilitating their integration into a wide range of experimental setups. Although susceptible to radiation damage, mitigation strategies are being studied to allow their reliable operation even in environments with elevated radiation levels. SiPMs excel in detecting low levels of light, making them well suited for applications involving scintillation and Cherenkov light. Their ability to operate effectively at cryogenic temperatures allows the construction of a new class of multi-tons rare event search experiments such as Darkside-20k. Insensitivity to the magnetic field and mitigation of the radiation damages are making SiPMs well-suited to be used in accelerator driven physics such as Cherenkov light detectors for Particle IDentification (PID) in the future Electron Ion Collider (EIC). [ABSTRACT FROM AUTHOR]

"Basal-like" (BL) morphology and the expression of cancer testis antigens (CTA) in breast cancer still have unclear prognostic significance. The aim of our research was to explore correlations of the morphological characteristics and tumor microenvironment in triple-negative breast carcinomas (TNBCs) with multi-MAGE-A CTA expression and to determine their prognostic significance. Clinical records of breast cancer patients who underwent surgery between January 2017 and December 2018 in four major Croatian clinical centers were analyzed. A total of 97 non-metastatic TNBCs with available tissue samples and treatment information were identified. Cancer tissue sections were additionally stained with programmed death-ligand 1 (PD-L1) Ventana (SP142) and multi-MAGE-A (mAb 57B). BL morphology was detected in 47 (49%) TNBCs and was associated with a higher Ki-67 proliferation index and histologic grade. Expression of multi-MAGE-A was observed in 77 (79%) TNBCs and was significantly associated with BL morphology. Lymphocyte-predominant breast cancer (LPBC) status was detected in 11 cases (11.3%) and significantly correlated with the Ki-67 proliferation index, increased number of intratumoral lymphocytes (itTIL), and PD-L1 expression. No impact of BL morphology, multi-MAGE-A expression, histologic type, or LPBC status on disease-free survival was observed. Our data suggest that tumor morphology could help identify patients with potential benefits from CTA-targeting immunotherapy. [ABSTRACT FROM AUTHOR]

This proposed work introduces a DC-DC converter with Switched-Capacitor Delay Deadtime Controller (SCD-DTC), Digitally Controlled Start-Up Block (DC-SUB), and Enhanced Unbalanced-Input Pair Zero-Current Detector (EUIP-ZCD) that helps to improve the overall power efficiency. It also introduces the discussion of key signal waveforms and the two major optimization flowcharts. This proposed DC-DC converter can simultaneously achieve optimized deadtime (body diode conduction < 3 ns) and almost fully eliminate the phenomenon of reverse inductor current (RIC). Furthermore, it also shows that it can achieve a well-regulated output voltage of 1.8 V with <0.01% of output ripple riding on it. All the post-layout simulation results are carried out using 0.18 µm 1P6M CMOS process using Cadence Virtuoso Spectre Circuit Simulator. The silicon chip area of our proposed work (including the output pad frame) is 1.44 mm2. The chip fabrication was sent out in January 2024 and the return of the measurement dies is expected in March 2024. The post-layout simulation results will no doubt closely resemble the measurement results since the proposed work is mostly controlled by digital blocks. [ABSTRACT FROM AUTHOR]

Background: Ovarian clear cell carcinoma (OCCC) represents a subtype of ovarian epithelial carcinoma (OEC) known for its limited responsiveness to chemotherapy, and the onset of distant metastasis significantly impacts patient prognoses. This study aimed to identify potential risk factors contributing to the occurrence of distant metastasis in OCCC. Methods: Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we identified patients diagnosed with OCCC between 2004 and 2015. The most influential factors were selected through the application of Gaussian Naive Bayes (GNB) and Adaboost machine learning algorithms, employing a Venn test for further refinement. Subsequently, six machine learning (ML) techniques, namely XGBoost, LightGBM, Random Forest (RF), Adaptive Boosting (Adaboost), Support Vector Machine (SVM), and Multilayer Perceptron (MLP), were employed to construct predictive models for distant metastasis. Shapley Additive Interpretation (SHAP) analysis facilitated a visual interpretation for individual patient. Model validity was assessed using accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and the area under the receiver operating characteristic curve (AUC). Results: In the realm of predicting distant metastasis, the Random Forest (RF) model outperformed the other five machine learning algorithms. The RF model demonstrated accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and AUC (95% CI) values of 0.792 (0.762–0.823), 0.904 (0.835–0.973), 0.759 (0.731–0.787), 0.221 (0.186–0.256), 0.974 (0.967–0.982), 0.353 (0.306–0.399), and 0.834 (0.696–0.967), respectively, surpassing the performance of other models. Additionally, the calibration curve's Brier Score (95%) for the RF model reached the minimum value of 0.06256 (0.05753–0.06759). SHAP analysis provided independent explanations, reaffirming the critical clinical factors associated with the risk of metastasis in OCCC patients. Conclusions: This study successfully established a precise predictive model for OCCC patient metastasis using machine learning techniques, offering valuable support to clinicians in making informed clinical decisions. [ABSTRACT FROM AUTHOR]

To describe sonographic features of the microcystic elongated and fragmented (MELF) pattern of myometrial invasion (MI) using the International Endometrial Tumor Analysis (IETA) criteria; to assess the effect of the MELF pattern on preoperative ultrasound evaluation of MI; and to determine the relationship of the MELF pattern to more advanced stage (>= IB) and lymph node metastases (LNM) in women with endometrioid endometrial cancer (EEC). Sonographic features and accuracy of ultrasound assessment of MI were compared in cases with the presence and the absence of the MELF pattern. [Extracted from the article]