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Cyclosporine A (CsA) is one of the systemic therapeutic options for moderate-to-severe psoriasis, based on its efficacy and rapidity of action. The current study investigated the response to CsA in patients with moderate-to-severe plaque psoriasis. TRANSITION was an observational, cross-sectional, multicentre study which evaluated the proportion of partial- and suboptimal-responders among patients with moderate-to-severe plaque psoriasis treated with continuous CsA for ≥12 weeks. Patients demonstrating a Psoriasis Area and Severity Index (PASI) response of ≥90, ≥75 and <90, ≥50 and <75 and <50 were defined as responders, suboptimal-responders, partial-responders, and non-responders, respectively. A total of 196 patients (mean age, 46.6 years; 62.8% males) from 14 sites in Italy were evaluated. At the study visit, the mean (SD) PASI score was 4.2(5.5) compared with 15.3(7.1) prior to the last CsA cycle. For response categories, 39.8%, 22.4%, 16.8%, and 20.9% of patients were responders, suboptimal-responders, partial-responders, and non-responders to CsA treatment. Overall, 28.6% of patients permanently discontinued treatment with CsA (lack of efficacy [10.2%], poor tolerability and voluntary discontinuation [3.6% each], and other [11.7%]). Patients were only partially satisfied with CsA treatment, reporting measurable impact on quality of life. Only 40% patients showed a satisfactory response to CsA. [ABSTRACT FROM AUTHOR]

We report on a free-space-coupled superconducting nanowire single-photon detector array developed for NASA's Deep Space Optical Communications project (DSOC). The array serves as the downlink detector for DSOC's primary ground receiver terminal located at Palomar Observatory's 200-inch Hale Telescope. The 64-pixel WSi array comprises four quadrants of 16 co-wound pixels covering a 320-µm diameter active area and embedded in an optical stack. The detector system also includes cryogenic optics for filtering and focusing the downlink signal and electronics for biasing the array and amplifying the output pulses. The detector system exhibits a peak system detection efficiency of 76% at 1550 nm, a background-limited false count rate as low as 3.7 kcps across the array, a timing jitter less than 120 ps FWHM, and a maximum count rate of ∼1 Gcps.

Introduction: The rapid development of software tools to assist systematic reviewers has led to varying degrees of adoption and selection among researchers. However, the actual usage patterns of these tools, their preferred features, and the criteria for selecting the most suitable tools remain unclear., Methods: To understand these aspects, we collected 175 responses from researchers across different continents., Results: In terms of handsearching, despite new tools developed, our findings reveal that manual handsearching remains prevalent among more than half of the participants. Databases are the most popular tools for citation searching, followed by citation management tools and spreadsheets. This reliance on citation management tools and spreadsheets is concerning as they are not specifically designed for systematic reviews. The primary factors influencing tool selection are the research environment and ease of use. Barriers stopping researchers from adopting alternative tools include limited awareness, challenges in learning new tools, and the financial costs associated with acquiring licenses. Moreover, researchers located in Europe show greater familiarity with a wider range of tools compared to their North American counterparts., Discussion: This preregistered study contributes valuable insights into the tool usage patterns of education researchers, emphasizing the importance of promoting awareness and facilitating the broader adoption of existing tools., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Pellegrini, Marsili and Neitzel.)

We present ATLAS, a 512 × 512 single-photon avalanche diode (SPAD) array with embedded autocorrelation computation, implemented in 3D-stacked CMOS technology, suitable for single-photon correlation spectroscopy applications, including diffuse correlation spectroscopy (DCS). The shared per-macropixel SRAM architecture provides a 128 × 128 macropixel resolution, with parallel autocorrelation computation, with a minimum autocorrelation lag-time of 1 µs. We demonstrate the direct, on-chip computation of the autocorrelation function of the sensor, and its capability to resolve changes in decorrelation times typical of body tissue in real time, at long source-detector separations similar to those achieved by the current leading optical modalities for cerebral blood flow monitoring. Finally, we demonstrate the suitability for in-vivo measurements through cuff-occlusion and forehead cardiac signal measurements., Competing Interests: Robert Henderson and Neil Finlayson are co-founders of Singular Photonics, a company producing SPAD cameras for a variety of applications., (© 2024 The Author(s).)

Background: Type 2 diabetes mellitus (T2DM) is a worldwide socioeconomic burden, and is accompanied by a variety of metabolic disorders, as well as nerve dysfunction referred to as diabetic neuropathy (DN). Despite a tremendous body of research, the pathogenesis of DN remains largely elusive. Currently, two schools of thought exist regarding the pathogenesis of diabetic neuropathy: a) mitochondrial-induced toxicity, and b) microvascular damage. Both mechanisms signify DN as an intractable disease and, as a consequence, therapeutic approaches treat symptoms with limited efficacy and risk of side effects., Objective: Here, we propose that the human body exclusively employs mechanisms of adaptation to protect itself during an adverse event. For this purpose, two control systems are defined, namely the autonomic and the neural control systems. The autonomic control system responds via inflammatory and immune responses, while the neural control system regulates neural signaling, via plastic adaptation. Both systems are proposed to regulate a network of temporal and causative connections which unravel the complex nature of diabetic complications., Results: A significant result of this approach infers that both systems make DN reversible, thus opening the door to novel therapeutic applications., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Cerebral blood flow (CBF) is crucial for brain health. Speckle contrast optical spectroscopy (SCOS) is a technique that has been recently developed to measure CBF, but the use of SCOS to measure human brain function at large source-detector separations with comparable or greater sensitivity to cerebral rather than extracerebral blood flow has not been demonstrated. We describe a fiber-based SCOS system capable of measuring human brain activation induced CBF changes at 33 mm source detector separations using CMOS detectors. The system implements a pulsing strategy to improve the photon flux and uses a data processing pipeline to improve measurement accuracy. We show that SCOS outperforms the current leading optical modality for measuring CBF, i.e. diffuse correlation spectroscopy (DCS), achieving more than 10x SNR improvement at a similar financial cost. Fiber-based SCOS provides an alternative approach to functional neuroimaging for cognitive neuroscience and health science applications., (© 2023. Springer Nature Limited.)

Significance: Diffuse correlation spectroscopy (DCS) is an indispensable tool for quantifying cerebral blood flow noninvasively by measuring the autocorrelation function (ACF) of the diffused light. Recently, a multispeckle DCS approach was proposed to scale up the sensitivity with the number of independent speckle measurements, leveraging the rapid development of single-photon avalanche diode (SPAD) cameras. However, the extremely high data rate from advanced SPAD cameras is beyond the data transfer rate commonly available and requires specialized high-performance computation to calculate large number of autocorrelators (ACs) for real-time measurements., Aim: We aim to demonstrate a data compression scheme in the readout field-programmable gate array (FPGA) of a large-pixel-count SPAD camera. On-FPGA, data compression should democratize SPAD cameras and streamline system integration for multispeckle DCS., Approach: We present a 192 × 128 SPAD array with 128 linear ACs embedded on an FPGA to calculate 12,288 ACFs in real time., Results: We achieved a signal-to-noise ratio (SNR) gain of 110 over a single-pixel DCS system and more than threefold increase in SNR with respect to the state-of-the-art multispeckle DCS., Conclusions: The FPGA-embedded autocorrelation algorithm offers a scalable data compression method to large SPAD array, which can improve the sensitivity and usability of multispeckle DCS instruments., (© 2023 The Authors.)

Non-invasive continuous blood pressure monitoring remains elusive. There has been extensive research using the photoplethysmographic (PPG) waveform for blood pressure estimation, but improvements in accuracy are still needed before clinical use. Here we explored the use of an emerging technique, speckle contrast optical spectroscopy (SCOS), for blood pressure estimation. SCOS provides measurements of both blood volume changes (PPG) and blood flow index (BFi) changes during the cardiac cycle, and thus provides a richer set of parameters compared to traditional PPG. SCOS measurements were taken on the finger and wrists of 13 subjects. We investigated the correlations between features extracted from both the PPG and BFi waveforms with blood pressure. Features from the BFi waveforms were more significantly correlated with blood pressure than PPG features ( R  = - 0.55, p  = 1.1 × 10 -4 for the top BFi feature versus R  = - 0.53, p  = 8.4 × 10 -4 for the top PPG feature). Importantly, we also found that features combining BFi and PPG data were highly correlated with changes in blood pressure ( R  = - 0.59, p  = 1.7 × 10 -4 ). These results suggest that the incorporation of BFi measurements should be further explored as a means to improve blood pressure estimation using non-invasive optical techniques., Competing Interests: DB: Meta Platforms Inc. (F), DR: Meta Platforms Inc (F)., (© 2023 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Diffuse correlation spectroscopy (DCS) is a promising noninvasive technique for monitoring cerebral blood flow and measuring cortex functional activation tasks. Taking multiple parallel measurements has been shown to increase sensitivity, but is not easily scalable with discrete optical detectors. Here we show that with a large 500 × 500 SPAD array and an advanced FPGA design, we achieve an SNR gain of almost 500 over single-pixel mDCS performance. The system can also be reconfigured to sacrifice SNR to decrease correlation bin width, with 400 ns resolution being demonstrated over 8000 pixels., Competing Interests: MAW: Meta Platforms Inc. (F), EJS: Meta Platforms Inc. (E), PM: Meta Platforms Inc. (F), FM: Meta Platforms Inc. (E), EC: Fasttree3D SA (I,S) and PI Imaging Technology SA (I, S), CB: PI Imaging Technology SA (I, S)., (© 2023 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Psoriasis is a common chronic skin disease characterized by a worldwide distribution and a natural tendency towards progression. According to the many clinical forms, the extension of the disease and the many comorbidities, almost the 20% of the patients require a systemic treatment. Biologics have greatly changed the ongoing of psoriasis and the quality of life of psoriasis patients. After the anti-TNF-alpha, which were the first biologics in use for psoriasis, the improvement in knowledge of the pathogenetic mechanisms underlying the disease has led to the development of a series of more specific therapies for psoriasis. This "second generation" of biologics includes the interleukin (IL)-12/23 inhibitor ustekinumab, IL-17 inhibitors (secukinumab and ixekizumab), the IL-17 receptor A (IL-17RA) antagonist brodalumab, and the IL-23 inhibitors guselkumab, risankizumab and tildrakizumab. This study represents an update of the Tuscany consensus focused on the use of new drugs, such as anti-IL-17 and anti-IL-23 in moderate-to-severe psoriasis and their correct place in therapy according to specific clinical requests and in full respect of the current financial restrictions.

We introduce a dynamic speckle model (DSM) to simulate the temporal evolution of fully developed speckle patterns arising from the interference of scattered light reemitted from dynamic tissue. Using this numerical tool, the performance of laser speckle contrast imaging (LSCI) or speckle contrast optical spectroscopy (SCOS) systems which quantify tissue dynamics using the spatial contrast of the speckle patterns with a certain camera exposure time is evaluated. We have investigated noise sources arising from the fundamental speckle statistics due to the finite sampling of the speckle patterns as well as those induced by experimental measurement conditions including shot noise, camera dark and read noise, and calibrated the parameters of an analytical noise model initially developed in the fundamental or shot noise regime that quantifies the performance of SCOS systems using the number of independent observables (NIO). Our analysis is particularly focused on the low photon flux regime relevant for human brain measurements, where the impact of shot noise and camera read noise can become significant. Our numerical model is also validated experimentally using a novel fiber based SCOS (fb-SCOS) system for a dynamic sample. We have found that the signal-to-noise ratio (SNR) of fb-SCOS measurements plateaus at a camera exposure time, which marks the regime where shot and fundamental noise dominates over camera read noise. For a fixed total measurement time, there exists an optimized camera exposure time if temporal averaging is utilized to improve SNR. For a certain camera exposure time, photon flux value, and camera noise properties, there exists an optimized speckle-to-pixel size ratio (s/p) at which SNR is maximized. Our work provides the design principles for any LSCI or SCOS systems given the detected photon flux and properties of the instruments, which will guide the experimental development of a high-quality, low-cost fb-SCOS system that monitors human brain blood flow and functions., Competing Interests: Dr. Boas consulted with Meta Platforms Inc. on topics related to speckle contrast optical spectroscopy and diffuse correlation spectroscopy that ultimately led to the ideas presented in this paper. Dr. Boas’s interests were reviewed and are managed by Boston University in accordance with their conflict of interest policies., (© 2022 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Atopic dermatitis (AD) is a common inflammatory skin disease often associated with a significant impairment in the quality of life of affected patients. The Italian Society of Dermatology and Venereology (SIDeMaST) planned a national information campaign, providing direct access to 27 dermatologic centers dedicated to the management of AD. The aim of this study aimed was to outline critical aspects related to AD in the general population. Overall, 643 adult subjects were included in this study, and in 44.2% (284/643) of cases, a diagnosis of AD was confirmed, whereas about 55% of subjects were affected by other pruritic cutaneous diseases. Higher intensity of pruritus and sleep disturbance, as well as an increased interference in sport, work, and social confidence was reported in the AD group compared to the non-AD group. In the AD subgroup, the mean duration of disease was of 15.3 years, with a mean eczema area and severity index (EASI) score of 11.2, and investigator global assessment (IGA) score of 1.9 and an itch numeric rating scale (NRS) of 6.9. Almost 32% of patients were untreated, either with topical or systemic agents, whereas 44.3% used routine topical compounds (topical corticosteroids and calcineurin inhibitors), and only 7.0% of patients were systemically treated. Only 2.8% of patients reported complete satisfaction with the treatment received for AD to date. This study reveals a profound unmet need in AD, showing a poorly managed and undertreated patient population despite a high reported burden of disease. This suggests the usefulness of information campaigns with the goal of improving patient awareness regarding AD and facilitating early diagnosis and access to dedicated healthcare institutions., Competing Interests: The authors declare no conflict of interest related to this study.

Significance: Diffuse correlation spectroscopy (DCS) is an optical technique that measures blood flow non-invasively and continuously. The time-domain (TD) variant of DCS, namely, TD-DCS has demonstrated a potential to improve brain depth sensitivity and to distinguish superficial from deeper blood flow by utilizing pulsed laser sources and a gating strategy to select photons with different pathlengths within the scattering tissue using a single source-detector separation. A quantitative tool to predict the performance of TD-DCS that can be compared with traditional continuous wave DCS (CW-DCS) currently does not exist but is crucial to provide guidance for the continued development and application of these DCS systems., Aims: We aim to establish a model to simulate TD-DCS measurements from first principles, which enables analysis of the impact of measurement noise that can be utilized to quantify the performance for any particular TD-DCS system and measurement geometry., Approach: We have integrated the Monte Carlo simulation describing photon scattering in biological tissue with the wave model that calculates the speckle intensity fluctuations due to tissue dynamics to simulate TD-DCS measurements from first principles., Results: Our model is capable of simulating photon counts received at the detector as a function of time for both CW-DCS and TD-DCS measurements. The effects of the laser coherence, instrument response function, detector gate delay, gate width, intrinsic noise arising from speckle statistics, and shot noise are incorporated in the model. We have demonstrated the ability of our model to simulate TD-DCS measurements under different conditions, and the use of our model to compare the performance of TD-DCS and CW-DCS under a few typical measurement conditions., Conclusion: We have established a Monte Carlo-Wave model that is capable of simulating CW-DCS and TD-DCS measurements from first principles. In our exploration of the parameter space, we could not find realistic measurement conditions under which TD-DCS outperformed CW-DCS. However, the parameter space for the optimization of the contrast to noise ratio of TD-DCS is large and complex, so our results do not imply that TD-DCS cannot indeed outperform CW-DCS under different conditions. We made our code available publicly for others in the field to find use cases favorable to TD-DCS. TD-DCS also provides a promising way to measure deep brain tissue dynamics using a short source-detector separation, which will benefit the development of technologies including high density DCS systems and image reconstruction using a limited number of source-detector pairs.