Cognitive flexibility, defined as the ability to shift mental strategies when environmental demands change, may influence psychological well-being and psychiatric treatment outcomes. Research increasingly implicates the renin angiotensin system (RAS) in cognition, yet its role in cognitive flexibility is inadequately understood. We conducted a double-masked trial with N = 60 healthy adults aged 18-50. Participants were randomly assigned a single 50 mg dose of losartan, an angiotensin type 1 receptor blocker, or placebo. Following a waiting period, participants completed a task-switching paradigm as a measure of cognitive flexibility, which required dynamically categorizing arrows based on location or direction. Statistical analyses were conducted to determine group (losartan vs placebo), task (location vs direction), and switch (switching vs repeating a task) effects on reaction time (RT) and accuracy independently. A composite bin score was also computed, integrating both RT and accuracy data. All participants displayed the expected switch costs. While participants on losartan exhibited numerically superior RTs and accuracy, losartan did not significantly improve task-switching relative to placebo. This was confirmed by composite bin scoring, which indicated no benefit of losartan when RT and accuracy were integrated. An exploratory probe suggested that losartan improved accuracy on direction-switch trials, indicating a potential drug effect under specific cognitive conditions. Overall, we found no significant benefits of losartan on task-switching in healthy adults. Our results may be explained by ceiling effects, which could have hindered the detection of group differences, or possibly reflect a negligible role for the RAS in cognitive flexibility.
We have recently shown that in simulations of unfolded globular proteins, the native contacts are distinguished by their mutual cooperativity, such that this can be used to identify native contact networks. Here we use this approach to analyze the unfolded states of fold-switching proteins. For a series of designed fold switching proteins bridging the GA and GB folds, we observe a systematic shift in the networks of cooperative contacts between those of the α and α/β folds. For the naturally occurring fold-switcher RfaH, we also observe that the cooperativities of the contacts corresponding to the alternative folds are much more similar in energy than in the case of the related NusG, which does not switch folds. The results suggest that the signatures of cooperativity of alternative folds encoded by fold-switching sequences are already present in the unfolded state.
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Next-generation 6G communication requires radio-frequency components capable of operating above 100 GHz with low loss, high isolation, and zero static power-requirements that challenge complementary metal-oxide-semiconductor (CMOS) and microelectromechanical systems (MEMS) technologies. Here, we report transfer-free, large-area millimeter-wave (mmWave) switches based on solution-processed MoS2. While solution-processed 2D materials are often viewed as inferior to their crystalline counterparts due to high defect densities, we demonstrate that their edge-rich morphology is, in fact, a performance enabler. These edge defects act as intrinsic templates that confine Cu-filament pathways, enabling rapid (76 ns) and low-energy switching (1.57 nJ) with > 2000 cycles and uniform zero static-power operation, as corroborated by Kelvin probe force microscopy, conductive atomic force microscopy and low-temperature studies. The resulting switches achieve an low insertion loss ( < 0.1 dB) and high isolation ( > 35 dB) at 67 GHz. Notably, they exhibit a switching figure-of-merit (RON·COFF) of ~ 0.8 fs (fco ~ 187 THz), surpassing previously reported 2D switches. Importantly, by adopting an inverse-state operational scheme in a SHUNT architecture, we mitigate self-switching and achieve improved power handling (P0.1dB > 10 dBm) and linearity (IIP3 > 42.1 dBm). Finally, we demonstrate the platform's circuit-level viability by integrating the switches into a true-time-delay and hybrid-coupled phase shifters targeting 30 GHz mmWave applications.
Increasing clinical complexity, rising admission volumes and shorter hospital stays have intensified demands on internal medicine residents. A 2015 time and motion study at our institution showed that residents spent nearly half of their day on computer work, with frequent task-switching and limited patient contact. These findings prompted organisational reforms to redistribute workload and improve workflow. We aimed to assess how resident time allocation changed after organisational reforms. We performed a before-and-after time and motion study in the division of internal medicine in a tertiary care centre in Switzerland. Direct observations were conducted over identical periods (May-July) in 2015 (baseline, before implementation of organisational reforms) and 2018 (first assessment after full implementation of these reforms). All residents were eligible. Shifts were randomly selected and stratified by weekday, with two shifts per resident observed whenever possible. Trained observers used a standardised electronic tool to record 22 mutually exclusive activities and contextual factors. The primary outcome was time spent on administrative tasks (patient-related and non-patient-related administration, discharge summaries, information retrieval). Secondary outcomes included task-switching rate, mismatch rate (deviation from planned schedule) and shift duration. Division workload data were collected to adjust analyses. Seventy-five residents were observed over 142 shifts (1478 hours). From 2015 to 2018, mean administrative time increased from 92 to 139 minutes/day (p <0.001) and mean task-switching from 15 to 20 per hour (p <0.001), while mean mismatch rate decreased (38.8% to 31.7%, p <0.001). The mean shift duration shortened (11h38m to 10h45m, p <0.001), with mean personal time increasing (32 to 63 minutes, p <0.001). Mean bedside time declined (113 to 92 minutes, p = 0.011) and mean computer use slightly decreased (327 to 290 minutes, p = 0.009). Mean weekly admissions rose (96 to 146, p <0.001) and mean length of stay was halved (15.5 to 8.5 days, p <0.001). Results were consistent after adjustment for division workload. Targeted reforms improved schedule alignment and work-rest balance but failed to reduce administrative burden in a high-turnover environment. Local time-management interventions should be integrated with hospital-wide strategies addressing workflow complexity, interprofessional communication and task distribution. These results may inform similar initiatives in other high-pressure inpatient training settings. ISRCTN 69703381, https://doi.org/10.1186/ISRCTN69703381.
Infrared polarization-sensitive visual synapses distinguish target details under background interference or low contrast, serving as the core for meeting critical fields' demand for efficient infrared optical information processing and recognition. Combining negative/positive photoelectric effects overcomes traditional single-polarity photoresponse limitations in simulating biological synapses' excitatory-inhibitory dual states, laying a crucial foundation for encoding complex neural signals and realizing brain-like multi-level information processing. Integrating wavelength-dependent positive/negative photoresponse switching with infrared polarization sensitivity is key to breaking through existing bottlenecks. Herein, we construct a two-dimensional heterojunction using anisotropic narrow-bandgap semiconductor PdSe2 and semi-metal NbSe2, successfully fabricating a visual synapse integrating the aforementioned two properties. Under 808/1064 nm light illumination, asymmetric current synaptic pulse modulation is achieved via positive/negative voltage regulation, and positive/negative photoresponse switching is realized under low-voltage modulation. Under 808-2200 nm light illumination, investigations on bias voltage, pulse frequency, and pulse intensity demonstrate that the heterojunction can implement synaptic functions at a low bias of 1 mV, with a single-pulse energy consumption as low as 0.298 pJ. Notably, the heterojunction possesses excellent polarization sensitivity, achieving a polarization ratio of 12.67 under 1550 nm light illumination. This work provides a highly promising platform for the development of high-performance multi-dimensional visual systems.
The visualization of mechanical stress in soft materials is highly desirable; however, real-time optical readouts using conventional sensing approaches are problematic because mechanophore-based systems typically require strong threshold-type activation with slow recovery. Herein, we report supramolecular hydrogels that enable the continuous and reversible visualization of mechanical stress in real time via stretch-induced phase separation. Supramolecular switching mechanotransduction (SSM) has been proposed as the key mechanism. Mechanical stimuli are transduced into a distinct network state transition through host-guest complexes between β-cyclodextrin and adamantane as supramolecular switches. In this design, guest-functionalized polymers undergo on-off transition between the hydrated and dehydrated states via host-guest complexation and decomplexation. Responsive polymers, incorporated into the hydrogel network via supramolecular bonds, function as reversible cross-links and switches. Upon stretching, the hydrogels macroscopically transition from transparent to opaque owing to the dehydration-induced heterogeneity within the responsive domains. The linear and reversible changes in the opacity with applied stress-attributable to sacrificial and reversible supramolecular switching-enable the visualization of stress distributions. This design principle offers a platform for spatiotemporally resolved mapping of the mechanical states in hydrogels with an intuitive, instrument-free readout, and lays the foundation for monitoring, timely intervention, and safer operation of soft-material systems.
To investigate the neurophysiological mechanisms of fluid intelligence (Gf), this study systematically examined neural activity differences between adolescents with high and low Gf using three core executive function (EF) tasks: inhibitory control (Flanker), working memory (4-back), and cognitive flexibility (task-switching), with a focus on event-related potentials (ERPs) and aperiodic activity. Electroencephalography (EEG) was recorded during both resting and task states, and the FOOOF algorithm was used to perform parametric spectral decomposition. The results revealed that the low-Gf group exhibited significantly larger P3 amplitudes across the Flanker, 4-back, and task-switching paradigms, a pattern consistent with the neural efficiency hypothesis and suggesting that Gf-related differences are primarily manifested in late-stage cognitive resource integration processes. Regarding aperiodic activity, group differences were task-specific. Notably, only in the Flanker paradigm did the high-Gf group exhibit a significantly larger aperiodic offset under the incongruent condition compared to the congruent condition, suggesting greater sensitivity in neural-state regulation when conflict demands increase. In contrast, the low-Gf group showed no significant difference in aperiodic offset between the two conditions, suggesting relatively limited condition-related adjustment of neural state across conflict conditions. By integrating conventional EEG measures with aperiodic components, this study provides multifaceted evidence for understanding the neural resource allocation and neural-state regulation associated with Gf and offers novel insights into the neurophysiological mechanisms underlying adolescent cognitive processing.
Excessive honking and improper use of the headlamp beam significantly impact driving safety at night through visual impairment caused by headlamp beam glare, driver discomfort and noise pollution in urban areas. Current adaptive lighting technologies are mostly aimed at controlling individual headlamps, and are not connected to the rest of the vehicle's response. To overcome this, this paper presents a hybrid control architecture, ALHCV (Automated Light and Honking Control for Vehicles), that integrates both Programmable Logic Controller (PLC) based control and Artificial Intelligence (AI) based perception for adaptive lighting and honking based on context. The system closely simulates various vehicle parameters such as speed, steering angle, turn rate and stability duration to perform real-time switching of the beam, alert signal at high speeds and modulation of the honk by PLC ladder logic. The vision module uses an AI algorithm to analyze live camera data to detect vehicles approaching the intersection, and to determine silence-sensitive areas, which are then translated into supervisory constraints that dynamically modify or override deterministic decisions as needed. A 33 rung PLC ladder program is used to implement the control strategy and validated using simulation and HIL testing. Experimental results show excellent performance with 99.3% beam switching accuracy, 96.8% glare prevention accuracy and 97.4% silent-zone honking compliance, with end-to-end latency of less than 60ms. The findings demonstrate the potential of the proposed hybrid PLC-AI framework for next-generation intelligent automotive systems, which prioritize safety, adaptability, and environmental sustainability, while maintaining scalability and practicality.
A two-dimensional beam-profile monitor has been constructed based on a scanning Faraday cup array, a 128-channel picoammeter system, and a LabVIEW-based data acquisition system. The Faraday cup array consists of 128 small Faraday cups, while each is connected to an independent picoammeter of the picoammeter system. It is driven across the ion beam by a servo motor and images the two-dimensional beam profile by directly measuring the absolute electric current distribution. The benefit from the avoidance of readout switching between different Faraday cups is that the crosstalk is negligible during a beam scanning. Typically, this monitor scans a beam cross section of 76.8 × 76.8 mm2 within 18-420 seconds. Tests with 50-keV O5+ and 1.8-MeV Xe25+ beams show that an ion beam with beam flux greater than ∼1 pA/mm2 can be clearly distinguished and a spatial resolution of ∼0.6 mm can be achieved. The total beam current measured by this device was calibrated using a Faraday cup, showing a systematic negative deviation of ∼6%-8% relative to the reference current, which is mainly attributed to inlet diameter tolerance and alignment errors.
The treatment with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) (ribociclib, palbociclib, and abemaciclib) combined with endocrine therapy (ET) has become the standard of care (SoC) for first-line treatment in patients with metastatic hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer. There is a lack of consensus on what treatment to offer after disease progression, and there are no established guidelines for therapeutic sequencing. This multicentric retrospective observational analysis aims to characterize systemic treatment following CDK4/6i, among patients with HR+/HER2- metastatic breast cancer (MBC). An observational retrospective study performed in 10 Portuguese oncological centers evaluated 237 patients with MBC who had been treated with at least one CDK4/6i, between January 2016 and July 2022, and had progressed with this treatment. We collected data on the initial staging, the date of diagnosis, HR status, Ki67 and HER2, the date of recurrence, metastatic site, the type of treatment, the date of initiation and the date of progression, and the reason for interruption. Rechallenging with a different CDK4/6 inhibitor demonstrated the highest overall survival (OS), though it is used in a small percentage of patients, highlighting a potential survival advantage and the need for further investigation into optimal sequencing strategies. While capecitabine showed favorable progression-free survival (PFS) and overall survival, ET alone provided a higher OS, reflecting the influence of disease phenotype and treatment selection. Paclitaxel's shorter survival outcomes likely indicate its use in patients with aggressive disease or visceral crisis. These findings underscore the variability in survival outcomes based on post-CDK4/6i therapy choices in HR+/HER2- MBC, with promising evidence for rechallenging strategies.  Switching CDK4/6i and ET conferred a statistically significant improvement of PFS in patients with progression or recurrence on prior CDK4/6i-containing therapy. These findings underscore the variability in survival outcomes based on post-CDK4/6i therapy choices in HR+/HER2- MBC, with promising evidence for rechallenging strategies.
Rheumatoid arthritis (RA) is a systemic autoimmune disease driven by complex immune dysregulation, in which macrophages play a central pathogenic role. Macrophages accumulate extensively in RA synovium, and their abundance and functional phenotypes are correlated with disease activity and severity. Disturbed macrophage polarization is a key feature of RA progression, characterized by an increased proportion of classically activated (M1) macrophages and a reduced proportion of alternatively activated (M2) macrophages. M1 macrophages produce pro-inflammatory mediators that sustain synovial inflammation and contribute to progressive joint damage. Accumulating evidence indicates that immune cell functions are closely linked to metabolic programs. The synovial microenvironment in RA is marked by hypoxia, acidosis, and nutrient limitation, which lead to substantial metabolic reprogramming during macrophage polarization. Importantly, metabolic changes occur not merely secondary to polarization but actively shape the phenotypic transition of macrophages. In this review, we summarize current evidence on how dysregulation of glucose, lipid, and amino acid metabolism regulates the phenotype switching of macrophages in RA. We discuss the roles of key metabolic enzymes and intermediates in macrophage polarization, consider the diagnostic potential of metabolic biomarkers, and highlight therapeutic opportunities targeting metabolic pathways, thereby resolving macrophage imbalance and improving RA outcomes.
This is a summary of the original article "Four-Year Outcomes of Faricimab in Diabetic Macular Edema: Results From the RHONE-X Extension Trial." RHONE-X was a phase 3, multicenter, nonrandomized, 2-year open-label extension of the YOSEMITE/RHINE clinical trials. RHONE-X assessed the long-term safety (primary endpoint) and efficacy (exploratory) of faricimab using a treat-and-extend (T&E) protocol in patients with diabetic macular edema (DME). Patients in YOSEMITE/RHINE who received faricimab 6.0 mg every 8 weeks (Q8W), faricimab 6.0 mg T&E, or aflibercept 2.0 mg Q8W received faricimab 6.0 mg up to Q16W T&E (based on prespecified vision and anatomic criteria) for a further 2 years in RHONE-X. Faricimab was well tolerated through 2 years of RHONE-X, and adverse events reported were consistent with the known safety profile of faricimab. Vision and anatomical improvements achieved during YOSEMITE/RHINE were maintained through RHONE-X. In patients treated with aflibercept during YOSEMITE/RHINE, the proportion achieving absence of DME (CST < 325 µm) increased after switching to faricimab. Approximately 80% of patients were on a faricimab dosing interval of ≥ Q12W at the end of 4 years. These findings demonstrated the long-term safety, efficacy, and durability of faricimab T&E in patients with DME.
Parkinson's disease (PD) is a therapeutically challenging neurodegenerative disease marked by profound disruptions in mitochondrial-redox axis. Current therapeutic agents such as Bromocriptine mesylate (BM) exhibit neuroprotective potential, however their clinical benefit remains largely symptomatic as they do not address the underlying cause of neurodegeneration. Moreover, the therapeutic efficacy of BM is compromised due to its poor solubility, low bioavailability, and inadequate brain penetration. To overcome these biological barriers and provide mechanistic interventions, we report the first drug-loaded porous cerium vanadate nanoplatform (MT-BM-CNP), in which BM, as a model drug is encapsulated within cerium vanadate nanoparticles and surface-functionalized with L-methyl ester tryptophan-conjugated triphenylphosphonium for mitochondrial targeting. The intrinsic Ce3+/Ce4+ and V4+/V5+ redox-switching of cerium vanadate provides strong antioxidant buffering, while the triphenylphosphonium moiety facilitates selective mitochondrial delivery, a central locus of PD pathology. The MT-BM-CNP complex illustrates higher neuroprotective potential by integrating dopaminergic stimulation with intrinsic redox regulation, while exhibiting enhanced stability and sustained drug release. In the preclinical 6-hydroxydopamine PD models, the nanoformulation preserved nigral dopaminergic neurons, restored dopamine levels and significantly improved motor function, with preferential protection of neuronal somata over striatal axon terminals. This study introduces a novel drug-loading strategy using porous cerium vanadate nanoparticles and establishes MT-BM-CNP as a novel mitochondrial-redox axis targeted therapeutic system. This strategy is a significant advancement in nanotechnology-mediated neuroprotection for PD offering not only symptomatic relief but disease-modifying potential as well.
Ionogels are promising for flexible electronics, but their use in triboelectric nanogenerators (TENGs) has been limited by weak mechanical performance and poor interfacial control. Here, we report a molecularly engineered ionogel (VP-IL) with a "rigid-flexible combined skeleton," featuring bicontinuous phase separation via multiple supramolecular interactions. Created by copolymerizing rigid 1-vinylimidazole (1-VIM) and flexible 2-phenoxyethyl acrylate (PhEA) with ionic liquid 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide([EMIM][TFSI]) as dynamic crosslinker and phase-separation driver, the VP-IL ionogel exhibits a well-defined bicontinuous phase separation orchestrated through strong cation-π anchoring of [EMIM]+ onto PhEA benzene rings. The synergistic interplay of this interaction with hydrogen bonds and π-π stacking results in efficient energy dissipation and strain-hardening in VP-IL. Solid-state NMR reveals the slow segmental motion activated by ionic liquids, thereby endowing the material with strong mechanical properties and charge transport capabilities. This dynamic network allows modulus switching over three orders of magnitude and rapid shape memory, supporting UV-curable 3D printing. An intelligent TENG with a reconfigurable friction interface was developed by this material, whose output charge can be regulated on demand through micro-patterning. This work offers a new material platform for the design of a new generation of adaptive soft robots and wearable self-powered systems.
Replacing even a single atom can profoundly alter the performance of photoswitches. Yet, using this strategy to co-tune light-responsiveness and supramolecular function in photoswitches remains unexplored. We synthesized two series of semicarbazone photoswitches, varying the C[double bond, length as m-dash]X unit (X = O, S, Se) and the substituent on the imine moiety (phenyl vs. methoxy-pyridyl). UV-vis spectroscopy and DFT analysis reveal a red-shift in absorption towards the visible region as the πHOMO-πLUMO gap narrows from O to Se. In parallel, heavier chalcogens increase the E → Z photoisomerization quantum yield. Beyond these optical effects, chalcogen substitution reshapes hydrogen-bonding pathways. In the phenyl series, it amplifies supramolecular self-association, yielding more stable π-π stacked, hydrogen-bonded aggregates. In the pyridyl series, it reinforces intramolecular hydrogen bonding, locking the sulfur and selenium analogue in the Z-isomer, whereas the oxygen derivative remains exclusively in the E-form. In mixtures of O-, S-, and Se-derivatives, we achieve wavelength-selective, stepwise deactivation of supramolecular aggregates, switching off the strongest associating species first. Overall, swapping a single chalcogen atom provides control over where these photoswitches absorb, how they isomerize, and how they self-associate. More broadly, this atom-level modification offers a strategy to modify both photophysics and supramolecular organization across carbonyl-containing photoswitch families.
Cold atoms form the backbone of many quantum technology applications, including quantum computation, sensing, and networking. These experiments require a robust cold atom source, precise control of beam parameters, and large optical access. We demonstrate a compact cesium magneto-optical trap (MOT) directly loaded from background vapor, with a footprint of 34 × 56 cm2. The quadrupole and compensation coils are mounted on additively manufactured components, eliminating the need for water cooling and minimizing eddy currents, which enables fast magnetic field switching with a measured settling time of 240 μs. Finite element analysis confirms the mechanical robustness and thermal stability of the coil mounts. The MOT achieves 5 × 106 atoms at a density of 109 cm-3, with a temperature of 76 ± 2 μK, demonstrating a reliable and compact platform suitable for quantum technology experiments.
Although water is an essential component of hydrogels, developing hydrogels that show distinct deformability depending on the surroundings remains interesting and challenging. Herein, a structural remolding strategy of hydrophilic poly(sodium acrylate) is proposed to develop anti-swelling hydrogels, which interestingly show a significant and reversible mechanical switching of underwater ultra-stretchability and overwater non-flexibility. The super anti-swelling hydrogels are derived based on super-swelling poly(sodium acrylate) hydrogels by simply immersing into 0.2-0.8 mol L-1 CaCl2 solutions to form strong Ca2+-carboxyl coordination. The strong Ca2+-carboxyl coordination in the hydrogels serves as a lock, which bundles neighboring poly(sodium acrylate) chains to resist water intrusion into the polymer network for structural maintenance in underwater conditions, as well as constructs loose porous structures exposing the inside water to the surroundings. The obtained hydrogels with coordination-locked networks show long-term stability, self-healing, and ultra-high stretchability of ∼30 with an equilibrium-water-content of ∼70 wt% in versatile underwater conditions, and achieve rapid dehydration and loss of flexibility within 30 min in overwater conditions. Owing to their unique switchable characteristics, the hydrogels demonstrate multiple concealed functionalities that are activated only in underwater conditions. The work here deepens the understanding of poly(sodium acrylate) hydrogels and paves a new way for the design and remolding of hydrogel topology tailored for underwater-only functions.
Head and neck squamous cell carcinoma (HNSCC) frequently exhibits metastatic progression and develops an immunosuppressive microenvironment. However, the tumor cell-intrinsic factors contributing to metastasis-associated immune remodeling remain incompletely understood. Here, we integrated two independent single-cell RNA-seq cohorts (GSE243933 and GSE181919) to compare primary and metastatic HNSCC ecosystems and identified vacuole membrane protein 1 (VMP1) as a malignant cell-intrinsic gene consistently upregulated across metastatic contexts. In TCGA-HNSCC and two GEO cohorts (GSE65858 and GSE117973), high VMP1 expression was associated with poor prognosis and enrichment of invasion-related programs, including epithelial-mesenchymal transition (EMT) and TNFα/NF-κB signaling, and was also associated with decreased CD8⁺ T-cell infiltration and impaired effector features. In an independent HNSCC tissue cohort, immunohistochemistry confirmed elevated VMP1 protein expression in tumors and its association with advanced clinicopathological features and unfavorable survival. Functionally, gain- and loss-of-function experiments in SCC25 and CAL27 cells showed that VMP1 enhances proliferation, migration, and invasion, accompanied by EMT-like marker switching, increased RelA/p65 phosphorylation, and elevated PD-L1 expression. Collectively, VMP1 identifies a metastasis-associated tumor-intrinsic factor associated with invasive progression and reduced CD8⁺ T-cell activity. The concomitant NF-κB activation and PD-L1 induction support a potential VMP1-associated NF-κB/PD-L1 link that may contribute to the association between invasion-related programs and immune modulation. These findings support the potential biomarker relevance of VMP1 and provide a rationale for further mechanistic and clinical investigation in HNSCC.
Benzalkonium chloride (BAK) is the most widely used preservative in multidose glaucoma eye drops. Medical management of glaucoma often requires the chronic use of preserved eye drops, resulting in a high incidence of BAK‑associated ocular discomfort, ocular surface disease, accumulation within ocular structures, and inflammatory tissue changes. The use of BAK has also been associated with reduced surgical success in trabeculectomy. Although alternative preservatives exist, they have also been associated with some toxic effects. Switching from BAK‑containing formulations to preservative‑free (PF) formulations results in significantly fewer side effects, improved ocular surface disease, and enhanced patient comfort. However, barriers such as cost and ease of use have impeded the more widespread adoption of PF glaucoma drops.