Progranulin Deficiency Promotes Circuit-Specific Synaptic Pruning by Microglia via Complement Activation.

Microglia maintain homeostasis in the brain, but whether aberrant microglial activation can cause neurodegeneration remains controversial. Here, we use transcriptome profiling to demonstrate that deficiency in frontotemporal dementia (FTD) gene progranulin (Grn) leads to an age-dependent, progressive upregulation of lysosomal and innate immunity genes, increased complement production, and enhanced synaptic pruning in microglia. During aging, Grn(-/-) mice show profound microglia infiltration and preferential elimination of inhibitory synapses in the ventral thalamus, which lead to hyperexcitability in the thalamocortical circuits and obsessive-compulsive disorder (OCD)-like grooming behaviors. Remarkably, deleting C1qa gene significantly reduces synaptic pruning by Grn(-/-) microglia and mitigates neurodegeneration, behavioral phenotypes, and premature mortality in Grn(-/-) mice. Together, our results uncover a previously unrecognized role of progranulin in suppressing aberrant microglia activation during aging. These results represent an important conceptual advance that complement activation and microglia-mediated synaptic pruning are major drivers, rather than consequences, of neurodegeneration caused by progranulin deficiency.

Preparing random states and benchmarking with many-body quantum chaos.

Producing quantum states at random has become increasingly important in modern quantum science, with applications being both theoretical and practical. In particular, ensembles of such randomly distributed, but pure, quantum states underlie our understanding of complexity in quantum circuits1 and black holes2, and have been used for benchmarking quantum devices3,4 in tests of quantum advantage5,6. However, creating random ensembles has necessitated a high degree of spatio-temporal control7-12 placing such studies out of reach for a wide class of quantum systems. Here we solve this problem by predicting and experimentally observing the emergence of random state ensembles naturally under time-independent Hamiltonian dynamics, which we use to implement an efficient, widely applicable benchmarking protocol. The observed random ensembles emerge from projective measurements and are intimately linked to universal correlations built up between subsystems of a larger quantum system, offering new insights into quantum thermalization13. Predicated on this discovery, we develop a fidelity estimation scheme, which we demonstrate for a Rydberg quantum simulator with up to 25 atoms using fewer than 104 experimental samples. This method has broad applicability, as we demonstrate for Hamiltonian parameter estimation, target-state generation benchmarking, and comparison of analogue and digital quantum devices. Our work has implications for understanding randomness in quantum dynamics14 and enables applications of this concept in a much wider context4,5,9,10,15-20.

Conformational surveillance of Orai1 by a rhomboid intramembrane protease prevents inappropriate CRAC channel activation.

Calcium influx through plasma membrane calcium release-activated calcium (CRAC) channels, which are formed of hexamers of Orai1, is a potent trigger for many important biological processes, most notably in T cell-mediated immunity. Through a bioinformatics-led cell biological screen, we have identified Orai1 as a substrate for the rhomboid intramembrane protease RHBDL2. We show that RHBDL2 prevents stochastic calcium signaling in unstimulated cells through conformational surveillance and cleavage of inappropriately activated Orai1. A conserved disease-linked proline residue is responsible for RHBDL2's recognizing the active conformation of Orai1, which is required to sharpen switch-like signaling triggered by store-operated calcium entry. Loss of RHBDL2 control of CRAC channel activity causes severe dysregulation of downstream CRAC channel effectors, including transcription factor activation, inflammatory cytokine expression, and T cell activation. We propose that this surveillance function may represent an ancient activity of rhomboid proteases in degrading unwanted signaling proteins.

A small molecule inhibitor prevents gut bacterial genotoxin production.

The human gut bacterial genotoxin colibactin is a possible key driver of colorectal cancer (CRC) development. Understanding colibactin's biological effects remains difficult owing to the instability of the proposed active species and the complexity of the gut microbiota. Here, we report small molecule boronic acid inhibitors of colibactin biosynthesis. Designed to mimic the biosynthetic precursor precolibactin, these compounds potently inhibit the colibactin-activating peptidase ClbP. Using biochemical assays and crystallography, we show that they engage the ClbP binding pocket, forming a covalent bond with the catalytic serine. These inhibitors reproduce the phenotypes observed in a clbP deletion mutant and block the genotoxic effects of colibactin on eukaryotic cells. The availability of ClbP inhibitors will allow precise, temporal control over colibactin production, enabling further study of its contributions to CRC. Finally, application of our inhibitors to related peptidase-encoding pathways highlights the power of chemical tools to probe natural product biosynthesis.

Incoherent merger network for robust ratiometric gene expression response.

A ratiometric response gives an output that is proportional to the ratio between the magnitudes of two inputs. Ratio computation has been observed in nature and is also needed in the development of smart probiotics and organoids. Here, we achieve ratiometric gene expression response in bacteria Escherichia coli with the incoherent merger network. In this network, one input molecule activates expression of the output protein while the other molecule activates an intermediate protein that enhances the output's degradation. When degradation rate is first order and faster than dilution, the output responds linearly to the ratio between the input molecules' levels over a wide range with R2 close to 1. Response sensitivity can be quantitatively tuned by varying the output's translation rate. Furthermore, ratiometric responses are robust to global perturbations in cellular components that influence gene expression because such perturbations affect the output through an incoherent feedforward loop. This work demonstrates a new molecular signal processing mechanism for multiplexed sense-and-respond circuits that are robust to intra-cellular context.

RTL1/PEG11 imprinted in human and mouse brain mediates anxiety-like and social behaviors and regulates neuronal excitability in the locus coeruleus.

RTL1/PEG11, which has been associated with anxiety disorders, is a retrotransposon-derived imprinted gene in the placenta. However, imprinting patterns and functions of RTL1 in the brain have not been well-investigated. We found Rtl1 was paternally, but not maternally, expressed in brain stem, thalamus, and hypothalamus of mice, and imprinting status of RTL1 was maintained in human brain. Paternal Rtl1 knockout (Rtl1m+/p-) mice had higher neonatal death rates due to impaired suckling, and low body weights beginning on embryonic day 16.5. High paternal expression of Rtl1 was detected in the locus coeruleus (LC) and Rtl1m+/p- mice showed an increased delay in time of onset for action potentials and inward currents with decreased neuronal excitability of LC neurons. Importantly, Rtl1m+/p- mice exhibited behaviors associated with anxiety, depression, fear-related learning and memory, social dominance, and low locomotor activity. Taken together, our findings demonstrate RTL1 is imprinted in brain, mediates emotional and social behaviors, and regulates excitability in LC neurons.

Compact efficient high-power continuous-wave Nd:YVO4/KGW/LBO Raman lasers for selectable wavelengths within 559-603†nm.

Compact efficient high-power continuous-wave Nd:YVO4 Raman lasers for selectable wavelengths within 559-603 nm are achieved by using KGW crystal for intracavity stimulated Raman scattering (SRS) and lithium triborate (LBO) crystal for intracavity sum frequency generation (SFG) and second harmonic generation (SHG). The LBO crystal with the cut angle in the XY plane for the type-I phase matching is used to perform intracavity SHG or SFG. Experimental results reveal that the participated Stokes lines include the internal vibration mode at 901 cm-1, the external vibrational mode at 209 cm-1, and the combination mode of the 901 cm-1 and 209 cm-1 Raman shifts. By tuning LBO temperature for attaining the maximum output power, the output spectrum reveals the triple peaks of 588.7, 595.7, and 603.1 nm with the intensity ratio of 10:4:1. Under this circumstance, the output power can reach the highest value of 10.8 W at a pump power of 40 W. Furthermore, the output spectrum can be simply concentrated on the single peaks among 588.7 (orange), 565.7 (yellow), and 559.1 nm (lime) by tuning LBO temperature to fulfill the selection of the critical phase matching. The output powers at a pump power of 40 W can be up to 8.0, 6.1, and 9.8 W for the single-peak emission at 588.7, 565.7, and 559.1 nm, respectively. Finally, a dual-peak emission of 565.7 and 572.3 nm with total output power of 5.2 W can be generated by tuning LBO temperature to match the SFG for 572.3 nm.

Highly efficient continuous-wave solid-state Raman crystal lasers at 555 and 559†nm.

High-power efficient continuous-wave Nd:YVO4/KGW Raman lasers at 555 and 559 nm are achieved by using a double-sided dichroic coating output coupler to improve the resonance quality factor. The Np-cut potassium gadolinium tungstate (KGW) is used to generate the Stokes waves at 1159 and 1177 nm by placing the polarization of the1064 nm fundamental wave parallel to the Ng and Nm axes, respectively. The lithium triborate (LBO) crystal with the cut angle in the XY plane for the type-I phase matching is used to perform the intracavity sum frequency generation for yielding the green light at 555 nm and the lime light at 559 nm at the optimal phase matching temperature. Experimental results were systematically accomplished to comprehend the optimal cavity length for the conversion efficiency. Under the optimal cavity length, the output powers can reach 6.6 and 6.3 W at a pump power of 22 W for the wavelengths of 555 and 559 nm, respectively. The conversion efficiencies can be up to 30% and 28.6% for 555 and 559 nm, respectively.

Tight Bounds on Pauli Channel Learning without Entanglement.

Quantum entanglement is a crucial resource for learning properties from nature, but a precise characterization of its advantage can be challenging. In this Letter, we consider learning algorithms without entanglement to be those that only utilize states, measurements, and operations that are separable between the main system of interest and an ancillary system. Interestingly, we show that these algorithms are equivalent to those that apply quantum circuits on the main system interleaved with mid-circuit measurements and classical feedforward. Within this setting, we prove a tight lower bound for Pauli channel learning without entanglement that closes the gap between the best-known upper and lower bound. In particular, we show that Θ(2^{n}ϵ^{-2}) rounds of measurements are required to estimate each eigenvalue of an n-qubit Pauli channel to ϵ error with high probability when learning without entanglement. In contrast, a learning algorithm with entanglement only needs Θ(ϵ^{-2}) copies of the Pauli channel. The tight lower bound strengthens the foundation for an experimental demonstration of entanglement-enhanced advantages for Pauli noise characterization.

M24B aminopeptidase inhibitors selectively activate the CARD8 inflammasome.

Inflammasomes are multiprotein complexes that sense intracellular danger signals and induce pyroptosis. CARD8 and NLRP1 are related inflammasomes that are repressed by the enzymatic activities and protein structures of the dipeptidyl peptidases 8 and 9 (DPP8/9). Potent DPP8/9 inhibitors such as Val-boroPro (VbP) activate both NLRP1 and CARD8, but chemical probes that selectively activate only one have not been identified. Here we report a small molecule called CQ31 that selectively activates CARD8. CQ31 inhibits the M24B aminopeptidases prolidase (PEPD) and Xaa-Pro aminopeptidase 1 (XPNPEP1), leading to the accumulation of proline-containing peptides that inhibit DPP8/9 and thereby activate CARD8. NLRP1 is distinct from CARD8 in that it directly contacts DPP8/9's active site; these proline-containing peptides, unlike VbP, do not disrupt this repressive interaction and thus do not activate NLRP1. We expect that CQ31 will now become a valuable tool to study CARD8 biology.

Comparing transfusion reactions between pre-storage and post-storage leukoreduced apheresis platelets: an analysis using propensity score matching.

Transfusion reactions induced by platelet transfusions may be reduced and alleviated by leukocyte reduction of platelets. Although leukoreduction of apheresis platelets can be performed either pre-storage or post-storage, seldom studies directly compare the incidence of transfusion reaction in these two different blood products. We conducted a retrospective study to compare the transfusion reactions between pre-storage and post-storage leukoreduced apheresis platelets. We reviewed the general characteristics and the transfusion reactions, symptoms, and categories for inpatients who received pre-storage or post-storage leukoreduced apheresis platelets. Propensity-score matching was performed to adjust for baseline differences between groups. A total of 40,837 leukoreduction apheresis platelet orders were reviewed. 116 (0.53%) transfusion reactions were reported in 21,884 transfusions with pre-storage leukoreduction, and 174 (0.91%) reactions were reported in 18,953 transfusions with post-storage leukoreduction. Before propensity-score matching, the odds ratio for transfusion reactions in the pre-storage group relative to the post-storage group was 0.57 (95% confidence interval [CI] 0.45-0.72, P < 0.01); the odds ratio after matching was 0.63 (95% CI 0.49-0.80, P < 0.01). A two-proportion z-test revealed pre-storage leukoreduction significantly decreases the symptoms of chills, fever, itching, urticaria, dyspnea, and hypertension as compared with those in post-storage leukoreduction. Pre-storage leukoreduced apheresis platelet significantly decreased febrile non-hemolytic transfusion reaction as compared with post-storage groups. This study suggests pre-storage leukoreduction apheresis platelet significantly decreases the transfusion reaction as compared with those in post-storage leukoreduction.

Physician adherence to anaphylaxis guidelines among different age groups in emergency departments: 20-Year observational study.

BACKGROUND: Anaphylaxis is an acute and serious allergic reaction. Little is known about physician adherence to anaphylaxis guidelines among patients across different age groups. OBJECTIVE: To investigate real-world physician adherence to anaphylaxis guidelines among children, adults, and older adults in emergency departments. METHODS: This study retrospectively analyzed all consecutive patients with anaphylaxis who presented to 2 emergency departments at 2 branches of the largest tertiary hospital in Taiwan, between 2001 and 2020. Patients who met the diagnostic criteria for anaphylaxis were enrolled and grouped by age: children (<18 years), adults (18-64 years), and older adults (≥65 years). RESULTS: We enrolled 771 patients with anaphylaxis (159 children, 498 adults, and 114 older adults). Intramuscular epinephrine was administered in 294 cases (38.1%). There was a significant age-group difference in the rate of intramuscular epinephrine administration (46.5% in children, 37.3% in adults, and 29.8% in older adults; P trend = .004). When stratified by severity, 14.3% of older adults with moderate reactions received intramuscular epinephrine, whereas 35.2% of adults and 55.3% of children received intramuscular epinephrine (P trend < .001), whereas such difference was not found in patients with severe reactions. Upon discharge from emergency departments, 15.3% received allergist referral (52.2% in children, 6.6% in adults, and 1.8% in older adults; P trend < .001); 12.5% received education on avoidance of triggers (18.9%, 11.4%, and 7.9%; P trend = .01), and 16.1% received education on alarm symptoms (21.4%, 15.1%, and 13.2%; P trend = .05). CONCLUSION: The real-world physician adherence to anaphylaxis guidelines remains suboptimal in emergency departments, particularly among older adults. Physician continuing education is needed to improve the gap between anaphylaxis guidelines and clinical practice.

Impact of Facility Dog and Certified Child Life Specialist Dyad on Children's Pain and Anxiety During Needlestick Procedures in a Pediatric Hematology Oncology Clinic Setting.

BACKGROUND: Pediatric Hematology Oncology patients undergo frequent needlestick procedures, often leading to negative outcomes including pain and anxiety. Animal-assisted therapy has been shown to minimize pediatric patient distress; however, its utilization by a Certified Child Life Specialist (CCLS) to reduce patient distress has not been widely studied. METHODS: Pediatric patients receiving needlesticks in the Hematology Oncology Clinic were enrolled between March 2018 and May 2021. Patients who had scheduled visits when the facility dog was present were assigned to the intervention group. Patients were assigned to the control group if the facility dog was not present. The primary objective was to use the Children's Anxiety and Pain Scale to determine whether the CCLS and facility dog dyad minimized patient pain and anxiety during procedures. RESULTS: A total of 285 patients, 5 to 17 years of age, were enrolled. One hundred forty-three patients were assigned the intervention and received procedural support from the CCLS and facility dog; 142 patients were assigned the control group and received support from the CCLS only. Patient-reported pain scores were significantly lower among patients who received the intervention ( P =0.033). CONCLUSIONS: Utilization of a CCLS and facility dog dyad during painful needlestick procedures decreases patient-reported pain compared with utilization of CCLS support alone.

Low-dose prasugrel versus standard-dose ticagrelor in east Asian patients with acute coronary syndrome.

Low-dose prasugrel demonstrated a similar effectiveness profile to clopidogrel in East Asian ACS patients, but its comparison with another new-generation potent P2Y12 inhibitor, ticagrelor, remains unclear. To compare the effectiveness and safety of low-dose prasugrel against those of standard-dose ticagrelor in East Asian patients with ACS. This retrospective cohort study used Taiwan's National Health and Welfare Database. This study included ACS patients who underwent percutaneous coronary intervention and, at discharge between January 1, 2018 and December 31, 2020, were prescribed with low-dose prasugrel plus aspirin or standard-dose ticagrelor plus aspirin. Stabilized inverse probability of treatment weighting was used to balance the covariates across these two groups. The primary effectiveness outcome was a composite of acute myocardial infarction, ischemic stroke, and cardiovascular death; the secondary effectiveness outcome was each of the individual components of the primary outcome, transient ischemic attack, and repeat revascularization. The primary safety outcome was a composite of intracranial hemorrhage and gastrointestinal bleeding, and the two secondary safety outcomes were intracranial hemorrhage and gastrointestinal bleeding. A total of 24,807 patients were included in this study. Among them, 1,493 were low-dose prasugrel users and 23,314 were standard-dose ticagrelor users. No significant differences were found in primary effectiveness [HR: 0.97 (0.74-1.28)] or primary safety outcomes [HR: 1.22 (0.73-2.01)] between the two study groups. For East Asian patients with ACS, low-dose prasugrel provides comparable effectiveness without increasing bleeding risk compared to standard-dose ticagrelor. Low-dose prasugrel may be an appropriate alternative for East Asian populations.

Comparative Cardiovascular Risks of Febuxostat and Allopurinol in Patients with Diabetes Mellitus and Chronic Kidney Disease.

BACKGROUND Hyperuricemia, which is common in chronic kidney disease and diabetes mellitus patients, raises health concerns. Febuxostat, a first-line urate-lowering agent, prompts cardiovascular risk questions, especially in high-risk patients. This study compared the effects of febuxostat and allopurinol on cardiovascular risk in diabetes mellitus and chronic kidney disease patients. MATERIAL AND METHODS This retrospective observational cohort study, conducted using Taiwan's National Health Insurance Research Database, focused on patients diagnosed with chronic kidney disease and diabetes between January 2012 and December 2017. The study population was divided into 2 groups: allopurinol users (n=12 901) and febuxostat users (n=2997). We performed 1: 1 propensity score matching, resulting in subgroups of 2997 patients each. The primary outcomes were assessed using a competing risk model, estimating hazard ratios (HR) for long-term outcomes, including the risks of all-cause hospitalization, hospitalization for heart failure, and hospitalization for cardiovascular interventions. RESULTS Febuxostat users, compared to allopurinol users, had higher all-cause hospitalization (HR: 1.33; 95% confidence interval [CI]: 1.25 to 1.42; P<.001), hospitalization for heart failure (HR: 1.62; 95% CI: 1.43 to 1.83; P<.001), and hospitalization for cardiovascular interventions (HR: 1.51; 95% CI: 1.32 to 1.74; P<.001). Moreover, the adverse effects of febuxostat on cardiac health were consistent across most subgroups. CONCLUSIONS Use of febuxostat in patients with diabetes mellitus and chronic kidney disease is associated with higher cardiovascular risks compared to allopurinol. Prudent evaluation is essential when recommending febuxostat for this at-risk group.

Optical Effects of Focused Fractional Nanosecond 1064-nm Nd:YAG Laser: Techniques of Application on Human Skin.

BACKGROUND AND OBJECTIVES: Considering the pulse widths of picosecond and nanosecond lasers used in cutaneous laser surgery differ by approximately one order of magnitude, can nanosecond lasers produce the optical effect in human skin similar to laser-induced optical breakdown (LIOB) caused by picosecond lasers? METHODS: Cutaneous changes induced by a focused fractional nanosecond 1064-nm Nd:YAG laser were evaluated by VISIA-CR imaging, histological examination, and harmonic generation microscopy (HGM). RESULTS: A focused fractional nanosecond 1064-nm Nd:YAG laser can generate epidermal vacuoles or dermal cavities similar to the phenomenon of LIOB produced by picosecond lasers. The location and extent of photodisruption can be controlled by the laser fluence and focus depth. Moreover, laser-induced shock wave propagation and thermal degeneration of papillary collagen can be observed by HGM imaging. CONCLUSION: Focused fractional nanosecond lasers can produce an optical effect on human skin similar to LIOB caused by picosecond lasers. With techniques of application, the treatment can induce epidermal and dermal repair mechanisms in a tunable fashion to improve skin texture, wrinkles, scars, and dyspigmentation, without disrupting the epidermal surface.

Contemporary Management of Pediatric Brainstem Tumors.

Brain tumors are the second most common malignancy in childhood. Around 15-20% of pediatric brain tumors occur in the brainstem. The most common type of brainstem tumor are diffuse tumors in the ventral pons, whereas focal tumors tend to arise from the midbrain, medulla, and dorsal pons. Glioma is the most common pathological entity. Contemporary management consists of surgery, radiotherapy, chemotherapy, and other adjuvant treatment. Surgical options range from biopsy to radical excision. Biopsy can be performed for diagnostic and prognostic purposes, or in the setting of clinical trials, mainly for diffuse intrinsic pontine gliomas. For focal tumors, surgeons need to carefully balance clinical outcomes against possible neurological sequelae in order to achieve maximal safe resection. Radiotherapy is essential for control of high-grade tumors and may be applied to residual or recurrent low-grade tumors. Proton therapy may provide similar efficacy and less neurotoxicity in comparison to conventional photon therapy. Oncological treatment continues to evolve from conventional chemotherapy to targeted therapy, immunotherapy, and other novel treatment methods and holds great potential as adjuvant therapy for pediatric brainstem tumors.

Reliability of predicting low-burden (≤ 2) positive axillary lymph nodes indicating sentinel lymph node biopsy in primary operable breast cancer - a retrospective comparative study with PET/CT and breast MRI.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is the standard of care for axillary staging in early breast cancer patients with low-burden axillary metastasis (≤ 2 positive nodes). This study aimed to determine the diagnostic performances of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and breast magnetic resonance imaging in detecting axillary lymph node (ALN) metastases and the reliability to predict ALN burden. METHODS: A total of 275 patients with primary operable breast cancer receiving preoperative PET/CT and upfront surgery from January 2001 to December 2022 in a single institution were enrolled. A total of 244 (88.7%) of them also received breast MRI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET/CT and breast MRI were assessed. The predictive values to determine ALN burden were evaluated using radio-histopathological concordance. RESULTS: PET/CT demonstrated a sensitivity of 53.4%, specificity of 82.1%, PPV of 65.5%, NPV of 73.5%, and accuracy of 70.9% for detecting ALN metastasis, and the corresponding values for MRI were 71.8%, 67.8%, 56%, 80.8%, and 69.2%, respectively. Combining PET/CT and MRI showed a significantly higher PPV than MRI (72.7% vs 56% for MRI alone, p = 0.037) and a significantly higher NPV than PET/CT (84% vs 73.5% for PET/CT alone, p = 0.041). For predicting low-burden axillary metastasis (1-2 positive nodes), the PPVs were 35.9% for PET/CT, 36.7% for MRI, and 55% for combined PET/CT and MRI. Regarding patients with 0-2 positive ALNs in imaging, who were indicated for SLNB, the predictive correctness was 96.1% for combined PET/CT and MRI, 95.7% for MRI alone, and 88.6% for PET/CT alone. CONCLUSIONS: PET/CT and breast MRI exhibit high predictive values for identifying low-burden axillary metastasis in patients with operable breast cancer with ≦ 2 positive ALNs on imaging.

Did the Comprehensive Care for Joint Replacement Bundled Payment Program Impact Sex Disparities in Total Hip and Knee Arthroplasties?

BACKGROUND: Sex disparities have been noted across various aspects of total hip/knee arthroplasty (THA/TKA). Given incentives to standardize care, bundled payment initiatives including the Comprehensive Care for Joint Replacement (CJR) program may reduce disparities. This study aimed to assess the CJR program's impact on sex disparities in THA/TKA care and outcomes. METHODS: This retrospective cohort study included 259,673 THAs (61.7% women) and 506,311 TKAs (64.0% women) from a large national database (2013 to 2017). Sex disparities were assessed for care and outcomes related to the period (1) before surgery, (2) during hospitalization for THA/TKA, and (3) after discharge. Disparities were reported as women:men ratios. Difference-in-differences analyses estimated the impact of the CJR program on pre-existing sex disparities. RESULTS: For both THA and TKA, women were less likely than men to present with a Charlson-Deyo comorbidity index >0 (women:men ratio 0.88 to 0.92), but were more likely to require blood transfusions (women:men ratio 1.48 to 1.79) and be discharged to institutional postacute care (women:men ratio 1.50 to 1.66). Difference-in-differences models demonstrated that the CJR bundled payment program reduced sex disparities in institutional postacute care discharges (THA: -2.28%; 95% confidence interval [CI] -4.20 to -0.35%, P = .02; TKA: -2.07%; 95% CI -3.93 to -0.20%; P = .03) and THA 90-day readmissions (-1.00%, 95% CI -1.88 to -0.13%, P = .02), indicating a differential impact of CJR in women versus men for some outcomes. CONCLUSIONS: While sex disparities in THA/TKA persist, the CJR program demonstrates potential to impact such differences. Future research should focus on how potential mechanisms could be leveraged to reduce disparities.

Slow Well-Being Gardening: Creating a Sensor Network for Radiation Therapy Patients via Horticultural Therapeutic Activity.

Well-being can reflect people's psychological conditions and be used alongside physiological parameters to evaluate patients' physical and mental health. The modern medical environment increasingly incorporates digital carriers, human-computer interaction devices, sensible spaces, and the execution of suitable algorithms. Slow design in healthy human-computer interaction is often used to reflect people's dependence on or support from behaviors or objects, promoting the stability of behaviors as well as meaningful and positive changes. Therefore, in this study, we propose a slow sensing model, develop a Slow Well-Being Gardening system, and use it to evaluate behavioral data from radiation therapy patients during treatment sessions and horticultural therapy. This study is based on SENS and slow design, setting the hospital lounge as a sensible space and establishing a sensor system. After a 10-day inspection, the process was evaluated and verified. Ultimately, data from facial detection (smile) and HRV showed that the patients in the experimental group experienced a significant improvement in their well-being, feeling better than those in the control group who maintained the most common state in normal treatment. Therefore, it can be inferred that the Slow Well-Being Gardening model is indeed valid and can be further developed.