Very-Large-Scale GPU-Accelerated Nuclear Gradient of Time-Dependent Density Functional Theory with Tamm-Dancoff Approximation and Range-Separated Hybrid Functionals.

Modern graphics processing units (GPUs) provide an unprecedented level of computing power. In this study, we present a high-performance, multi-GPU implementation of the analytical nuclear gradient for Kohn-Sham time-dependent density functional theory (TDDFT), employing the Tamm-Dancoff approximation (TDA) and Gaussian-type atomic orbitals as basis functions. We discuss GPU-efficient algorithms for the derivatives of electron repulsion integrals and exchange-correlation functionals within the range-separated scheme. As an illustrative example, we calculate the TDA-TDDFT gradient of the S1 state of a full-scale green fluorescent protein with explicit water solvent molecules, totaling 4353 atoms, at the ωB97X/def2-SVP level of theory. Our algorithm demonstrates favorable parallel efficiencies on a high-speed distributed system equipped with 256 Nvidia A100 GPUs, achieving >70% with up to 64 GPUs and 31% with 256 GPUs, effectively leveraging the capabilities of modern high-performance computing systems.

Treatment preference archetypes in eosinophilic esophagitis and their implications for therapy.

BACKGROUND: Little is known about how patients make decisions about and prioritize, therapies and disease management in eosinophilic esophagitis (EoE). We aimed to systematically identify and characterize patient perspectives and attitudes that influence decision making for EoE management. METHODS: To understand the diverse attitudes and values of EoE patients, we designed a study using the Q-method. We iteratively developed 31 statements related to EoE disease management. Participants sorted statements by ranking from +4 (most agree) to -4 (most disagree). By-person factor analysis, using 2- and 3- factor rotation, revealed distinct preference archetypes. RESULTS: Thirty-four adults with EoE (mean age 40.9, 51.4% male, 82.9% White) were recruited from gastroenterology and allergy clinics from a single center. We identified two treatment-centered archetypes: Medication preference, driven by symptoms and the desire to minimize risk of complications, and Natural treatment preference, focusing on identifying trigger foods and diet adherence. Three-factor analysis revealed an additional archetype: Treatment ambivalent, a view of EoE as a mild and episodic (not chronic) disease with low priority to treat. Comparison by factor revealed 54% of those in the natural preference archetype were recategorized as treatment ambivalent, suggesting that they see natural treatment as a less complicated or milder strategy and may be at risk of nonadherence and reduced treatment uptake. CONCLUSIONS: We identified three distinct treatment preference archetypes among individuals with EoE, underscoring the need for personalized treatment strategies, especially for those favoring natural approaches but masking ambivalence, and may be at risk for nonadherence or loss to follow-up.

Black Phosphorus for Mid-Infrared Optoelectronics: Photophysics, Scalable Processing, and Device Applications.

High efficiency mid-infrared (λ = 3-8 µm) light emitters and photodetectors are pivotal for advancing next-generation optoelectronics. However, narrow-bandgap semiconductors face fundamental challenges such as pronounced nonradiative carrier recombination and thermally generated noise, which impede device performance. Recently, two-dimensional layered black phosphorus (BP) and its alloys have attracted substantial interest for mid-infrared device applications, demonstrating superior performance relative to conventional III-V and II-VI semiconductors with similar bandgaps. In this review, we discuss the optical properties of BP, contrasting these with those of covalent compounds. Owing to its inherently self-terminated surface structure and reduced nonradiative recombination, BP exhibits high performance in light emission and photodetection at room temperature. Furthermore, this review highlights recent advances in the large-area processing of BP thin films, paving the way for practical device applications and integration. Finally, we explore ongoing challenges and emerging opportunities in the utilization of BP for functional mid-infrared devices.

A 4-week morning light treatment reduces amygdala reactivity and clinical symptoms in adults with traumatic stress.

Trauma leads to mental health problems including posttraumatic stress disorder (PTSD), depression, and anxiety. New treatments are needed for traumatic stress that can overcome barriers to care while targeting underlying biological mechanisms of the pathology. Morning light treatment has potential as a novel intervention for traumatic stress. We conducted a randomized clinical trial testing 3 doses of a 4-week morning light treatment in people with traumatic stress to evaluate brain mechanisms underlying the treatment. Forty-six participants completed a baseline week followed by a 4-week morning light treatment (15, 30 or 60 mins each morning). Functional magnetic resonance imaging was conducted at pre- and post-treatment using an emotional faces task to probe the amygdala, based on prior work showing direct effects of light on the amygdala and the role of amygdala in traumatic stress. Clinician-rated symptoms and self-reported symptoms were also assessed at pre- and post-treatment. No group differences were observed in left amygdala reactivity, but right amygdala reactivity reduced only in the 30 and 60 min groups with medium effect sizes. Clinical symptoms reduced in all groups with medium to large effect sizes. Self-reported depression and anxiety scores reduced more in the 60 min than in the 15 min group (p = .02). The results suggest that 4 weeks of morning light treatment of at least 30 min per day can reduce amygdala reactivity and symptoms of traumatic stress. Morning light treatment should be further explored as a potential treatment for traumatic stress, given it is relatively safe, acceptable, accessible and scalable.

Heightened migraine risk in patients with rheumatoid arthritis: A national retrospective cohort study.

OBJECTIVE: This study aimed to evaluate the association between rheumatoid arthritis (RA) and subsequent migraine risk using the Korean National Health Insurance Service database. BACKGROUND: Migraine may be related to immune dysfunction and previous studies have suggested an association with chronic inflammatory rheumatic diseases; however, the relationship between RA and migraine remains unclear. METHODS: This was a population-based, nationwide, retrospective, longitudinal cohort study. Participants were enrolled from 2010 to 2017 and followed up until 2019. A total of 42,674 patients who had undergone a health checkup within 2 years prior to the initial diagnosis of RA were included in the study, after applying the exclusion criteria (previous migraine, other rheumatic disease, missing variables of interest). A non-RA control was obtained by age and sex-matching (1:5). Finally, 42,644 patients with RA were enrolled, with 213,370 individuals without RA included as controls. Among the patients with RA, 29,744 had seropositive RA (SPRA), and 12,900 had seronegative RA (SNRA). SPRA was defined by the International Classification of Diseases 10th revision (ICD-10) code M05, prescription of disease-modifying anti-rheumatic drugs (DMARDs), and enrollment in a special copayment reduction program. SNRA was defined by the ICD-10 code M06 and prescription of any DMARD. The primary endpoint was the occurrence of migraine incidents, defined using the ICD-10 code of migraine (G43). RESULTS: A total of 22,294 migraine cases (17,912/213,370 [8.3%] in controls and 4382/42,674 [10.2%] in RA) were reported during a mean follow-up of 4.4 years after a 1-year lag period. Patients with RA had a 1.2-fold higher risk of migraine compared with controls (adjusted hazard ratio [aHR] 1.21, 95% confidence interval [CI] 1.17-1.26). Increased risk of migraine was found in both patients with SNRA and SPRA compared with controls (aHR 1.20, CI 1.15-1.24 in SPRA; aHR 1.26, CI 1.19-1.34 in SNRA). Compared to patients with SNRA, those with SPRA did not demonstrate a heightened risk (aHR 0.94, CI 0.88-1.01). A significant interaction was confirmed between covariates (male, current smoker, those with diabetes mellitus, and dyslipidemia) and the risk of migraine (p for interaction of <0.05). CONCLUSION: RA was linked to a higher migraine risk, regardless of seropositivity.

Association of rheumatoid arthritis with age-related macular degeneration in nationwide longitudinal cohort study.

Previous studies on the association between age-related macular degeneration (AMD) and rheumatoid arthritis (RA) have shown conflicting results. We sought to assess the association between AMD with/without visual disability (VD) and the risk of RA using National Health Insurance data in South Korea. In total, 3,537,293 individuals who underwent health checkups in 2009 were included and followed until 2019. Participants with VD were defined as those with loss of vision or a visual field defect as certified by the Ministry of Health and Welfare of Korea. Using multivariable adjusted Cox regression analysis, RA hazard ratios were estimated for control and AMD with/without VD groups. In total, 43,772 participants (1.24%) were diagnosed with RA. Individuals with AMD were at higher risk of RA compared to controls, regardless of the presence of VD (aHR 1.11; 95% CI 1.02-1.21). Among individuals with AMD, different risk levels of RA were observed between those without VD (aHR 1.13; 95% CI 1.03-1.21) and those with VD (aHR 0.90; 95% CI 0.64-1.27). AMD was associated with a higher risk of RA, which remained significant as a trend even after adjusting for lifestyle factors and comorbidities.

Memristive Architectures Exploiting Self-Compliance Multilevel Implementation on 1 kb Crossbar Arrays for Online and Offline Learning Neuromorphic Applications.

This paper suggests the practical implications of utilizing a high-density crossbar array with self-compliance (SC) at the conductive filament (CF) formation stage. By limiting the excessive growth of CF, SC functions enable the operation of a crossbar array without access transistors. An AlOx/TiOy, internal overshoot limitation structure, allows the SC to have resistive random-access memory. In addition, an overshoot-limited memristor crossbar array makes it possible to implement vector-matrix multiplication (VMM) capability in neuromorphic systems. Furthermore, AlOx/TiOy structure optimization was conducted to reduce overshoot and operation current, verifying uniform bipolar resistive switching behavior and analog switching properties. Additionally, extensive electric pulse stimuli are confirmed, evaluating long-term potentiation (LTP), long-term depression (LTD), and other forms of synaptic plasticity. We found that LTP and LTD characteristics for training an online learning neural network enable MNIST classification accuracies of 92.36%. The SC mode quantized multilevel in offline learning neural networks achieved 95.87%. Finally, the 32 × 32 crossbar array demonstrated spiking neural network-based VMM operations to classify the MNIST image. Consequently, weight programming errors make only a 1.2% point of accuracy drop to software-based neural networks.

Photoluminescence of Chemically and Electrically Doped Two-Dimensional Monolayer Semiconductors.

Two-dimensional (2D) transition metal dichalcogenide (TMDC) monolayers exhibit unique physical properties, such as self-terminating surfaces, a direct bandgap, and near-unity photoluminescence (PL) quantum yield (QY), which make them attractive for electronic and optoelectronic applications. Surface charge transfer has been widely used as a technique to control the concentration of free charge in 2D semiconductors, but its estimation and the impact on the optoelectronic properties of the material remain a challenge. In this work, we investigate the optical properties of a WS2 monolayer under three different doping approaches: benzyl viologen (BV), potassium (K), and electrostatic doping. Owing to the excitonic nature of 2D TMDC monolayers, the PL of the doped WS2 monolayer exhibits redshift and a decrease in intensity, which is evidenced by the increase in trion population. The electron concentrations of 3.79×1013 cm-2, 6.21×1013 cm-2, and 3.12×1012 cm-2 were measured for WS2 monolayers doped with BV, K, and electrostatic doping, respectively. PL offers a direct and versatile approach to probe the doping effect, allowing for the measurement of carrier concentration in 2D monolayer semiconductors.

Indigo Naturalis in Inflammatory Bowel Disease: mechanisms of action and insights from clinical trials.

This study investigates the therapeutic potential of Indigo Naturalis (IN) in treating a Inflammatory Bowel Disease (IBD). The objective is to comprehensively examine the effects and pharmacological mechanisms of IN on IBD, assessing its potential as an novel treatment for IBD. Analysis of 11 selected papers is conducted to understand the effects of IN, focusing on compounds like indirubin, isatin, indigo, and tryptanthrin. This study evaluates their impact on Disease Activity Index (DAI) score, colon length, mucosal damage, and macrophage infiltration in Dextran Sulfate Sodium (DSS)-induced colitis mice. Additionally, It investigate into the anti-inflammatory mechanisms, including Aryl hydrocarbon Receptor (AhR) pathway activation, Nuclear Factor kappa B (NF-κB)/nod-like receptor family pyrin domain containing 3 (NLRP3)/Interleukin 1 beta (IL-1ß) inhibition, and modulation of Toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MYD88)/NF-κB and Mitogen Activated Protein Kinase (MAPK) pathways. Immunomodulatory effects on T helper 17 (Th17)/regulatory T cell (Treg cell) balance and Glycogen synthase kinase-3 beta (GSK3-ß) expression are also explored. Furthermore, the study addresses the role of IN in restoring intestinal microbiota diversity, reducing pathogenic bacteria, and increasing beneficial bacteria. The findings reveal that IN, particularly indirubin and indigo, demonstrates significant improvements in DAI score, colon length, mucosal damage, and macrophage infiltration in DSS-induced colitis mice. The anti-inflammatory effects are attributed to the activation of the AhR pathway, inhibition of inflammatory pathways, and modulation of immune responses. These results exhibit the potential of IN in IBD treatment. Notably, the restoration of intestinal microbiota diversity and balance further supports its efficacy. IN emerges as a promising and effective treatment for IBD, demonstrating anti-inflammatory effects and positive outcomes in preclinical studies. However, potential side effects necessitate further investigation for safe therapeutic development. The study underscores the need for future research to explore a broader range of active ingredients in IN to enhance therapeutic efficacy and safety.

Effect of a Combination of Lactiplantibacillus plantarum KC3 and Leonurus japonicus Extracts in Respiratory Discomfort: A Randomized, Double-Blind, Placebo-Controlled Trial.

The increased global prevalence of chronic respiratory diseases in recent years has caused a substantial public health burden. Lactiplantibacillus plantarum KC3 and Leonurus japonicus Houtt. (LJH) extracts can alleviate respiratory symptoms and improve lung function in vitro and in vivo. However, the clinical efficacy and safety profile of this combination in patients with respiratory diseases remain unclear. Therefore, this multicenter, randomized, double-blind, placebo-controlled clinical trial aimed to evaluate the efficacy and safety of L. plantarum KC3 and LJH extracts in adults with respiratory discomfort. This mixture was termed 'CKDB-315'. Participants, randomly assigned to the CKDB-315 or placebo groups, were treated for 12 weeks. Assessments included the St. George's Respiratory Questionnaire (SGRQ) and the Chronic Obstructive Pulmonary Disease Assessment Test (CAT). The CKDB-315 group showed considerably improved SGRQ and CAT scores compared with the placebo group. Secondary outcomes, including dyspnea, pulmonary function, total antioxidant status, and inflammatory cytokine levels, were consistent with the primary outcomes. Exploratory analyses of the gut microbiota and short-chain fatty acid contents revealed the potential mechanisms underlying the effects of CKDB-315. Finally, safety analysis indicated that CKDB-315 was well tolerated and caused few adverse events. Our findings indicate that CKDB-315 is a promising therapeutic option for respiratory discomfort in adults.

Delivery of Outpatient Cirrhosis Care Through Tele-Visit Is Not Associated With Increased Mortality as Compared With Traditional In-Person Visits.

INTRODUCTION: Providers and patients have expressed concern that care provided through telehealth results in poorer outcomes than traditional in-person care. On the contrary, we hypothesized that patients with cirrhosis engaging in video/phone-based outpatient gastroenterology/hepatology tele-visits do not differ in mortality from those receiving in-person outpatient clinic visits. METHODS: This was a retrospective, case-control study using Veterans Health Administration administrative data of veterans with a cirrhosis diagnosis. Cases were patients who died between April 2021 and July 2022 and had a cirrhosis diagnosis for ≥1 year before death. For each case, a control was randomly selected from the pool of patients alive on the date of death of the case (index date) and matched on age, average Model for End-Stage Liver Disease, and number of gastroenterology/hepatology clinic visits in the prior year. Primary exposure variable was % tele-visits (video/phone) out of total visits in the year before the index date, scaled in 10% increments. Conditional logistic regression was used to assess the association between mortality and % tele-visits. A secondary analysis matched on electronic Child-Turcotte-Pugh score rather than Model for End-Stage Liver Disease. RESULTS: Two thousand nine hundred thirty-three cases were identified and matched with 2,933 controls. After adjusting for covariates, tele-visit-based outpatient care was associated with a small reduction in mortality (odds ratio TH = 0.95, 95% confidence interval = 0.94-0.97). Matching on electronic Child-Turcotte-Pugh score did not change the results. DISCUSSION: Our findings suggest that outpatient cirrhosis care by tele-visit is associated with outcomes no worse than traditional in-person visits. This should reassure providers who hesitate to provide virtual care to patients with cirrhosis due to concerns for poorer outcomes.

External Testing of a Deep Learning Model to Estimate Biologic Age Using Chest Radiographs.

Purpose To assess the prognostic value of a deep learning-based chest radiographic age (hereafter, CXR-Age) model in a large external test cohort of Asian individuals. Materials and Methods This single-center, retrospective study included chest radiographs from consecutive, asymptomatic Asian individuals aged 50-80 years who underwent health checkups between January 2004 and June 2018. This study performed a dedicated external test of a previously developed CXR-Age model, which predicts an age adjusted based on the risk of all-cause mortality. Adjusted hazard ratios (HRs) of CXR-Age for all-cause, cardiovascular, lung cancer, and respiratory disease mortality were assessed using multivariable Cox or Fine-Gray models, and their added values were evaluated by likelihood ratio tests. Results A total of 36 924 individuals (mean chronological age, 58 years ± 7 [SD]; CXR-Age, 60 years ± 5; 22 352 male) were included. During a median follow-up of 11.0 years, 1250 individuals (3.4%) died, including 153 cardiovascular (0.4%), 166 lung cancer (0.4%), and 98 respiratory (0.3%) deaths. CXR-Age was a significant risk factor for all-cause (adjusted HR at chronological age of 50 years, 1.03; at 60 years, 1.05; at 70 years, 1.07), cardiovascular (adjusted HR, 1.11), lung cancer (adjusted HR for individuals who formerly smoked, 1.12; for those who currently smoke, 1.05), and respiratory disease (adjusted HR, 1.12) mortality (P < .05 for all). The likelihood ratio test demonstrated added prognostic value of CXR-Age to clinical factors, including chronological age for all outcomes (P < .001 for all). Conclusion Deep learning-based chest radiographic age was associated with various survival outcomes and had added value to clinical factors in asymptomatic Asian individuals, suggesting its generalizability. Keywords: Conventional Radiography, Thorax, Heart, Lung, Mediastinum, Outcomes Analysis, Quantification, Prognosis, Convolutional Neural Network (CNN) Supplemental material is available for this article. © RSNA, 2024 See also the commentary by Adams and Bressem in this issue.

Neuron Circuit Based on a Split-gate Transistor with Nonvolatile Memory for Homeostatic Functions of Biological Neurons.

To mimic the homeostatic functionality of biological neurons, a split-gate field-effect transistor (S-G FET) with a charge trap layer is proposed within a neuron circuit. By adjusting the number of charges trapped in the Si3N4 layer, the threshold voltage (Vth) of the S-G FET changes. To prevent degradation of the gate dielectric due to program/erase pulses, the gates for read operation and Vth control were separated through the fin structure. A circuit that modulates the width and amplitude of the pulse was constructed to generate a Program/Erase pulse for the S-G FET as the output pulse of the neuron circuit. By adjusting the Vth of the neuron circuit, the firing rate can be lowered by increasing the Vth of the neuron circuit with a high firing rate. To verify the performance of the neural network based on S-G FET, a simulation of online unsupervised learning and classification in a 2-layer SNN is performed. The results show that the recognition rate was improved by 8% by increasing the threshold of the neuron circuit fired.

Threshold learning algorithm for memristive neural network with binary switching behavior.

On-chip learning is an effective method for adjusting artificial neural networks in neuromorphic computing systems by considering hardware intrinsic properties. However, it faces challenges due to hardware nonidealities, such as the nonlinearity of potentiation and depression and limitations on fine weight adjustment. In this study, we propose a threshold learning algorithm for a variation-tolerant ternary neural network in a memristor crossbar array. This algorithm utilizes two tightly separated resistance states in memristive devices to represent weight values. The high-resistance state (HRS) and low-resistance state (LRS) defined as read current of < 0.1 µA and > 1 µA, respectively, were successfully programmed in a 32 × 32 crossbar array, and exhibited half-normal distributions due to the programming method. To validate our approach experimentally, a 64 × 10 single-layer fully connected network were trained in the fabricated crossbar for an 8 × 8 MNIST dataset using the threshold learning algorithm, where the weight value is updated when a gradient determined by backpropagation exceeds a threshold value. Thanks to the large margin between the two states of the memristor, we observed only a 0.42 % drop in classification accuracy compared to the baseline network results. The threshold learning algorithm is expected to alleviate the programming burden and be utilized in variation-tolerant neuromorphic architectures.

Morning light treatment for inflammatory bowel disease: a clinical trial.

BACKGROUND: Inflammatory bowel disease (IBD) affects over 3 million Americans and has a relapsing and remitting course with up to 30% of patients experiencing exacerbations each year despite the availability of immune targeted therapies. An urgent need exists to develop adjunctive treatment approaches to better manage IBD symptoms and disease activity. Circadian disruption is associated with increased disease activity and may be an important modifiable treatment target for IBD. Morning light treatment, which advances and stabilizes circadian timing, may have the potential to improve IBD symptoms and disease activity, but no studies have explored these potential therapeutic benefits in IBD. Therefore, in this study, we aim to test the effectiveness of morning light treatment for patients with IBD. METHODS: We will recruit sixty-eight individuals with biopsy-proven IBD and clinical symptoms and randomize them to 4-weeks of morning light treatment or 4-weeks of treatment as usual (TAU), with equivalent study contact. Patient-reported outcomes (IBD-related quality of life, mood, sleep), clinician-rated disease severity, and a biomarker of gastrointestinal inflammation (fecal calprotectin) will be assessed before and after treatment. Our primary objective will be to test the effect of morning light treatment versus TAU on IBD-related quality of life and our secondary objectives will be to test the effects on clinician-rated disease activity, depression, and sleep quality. We will also explore the effect of morning light treatment versus TAU on a biomarker of gastrointestinal inflammation (fecal calprotectin), and the potential moderating effects of steroid use, restless leg syndrome, and biological sex. DISCUSSION: Morning light treatment may be an acceptable, feasible, and effective adjunctive treatment for individuals with active IBD suffering from impaired health-related quality of life. TRIAL REGISTRATION: The study protocol was registered on ClinicalTrials.gov as NCT06094608 on October 23, 2023, before recruitment began on February 1, 2024.

The TIMELESS and PARP1 interaction suppresses replication-associated DNA gap accumulation.

TIMELESS (TIM) in the fork protection complex acts as a scaffold of the replisome to prevent its uncoupling and ensure efficient DNA replication fork progression. Nevertheless, its underlying basis for coordinating leading and lagging strand synthesis to limit single-stranded DNA (ssDNA) exposure remains elusive. Here, we demonstrate that acute degradation of TIM at ongoing DNA replication forks induces the accumulation of ssDNA gaps stemming from defective Okazaki fragment (OF) processing. Cells devoid of TIM fail to support the poly(ADP-ribosyl)ation necessary for backing up the canonical OF processing mechanism mediated by LIG1 and FEN1. Consequently, recruitment of XRCC1, a known effector of PARP1-dependent single-strand break repair, to post-replicative ssDNA gaps behind replication forks is impaired. Physical disruption of the TIM-PARP1 complex phenocopies the rapid loss of TIM, indicating that the TIM-PARP1 interaction is critical for the activation of this compensatory pathway. Accordingly, combined deficiency of FEN1 and the TIM-PARP1 interaction leads to synergistic DNA damage and cytotoxicity. We propose that TIM is essential for the engagement of PARP1 to the replisome to coordinate lagging strand synthesis with replication fork progression. Our study identifies TIM as a synthetic lethal target of OF processing enzymes that can be exploited for cancer therapy.

Lens-free reflective topography for high-resolution wafer inspection.

The demand for high-resolution and large-area imaging systems for non-destructive wafer inspection has grown owing to the increasing complexity and extremely fine nature of semiconductor processes. Several studies have focused on developing high-resolution imaging systems; however, they were limited by the tradeoff between image resolution and field of view. Hence, computational imaging has arisen as an alternative method to conventional optical imaging, aimed at enhancing the aforementioned parameters. This study proposes a method for improving the resolution and field of view of an image in a lens-less reflection-type system. Our method was verified by computationally restoring the final image from diffraction images measured at various illumination positions using a visible light source. We introduced speckle illumination to expand the numerical aperture of the entire system, simultaneously improving image resolution and field of view. The image reconstruction process was accelerated by employing a convolutional neural network. Using the reconstructed phase images, we implemented high-resolution topography and demonstrated its applicability in wafer surface inspection. Furthermore, we demonstrated an ideal diffraction-limited spatial resolution of 1.7 µm over a field of view of 1.8 × 1.8 mm2 for the topographic imaging of targets with various surface roughness. The proposed approach is suitable for applications that simultaneously require high throughput and resolution, such as wafer-wide integrated metrology, owing to its compact design, cost-effectiveness, and mechanical robustness.