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.

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.

Delivery of Outpatient Cirrhosis Care Via Tele-visit is Not Associated with Increased Mortality as Compared to Traditional In-Person Visits.

INTRODUCTION: Providers and patients have expressed concern that care provided via 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 GI/Hepatology tele-visits do not differ in mortality from those receiving in-person outpatient clinic visits. METHODS: Retrospective, case-control study using VHA administrative data of veterans with a cirrhosis diagnosis. Cases were patients who died between 04/2021-07/2022 and had a cirrhosis diagnosis for ≥1 year prior to 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 MELD, and number of GI/Hepatology clinic visits in the prior year. Primary exposure variable was % tele-visits (video/phone) out of total visits in the year prior to 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 Child Turcotte Pugh (eCTP) score rather than MELD. RESULTS: 2,933 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 (ORTH = 0.95, 95% CI = 0.94-0.97). Matching on eCTP 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.

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.

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.

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.

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.

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.

A comprehensive review of advanced trends: from artificial synapses to neuromorphic systems with consideration of non-ideal effects.

A neuromorphic system is composed of hardware-based artificial neurons and synaptic devices, designed to improve the efficiency of neural computations inspired by energy-efficient and parallel operations of the biological nervous system. A synaptic device-based array can compute vector-matrix multiplication (VMM) with given input voltage signals, as a non-volatile memory device stores the weight information of the neural network in the form of conductance or capacitance. However, unlike software-based neural networks, the neuromorphic system unavoidably exhibits non-ideal characteristics that can have an adverse impact on overall system performance. In this study, the characteristics required for synaptic devices and their importance are discussed, depending on the targeted application. We categorize synaptic devices into two types: conductance-based and capacitance-based, and thoroughly explore the operations and characteristics of each device. The array structure according to the device structure and the VMM operation mechanism of each structure are analyzed, including recent advances in array-level implementation of synaptic devices. Furthermore, we reviewed studies to minimize the effect of hardware non-idealities, which degrades the performance of hardware neural networks. These studies introduce techniques in hardware and signal engineering, as well as software-hardware co-optimization, to address these non-idealities through compensation approaches.

Sex-specific disparities in disease activity scores among patients with axial spondyloarthritis and their implications for evaluating the response to tumor necrosis factor alpha inhibitor therapy.

BACKGROUND: We aimed to investigate whether there are sex differences in disease activity measures among patients with axial spondyloarthritis (axSpA) and to determine any potential impact on the assessment of treatment responses to tumor necrosis factor alpha inhibitors (TNFi). METHODS: Using the Korean College of Rheumatology Biologics and Targeted Therapy (KOBIO) registry data, we compared sex differences in changes in the Bath Ankylosing Spondylitis Disease Activity Score (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) levels at baseline and one year after TNFi initiation in patients with axSpA. RESULTS: This study included 1,753 patients with axSpA who started or changed TNFi, of whom 1,343 (76.6%) were male. At baseline, the mean BASDAI and ASDAS scores of all patients were 5.98 and 3.6, respectively. The BASDAI changes between baseline and the one-year follow-up were independently associated with sex (𝛽 = 0.343, p = 0.011), whereas ASDAS was not (𝛽 = 0.079, p = 0.235). When judging the effect of TNFi at one-year of treatment, male patients were more likely to be assessed as effective by the BASDAI-based criterion (ΔBASDAI ≥ 50% or ≥ 2; OR 1.700, 95% CI 1.200-2.406), while the ASDAS-based criterion (ΔASDAS ≥ 1.1) showed no significant difference between sexes (OR 0.993, 95% CI 0.678-1.455), after adjusting for other baseline characteristics. CONCLUSIONS: The changes in disease activity before and after TNFi use were significantly different between sexes when measured by BASDAI, but not ASDAS. TNFi treatment effects may be interpreted differently between sexes depending on the disease activity measure used.

Impact of large scale, multicomponent intervention to reduce proton pump inhibitor overuse in integrated healthcare system: difference-in-difference study.

OBJECTIVE: To determine how a large scale, multicomponent, pharmacy based intervention to reduce proton pump inhibitor (PPI) overuse affected prescribing patterns, healthcare utilization, and clinical outcomes. DESIGN: Difference-in-difference study. SETTING: US Veterans Affairs Healthcare System, in which one regional network implemented the overuse intervention and all 17 others served as controls. PARTICIPANTS: All individuals receiving primary care from 2009 to 2019. INTERVENTION: Limits on PPI refills for patients without a documented indication for long term use, voiding of PPI prescriptions not recently filled, facilitated electronic prescribing of H2 receptor antagonists, and education for patients and clinicians. MAIN OUTCOME MEASURES: The primary outcome was the percentage of patients who filled a PPI prescription per 6 months. Secondary outcomes included percentage of days PPI gastroprotection was prescribed in patients at high risk for upper gastrointestinal bleeding, percentage of patients who filled either a PPI or H2 receptor antagonist prescription, hospital admission for acid peptic disease in older adults appropriate for PPI gastroprotection, primary care visits for an upper gastrointestinal diagnosis, upper endoscopies, and PPI associated clinical conditions. RESULTS: The number of patients analyzed per interval ranged from 192 607 to 250 349 in intervention sites and from 3 775 953 to 4 360 868 in control sites, with 26% of patients receiving PPIs before the intervention. The intervention was associated with an absolute reduction of 7.3% (95% confidence interval -7.6% to -7.0%) in patients who filled PPI prescriptions, an absolute reduction of 11.3% (-12.0% to -10.5%) in PPI use among patients appropriate for gastroprotection, and an absolute reduction of 5.72% (-6.08% to -5.36%) in patients who filled a PPI or H2 receptor antagonist prescription. No increases were seen in primary care visits for upper gastrointestinal diagnoses, upper endoscopies, or hospital admissions for acid peptic disease in older patients appropriate for gastroprotection. No clinically significant changes were seen in any PPI associated clinical conditions. CONCLUSIONS: The multicomponent intervention was associated with reduced PPI use overall but also in patients appropriate for gastroprotection, with minimal evidence of either clinical benefits or harms.

Clinical Utility of a CT-based AI Prognostic Model for Segmentectomy in Non-Small Cell Lung Cancer.

Background Currently, no tool exists for risk stratification in patients undergoing segmentectomy for non-small cell lung cancer (NSCLC). Purpose To develop and validate a deep learning (DL) prognostic model using preoperative CT scans and clinical and radiologic information for risk stratification in patients with clinical stage IA NSCLC undergoing segmentectomy. Materials and Methods In this single-center retrospective study, transfer learning of a pretrained model was performed for survival prediction in patients with clinical stage IA NSCLC who underwent lobectomy from January 2008 to March 2017. The internal set was divided into training, validation, and testing sets based on the assignments from the pretraining set. The model was tested on an independent test set of patients with clinical stage IA NSCLC who underwent segmentectomy from January 2010 to December 2017. Its prognostic performance was analyzed using the time-dependent area under the receiver operating characteristic curve (AUC), sensitivity, and specificity for freedom from recurrence (FFR) at 2 and 4 years and lung cancer-specific survival and overall survival at 4 and 6 years. The model sensitivity and specificity were compared with those of the Japan Clinical Oncology Group (JCOG) eligibility criteria for sublobar resection. Results The pretraining set included 1756 patients. Transfer learning was performed in an internal set of 730 patients (median age, 63 years [IQR, 56-70 years]; 366 male), and the segmentectomy test set included 222 patients (median age, 65 years [IQR, 58-71 years]; 114 male). The model performance for 2-year FFR was as follows: AUC, 0.86 (95% CI: 0.76, 0.96); sensitivity, 87.4% (7.17 of 8.21 patients; 95% CI: 59.4, 100); and specificity, 66.7% (136 of 204 patients; 95% CI: 60.2, 72.8). The model showed higher sensitivity for FFR than the JCOG criteria (87.4% vs 37.6% [3.08 of 8.21 patients], P = .02), with similar specificity. Conclusion The CT-based DL model identified patients at high risk among those with clinical stage IA NSCLC who underwent segmentectomy, outperforming the JCOG criteria. © RSNA, 2024 Supplemental material is available for this article.

Partner Plan Choices and Medicare Advantage Enrollment Decisions Among Older Adults.

This study examines the association of partner Medicare Advantage plan status over 1 year with beneficiary and plan characteristics.

Telehealth and delivery of alcohol use disorder treatment in the Veterans Health Administration.

BACKGROUND: The use of telehealth treatment of alcohol use disorder (AUD) has increased since the start of the COVID-19 pandemic. However, it is unclear which patients are using telehealth and how telehealth visits are associated with treatment duration. This study examined characteristics associated with telehealth use among Veterans Health Administration patients receiving AUD treatment. METHODS: Using a national retrospective cohort study, we examined data from March 01, 2020 to February 28, 2021 to: First, identify patient characteristics associated with (a) any telehealth versus only in-person care for AUD treatment, and (b) video (≥1 video visit) versus only telephone visits for AUD treatment (≥1 telephone visit, no video) among any telehealth users. This analysis used mixed-effects logistic regression models to adjust for potential correlation across patients treated at the same facility. Second, we assessed whether visit modality was associated with the amount of AUD treatment received (number of AUD psychotherapy visits or medication coverage days). This analysis used mixed-effects negative binomial regression models. RESULTS: Among 138,619 patients who received AUD treatment, 52.8% had ≥1 video visit, 38.1% had ≥1 telephone but no video visits, and 9.1% had only in-person visits. In the regression analyses, patients who were male or had an opioid or stimulant use disorder (compared to having no non-AUD substance use disorder) were less likely to receive any telehealth-delivered AUD treatment compared to only in-person AUD treatment. Among patients who received any telehealth-delivered AUD treatment, those who were ≥45 years old (compared to 18-29 years old), Black (compared to White), diagnosed with a cannabis or stimulant use disorder, or diagnosed with a serious mental illness were less likely to receive a video visit than only telephone visits. Receiving any AUD telehealth was associated with receiving more psychotherapy visits and medication coverage days than only in-person care. CONCLUSIONS: Telehealth, a common modality for AUD treatment, supported a greater number of psychotherapy visits and a longer duration of medication treatment for AUD. However, some groups were less likely to receive any video telehealth than telephone visits, suggesting that multiple treatment modalities should remain available to ensure treatment access.

Programmable Threshold Logic Implementations in a Memristor Crossbar Array.

In this study, we demonstrate the implementation of programmable threshold logics using a 32 × 32 memristor crossbar array. Thanks to forming-free characteristics obtained by the annealing process, its accurate programming characteristics are presented by a 256-level grayscale image. By simultaneous subtraction between weighted sum and threshold values with a differential pair in an opposite way, 3-input and 4-input Boolean logics are implemented in the crossbar without additional reference bias. Also, we verify a full-adder circuit and analyze its fidelity, depending on the device programming accuracy. Lastly, we successfully implement a 4-bit ripple carry adder in the crossbar and achieve reliable operations by read-based logic operations. Compared to stateful logic driven by device switching, a 4-bit ripple carry adder on a memristor crossbar array can perform more reliably in fewer steps thanks to its read-based parallel logic operation.

mFOLFIRINOX versus mFOLFOX 6 as adjuvant treatment for high-risk stage III colon cancer - the FROST trial: study protocol for a multicenter, randomized controlled, phase II trial.

BACKGROUND: High-risk stage III colon cancer has a considerably poorer prognosis than stage II and low-risk stage III colon cancers. Nevertheless, most guidelines recommend similar adjuvant treatment approaches for all these stages despite the dearth of research focusing on high-risk stage III colon cancer and the potential for improved prognosis with intensive adjuvant treatment. Given the the proven efficacy of triplet chemotherapy in metastatic colorectal cancer treatment, the goal of this study is to evaluate the oncologic efficacy and safety of mFOLFIRINOX in comparison to those of the current standard of care, mFOLFOX 6, as an adjuvant treatment for patients diagnosed with high-risk stage III colon cancer after radical resection. METHODS: This multicenter, randomized (1:1), open-label, phase II trial will assess and compare the effectiveness and toxicity of mFOLFIRINOX and mFOLFOX 6 in patients with high-risk stage III colon cancer after radical resection. The goal of the trial is to enroll 312 eligible patients, from 11 institutes, aged between 20 and 70 years, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, or between 70 and 75 with an ECOG performance status of 0. Patients will be randomized into two arms - Arm A, the experimental arm, and Arm B, the reference arm - and will receive 12 cycles of mFOLFIRINOX and mFOLFOX 6 every 2 weeks, respectively. The primary endpoint of this study is the 3-year disease-free survival, and secondary endpoints include the 3-year overall survival and treatment toxicity. DISCUSSION: The Frost trial would help determine the oncologic efficacy and safety of adjuvant triplet chemotherapy for high-risk stage III colon cancers and ultimately improve prognoses. TRIAL REGISTRATION: ClinicalTrials.gov NCT05179889, registered on 17 December 2021.

The Importance of Autonomy and Performance Goals in Perceived Workload Among Behavioral Health Providers.

OBJECTIVE: The authors sought to assess workplace characteristics associated with perceived reasonable workload among behavioral health care providers in the Veterans Health Administration. METHODS: The authors evaluated perceived reasonable workload and workplace characteristics from the 2019 All Employee Survey (AES; N=14,824) and 2019 Mental Health Provider Survey (MHPS; N=10,490) and facility-level staffing ratios from Mental Health Onboard Clinical Dashboard data. Nine AES and 15 MHPS workplace predictors of perceived reasonable workload, 11 AES and six MHPS demographic predictors, and facility-level staffing ratios were included in mixed-effects logistic regression models. RESULTS: In total, 8,874 (59.9%) AES respondents and 5,915 (56.4%) MHPS respondents reported having a reasonable workload. The characteristics most strongly associated with perceived reasonable workload were having attainable performance goals (average marginal effect [AME]=0.10) in the AES and ability to schedule patients as frequently as indicated (AME=0.09) in the MHPS. Other AES characteristics significantly associated with reasonable workload included having appropriate resources, support for personal life, skill building, performance recognition, concerns being addressed, and no supervisor favoritism. MHPS characteristics included not having collateral duties that reduce care time, staffing levels not affecting care, support staff taking over some responsibilities, having spirit of teamwork, primary care-mental health integration, participation in performance discussions, well-coordinated mental health care, effective veteran programs, working at the top of licensure, and feeling involved in improving access. Facility-level staffing ratios were not significantly associated with perceived reasonable workload. CONCLUSIONS: Leadership may consider focusing resources on initiatives that support behavioral health providers' autonomy to schedule patients as clinically indicated and develop attainable performance goals.

Rheumatoid Arthritis and Risk of Depression in South Korea.

Importance: Depression is among the most common comorbidities in rheumatoid arthritis (RA). There is a lack of data regarding the association of RA seropositivity and biologic agents with depression risk among individuals with RA. Objective: To investigate the risk of depression following RA diagnosis among patients in South Korea. Design, Setting, and Participants: This retrospective cohort study included 38 487 patients with RA and a comparison group of 192 435 individuals matched 1:5 for age, sex, and index date. Data were from the Korean National Health Insurance Service database. Participants were enrolled from 2010 to 2017 and were followed up until 2019. Participants who had previously been diagnosed with depression or were diagnosed with depression within 1 year after the index date were excluded. Statistical analysis was performed in May 2023. Exposures: Seropositive RA (SPRA) was defined with the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes M05 and enrollment in the Korean Rare and Intractable Diseases program. Seronegative RA (SNRA) was defined with ICD-10 codes M06 (excluding M06.1 and M06.4) and a prescription of any disease-modifying antirheumatic drugs (DMARDs) for 270 days or more. Main Outcomes and Measures: Newly diagnosed depression (ICD-10 codes F32 or F33). Results: The mean (SD) age of the total study population was 54.6 (12.1) years, and 163 926 individuals (71.0%) were female. During a median (IQR) follow-up of 4.1 (2.4-6.2) years, 27 063 participants (20 641 controls and 6422 with RA) developed depression. Participants with RA had a 1.66-fold higher risk of depression compared with controls (adjusted hazard ratio [aHR], 1.66 [95% CI, 1.61-1.71]). The SPRA group (aHR, 1.64 [95% CI, 1.58-1.69]) and the SNRA group (aHR, 1.73 [95% CI, 1.65-1.81]) were associated with an increased risk of depression compared with controls. Patients with RA who used biologic or targeted synthetic DMARDs (aHR, 1.33 [95% CI, 1.20-1.47]) had a lower risk of depression compared with patients with RA who did not use these medications (aHR, 1.69 [95% CI, 1.64-1.74]). Conclusions and Relevance: This nationwide cohort study found that both SPRA and SNRA were associated with a significantly higher risk of depression. These results suggest the importance of early screening and intervention for mental health in patients with RA.

Correction: Soung et al. Therapeutic Potential of Chemically Modified MiR-489 in Triple-Negative Breast Cancers. Cancers 2020, 12, 2209.

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