Associations of serum persistent organic pollutant concentrations with incident diabetes in midlife women: The Study of Women's Health Across the Nation Multi-Pollutant Study.

BACKGROUND: Organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs), and polychlorinated biphenyls (PCBs) are persistent organic pollutants (POPs) that can negatively impact metabolic health through pathways including endocrine disruption. Few studies have evaluated diabetes risk associated with PBDEs. Little is known about the joint effect of exposure to POP mixtures on diabetes risk. OBJECTIVES: We investigated the relationship between POPs, individually and as mixtures, and diabetes development over 18 years (1999-2016) in midlife women. METHODS: We measured lipid-standardized serum concentrations of 34 PCBs, 19 OCPs, and 14 PBDEs in 1040 midlife women aged 45-56 years from the Study of Women's Health Across the Nation. We tested the association between POPs measured in 1999/2000 and incident diabetes using Cox proportional hazards models. We evaluated diabetes risk associated with the overall POP mixture using Quantile-Based G-Computation (QBGC). RESULTS: For most mixture components, single pollutant and mixtures analyses indicated null associations with diabetes risk, however results were inconsistent. After adjustment, hazard ratios (HRs) of developing diabetes (95% CI) associated with upper exposure tertiles (T2/T3) compared with the first tertile (T1), were 1.7 (1.0, 2.8) at T2 and 1.5 (0.84, 2.7) at T3 for hexachlorobenzene and 1.9 (1.1, 3.3) at T2 and 1.6 (0.88, 2.9) at T3 for PCB 123. A doubling of PBDE 47 was associated with 1.11 (1.00, 1.24) times the risk of T2D. QBGC identified no association for the overall joint effect of the POP mixture on diabetes (HR = 1.04 [0.53, 2.07]). CONCLUSION: Exposure to a mixture of PCBs, OCPs, and PBDEs was not associated with incident diabetes in midlife U.S. women, although some individual POPs demonstrated significant yet inconsistent associations with diabetes. Non-linear and non-monotonic dose-response dynamics deserve further exploration. More research is needed on the diabetogenic effects of PBDEs.

Lessons learned from follow up of spleen-preserving distal pancreatectomy with artery saving and vein sacrificing.

Background: The Warshaw method as a technique for spleen-preserving distal pancreatectomy (SPDP) carries the risk of splenic infarction following splenic artery ligation. This study introduces a modified Warshaw method, which preserves the splenic artery while sacrificing the splenic vein, and compares its outcomes with the traditional Warshaw method. Methods: According to the bleeding status during vessel dissection, either the Warshaw method (group W) or the modified Warshaw method (group MW) was used. Guided by preoperative imaging, we utilized the planned modified Warshaw method (group PMW) when the splenic vein was embedded in the pancreatic parenchyma. Results: Group MW demonstrated a lower incidence of splenic infarction and engorged gastric collaterals than group W (6.3% vs. 69.8%, P<0.001; 25.0% vs. 55.8%, P=0.003, respectively). There were no significant differences in perioperative changes of splenic volume between the two groups. Group PMW experienced less estimated blood loss than group W (71.9±59.13 vs. 357.9±447.72 cc, P=0.006). Conclusions: The planned modified Warshaw method is an efficient and safe technique, resulting in lower estimated blood loss and favorable outcomes concerning splenic infarction and gastric collaterals than the Warshaw method without inducing congestive splenomegaly.

Minimal residual disease assessment in transplant-eligible patients with multiple myeloma: real-world applications of multiparametric flow cytometry-DURAClone (CAREMM-2104).

Not available.

Surgical Strategy for Dumbbell-Shaped Cervical Schwannoma at the Vicinity of the Vertebral Artery: The Utilization of Anatomic Layer.

BACKGROUND AND OBJECTIVES: In cases where dumbbell-shaped cervical schwannoma encases the vertebral artery (VA), there is a risk of VA injury during surgery. The objective of this study is to propose a strategy for preserving the VA during the surgical excision of tumors adjacent to the VA through the utilization of anatomic layers. METHODS: A retrospective analysis was conducted on 37 patients who underwent surgery for dumbbell-shaped cervical schwannoma with contacting VA from January 2004 to July 2023. The VA encasement group consisted of 12 patients, and the VA nonencasement group included 25 patients. RESULTS: The perineurium acted as a protective barrier from direct VA exposure or injury during surgery. However, in the VA encasement group, 1 patient was unable to preserve the perineurium while removing a tumor adjacent to the VA, resulting in VA injury. The patient had the intact dominant VA on the opposite side, and there were no new neurological deficits or infarctions after the surgery. Gross total resection was achieved in 25 patients (67.6%), while residual tumor was confirmed in 12 patients (32.4%). Four patients (33.3% of 12 patients) underwent reoperation because of the regrowth of the residual tumor within the neural foramen. In the case of the 8 patients (66.7% of 12 patients) whose residual tumor was located outside the neural foramen, no regrowth was observed, and there was no recurrence of the tumor within the remaining perineurium after total resection. CONCLUSION: In conclusion, when resecting a dumbbell-shaped cervical schwannoma contacting VA, subperineurium dissection prevents VA injury because the perineurium acts as a protective barrier.

Junctionless Structure Indium-Tin Oxide Thin-Film Transistors Enabling Enhanced Mechanical and Contact Stability.

In recent years, considerable attention has focused on high-performance and flexible crystalline metal oxide thin-film transistors (TFTs). However, achieving both high performance and flexibility in semiconductor devices is challenging due to the inherently conductive and brittle nature of crystalline metal oxide. In this study, we propose a facile way to overcome this limitation by employing a junctionless (JL) TFT structure via oxygen plasma treatment of the crystalline indium-tin oxide (ITO) films. The oxygen plasma treatment significantly reduced oxygen vacancies in the ITO films, contributing to the significant reduction in the carrier concentration from 4.67 × 1020 to 1.39 × 1016. Importantly, this reduction was achieved without inducing any noticeable structural changes in the ITO, enabling the successful realization of ITO JL TFTs with an adjustable threshold voltage. Furthermore, the ITO JL TFTs demonstrate good stability and reliability under various bias stress conditions, aging in the air atmosphere, and high-temperature processes. In addition, the ITO JL TFTs exhibit low light sensitivity due to the wide bandgap of ITO and further suppression of Vo defects, making them suitable for applications requiring stable performance under light exposure. To compare and analyze the flexibility of the JL structure and conventional structure with additional source/drain (S/D) junction in ITO TFTs with nonencapsulation, we utilized mechanical simulations and transmission line method (TLM). By employing the JL structure in ITO TFT through carefully optimized oxygen plasma treatment, we successfully mitigated stress concentration at the S/D-channel interface. This resulted in a JL ITO TFT that exhibited a change in contact resistance of less than 20% even after 20,000 bending cycles. Consequently, a stable and flexible ITO TFT with field-effect mobility (µFE) of 12.74 cm2/(V s) was realized, outperforming conventionally structured ITO TFTs with additional S/D junction, where the contact resistance nearly tripled.

A Computed Tomography-Based Fracture Prediction Model With Images of Vertebral Bones and Muscles by Employing Deep Learning: Development and Validation Study.

BACKGROUND: With the progressive increase in aging populations, the use of opportunistic computed tomography (CT) scanning is increasing, which could be a valuable method for acquiring information on both muscles and bones of aging populations. OBJECTIVE: The aim of this study was to develop and externally validate opportunistic CT-based fracture prediction models by using images of vertebral bones and paravertebral muscles. METHODS: The models were developed based on a retrospective longitudinal cohort study of 1214 patients with abdominal CT images between 2010 and 2019. The models were externally validated in 495 patients. The primary outcome of this study was defined as the predictive accuracy for identifying vertebral fracture events within a 5-year follow-up. The image models were developed using an attention convolutional neural network-recurrent neural network model from images of the vertebral bone and paravertebral muscles. RESULTS: The mean ages of the patients in the development and validation sets were 73 years and 68 years, and 69.1% (839/1214) and 78.8% (390/495) of them were females, respectively. The areas under the receiver operator curve (AUROCs) for predicting vertebral fractures were superior in images of the vertebral bone and paravertebral muscles than those in the bone-only images in the external validation cohort (0.827, 95% CI 0.821-0.833 vs 0.815, 95% CI 0.806-0.824, respectively; P<.001). The AUROCs of these image models were higher than those of the fracture risk assessment models (0.810 for major osteoporotic risk, 0.780 for hip fracture risk). For the clinical model using age, sex, BMI, use of steroids, smoking, possible secondary osteoporosis, type 2 diabetes mellitus, HIV, hepatitis C, and renal failure, the AUROC value in the external validation cohort was 0.749 (95% CI 0.736-0.762), which was lower than that of the image model using vertebral bones and muscles (P<.001). CONCLUSIONS: The model using the images of the vertebral bone and paravertebral muscle showed better performance than that using the images of the bone-only or clinical variables. Opportunistic CT screening may contribute to identifying patients with a high fracture risk in the future.

Comparative analysis of reduced toxicity conditioning regimens between fludarabine plus melphalan and fludarabine plus busulfex in adult patients with acute lymphoblastic leukemia.

Reduced-toxicity conditioning (RTC) regimens aim to mitigate regimen-related toxicity while maintaining anti-leukemic efficacy in allogeneic hematopoietic stem cell transplantation (allo-HSCT). We assessed outcomes of RTC regimens utilizing melphalan versus intravenous busulfan combined with fludarabine in adult acute lymphoblastic leukemia (ALL) patients. A retrospective analysis was conducted with 149 consecutive adult ALL patients (median age 51, range 18-60) in remission undergoing allo-HSCT. Patients received either fludarabine 150 mg/BSA plus 2 days of melphalan 70 mg/BSA (FM140, n = 76) from 2009 to 2015 or fludarabine plus 3 days of busulfan 3.2 mg/kg (FB9.6, n = 73) from 2016 to 2021. At 5 years post-HSCT, FM140 demonstrated superior disease-free survival (53.4% vs. 30.5%, p = 0.007) and lower cumulative relapse (27.4% vs. 46.8%, p = 0.026) than FB9.6. Five-year overall survival and non-relapse mortality did not significantly differ. FM140 exhibited a higher incidence of acute graft-versus-host disease (GVHD) grades II-IV (49.3% vs. 30.3%, p = 0.016), though rates of acute GVHD grades III-IV and chronic GVHD were similar. Multivariate analysis identified Philadelphia chromosome and minimal residual disease positive status, and FB9.6 conditioning as predictors of increased relapse and poorer disease-free survival. FM140 RTC regimen displayed significantly reduced relapse and superior disease-free survival compared to FB9.6 in ALL patients undergoing allo-HSCT, highlighting its current clinical utility.

Prescribing trends of glaucoma medication in Korea from 2007 to 2020: A nationwide population-based study.

PURPOSE: Investigating long-term trends in glaucoma medication. METHODS: All patients diagnosed with glaucoma and prescribed glaucoma eye drops between 2007 and 2020 in Korea's Health Insurance Review and Assessment Service database participated in this study. A weight was assigned to each prescription using the reciprocal of the total number of prescriptions received by the individual in that year. The number of patients who received each type of glaucoma eye drop prescription was calculated by summing the weights for each year. RESULTS: During the study period, prostaglandin analog eye drop monotherapy was the most frequently given type of glaucoma eye drop prescription. Until 2008, the second most frequently given type of glaucoma eye drop prescription was beta blocker eye drop monotherapy; thereafter, it changed to carbonic anhydrase inhibitor/beta blocker fixed-combination eye drop monotherapy. The prescription proportion of single-ingredient glaucoma eye drops decreased (-1.290%/year, P < 0.001), whereas that of fixed-combination glaucoma eye drops increased (1.291%/year, P < 0.001). The number of glaucoma eye drops prescribed per patient remained constant (-0.00030/year, P = 0.167) with an average of 1.302, while the number of active ingredients prescribed per patient increased (0.01737/year, P < 0.001) from 1.659 in 2007 to 1.896 in 2020. CONCLUSION: Over 14 years, there was no change in the number of glaucoma eye drops prescribed to individual patients in Korea. However, the number of active ingredients prescribed increased owing to the increased prescription of fixed-combination eye drops. The current trends in glaucoma medication are expected to help establish future treatment strategies.

3D printable and biocompatible PEDOT:PSS-ionic liquid colloids with high conductivity for rapid on-demand fabrication of 3D bioelectronics.

3D printing has been widely used for on-demand prototyping of complex three-dimensional structures. In biomedical applications, PEDOT:PSS has emerged as a promising material in versatile bioelectronics due to its tissue-like mechanical properties and suitable electrical properties. However, previously developed PEDOT:PSS inks have not been able to fully utilize the advantages of commercial 3D printing due to its long post treatment times, difficulty in high aspect ratio printing, and low conductivity. We propose a one-shot strategy for the fabrication of PEDOT:PSS ink that is able to simultaneously achieve on-demand biocompatibility (no post treatment), structural integrity during 3D printing for tall three-dimensional structures, and high conductivity for rapid-prototyping. By using ionic liquid-facilitated PEDOT:PSS colloidal stacking induced by a centrifugal protocol, a viscoplastic PEDOT:PSS-ionic liquid colloidal (PILC) ink was developed. PILC inks exhibit high-aspect ratio vertical stacking, omnidirectional printability for generating suspended architectures, high conductivity (~286 S/cm), and high-resolution printing (~50 µm). We demonstrate the on-demand and versatile applicability of PILC inks through the fabrication of 3D circuit boards, on-skin physiological signal monitoring e-tattoos, and implantable bioelectronics (opto-electrocorticography recording, low voltage sciatic nerve stimulation and recording from deeper brain layers via 3D vertical spike arrays).

Characterization of Functional Ingredients Extracted with Ethanol Solvents from Ponkan (Citrus reticulata) By-Products Using the Microwave Vacuum Drying Method Combined with Ultrasound-Assisted Extraction.

For this study, microwave vacuum drying (MVD) was combined with ultrasound-assisted extraction to compare the effects of different ethanol volumes on ponkan extract and to evaluate the total phenolic content (TPC), total flavonoid content (TFC), and total ascorbic acid content (TAAC). High-performance liquid chromatography with photodiode array detection (HPLC-PDA) was used to analyze the flavanone contents and antioxidant activity of ponkan (Citrus reticulata) peels. The experimental results showed that the TPC and TFC increase with ethanol volume. Ethanol extraction (75%) showed significant advantages by increasing the TPC to 17.48 mg GAE/g (DW) and the TFC to 2.96 mg QE/g (DW) of ponkan extract and also exhibited the highest antioxidant activity. The TAAC improved along with increased water content. Water extraction showed the highest content (13.07 mg VitC/100 g, DW). The hesperidin content analyzed by HPLC-PDA was 102.95-622.57 mg/100 g (DW), which was the highest among the flavanones. Then, the ethanol insoluble residue extracts were taken from the pectin with four different solvents, evaluating TPC, TFC, and antioxidant activity. The TPC, TFC, and antioxidant capacity of pectin are significantly lower than those of the peels. Combining MVD and 75% ethanol with ultrasound-assisted extraction in the pre-treatment process can effectively eliminate polyphenols, flavonoids, and other compounds, thus enabling the extraction of high-methoxyl pectin. The total dietary fiber (TDF) content of MVD ponkan by-products was 25.83%. Ponkan by-products have the potential for the future development of functional foods and supplements.

Advancing COVID-19 Diagnosis: Enhancement in SERS-PCR with 30-nm Au Nanoparticle-Internalized Nanodimpled Substrates.

Real-time polymerase chain reaction (RT-PCR) with fluorescence detection is the gold standard for diagnosing coronavirus disease 2019 (COVID-19) However, the fluorescence detection in RT-PCR requires multiple amplification steps when the initial deoxyribonucleic acid (DNA) concentration is low. Therefore, this study has developed a highly sensitive surface-enhanced Raman scattering-based PCR (SERS-PCR) assay platform using the gold nanoparticle (AuNP)-internalized gold nanodimpled substrate (AuNDS) plasmonic platform. By comparing different sizes of AuNPs, it is observed that using 30 nm AuNPs improves the detection limit by approximately ten times compared to 70 nm AuNPs. Finite-difference time-domain (FDTD) simulations show that multiple hotspots are formed between AuNPs and the cavity surface and between AuNPs when 30 nm AuNPs are internalized in the cavity, generating a strong electric field. With this 30 nm AuNPs-AuNDS SERS platform, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ribonucleic acid (RNA)-dependent RNA polymerase (RdRp) can be detected in only six amplification cycles, significantly improving over the 25 cycles required for RT-PCR. These findings pave the way for an amplification-free molecular diagnostic system based on SERS.

Treatment for appendicitis in cancer patients on chemotherapy: a retrospective cohort study.

Purpose: Whether to perform surgery or conservatively manage appendicitis in immunosuppressed patients is a concern for clinicians. This study aimed to compare the outcomes of these 2 treatment options for appendicitis in patients with cancer undergoing chemotherapy. Methods: This retrospective study included 206 patients with cancer who were diagnosed with acute appendicitis between August 2001 and December 2021. Among them, patients who received chemotherapy within 1 month were divided into surgical and conservative groups. We evaluated the outcomes, including treatment success within 1 year, 1-year recurrence, and the number of days from the diagnosis of appendicitis to chemotherapy restart, between the 2 groups. Results: Among the 206 patients with cancer who were diagnosed with acute appendicitis, 78 received chemotherapy within 1 month. The patients were divided into surgery (n = 63) and conservative (n = 15) groups. In the surgery group, the duration of antibiotic therapy (7.0 days vs. 16.0 days, P < 0.001) and length of hospital stay (8.0 days vs. 27.5 days, P = 0.002) were significantly shorter than conservative groups. The duration from the diagnosis of appendicitis to the restart of chemotherapy was shorter in the surgery group (20.8 ± 15.1 days vs. 35.2 ± 28.2 days, P = 0.028). The treatment success rate within 1 year was higher in the surgery group (100% vs. 33.3%, P < 0.001). Conclusion: Surgical treatment showed a significantly higher success rate than conservative treatment for appendicitis in patients less than 1 month after chemotherapy. Further prospective studies will be needed to clinically determine treatment options.

Safety and Effectiveness of Bone Allografts for Mastoid Obliteration After Mastoidectomy: A Pilot Study.

Background and Objectives: : Various materials are used to perform post-mastoidectomy mastoid obliteration (MO) to reduce the risk of recurrent infections, stasis of secretions, or caloric dizziness. Autologous materials used as fillers for MO tend to be insufficient owing to shrinkage over time or inadequate volume of these substances. Synthetic materials are unsatisfactory for MO because of the risk of rejection and extrusion. We investigated the safety and effectiveness of bone allografts for post-mastoidectomy MO. Subjects and Methods: : We reviewed the medical records of patients who underwent mastoidectomy with MO between January 2013 and January 2021. In the MO group, bone allografts were additionally used to fill the residual mastoid cavity. In the canal wall down (CWD) group, all patients underwent CWD mastoidectomy with use of additional inferiorly based mucoperiosteal flaps. Results: : The study included the MO group (23 ears) and the CWD group (53 ears). In the MO group, compared with the preoperative status, we observed a decrease in the tendency of the air-bone gap postoperatively. Compared with the CWD group, the total complication rate showed a decreasing tendency in the MO group. Conclusions: : No patient showed post-MO shrinkage of the grafted bone allograft or otorrhea. Further large-scale studies are warranted to confirm the advantages of bone allografts for MO, including maintenance with time and sufficient amount.

Proximal Gastrectomy is Associated with Lower Incidence of Anemia and Vitamin B12 Deficiency Compared to Total Gastrectomy in Patients with Upper Gastric Cancer.

Purpose: Proximal gastrectomy is an alternative to total gastrectomy (TG) for early gastric cancer (EGC) treatment in the upper stomach. However, its benefits in terms of perioperative and long-term outcomes remain controversial. The aim of this study was to compare the perioperative, body compositional, nutritional, and survival outcomes of patients undergoing proximal gastrectomy with double-tract reconstruction (PG-DTR) and TG for pathological stage I gastric cancer in upper stomach. Materials and Methods: The study included 506 patients who underwent gastrectomy for pathological stage I gastric cancer in the upper stomach between 2015 and 2019. Clinicopathological, perioperative, body compositional, nutritional, and survival outcomes were compared between the PG-DTR and TG groups. Results: The PG-DTR and TG groups included 197 (38.9%) and 309 (61.1%) patients, respectively. The PG-DTR group had a lower rate of early complications (p=0.041), lower diagnosis rate of anemia and vitamin B12 deficiency (all p<0.001), and lower replacement rate of iron and vitamin B12 compared to TG group (all p<0.001). The PG-DTR group showed reduced incidence of sarcopenia at 6-months postoperatively, preserved higher amount of visceral fat after surgery (p=0.032 and p=0.040, respectively), and showed a higher hemoglobin level (p=0.007). Oncologic outcomes were comparable between the groups. Conclusion: The PG-DTR for EGC located in the upper stomach offered advantages of fewer complications, lower incidence of anemia and vitamin B12 deficiency, less decrease in visceral fat volume, and similar survival compared to TG. Consequently, PG-DTR may be considered a superior alternative treatment option to TG.

Comparison of Statin With Ezetimibe Combination Therapy Versus Statin Monotherapy for Primary Prevention in Middle-Aged Adults.

BACKGROUND AND OBJECTIVES: Lipid lowering therapy is essential to reduce the risk of major cardiovascular events; however, limited evidence exists regarding the use of statin with ezetimibe as primary prevention strategy for middle-aged adults. We aimed to investigate the impact of single pill combination therapy on clinical outcomes in relatively healthy middle-aged patients when compared with statin monotherapy. METHODS: Using the Korean National Health Insurance Service database, a propensity score match analysis was performed for baseline characteristics of 92,156 patients categorized into combination therapy (n=46,078) and statin monotherapy (n=46,078) groups. Primary outcome was composite outcomes, including death, coronary artery disease, and ischemic stroke. And secondary outcome was all-cause death. The mean follow-up duration was 2.9±0.3 years. RESULTS: The 3-year composite outcomes of all-cause death, coronary artery disease, and ischemic stroke demonstrated no significant difference between the 2 groups (10.3% vs. 10.1%; hazard ratio (HR), 1.022; 95% confidence interval [CI], 0.980-1.064; p=0.309). Meanwhile, the 3-year all-cause death rate was lower in the combination therapy group than in the statin monotherapy group (0.2% vs. 0.4%; p<0.001), with a significant HR of 0.595 (95% CI, 0.460-0.769; p<0.001). Single pill combination therapy exhibited consistently lower mortality rates across various subgroups. CONCLUSIONS: Compared to the statin monotherapy, the combination therapy for primary prevention showed no difference in composite outcomes but may reduce mortality risk in relatively healthy middle-aged patients. However, since the study was observational, further randomized clinical trials are needed to confirm these findings.

Factors affecting implant length in primary inflatable penile prosthesis placement.

OBJECTIVES: To evaluate predictors of implant length for men undergoing primary IPP placement. METHODS: A multicenter, retrospective cohort study was performed for men undergoing primary IPP placement at 16 high-volume surgical centers. Patient demographics, comorbidities, operative approach, and implanted cylinder and rear tip extender length were recorded. Associations between potential preoperative and intraoperative predictors of total device length were tested using non-parametric correlation and Kruskal-Wallis tests, followed by multiple regression. RESULTS: Of 3,951 men undergoing primary IPP placement from July 2016 - July 2021, the median implant length was 20 cm (IQR: 19 - 22). Shorter implant length was associated with increasing age in years (ß = -0.01, p=0.009), Asian ethnicity (ß = -2.34, p=0.008), history of radical prostatectomy (ß = -0.35, p=0.001), and use of an infrapubic surgical approach (ß = -1.02, p<0.001). Black or African American ethnicity was associated with the implantation of longer devices (ß = 0.35, p<0.001). No significant associations were recorded with BMI, history of intracavernosal injections, diabetes mellitus, tobacco use, radiation therapy, Peyronie's disease, priapism, or cavernosal dilation technique. CONCLUSIONS: The length of an implanted penile prosthesis was found to be associated with preoperative and intraoperative factors including history of radical prostatectomy and operative approach. The knowledge of these associations may assist in the preoperative counseling of patients receiving IPP and help create accurate postoperative expectations.

Integrative analysis of cancer multimodality data identifying COPS5 as a novel biomarker of diffuse large B-cell lymphoma.

Preventing, diagnosing, and treating diseases requires accurate clinical biomarkers, which remains challenging. Recently, advanced computational approaches have accelerated the discovery of promising biomarkers from high-dimensional multimodal data. Although machine-learning methods have greatly contributed to the research fields, handling data sparseness, which is not unusual in research settings, is still an issue as it leads to limited interpretability and performance in the presence of missing information. Here, we propose a novel pipeline integrating joint non-negative matrix factorization (JNMF), identifying key features within sparse high-dimensional heterogeneous data, and a biological pathway analysis, interpreting the functionality of features by detecting activated signaling pathways. By applying our pipeline to large-scale public cancer datasets, we identified sets of genomic features relevant to specific cancer types as common pattern modules (CPMs) of JNMF. We further detected COPS5 as a potential upstream regulator of pathways associated with diffuse large B-cell lymphoma (DLBCL). COPS5 exhibited co-overexpression with MYC, TP53, and BCL2, known DLBCL marker genes, and its high expression was correlated with a lower survival probability of DLBCL patients. Using the CRISPR-Cas9 system, we confirmed the tumor growth effect of COPS5, which suggests it as a novel prognostic biomarker for DLBCL. Our results highlight that integrating multiple high-dimensional data and effectively decomposing them to interpretable dimensions unravels hidden biological importance, which enhances the discovery of clinical biomarkers.

NRF2 is a spatiotemporal metabolic hub essential for the polyfunctionality of Th2 cells.

Upon encountering allergens, CD4+ T cells differentiate into IL-4-producing Th2 cells in lymph nodes, which later transform into polyfunctional Th2 cells producing IL-5 and IL-13 in inflamed tissues. However, the precise mechanism underlying their polyfunctionality remains elusive. In this study, we elucidate the pivotal role of NRF2 in polyfunctional Th2 cells in murine models of allergic asthma and in human Th2 cells. We found that an increase in reactive oxygen species (ROS) in immune cells infiltrating the lungs is necessary for the development of eosinophilic asthma and polyfunctional Th2 cells in vivo. Deletion of the ROS sensor NRF2 specifically in T cells, but not in dendritic cells, significantly abolished eosinophilia and polyfunctional Th2 cells in the airway. Mechanistically, NRF2 intrinsic to T cells is essential for inducing optimal oxidative phosphorylation and glycolysis capacity, thereby driving Th2 cell polyfunctionality independently of IL-33, partially by inducing PPARγ. Treatment with an NRF2 inhibitor leads to a substantial decrease in polyfunctional Th2 cells and subsequent eosinophilia in mice and a reduction in the production of Th2 cytokines from peripheral blood mononuclear cells in asthmatic patients. These findings highlight the critical role of Nrf2 as a spatial and temporal metabolic hub that is essential for polyfunctional Th2 cells, suggesting potential therapeutic implications for allergic diseases.