Large-scale 2D heterostructures from hydrogen-bonded organic frameworks and graphene with distinct Dirac and flat bands.

The current strategies for building 2D organic-inorganic heterojunctions involve mostly wet-chemistry processes or exfoliation and transfer, leading to interface contaminations, poor crystallizing, or limited size. Here we show a bottom-up procedure to fabricate 2D large-scale heterostructure with clean interface and highly-crystalline sheets. As a prototypical example, a well-ordered hydrogen-bonded organic framework is self-assembled on the highly-oriented-pyrolytic-graphite substrate. The organic framework adopts a honeycomb lattice with faulted/unfaulted halves in a unit cell, resemble to molecular "graphene". Interestingly, the topmost layer of substrate is self-lifted by organic framework via strong interlayer coupling, to form effectively a floating organic framework/graphene heterostructure. The individual layer of heterostructure inherits its intrinsic property, exhibiting distinct Dirac bands of graphene and narrow bands of organic framework. Our results demonstrate a promising approach to fabricate 2D organic-inorganic heterostructure with large-scale uniformity and highly-crystalline via the self-lifting effect, which is generally applicable to most of van der Waals materials.

Monocular Metasurface for Structured Light Generation and 3D Imaging with a Large Field-of-View.

Structured light three-dimensional (3D) imaging technology captures the geometric information on 3D objects by recording waves reflected from the objects' surface. The projection angle and point number of the laser dots directly determine the field-of-view (FOV) and the resolution of the reconstructed image. Conventionally, diffractive optical elements with micrometer-scale pixel size have been used to generate laser dot arrays, leading to limited FOV and point number within the projection optical path. Here, we theoretically put forward and experimentally demonstrate a monocular geometric phase metasurface composed of deep subwavelength meta-atoms to generate a 10 798 dot array within an FOV of 163°. Attributed to the vast number and high-density point cloud generated by the metasurface, the 3D reconstructed results showcase a maximum relative error in depth of 5.3 mm and a reconstruction error of 6.07%. Additionally, we propose a spin-multiplexed metasurface design method capable of doubling the number of lattice points. We demonstrate its application in the field of 3D imaging through experiments, where the 3D reconstructed results show a maximum relative depth error of 0.44 cm and a reconstruction error of 2.78%. Our proposed metasurface featuring advanced point cloud generation holds substantial potential for various applications such as facial recognition, autonomous driving, virtual reality, and beyond.

Efficacy and advantage of immunotherapy for melanoma via intramuscular co-expression of plasmid-encoded PD-1 and CTLA-4 scFvs.

Immunotherapy, in the shape of immune checkpoint inhibitors (ICIs), has completely changed the treatment of cancer. However, the increasing expense of treatment and the frequency of immune-related side effects, which are frequently associated with combination antibody therapies and Fc fragment of antibody, have limited the patient's ability to benefit from these treatments. Herein, we presented the therapeutic effects of the plasmid-encoded PD-1 and CTLA-4 scFvs (single-chain variable fragment) for melanoma via an optimized intramuscular gene delivery system. After a single injection, the plasmid-encoded ICI scFv in mouse sera continued to be above 150 ng/mL for 3 weeks and reached peak amounts of 600 ng/mL. Intramuscular delivery of plasmid encoding PD-1 and CTLA-4 scFvs significantly changed the tumor microenvironment, delayed tumor growth, and prolonged survival in melanoma-bearing mice. Furthermore, no significant toxicity was observed, suggesting that this approach could improve the biosafety of ICIs combination therapy. Overall, the expression of ICI scFvs in vivo using intramuscular plasmid delivery could potentially develop into a reliable, affordable, and safe immunotherapy technique, expanding the range of antibody-based gene therapy systems that are available.

Structured-Light 3D Imaging Based on Vector Iterative Fourier Transform Algorithm.

Quasi-continuous-phase metasurfaces overcome the side effects imposed by high-order diffraction on imaging and can impart optical parameters such as amplitude, phase, polarization, and frequency to incident light at sub-wavelength scales with high efficiency. Structured-light three-dimensional (3D) imaging is a hot topic in the field of 3D imaging because of its advantages of low computation cost, high imaging accuracy, fast imaging speed, and cost-effectiveness. Structured-light 3D imaging requires uniform diffractive optical elements (DOEs), which could be realized by quasi-continuous-phase metasurfaces. In this paper, we design a quasi-continuous-phase metasurface beam splitter through a vector iterative Fourier transform algorithm and utilize this device to realize structured-light 3D imaging of a target object with subsequent target reconstruction. A structured-light 3D imaging system is then experimentally implemented by combining the fabricated quasi-continuous-phase metasurface illuminated by the vertical-cavity surface-emitting laser and a binocular recognition system, which eventually provides a new technological path for the 3D imaging field.

Patient reported outcomes and patient experiences of immune checkpoint modulators for advanced or recurrent melanoma: a mixed methods study.

PURPOSE: Little is known about late and long-term patient-reported outcomes (PROs) of immune checkpoint modulators (ICMs) outside clinical trials. We conducted a cross-sectional, mixed-methods study to describe long-term PROs among advanced melanoma patients who began standard of care treatment with ICMs at least 1 year previously. METHODS: All participants completed the Functional Assessment of Cancer Therapy-Immune Checkpoint Modulator (FACT-ICM), assessing 46 immune-related side effects on a 5-point Likert scale, and a subset completed individual interviews. Descriptive statistics were computed for quantitative data and applied thematic analysis was used to examine qualitative data. RESULTS: Participants (N = 80) had a mean age of 67 years, and the majority were male (66%), non-Hispanic White (96%), and college graduates (61%). Single-agent nivolumab was the most common first (47%) and current/recent ICM (64%). On the FACT-ICM, 98% of participants reported at least one side effect, and 78% reported moderate or severe side effects. The most common moderate or severe side effects were aching joints (43%) and fatigue (38%). In interviews (n = 20), we identified five themes regarding patients' longer-term experiences after ICMs: lasting fatigue or decline in functioning, minimal side effects, manageable thyroid and pituitary dysfunction, skin conditions can be difficult to manage, and treating the cancer is worth the side effects. CONCLUSIONS: Nearly all patients reported side effects of ICMs at least 1 year after starting treatment. Our findings suggest that ICM side effect screening and management-especially for aching joints and fatigue-are indicated during long-term care of people living with advanced melanoma.

Electroacupuncture modulates the TLR4-NF-κB inflammatory signaling pathway to attenuate ocular surface inflammation in dry eyes of type 2 diabetic rats.

Bioinformatics analysis was performed to reveal the underlying pathogenesis of type 2 diabetes (T2DM) dry eye(DE) and to predict the core targets and potential pathways for electroacupuncture (EA) treatment of T2DM DE, in which key targets such as Toll-likereceptor4 (TLR4), NF-κB and Tumor necrosis factor-α (TNF-α) may be involved. Next, streptozotocin and a high-fat diet were used to generate T2DM-DE rats. Randomly picked EA, fluorometholone, model, and sham EA groups were created from successfully modelled T2DM DE rats. Six more rats were chosen as the blank group from among the normal rats. The results of DE index showed that EA improved the ocular surface symptoms.HE staining showed that EA attenuated the pathological changes in the cornea, conjunctiva and lacrimal gland of T2DM DE rats. EA decreased the expression of TLR4, MyD88, P-NF-κB P65, and TNF-α in the cornea, conjunctiva, and lacrimal gland, in accordance with immunofluorescence and Western blot data. Thus, EA reduced ocular surface symptoms and improved pathological changes of cornea, conjunctiva, and lacrimal gland induced by T2DM DE inT2DM DE rats, and the mechanism may be related to the inhibition of overactivation of the TLR4/NF-κB signaling pathway by EA and thus attenuating ocular surface inflammation.

Functional quality of life among newly diagnosed young adult colorectal cancer survivors compared to older adults: results from the ColoCare Study.

PURPOSE: Colorectal cancer (CRC) incidence and mortality are increasing among young adults (YAs) aged 18-39. This study compared quality of life (QOL) between YA and older adult CRC survivors in the ColoCare Study. METHODS: Participants were grouped by age (years) as follows: 18-39 (YA), 40-49, 50-64, and 65 + . Functional QOL (physical, social, role, emotional, cognitive) and global QOL were assessed with the EORTC-QLQ-C30 at enrollment, 3, 6, and 12 months. Average scores were compared between groups over time using longitudinal mixed-effect modeling. Proportions with clinically meaningful QOL impairment were calculated using age-relevant thresholds and compared between groups over time using logistic regression with mixed effects. RESULTS: Participants (N = 1590) were n = 81 YAs, n = 196 aged 40-49, n = 627 aged 50-64, and n = 686 aged 65 + . Average physical function was better among YAs than participants aged 50-64 (p = 0.010) and 65 + (p < 0.001), and average social function was worse among YAs than aged 65 + (p = 0.046). Relative to YAs, all age groups were less likely to report clinically meaningful social dysfunction (aged 40-49 OR = 0.13, 95%CI = 0.06-0.29; aged 50-64 OR = 0.10, 95%CI = 0.05-0.21; aged 65 + OR = 0.07, 95%CI = 0.04-0.15) and role dysfunction (aged 40-49 OR = 0.36, 95%CI = 0.18-0.75; aged 50-64 OR = 0.41, 95%CI = 0.22-0.78; aged 65 + OR = 0.32, 95%CI = 0.17-0.61). Participants aged 40-49 were also less likely to report physical dysfunction (OR = 0.42, 95%CI = 0.19-0.93). CONCLUSION: YA CRC survivors reported better physical and worse social function compared to older CRC survivors, and YA CRC survivors were more likely to report clinically meaningful social, role, and physical disfunction. Future work should further investigate QOL using age-relevant benchmarks to inform best practices for CRC survivorship care. TRIAL REGISTRATION: NCT02328677, registered December 2014.

Analysis of the incidence and risk factors of blood transfusion in total knee revision: a retrospective nationwide inpatient sample database study.

OBJECTIVE: This study sought to determine the incidence and risk factors of blood transfusion among patients undergoing total knee revision (TKR) using a nationwide database. METHODS: A retrospective data analysis was conducted based on the Nationwide Inpatient Sample (NIS), enrolling patients who underwent TKR from 2010 to 2019 with complete information. The patients were divided into two groups based on whether they received blood transfusion or not. The demographic characteristics (race, sex, and age), length of stay (LOS), total charge of hospitalization, hospital characteristics (admission type, insurance type, bed size, teaching status, location, and region of hospital), hospital mortality, comorbidities, and perioperative complications were analyzed. Finally, we conducted univariate and multivariate logistic regression to identify factors that were associated with TKR patients to require blood transfusion. RESULTS: The NIS database included 115,072 patients who underwent TKR. Among them, 14,899 patients received blood transfusion, and the incidence of blood transfusion was 13.0%. There was a dramatic decrease in the incidence over the years from 2010 to 2019, dropping from 20.4 to 6.5%. TKR patients requiring transfusions had experienced longer LOS, incurred higher total medical expenses, utilized Medicare more frequently, and had increased in-hospital mortality rates (all P < 0.001). Independent predictors for blood transfusion included advanced age, female gender, iron-deficiency anemia, rheumatoid disease, chronic blood loss anemia, congestive heart failure, coagulopathy, uncomplicated diabetes, lymphoma, fluid and electrolyte disorders, metastatic carcinoma, other neurological diseases, paralysis, peripheral vascular disorders, pulmonary circulation disorders, renal failure, valvular disease, and weight loss. In addition, risk factors for transfusion in TKR surgery included sepsis, acute myocardial infarction, deep vein thrombosis, pulmonary embolism, gastrointestinal bleeding, heart failure, renal insufficiency, pneumonia, wound infection, lower limb nerve injury, hemorrhage/seroma/hematoma, wound rupture/non healing, urinary tract infection, acute renal failure, and postoperative delirium. CONCLUSIONS: Our findings highlight the importance of recognizing the risk factors of blood transfusion in TKR to reduce the occurrence of adverse events.

Clinical drug screening reveals clofazimine potentiates the efficacy while reducing the toxicity of anti-PD-1 and CTLA-4 immunotherapy.

Emerging as the most potent and durable combinational immunotherapy, dual anti-PD-1 and CTLA-4 immune checkpoint blockade (ICB) therapy notoriously increases grade 3-5 immune-related adverse events (irAEs) in patients. Accordingly, attempts to improve the antitumor potency of anti-PD-1+CTLA-4 ICB by including additional therapeutics have been largely discouraged due to concerns of further increasing fatal toxicity. Here, we screened ∼3,000 Food and Drug Administration (FDA)-approved drugs and identified clofazimine as a potential third agent to optimize anti-PD-1+CTLA-4 ICB. Remarkably, clofazimine outperforms ICB dose reduction or steroid treatment in reversing lethality of irAEs, but unlike the detrimental effect of steroids on antitumor efficacy, clofazimine potentiates curative responses in anti-PD-1+CTLA-4 ICB. Mechanistically, clofazimine promotes E2F1 activation in CD8+ T cells to overcome resistance and counteracts pathogenic Th17 cells to abolish irAEs. Collectively, clofazimine potentiates the antitumor efficacy of anti-PD-1+CTLA-4 ICB, curbs intractable irAEs, and may fill a desperate clinical need to improve patient survival.

The formation mechanism and textural properties of a complex gel based on soybean glycinin-chitosan complex coacervates: Effects of pH, heat treatment temperature and centrifugation.

The soybean glycinin (11S)-chitosan (CS) complex gels with various textural properties were successfully constructed. The process involved the initial formation of 11S-CS coacervates through electrostatic interactions, followed by a heating treatment to obtain the final complex gels. The impacts of pH, heating temperature, and centrifugation on 11S-CS complex gel properties were investigated. The results indicated that the pore arrangement of the gel formed at pH 7.3 was more tightly and uniformly packed than those formed at pH 6.8 and 7.8. Centrifugation facilitated denser and more ordered gel structures at the three pH values, while increasing the heating temperature exhibited the opposite trend at pH 6.8 and 7.8. These structural differences were also reflected in the rheological and textural properties of the gel. The 11S-CS complex gels exhibited an elasticity-based gel property. The textural properties of gels formed at pH 6.8 were stronger compared to those formed at pH 7.3 and 7.8. However, when the 11S-CS coacervates were heated without centrifugation, the resulting gels were weak. This study emphasizes the potential of using protein/polysaccharide associative interactions during gel formation to alter the microstructure of the gel, meeting various production requirements.

Feasibility and acceptability of C-PRIME: A health promotion intervention for family caregivers of patients with colorectal cancer.

PURPOSE: This study aimed to test the feasibility and acceptability of a digital health promotion intervention for family caregivers of patients with advanced colorectal cancer and explore the intervention's preliminary efficacy for mitigating the impact of caregiving on health and well-being. METHODS: We conducted a single-arm pilot feasibility trial of C-PRIME (Caregiver Protocol for Remotely Improving, Monitoring, and Extending Quality of Life), an 8-week digital health-promotion behavioral intervention involving monitoring and visualizing health-promoting behaviors (e.g., objective sleep and physical activity data) and health coaching (NCT05379933). A priori benchmarks were established for feasibility (≥ 50% recruitment and objective data collection; ≥ 75% session engagement, measure completion, and retention) and patient satisfaction (> 3 on a 1-5 scale). Preliminary efficacy was explored with pre- to post-intervention changes in quality of life (QOL), sleep quality, social engagement, and self-efficacy. RESULTS: Participants (N = 13) were M = 52 years old (SD = 14). Rates of recruitment (72%), session attendance (87%), assessment completion (87%), objective data collection (80%), and retention (100%) all indicated feasibility. All participants rated the intervention as acceptable (M = 4.7; SD = 0.8). Most participants showed improvement or maintenance of QOL (15% and 62%), sleep quality (23% and 62%), social engagement (23% and 69%), and general self-efficacy (23% and 62%). CONCLUSION: The C-PRIME digital health promotion intervention demonstrated feasibility and acceptability among family caregivers of patients with advanced colorectal cancer. A fully powered randomized controlled trial is needed to test C-PRIME efficacy, mechanisms, and implementation outcomes, barriers, and facilitators in a divserse sample of family caregivers. TRIAL REGISTRATION: The Caregiver Protocol for Remotely Improving, Monitoring, and Extending Quality of Life (C-PRIME) study was registered on clinicaltrials.gov, NCT05379933, in May 2022.

Inequities in the Impacts of Hurricanes and Other Extreme Weather Events for Cancer Survivors.

In this minireview, we examine the impacts of hurricanes and other extreme weather events on cancer survivors, focusing on structural and social determinants of health. We briefly explore influences on biological, psychosocial, and behavioral outcomes and discuss risk and resilience factors in cancer survivorship during and after hurricanes. Our goal is to inform future directions for research that can identify areas in which we can most efficiently improve cancer outcomes and inform changes in health systems, clinical practice, and public health policies. This timely minireview provides researchers and clinicians with an overview of challenges and opportunities for improving disaster preparedness and response for cancer survivors.

"I couldn't connect the wires in my brain." Young adult cancer survivors' experience with cognitive functioning.

OBJECTIVE: There is a dearth of literature describing young adult (YA) cancer survivors' experiences with cancer-related cognitive impairment (CRCI). We aimed to elucidate CRCI among YA cancer survivors and identify potentially modifiable risk factors. METHODS: We conducted individual qualitative interviews with YA cancer survivors aged 18-30 years at study enrollment and used applied thematic analysis to identify themes across three topics (i.e., affected cognitive abilities, risk and protective factors influencing the impact of CRCI, and strategies for coping with CRCI). RESULTS: YA cancer survivors (N = 20) were, on average, 23 years old at diagnosis and 26 years old when interviewed. Diverse cancer types and treatments were represented; most participants (85%) had completed cancer treatment. Participants described experiences across three qualitative topics: (1) affected cognitive abilities (i.e., concentration and attention, prospective memory, and long-term memory), (2) Risk factors (i.e., fatigue, sleep problems, mood, stress/distractions, and social isolation) and protective factors (i.e., social support), and (3) coping strategies, including practical strategies that helped build self-efficacy (e.g., writing things down, reducing distractions), beneficial emotion-focused coping strategies (e.g., focus on health, faith/religion), strategies with mixed effects (i.e., apps/games, medications/supplements, and yoga), and "powering through" strategies that exacerbated stress. CONCLUSIONS: YA cancer survivors experience enduring cognitive difficulties after treatment. Specific concerns highlight the importance of attention and executive functioning impairments, long-term memory recall, and sensitivity to distractions. Future work is needed to improve assessment and treatment of CRCI among YA cancer survivors.

Acute cancer-related symptoms and concerns among patients receiving chemotherapy: current state of the science.

PURPOSE: This study provides an updated evaluation of the prevalence and severity of acute cancer-related symptoms and quality of life (QOL) concerns among patients treated with emetogenic chemotherapy. METHODS: Patients were recruited to a larger, multi-site observational study prior to starting chemotherapy. Participants completed sociodemographic questionnaires and clinical data were abstracted via medical record review. Symptoms and QOL were assessed 5 days after starting moderately or highly emetogenic chemotherapy. Functional Assessment of Cancer Therapy - General assessed QOL concerns. Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events evaluated symptoms. Symptoms were considered severe when participants responded "severe" or "very severe." RESULTS: Participants (N = 1174) were on average 58 ± 13 years, mostly female (73%), non-Hispanic (89%), and White (87%). Most participants were diagnosed with breast (38.1%), gynecological (20%), and gastrointestinal (17.1%) cancer. The most common QOL concerns of any severity were fatigue (94%), anhedonia (89%), dissatisfaction with QOL (86%), and sleep disturbance (86%). The most common severe QOL concerns were anhedonia (44%), fatigue (40%), and inability to work (38%). Decreased appetite (74%), pain (71%), and constipation (70%) were the most common symptoms of any severity, as well as most common severe symptoms (13%, 18%, and 18%, respectively). CONCLUSION: Herein, updates are provided in regard to QOL concerns and symptoms reported by patients in the days after chemotherapy and demonstrates that concerns and symptoms have shifted in the last decade.

Topological Nodal-Point Superconductivity in Two-Dimensional Ferroelectric Hybrid Perovskites.

Two-dimensional (2D) hybrid organic-inorganic perovskites (HOIPs) with enhanced stability, high tunability, and strong spin-orbit coupling have shown great potential in vast applications. Here, we extend the already rich functionality of 2D HOIPs to a new territory, realizing topological superconductivity and Majorana modes for fault-tolerant quantum computation. Especially, we predict that room-temperature ferroelectric BA2PbCl4 (BA for benzylammonium) exhibits topological nodal-point superconductivity (NSC) and gapless Majorana modes on selected edges and ferroelectric domain walls when proximity-coupled to an s-wave superconductor and an in-plane Zeeman field, attractive for experimental verification and application. Since NSC is protected by spatial symmetry of 2D HOIPs, we envision more exotic topological superconducting states to be found in this class of materials due to their diverse noncentrosymmetric space groups, which may open a new avenue in the fields of HOIPs and topological superconductivity.

Relationships Among Physical Activity, Sleep, and Cancer-related Fatigue: Results From the International ColoCare Study.

BACKGROUND: Risk factors for cancer-related fatigue are understudied in colorectal cancer. PURPOSE: This study aimed to address this critical gap in the literature by (a) describing changes in colorectal cancer-related fatigue and health behavior (physical activity, sleep problems) and (b) examining if physical activity and sleep problems predict fatigue trajectories from baseline (approximately at the time of diagnosis), to 6- and 12 months after enrollment. METHODS: Patients participating in the international ColoCare Study completed self-report measures at baseline (approximately time of diagnosis), 6-, and 12 months assessing physical activity using the International Physical Activity Questionnaire (IPAQ) and fatigue and sleep using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30). Mixed-effect models examined changes in physical activity, sleep problems, and fatigue. Cross-lagged panel models examined bidirectional relationships between physical activity or sleep and fatigue across time. RESULTS: Colorectal cancer patients (n = 649) had a mean age of 61 ± 13 years. Most were male (59%), non-Hispanic White (91%), diagnosed with Stages III-IV (56%) colon cancer (58%), and treated with surgery (98%). Within-person cross-lagged models indicated higher physical activity at Month 6 was associated with higher fatigue at Month 12 (ß = 0.26, p = .016). When stratified by cancer stage (I-II vs. III-IV), the relationship between physical activity at Month 6 and fatigue at Month 12 existed only for patients with advanced cancer (Stages III and IV, ß = 0.43, p = .035). Cross-lagged associations for sleep and fatigue from baseline to Month 6 were only observed in patients with Stages III or IV cancer, however, there was a clear cross-sectional association between sleep problems and fatigue at baseline and Month 6. CONCLUSIONS: Within-person and cross-lagged association models suggest fatiguability may become increasingly problematic for patients with advanced colorectal cancer the first year after diagnosis. In addition, sleep problems were consistently associated with higher fatigue in the first year, regardless of cancer stage. TRIAL REGISTRATION: The international ColoCare Study was registered on clinicaltrials.gov, NCT02328677, in December 2014.

Within-person and cross-lagged association models suggest fatiguability may become increasingly problematic for patients with advanced (Stages III and IV) colorectal cancer the first year after diagnosis.

Aphid Recognition and Counting Based on an Improved YOLOv5 Algorithm in a Climate Chamber Environment.

Due to changes in light intensity, varying degrees of aphid aggregation, and small scales in the climate chamber environment, accurately identifying and counting aphids remains a challenge. In this paper, an improved YOLOv5 aphid detection model based on CNN is proposed to address aphid recognition and counting. First, to reduce the overfitting problem of insufficient data, the proposed YOLOv5 model uses an image enhancement method combining Mosaic and GridMask to expand the aphid dataset. Second, a convolutional block attention mechanism (CBAM) is proposed in the backbone layer to improve the recognition accuracy of aphid small targets. Subsequently, the feature fusion method of bi-directional feature pyramid network (BiFPN) is employed to enhance the YOLOv5 neck, further improving the recognition accuracy and speed of aphids; in addition, a Transformer structure is introduced in front of the detection head to investigate the impact of aphid aggregation and light intensity on recognition accuracy. Experiments have shown that, through the fusion of the proposed methods, the model recognition accuracy and recall rate can reach 99.1%, the value mAP@0.5 can reach 99.3%, and the inference time can reach 9.4 ms, which is significantly better than other YOLO series networks. Moreover, it has strong robustness in actual recognition tasks and can provide a reference for pest prevention and control in climate chambers.

Gene-educational attainment interactions in a multi-population genome-wide meta-analysis identify novel lipid loci.

Introduction: Educational attainment, widely used in epidemiologic studies as a surrogate for socioeconomic status, is a predictor of cardiovascular health outcomes. Methods: A two-stage genome-wide meta-analysis of low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG) levels was performed while accounting for gene-educational attainment interactions in up to 226,315 individuals from five population groups. We considered two educational attainment variables: "Some College" (yes/no, for any education beyond high school) and "Graduated College" (yes/no, for completing a 4-year college degree). Genome-wide significant (p < 5 × 10-8) and suggestive (p < 1 × 10-6) variants were identified in Stage 1 (in up to 108,784 individuals) through genome-wide analysis, and those variants were followed up in Stage 2 studies (in up to 117,531 individuals). Results: In combined analysis of Stages 1 and 2, we identified 18 novel lipid loci (nine for LDL, seven for HDL, and two for TG) by two degree-of-freedom (2 DF) joint tests of main and interaction effects. Four loci showed significant interaction with educational attainment. Two loci were significant only in cross-population analyses. Several loci include genes with known or suggested roles in adipose (FOXP1, MBOAT4, SKP2, STIM1, STX4), brain (BRI3, FILIP1, FOXP1, LINC00290, LMTK2, MBOAT4, MYO6, SENP6, SRGAP3, STIM1, TMEM167A, TMEM30A), and liver (BRI3, FOXP1) biology, highlighting the potential importance of brain-adipose-liver communication in the regulation of lipid metabolism. An investigation of the potential druggability of genes in identified loci resulted in five gene targets shown to interact with drugs approved by the Food and Drug Administration, including genes with roles in adipose and brain tissue. Discussion: Genome-wide interaction analysis of educational attainment identified novel lipid loci not previously detected by analyses limited to main genetic effects.

Patient-Reported Outcomes among Multiple Myeloma Patients Treated with Standard of Care Idecabtagene Vicleucel.

Idecabtagene vicleucel (ide-cel) was the first FDA-approved chimeric antigen receptor T-cell therapy for relapsed/refractory multiple myeloma (RRMM) patients. This was the first study to evaluate patient-reported outcomes (PROs) among RRMM patients receiving ide-cel in standard of care (SOC). We prospectively assessed health-related quality of life (HRQOL) and symptoms from pre-infusion (baseline) through day (D)90 post-infusion. Baseline PRO associations with patient characteristics, mean PRO changes, and time to stable change were evaluated with t-tests, linear mixed-effects models, and Kaplan-Meier analyses, respectively. Within-person change scores and minimally important difference thresholds determined clinical and meaningful significance. Participants (n = 42) were a median of 66 years old (range: 43-81). At baseline, extramedullary disease was associated with worse physical well-being (p = 0.008), global pain (p < 0.001), performance status (p = 0.002), and overall symptom burden (p < 0.001). Fatigue (p < 0.001) and functional well-being (p = 0.003) worsened by D7 before returning to baseline levels. Overall HRQOL (p = 0.008) and physical well-being (p < 0.001) improved by D60. Most participants reported PRO improvement (10-57%) or maintenance (23-69%) by D90. The median time it took to stabile deterioration in functional well-being was 14 days. The median time it took to stabile improvement in physical and emotional well-being was 60 days. Overall, RRMM patients reported improvements or maintenance of HRQOL and symptom burden after SOC ide-cel.