Miracle-dz/UniFAR-FTUs huggingface dataset:
Health‐related quality of life in patients with relapsed or refractory multiple myeloma: treatment with daratumumab, lenalidomide, and dexamethasone in the phase 3 POLLUX trial

In the phase 3 POLLUX trial, daratumumab in combination with lenalidomide and dexamethasone (D‐Rd) significantly improved progression‐free survival in patients with relapsed/refractory multiple myeloma (RRMM) compared with lenalidomide and dexamethasone (Rd) alone. Here, we present patient‐reported outcomes (PROs) from POLLUX, assessed using the validated European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30‐item (EORTC QLQ‐C30) and the EuroQol 5‐dimensional descriptive system (EQ‐5D‐5L) questionnaires. Changes from baseline are presented as least‐squares mean changes with 95% confidence intervals (CIs) derived from a mixed‐effects model. PRO assessment compliance rates were high and similar in both D‐Rd and Rd groups through cycle 40 (week 156). In this on‐treatment analysis, mean changes from baseline were significantly greater in EORTC QLQ‐C30 global health status, physical functioning, and pain scores in the D‐Rd group versus the Rd group at multiple time points; however, magnitude of changes was low, suggesting no meaningful impact on health‐related quality of life (HRQoL). Subgroup results were similar to those in the overall population. In the POLLUX study, baseline HRQoL was maintained with prolonged D‐Rd treatment. These findings complement the sustained and significant improvement in progression‐free survival observed with D‐Rd and supports its use in patients with RRMM.
68Ga-DOTATATE PET/CT for Neuroblastoma Staging: Utility for Clinical Use

Visual Abstract Metaiodobenzylguanidine (MIBG) imaging has been the standard for neuroblastoma staging for many decades. Novel agents such as 18F-DOPA and 68Ga-DOTATATE are being used nowadays in academic centers. During the coronavirus disease 2019 (COVID-19) pandemic, procurement of 123I-MIBG has proved particularly challenging, necessitating the use of 68Ga-DOTATATE PET. 68Ga-DOTATATE is Food and Drug Administration–approved for imaging of somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors. Methods: 68Ga-DOTATATE PET/CT imaging was performed for staging of 3 pediatric patients with neuroblastoma at our institution. A review of the literature was also completed. Results: 68Ga-DOTATATE PET/CT scans were successfully performed on all patients. All patients showed 68Ga-DOTATATE–avid disease. PET scans showed an excellent spatial resolution and demonstrated high accuracy in concordance with current European Association of Nuclear Medicine guidelines. Conclusion: We have presented 68Ga-DOTATATE PET/CT imaging for staging of neuroblastoma and believe it can reliably be used as an alternative to 123I-MIBG. It has technical, clinical, and practical advantages making it an attractive option. Further multicenter studies are required before it can be recommended for standard clinical use.
Systems Approach to Discovery of Therapeutic Targets for Vein Graft Disease

Supplemental Digital Content is available in the text. Background: Vein graft failure remains a common clinical challenge. We applied a systems approach in mouse experiments to discover therapeutic targets for vein graft failure. Methods: Global proteomics and high-dimensional clustering on multiple vein graft tissues were used to identify potential pathogenic mechanisms. The PPARs (peroxisome proliferator-activated receptors) pathway served as an example to substantiate our discovery platform. In vivo mouse experiments with macrophage-targeted PPARα small interfering RNA, or the novel, selective activator pemafibrate demonstrate the role of PPARα in the development and inflammation of vein graft lesions. In vitro experiments further included metabolomic profiling, quantitative polymerase chain reaction, flow cytometry, metabolic assays, and single-cell RNA sequencing on primary human and mouse macrophages. Results: We identified changes in the vein graft proteome associated with immune responses, lipid metabolism regulated by the PPARs, fatty acid metabolism, matrix remodeling, and hematopoietic cell mobilization. PPARα agonism by pemafibrate retarded the development and inflammation of vein graft lesions in mice, whereas gene silencing worsened plaque formation. Pemafibrate also suppressed arteriovenous fistula lesion development. Metabolomics/lipidomics, functional metabolic assays, and single-cell analysis of cultured human macrophages revealed that PPARα modulates macrophage glycolysis, citrate metabolism, mitochondrial membrane sphingolipid metabolism, and heterogeneity. Conclusions: This study explored potential drivers of vein graft inflammation and identified PPARα as a novel potential pharmacological treatment for this unmet medical need.
Hospitalization for Heart Failure Among Patients With Diabetes Mellitus and Reduced Kidney Function Treated With Metformin Versus Sulfonylureas: A Retrospective Cohort Study

Background Metformin and sulfonylurea are commonly prescribed oral medications for type 2 diabetes mellitus. The association of metformin and sulfonylureas on heart failure outcomes in patients with reduced estimated glomerular filtration rate remains poorly understood. Methods and Results This retrospective cohort combined data from National Veterans Health Administration, Medicare, Medicaid, and the National Death Index. New users of metformin or sulfonylurea who reached an estimated glomerular filtration rate of 60 mL/min per 1.73 m2 or serum creatinine of 1.5 mg/dL and continued metformin or sulfonylurea were included. The primary outcome was hospitalization for heart failure. Echocardiogram reports were obtained to determine each patient's ejection fraction (EF) (reduced EF <40%; midrange EF 40%–49%; ≥50%). The primary analysis estimated the cause‐specific hazard ratios for metformin versus sulfonylurea and estimated the cumulative incidence functions for heart failure hospitalization and competing events. The weighted cohort included 24 685 metformin users and 24 805 sulfonylurea users with reduced kidney function (median age 70 years, estimated glomerular filtration rate 55.8 mL/min per 1.73 m2). The prevalence of underlying heart failure (12.1%) and cardiovascular disease (31.7%) was similar between groups. There were 16.9 (95% CI, 15.8–18.1) versus 20.7 (95% CI, 19.5–22.0) heart failure hospitalizations per 1000 person‐years for metformin and sulfonylurea users, respectively, yielding a cause‐specific hazard of 0.85 (95% CI, 0.78–0.93). Among heart failure hospitalizations, 44.5% did not have echocardiogram information available; 29.3% were categorized as reduced EF, 8.9% as midrange EF, and 17.2% as preserved EF. Heart failure hospitalization with reduced EF (hazard ratio, 0.79; 95% CI, 0.67–0.93) and unknown EF (hazard ratio, 0.84; 95% CI 0.74–96) were significantly lower in metformin versus sulfonylurea users. Conclusions Among patients with type 2 diabetes mellitus who developed worsening kidney function, persistent metformin compared with sulfonylurea use was associated with reduced heart failure hospitalization.
Sweet systems: technologies for glycomic analysis and their integration into systems biology

Abstract Found in virtually every organism, glycans are essential molecules that play important roles in almost every aspect of biology. The composition of glycome, the repertoire of glycans in an organism or a biological sample, is often found altered in many diseases, including cancer, infectious diseases, metabolic and developmental disorders. Understanding how glycosylation and glycomic changes enriches our knowledge of the mechanisms of disease progression and sheds light on the development of novel therapeutics. However, the inherent diversity of glycan structures imposes challenges on the experimental characterization of glycomes. Advances in high-throughput glycomic technologies enable glycomic analysis in a rapid and comprehensive manner. In this review, we discuss the analytical methods currently used in high-throughput glycomics, including mass spectrometry, liquid chromatography and lectin microarray. Concomitant with the technical advances is the integration of glycomics into systems biology in the recent years. Herein we elaborate on some representative works from this recent trend to underline the important role of glycomics in such integrated approaches to disease.
Determining the Heavy Metal Concentrations in Plants Exposed to Exhaust Gases Alongside the Sanliurfa Highway

In this study, the aim was to determine the heavy metal accumulation in plants that grow alongside the highways connecting Şanliurfa with neighboring cities that are exposed to exhaust gases. Thus, the lead, copper, iron, cadmium, nickel, and zinc concentration in plants were analyzed. Moreover, these were assessed by determining the parameters such as chlorophyll, malondialdehyde and proline to indicate to what extent the plants were affected by the heavy metal stress. The findings of the study revealed that the heavy metal accumulation in plants varied depending on the distance between the plant and the highway, on density of vehicles, on climate changes, and on air and environmental conditions. It was also determined that there is a clear increase in the heavy metal accumulation in summer. Furthermore, it was revealed that the stress caused by the heavy metal accumulation reduced the chlorophyll ratio and increased the malondialdehyde and proline concentrations, which is an indication of exhaust gases' heavily affecting the environment. The fact that vegetation is seriously affected by exhaust gases means that humans are also
Overexpression of AGAMOUS-like gene PfAG5 promotes early flowering in Polypogon fugax

Background: Herbicides are the major tool for controlling large populations of yield depleting weeds. However, overreliance on herbicides has resulted in weed adaptation and herbicide resistance. In recent years, early flowering weed species related to herbicide resistance is emerging, which may cause seed loss before crop harvest, creating a new problem for non-chemical weed management. However, mechanisms regulating early flowering in weedy species is rarely investigated. Results: The MADS-box gene family plays an important role in flowering time regulation and floral organogenesis. In this study, a homolog gene of AGAMOUS sub-family (referred to as PfAG5) of the MADS-box family was cloned from plants of an early flowering Polypogon fugax population resistant to the ACCase inhibitor herbicide (clodinafop-propargyl). The PfAG5 gene was functionally characterized in Arabidopsis thaliana. Over-expression of the PfAG5 gene in Arabidopsis resulted in early flowering with abnormal flowers (e.g. small petals, short plants and reduced seed set) compared to the wild type. The expression of the PfAG5 gene was high in leaves and flowers, but low in pods in transgenic Arabidopsis. The PfAG5 gene was earlier and higher expressed in the resistant (R) than the susceptible (S) P. fugax plants. Furthermore, one protein (FRIGIDA-like protein) interacting with PfAG5 in R P. fugax was identified by the yeast two-hybrid system with relevance to flowering time regulation. Conclusions: These results suggest that the PfAG5 gene is involved in modulating early flowering in P. fugax. This study provides the first evidence for the regulation mechanism of early flowering in an herbicide resistant weed species.
Characterization of smelter slags

Abstract The chemical and phase compositions of four different slags were studied with emphases on the form of Nickel, Cobalt and Copper. These were INCO slow cooled (IS), INCO fast cooled (IF), Falconbridge‐Sudbury fast cooled (FFS) and Falconbridge‐Timmins fast cooled (FFT) slags. The amount of each of Ni, Co and Cu in all the slags was less than 1%. IS contained the highest amount of Ni and Co of 0.57% and 0.21% respectively. The highest Cu content was found in FFS (0.87 %). The form of Co in all the slags was primarily oxide (> 98%). However, significant portions of Ni and Cu (20%) in IF and IS slag were in the sulphide form. Finer fractions (<270 mesh) of these slags were richer in sulphide forms of Ni and Cu (40%). X‐ray analysis revealed FFS and FFT as predominantly amorphous. Both slags were homogenous, consisting of mainly iron silicate glass. However, IF and IS slags were mostly crystalline, with two predominant phases, fayalite and spinel. In addition, a smaller amount of feldspar (albite) was observed in IS. Reflected light microscopy observation showed more crystalline phases in IS than IF. SEM‐EDS analysis, EMPA elemental mapping and reflected light microscopy studies all indicated the presence of entrained sulphide particles in the slag samples.
Policies and actions to reduce maternal mortality in Nepal: perspectives of key informants

Abstract Nepal made impressive progress in reducing maternal mortality until 2015. Since then, progress has stagnated, coinciding with Nepal’s transition to a federation with significant devolution in health management. In this context, we conducted key informant interviews (KII) to solicit perspectives on policies responsible for the reduction in maternal mortality, reasons for the stagnation in maternal mortality, and interventions needed for a faster decline in maternal mortality. We conducted 36 KIIs and analysed transcripts using standard framework analysis methods. The key informants identified three policies as the most important for maternal mortality reduction in Nepal: the Safe Motherhood Policy, Skilled Birth Attendant Policy, and Safe Abortion Policy. They opined that policies were adequate, but implementation was weak and ineffective, and strategies needed to be tailored to the local context. A range of health system factors, including poor quality of care, were identified by key informants as underlying the stagnation in Nepal’s maternal mortality ratio, as well as a few demand-side aspects. According to key informants, to reduce maternal deaths further Nepal needs to ensure that the current family planning, birth preparedness, financial incentives, free delivery services, abortion care, and community post-partum care programmes reach marginalised and vulnerable communities. Facilities offering comprehensive emergency obstetric care need to be accessible, and in hill and mountain areas, access could be supported by establishing maternity waiting homes. Social accountability can be strengthened through social audits, role models, and empowerment of health and management committees.
Emotional Vulnerability to Short Sleep Predicts Increases in Chronic Health Conditions Across 8 Years.

BACKGROUND Sleep is a robust determinant of next-day emotions, but people vary in the extent that their emotions fluctuate on days following short sleep duration. These individual differences in day-to-day sleep and emotion dynamics may have long-term health implications. PURPOSE To evaluate emotional vulnerability to short sleep (within-person associations between sleep duration and next-day emotions) as a risk factor for future chronic conditions. METHODS Adults aged 33-84 (N = 1,426; 57% female) in the Midlife in the United States Study reported sleep duration and emotions by telephone for eight consecutive days. Chronic conditions were assessed via checklist at baseline and at a median follow-up of eight years (range: 5-10 years). Short sleep was examined in three ways: person-centered continuous variable, ≤6 hr, and <7 hr; long sleep was defined as ≥9 hr. RESULTS Multilevel structural equation models revealed that people with greater negative emotions following nights of sleep ≤6 hr (vs. their negative emotions after longer sleep) had increased chronic conditions at follow-up, compared to people who were less emotionally vulnerable to short sleep (Est. = 1.04, SE = .51, p < .028). Smaller declines in positive emotions following ≤6 hr of sleep were marginally predictive of lower risk for chronic conditions (Est. = -.77, SE = .44, p = .054). Emotional vulnerability to <7, ≥9, and continuous sleep hours were not associated with subsequent chronic conditions. CONCLUSIONS Emotional vulnerability to short sleep is a unique risk factor for the development of chronic conditions, independent of mean-level sleep duration and emotions.
SET Domain-Containing Protein 5 Enhances the Cell Stemness of Non-Small Cell Lung Cancer via the PI3K/Akt/mTOR Pathway.

BACKGROUND SET domain-containing protein 5 (SETD5) could promote non-small cell lung cancer (NS-CLC) cell invasion, but the effect of SETD5 on NSCLC cell stemness characteristics is unknown. Thus we attempted to evaluate the effect of SETD5 on NSCLC stemness and its mechanism. METHODS The expressions of SETD5 and stemness-related genes (SOX2, OCT4, ABCG2) were detected in NSCLC tissues by immunohistochemistry assay, qRT-PCR, and western blot. A SETD5 knockdown cell model was constructed by siRNA transfection in A549 and H1299 cells. A CCK8 assay was used to examine cell viability. A sphere-forming assay and side population cell assay were conducted to measure the cancer cell stem properties. The cells with SETD5 deletion were treated with an activator of AKT, SC79, and the protein expressions of Akt, p-Akt, mTOR, and p-mTOR were assessed. RESULTS SETD5 and cancer stem-related genes SOX2, OCT4, and ABCG2 were co-expressed and co-localized in tumor tissues and cell lines of NSCLC. The deletion of SETD5 significantly reduced the cell viability, cancer stem properties, and activity of the PI3K/Akt/mTOR pathway, while the decreased SETD5-induced effects were partially restored with SC79 treatment. CONCLUSION In this study, SETD5 promoted the cancer stem cell property of NSCLC through mitigating the activation of the PI3K/Akt/mTOR pathway, suggesting a candidate target role for SETD5 in NSCLC treatment.
Achieving the shot-noise limit using experimental multi-shot digital holography data.

In this paper, we achieve the shot-noise limit using straightforward image-post-processing techniques with experimental multi-shot digital holography data (i.e., off-axis data composed of multiple noise and speckle realizations). First, we quantify the effects of frame subtraction (of the mean reference-only frame and the mean signal-only frame from the digital-hologram frames), which boosts the signal-to-noise ratio (SNR) of the baseline dataset with a gain of 2.4 dB. Next, we quantify the effects of frame averaging, both with and without the frame subtraction. We show that even though the frame averaging boosts the SNR by itself, the frame subtraction and the stability of the digital-hologram fringes are necessary to achieve the shot-noise limit. Overall, we boost the SNR of the baseline dataset with a gain of 8.1 dB, which is the gain needed to achieve the shot-noise limit.
The Children's Action-Reaction Assessment Tool (CARAT) as an observational technique for assessing symptom management: An initial validation study with children aged 3-7 years undergoing needle procedures.

PURPOSE For many children, needle procedures are fearful events that are often painful. The first step in symptom management is to assess the child's pain and fear, and the next step is to use coping strategies to provide symptom relief for children who experience or feel pain and fear during procedures. The Children's Action-Reaction Assessment Tool (CARAT) is built on action-reaction strategies. This study aimed to determine the inter-rater reliability of the CARAT when used during needle procedures with 3- to 7-year-old children. DESIGN AND METHODS: We used a quantitative approach in which 21 children were observed by two independent observers during needle procedures to evaluate the inter-rater reliability of the CARAT. Data were analysed with descriptive statistics, and the observation scores were calculated with an intraclass correlation coefficient (ICC) test on SPSS for Windows, version 25. RESULTS The completed CARAT indicated the use of action-reaction strategies. Neither action nor reaction strategies were frequently used. The parents were seldom involved in the procedure. The inter-rater reliability showed a sufficient correlation between the observers. PRACTICE IMPLICATIONS: This study showed promising results for the inter-rater reliability of the CARAT, which can be used to facilitate care for children. The observational tool can be used to assess the use of action-reaction strategies in conjunction with needle procedures in children aged 3-7 years.
Differences in Burden Severity in Adult-Child Family Caregivers and Spousal Caregivers of Persons with Dementia

ABSTRACT Researchers are continuing to focus on the nature and sources of burden of family caregivers of persons living with dementia. Caregiving stress and burden are assessed and addressed by social workers, including at high-risk times such as hospitalization. This study tested whether adult-child family caregivers experience greater perceived burden than spousal caregivers, accounting for risks of acute stress which can accompany hospitalization for their care recipient, where social workers may be meeting with family caregivers for the first time. Family caregivers (N = 76; n = 42 adult-child; n = 34 spouse) were recruited during care-recipient clinical treatment. The settings of care included an outpatient memory care program and an inpatient geriatric psychiatry service. Results showed that adult-child caregivers reported greater burden as compared with spousal caregivers, but no differences regarding depressive symptoms, perceived stress, or grief. After controlling for demographics and location of care, being an adult-child caregiver remained a predictor of greater burden severity. Being an adult-child family caregiver may place an individual at increased risk for experiencing high burden. These findings suggest socials workers should consider how adult-child caregivers may benefit from strategies to address and reduce burden, beyond those typically offered to spousal caregivers.
Cyclophosphamide-Free Adjuvant Chemotherapy for Ovarian Protection in Young Women With Breast Cancer: A Randomized Phase 3 Trial

Abstract Background Chemotherapy-induced premature menopause leads to some consequences, including infertility. We initiated this randomized phase III trial to determine whether a cyclophosphamide-free adjuvant chemotherapy regimen would increase the likelihood of menses resumption and improve survival outcomes. Methods Young women with operable estrogen receptor-positive HER2-negative breast cancer after definitive surgery were randomly assigned to receive adjuvant epirubicin and cyclophosphamidefollowed by weekly paclitaxel (EC-wP) or epirubicin and paclitaxel followed by weekly paclitaxel (EP-wP). All patients received at least 5-year adjuvant endocrine therapy after chemotherapy. Two coprimary endpoints were the rate of menstrual resumption at 12 months after chemotherapy and 5-year disease-free survival in the intention-to-treat population. This study is registered at ClinicalTrials.gov (NCT01026116). All statistical tests were 2-sided. Results Between January 2011 and December 2016, 521 patients (median age = 34 years; interquartile range = 31-38 years) were enrolled, with 261 in the EC-wP group and 260 in the EP-wP group. The rate of menstrual resumption at 12 months after chemotherapy was 48.3% in EC-wP (95% confidence interval [CI] = 42.2% to 54.3%) and 63.1% in EP-wP (95% CI = 57.2% to 68.9%), with an absolute difference of 14.8% (95% CI = 6.37% to 23.2%, P < .001). The posthoc exploratory analysis by patient-reported outcome questionnaires indicated that pregnancy might occur in fewer women in the EC-wP group than in the EP-wP group. At a median follow-up of 62 months, the 5-year disease-free survival was 78.3% (95% CI = 72.2% to 83.3%) in EC-wP and 84.7% (95% CI = 79.3% to 88.8%) in EP-wP (stratified log-rank P = .07). The safety data were consistent with the known safety profiles of relevant drugs. Conclusions The cyclophosphamide-free chemotherapy regimen might be associated with a higher probability of menses resumption.