Miracle-dz/UniFAR-FTUs huggingface dataset:
COVID‐19 elicits an impaired antibody response against SARS‐CoV‐2 in patients with haematological malignancies

COVID‐19 is associated with high mortality in patients with haematological malignancies (HM) and rate of seroconversion is unknown. The ITA‐HEMA‐COV project (NCT04352556) investigated patterns of seroconversion for SARS‐CoV‐2 IgG in patients with HMs. A total of 237 patients, SARS‐CoV‐2 PCR‐positive with at least one SARS‐CoV‐2 IgG test performed during their care, entered the analysis. Among these, 62 (26·2%) had myeloid, 121 (51·1%) lymphoid and 54 (22·8%) plasma cell neoplasms. Overall, 69% of patients (164 of 237) had detectable IgG SARS‐CoV‐2 serum antibodies. Serologically negative patients (31%, 73 of 237) were evenly distributed across patients with myeloid, lymphoid and plasma cell neoplasms. In the multivariable logistic regression, chemoimmunotherapy [odds ratio (OR), 3·42; 95% confidence interval (CI), 1·04–11·21; P = 0·04] was associated with a lower rate of seroconversion. This effect did not decline after 180 days from treatment withdrawal (OR, 0·35; 95% CI: 0·11–1·13; P = 0·08). This study demonstrates a low rate of seroconversion in HM patients and indicates that treatment‐mediated immune dysfunction is the main driver. As a consequence, we expect a low rate of seroconversion after vaccination and thus we suggest testing the efficacy of seroconversion in HM patients.
Signaled night awakening and its association with social information processing and socio-emotional development across the first two years

Abstract Study Objectives Night awakening is common in infancy, and some infants continue to have signaled night awakenings throughout early childhood. However, the influence of signaled night awakening on children’s social development is less explored. In the present study, longitudinal associations between signaled night awakening, social information processing, and socio-emotional development were measured within the CHILD-SLEEP birth cohort in two groups formed based on parent-reported night awakenings. Methods At 8 months, there were 77 infants in the waking group (≥3 awakenings) and 69 infants in the nonwaking group (≤1 awakening). At 8 and 24 months, social information processing was measured as children’s attention to neutral and emotional faces, and at 24 months, parent-reported socio-emotional behavior was measured with the Brief Infant-Toddler Social and Emotional Assessment (BITSEA) questionnaire. Results The two groups showed different patterns of attention to emotional faces. The waking group had a more pronounced attentional bias to fearful versus happy faces, whereas in the nonwaking group, attention to fearful and happy faces did not differ. In addition, at 24 months, the waking group had more dysregulation problems and lower social competence than the nonwaking group, but no clear differences in internalizing or externalizing problems were found. Conclusions Our results contribute to the literature by showing that during the first 2 years of life, signaled night awakening is associated with social information processing and socio-emotional behavior.
Reexamining the role of tissue inflammation in radiation carcinogenesis: a hypothesis to explain an earlier onset of cancer

Abstract Purpose Ionizing radiation is a well-known carcinogen, and epidemiologic efforts have been made to evaluate cancer risks following a radiation exposure. The basic approach has been to estimate increased levels of cancer mortality resulting from exposures to radiation, which is consistent with the somatic mutation theory of cancer. However, the possibility that an irradiation might cause an earlier onset of cancer has also been raised since the earliest days of animal studies. Recently, the mutation induction model has been challenged because it is unable to explain the observed dose-related parallel shift of entire mouse survival curves toward younger ages following an irradiation. This is because if it is assumed that only a fraction of the irradiated individuals are affected, the irradiated population would consist of two subpopulations with different mean lifespans, which makes the overall distribution of individual lifespans broader, and hence the slope of the survival curves shallower. To explain this parallel shift, it is necessary to assume that all individuals of a population are affected. As a result of these observations, possible mechanisms which could account for the parallel shift of mouse survival curves were sought by examining the radiation induction of various types of tissue damage which could facilitate an earlier onset of spontaneously arising cancers. Conclusion A proposed mechanism postulates that a radiation exposure leads to tissue inflammation which subsequently stimulates spontaneously arising cancers and allows them to appear earlier than usual. This notion is not unprecedented, and because the background incidence of cancer increases exponentially with an increase in age, a slight shift of the onset age toward younger ages may make it appear as if the risk is increased. In this scenario, a radiation exposure induces DNA damage, cell death, chromosome aberrations etc., which leads to the multi-pathway responses including activation of stromal fibroblasts, macrophages and various inflammatory factors. Such an inflamed microenvironment favors the growth of spontaneously arising tumor cells although currently, the sequential order or relative importance of the individual factors remains to be known.
Safety of PSMA-Targeted Molecular Radioligand Therapy with 177Lu-PSMA-617: Results from the Prospective Multicenter Phase 2 Trial RESIST-PC (NCT03042312)

The purpose of this analysis was to report the safety evaluation of 177Lu-PSMA-617 derived from the cohort of 64 patients exposed to 177Lu-PSMA-617 in the RESIST-PC trial NCT03042312. Methods: RESIST-PC was a prospective multicenter phase 2 trial. Patients with progressive metastatic castration-resistant prostate cancer after ≥ 1 novel androgen-axis drug, either chemotherapy naïve or postchemotherapy, with sufficient bone marrow reserve, normal kidney function, sufficient PSMA expression by PSMA PET, and no PSMA-negative soft-tissue lesions were eligible. Patients were randomized (1:1) into 2 activity groups (6.0 or 7.4 GBq per cycle) and received up to 4 cycles every 8 wk. The primary safety endpoint was assessed by collecting and grading adverse events using the Common Terminology Criteria for Adverse Events. Patients were followed until disease progression, death, serious or intolerable adverse events, study termination by sponsor, patient withdrawal, lost to follow-up, or 24 mo after the first cycle. Results: The study was closed at enrollment of 71 of 200 planned patients because of sponsorship transfer. A total of 64 (90.1%) patients received at least 1 cycle of 177Lu-PSMA-617: 28 (36%) in arm 1 (6.0 GBq) and 41 (64%) in arm 2 (7.4 GBq). There were 10 (43.5%), 19 (46.5%), and 29 (45.3%) patients who completed 4 cycles of 177Lu-PSMA-617 in the 6.0-GBq arm, 7.4-GBq arm, and overall, respectively. The most common treatment-emergent adverse events (TEAEs) of any grade in the 6.0-GBq arm, the 7.4-GBq arm and overall, were dry mouth (47.8%; 63.4%; 57.8%, respectively), fatigue (56.5%; 51.2%; 53.1%, respectively), nausea (52.2%; 43.9%; 46.9%, respectively), and diarrhea (13.0%; 31.7%; 25.0%, respectively). Frequencies of all other TEAEs were comparable among the 2 groups (within 10% difference). Serious possibly drug-related TEAEs were reported for 5 (7.8%) patients overall (none were considered as probably or definitely related to treatment): 1 subdural hematoma grade 4, 1 anemia grade 3, 1 thrombocytopenia grade 4, 1 gastrointestinal hemorrhage grade 3, and 1 acute kidney injury grade 3. There were no clinically significant changes in vital signs in electrocardiograms in the 2 treatment groups. No trend to creatinine increase or increasing frequency of shifts from normal to abnormal over time for any hematologic parameter was noted. Conclusion: 177Lu-PSMA-617 was safe and well-tolerated at 6.0 and 7.4 GBq per cycle given at 8-wk intervals with side effects easily managed with standard medical support. With established safety, further clinical trials applying individualized dosimetry and testing different 177Lu-PSMA-617 administration schemes (activity levels, time intervals) are needed to optimize tumor dose delivery and treatment efficacy.
Evaluation of neighborhood deprivation and store characteristics in relation to tobacco retail outlet sales violations

Introduction Regulations of the sale of tobacco products to minors have been effective at reducing adolescent tobacco use overall. However, these efforts may not be uniformly enforced in all areas, creating uneven protection against adolescent smoking. Knowledge regarding factors associated with tobacco retail outlet (TRO) violations could help inform better enforcement strategies. Methods In this study, we used Bayesian index regression models to determine if tobacco sales to minors violations across Virginia (2012–2021) were related to store characteristics and neighborhood deprivation and identify geographic areas at significantly elevated risk for violations after adjusting for these factors. Results Results show that there were multiple factors associated with a higher likelihood of tobacco sales violations. Store type was an important factor, as grocery stores and pharmacies had significantly lowered likelihood of violations compared with convenience stores. Being located near another TRO was significantly associated with increased risk of sales to a minor. Neighborhood deprivation was also positively associated with TRO sales violations. Further, there were statistically higher likelihood of sales violations occurring in specific areas (e.g., southwest and southeast) of the state that were not explained by neighborhood deprivation and store attributes. Conclusions Together, results highlight the need to better understand where and why TRO sales violations are occurring in order to improve efforts aimed at monitoring and remediating TRO sales violations.
Hydroxyurea treatment and neurocognitive functioning in sickle cell disease from school age to young adulthood

Neurocognitive impairment is common in sickle cell disease (SCD) and is associated with significant functional limitations. In a cross‐sectional analysis, we examined the association between hydroxyurea (HU) treatment and neurocognitive functioning from school‐age to young adulthood in individuals with SCD. A total of 215 patients with HbSS/HbSβ0‐thalassaemia (71% HU treated) and 149 patients with HbSC/HbSβ+‐thalassaemia (20% HU treated) completed neurocognitive measures at one of four developmental stages: school‐age (age 8–9 years), early adolescence (age 12–13 years), late adolescence (age 16–17 years) and young adulthood (ages 19–24 years). For participants with multiple assessments, only the most recent evaluation was included. In multivariable analysis adjusted for social vulnerability, HU treatment and sex, older age was associated with a reduction in overall intelligence quotient (IQ) of 0·55 points per year of life [standard error (SE) = 0·18, false discovery rate adjusted P value (PFDR) = 0.01] for patients with HbSS/HbSβ0‐thalassaemia. Earlier initiation of HU (n = 152) in HbSS/HbSβ0‐thalassaemia was associated with higher scores on neurocognitive measures across most domains, including IQ [estimate (SE) 0·77 (0·25)/year, PFDR = 0·01], after adjusting for social vulnerability, sex and treatment duration. These results support the early use of HU to limit the detrimental neurocognitive effects of SCD, while highlighting the need for additional measures to further mitigate neurocognitive deterioration.
Self-management for chronic widespread pain including fibromyalgia: A systematic review and meta-analysis

Background Chronic widespread pain (CWP) including fibromyalgia has a prevalence of up to 15% and is associated with substantial morbidity. Supporting psychosocial and behavioural self-management is increasingly important for CWP, as pharmacological interventions show limited benefit. We systematically reviewed the effectiveness of interventions applying self-management principles for CWP including fibromyalgia. Methods MEDLINE, Embase, PsycINFO, The Cochrane Central Register of Controlled Trials and the WHO International Clinical Trials Registry were searched for studies reporting randomised controlled trials of interventions adhering to self-management principles for CWP including fibromyalgia. Primary outcomes included physical function and pain intensity. Where data were sufficient, meta-analysis was conducted using a random effects model. Studies were narratively reviewed where meta-analysis could not be conducted Evidence quality was rated using GRADE (Grading of Recommendations, Assessment, Development and Evaluations) (PROSPERO-CRD42018099212). Results Thirty-nine completed studies were included. Despite some variability in studies narratively reviewed, in studies meta-analysed self-management interventions improved physical function in the short-term, post-treatment to 3 months (SMD 0.42, 95% CI 0.20, 0.64) and long-term, post 6 months (SMD 0.36, 95% CI 0.20, 0.53), compared to no treatment/usual care controls. Studies reporting on pain narratively had greater variability, however, those studies meta-analysed showed self-management interventions reduced pain in the short-term (SMD -0.49, 95% CI -0.70, -0.27) and long-term (SMD -0.38, 95% CI -0.58, -0.19) compared to no treatment/usual care. There were few differences in physical function and pain when self-management interventions were compared to active interventions. The quality of the evidence was rated as low. Conclusion Reviewed studies suggest self-management interventions can be effective in improving physical function and reducing pain in the short and long-term for CWP including fibromyalgia. However, the quality of evidence was low. Future research should address quality issues whilst making greater use of theory and patient involvement to understand reported variability.
Moringa leaf extract improves biochemical attributes, yield and grain quality of rice (Oryza sativa L.) under drought stress

Changing climate, food shortage, water scarcity and rapidly increasing population are some of the emerging challenges globally. Drought stress is the most devastating threat for agricultural productivity. Natural plant growth substances are intensively used to improve the productivity of crop plants grown under stressed and benign environments. The current study evaluated whether leaf extract of different moringa (Moringa oleifera L.) could play a role in improving drought-tolerance of rice (Oryza sativa L.). Rice plants were grown under three drought conditions, i.e., no, moderate and severe drought (100, 75 and 50% field capacity, respectively). Moringa leaf extract (MLE) obtained from four landraces (Multan, Faisalabad, D. G. Khan and exotic landrace from India) was applied during critical crop growth stages, i.e., tillering, panicle initiation and grain filling. Drought stress adversely affected the gas exchange attributes, photosynthetic pigments, antioxidant enzymes’ activities, yield and quality parameters of rice. Application of MLE from all landraces significantly improved physiological, biochemical and yield parameters under stressed and normal environmental conditions. The highest improvement in gas exchange traits (photosynthetic rate, stomatal conductance and respiration rate), photosynthetic pigments (chlorophyll a, b and carotenoids) and enzymatic activities (superoxide dismutase, catalase) and oxidative marker (H2O2) was recorded with MLE obtained from Faisalabad landrace. The application of MLE of Faisalabad landrace also improved yield and grain quality of rice grown under drought stress as well as drought-free environment. Thus, MLE of Faisalabad can be successfully used to improve growth, productivity and grain quality of rice under drought stress.
“More Guts Than Brains?”–The Role of Gut Microbiota in Idiopathic Intracranial Hypertension

Background: Idiopathic intracranial hypertension syndrome (IIH) is most common among obese women. Weight loss is an important factor in improving papilledema. Over the last decade, growing evidence has identified gut microbiota as a potential factor in the pathophysiology of obesity. Accordingly, we investigated whether the gut microbiome is modified in IIH patients compared with healthy controls, and provide possible new treatment venues. Methods: Shotgun metagenomic sequencing of the gut microbiome of 25 cases of IIH patients (according to the modified Dandy criteria) and 20 healthy controls. Participants were further stratified according to their body mass index. The total DNA from each sample was extracted using the PureLink Microbiome DNA Purification Kit A29789 (Invitrogen, Thermo Fisher Scientific, US). Library preparation was performed using the Nextera DNA Flex Library Prep Kit. Samples were sequenced on the Illumina Novaseq 6000 device. A list of bacterial species that significantly differed between the IIH patients and healthy controls was produced in addition to species diversity. In addition, patients' cohort alone was analyzed, (excluding the healthy controls), and the effect of acetazolamide treatment on their gut microbiota was analyzed. Results: IIH patients have a lower diversity of bacterial species compared with healthy individuals. These bacteria, that is, Lactobacillus ruminis (L. ruminis) (p<6.95E-08), Atopobium parvulum (p<3.9E-03), Megamonas hypermegale (p<5.61E-03), Ruminococcus gnavus (p<1.29E-02), MEL.A1 (p<3.04E-02), and Streptococcus sp. I-G2 (p<3.04E-02), were previously characterized with beneficial health effects. Moreover, we found that Lactobacillus brevis, a beneficial bacterium as well, is more abundant in acetazolamide treated patients (p<7.07E-06). Conclusions: Gut microbiota plays a potential role in IIH etiology and therefore, can provide a promising new treatment approach for this disease.
Opisthorchis viverrini Infection Induces Metabolic and Fecal Microbial Disturbances in Association with Liver and Kidney Pathologies in Hamsters.

Opisthorchis viverrini (Ov) infection causes hepatobiliary diseases and is a major risk factor for cholangiocarcinoma. While several omics approaches have been employed to understand the pathogenesis of opisthorchiasis, effects of Ov infection on the host systemic metabolism and fecal microbiota have not been fully explored. Here, we used a 1H NMR spectroscopy-based metabolic phenotyping approach to investigate Ov infection-induced metabolic disturbances at both the acute (1 month postinfection, 1 mpi) and chronic (4 mpi) stages in hamsters. A total of 22, 3, and 4 metabolites were found to be significantly different in the liver, serum, and urine, respectively, between Ov+ and Ov- groups. Elevated levels of hepatic amino acids and tricarboxylic acid (TCA)-cycle intermediates (fumarate and malate) were co-observed with liver injury in acute infection, whereas fibrosis-associated metabolites (e.g., glycine and glutamate) increased at the chronic infection stage. Lower levels of lipid signals ((CH2)n and CH2CH2CO) and higher levels of lysine and scyllo-inositol were observed in serum from Ov+ hamsters at 1 mpi compared to Ov- controls. Urinary levels of phenylacetylglycine (a host-bacterial cometabolite) and tauro-β-muricholic acid were higher in the Ov+ group, which coexisted with hepatic and mild kidney fibrosis. Furthermore, Ov+ animals showed higher relative abundances of fecal Methanobrevibacter (Archaea), Akkermansia, and Burkholderia-Paraburkholderia compared to the noninfected controls. In conclusion, along with liver and kidney pathologies, O. viverrini infection resulted in hepatic and mild renal pathologies, disturbed hepatic amino acid metabolism and the TCA cycle, and induced changes in the fecal microbial composition and urinary host-microbial cometabolism. This study provides the initial step toward an understanding of local and systemic metabolic responses of the host to O. viverrini infection.
Identification of the TP53 p.R337H Variant in Tumor Genomic Profiling Should Prompt Consideration of Germline Testing for Li-Fraumeni Syndrome

PURPOSE Li-Fraumeni syndrome (LFS) is rare in the worldwide population, but it is highly prevalent in the Brazilian population because of a founder mutation, TP53 p.R337H, accounting for 0.3% of south and southeastern population. Clinical criteria for LFS may not identify all individuals at risk of carrying the Brazilian founder mutation because of its lower penetrance and variable expressivity. This variant is rarely described in databases of somatic mutations. Somatic findings in tumor molecular profiling may give insight to identify individuals who might be carriers of LFS and allow the adoption of risk reduction strategies for cancer. MATERIALS AND METHODS We determined the frequency of the TP53 p.R337H variant in tumor genomic profiling from 755 consecutive Brazilian patients with pan-cancer. This is a retrospective cohort from January 2013 to March 2020 at a tertiary care center in Brazil. RESULTS The TP53 p.R337H variant was found in 2% (15 of 755) of the samples. The mutation allele frequency ranged from 30% to 91.7%. A total of seven patients were referred for genetic counseling and germline testing after tumor genomic profiling results were disclosed. All the patients who proceeded with germline testing (6 of 6) confirmed the diagnosis of LFS. Family history was available in 12 cases. Nine patients (9 of 12) did not meet LFS clinical criteria. CONCLUSION The identification of the TP53 p.R337H variant in tumor genomic profiling should be a predictive finding of LFS in the Brazilian population and should prompt testing for germline status confirmation.
Anti-adalimumab Antibodies in Patients with Non-infectious Ocular Inflammatory Disease: A Case Series

ABSTRACT Purpose To report the clinical course of patients with ocular inflammatory disease treated with adalimumab in whom anti-adalimumab antibodies (AAA) were detected. Methods Single center case series. Results Eight patients with initial response to adalimumab developed a disease flare associated with positive AAA testing after 5 to 76 months of therapy. Six patients were receiving no concurrent antimetabolite therapy at the time of AAA diagnosis and four had a temporary lapse in adalimumab therapy prior to AAA discovery. AAA resulted in undetectable drug levels in five of the seven patients for whom data were available, and adalimumab was discontinued in six of the eight patients. Of two patients continued on adalimumab, one maintained detectable serum adalimumab despite AAA and one had a low AAA titer. Conclusions For patients receiving adalimumab for ocular inflammatory disease, a disease flare in the setting of previously well-controlled disease should prompt consideration of AAA testing.
Lived experience of advanced hybrid closed-loop versus hybrid closed loop: patient-reported outcomes and perspectives.

This paper reports on the lived experience of Medtronic Advanced Hybrid Closed-Loop (AHCL) in comparison to first generation hybrid closed-loop (HCL) in a randomized, open-label, two-period crossover trial. Patient-reported outcome measures (PROs) were administered prior to randomization and at the end of each study period in 113 adolescents and young adults with type 1 diabetes. Glucose monitoring satisfaction subscales for emotional burden and behavioral burden improved significantly (p<0.01) over time with use of AHCL versus HCL, and co-occurred with glycemic improvements (reduced percent time above 180 mg/dL during the day and no change in % time less than 54 mg/dL across 24 hours) and greater time in Auto Mode. PROs including distress, technology attitudes, and hypoglycemia confidence were not different. AHCL use was associated with improved glucose monitoring satisfaction. Satisfaction was greater in those participants who had more appreciable glycemic benefit and stayed in Auto Mode more often.