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BACKGROUND: Odronextamab, a CD20×CD3 bispecific antibody that engages cytotoxic T cells to destroy malignant B cells, has demonstrated encouraging activity across multiple subtypes of relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma. PATIENTS AND METHODS: This phase II study (ELM-2; NCT03888105) evaluated odronextamab in patients with R/R follicular lymphoma after two or more lines of systemic therapy. Patients received intravenous odronextamab in 21-day cycles, with step-up dosing in cycle 1 to help mitigate the risk of cytokine release syndrome, until disease progression or unacceptable toxicity. The primary endpoint was objective response rate by independent central review. RESULTS: Among 128 patients evaluated, 95% completed cycle 1, and 85% completed four or more cycles. At 20.1 months' efficacy follow-up, objective response rate was 80.0% and complete response rate was 73.4%. Median duration of complete response was 25.1 months. Median progression-free survival was 20.7 months, and median overall survival was not reached. Discontinuation of odronextamab due to adverse events occurred in 16% of patients. The most common treatment-emergent adverse events were cytokine release syndrome [56%; grade ≥3 1.7% (1/60) with 0.7/4/20 mg step-up], neutropenia (39%), and pyrexia (38%). CONCLUSIONS: Odronextamab achieved high complete response rates with generally manageable safety in patients with heavily pretreated R/R follicular lymphoma.

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URBAN is a multicentric, ambispective study evaluating the effectiveness and safety of obinutuzumab-based immuno-chemotherapy and maintenance in patients with untreated advanced follicular lymphoma (FL). The study began before the COVID-19 emergency declaration in Italy. It is currently ongoing for follow-up, and the enrolment timeline encompassed different stages of the pandemic, various vaccination roll-out phases and prevalence of SARS-CoV-2 variants. Outcomes of interest of the present sub-analysis included SARS-CoV-2 infection rates and COVID-19-related hospitalizations/deaths. At data cut-off, 86 (28.8%) and 213 patients (71.2%) were treated before and during/after the COVID-19 outbreak respectively; 294 (98.3%) completed the induction, 31 (10.4%) completed maintenance and 170 (56.9%) were still on maintenance. Overall, 245 patients (81.9%) received at least one SARS-CoV-2 vaccine dose: 13.5%, 31.4% and 55.1% received one, two and three doses respectively. We observed a substantial decrease in COVID-19-related mortality rates in pre- versus post-vaccination phases, along with a reduction in COVID-19-related outcomes due to the shift from alpha/delta to omicron variant predominance. No differences emerged between patients given maintenance or not, although the schedule was modified in 65% of cases. To our knowledge, URBAN represents the largest dataset of COVID-19-related outcomes in FL patients extensively exposed to obinutuzumab. ClinicalTrials.gov identifier: NCT04034056.

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Much of what we know about the intellectual landscape of anglophone demography comes from two sources: subjective narratives authored by leaders in the field, whose reviews and observations are derived from their research experience and field-specific knowledge; and professional histories covering the field's foundational controversies, which tend to focus on individuals, institutions, and influence. Here we use bibliographic information from all articles published in the three leading journals of anglophone demography-Demography, Population Studies, and Population and Development Review-to survey the changing contours of anglophone demography's key research areas over the past 70 years. We characterize the field of demography by applying a two-pronged, data-grounded approach from the sociology of science. The first uses natural language processing that lets the substance of the field emerge from the contents of publication records and applies social network analyses to identify groups of papers that talk about the same thing. The second uses bibliometric tools to capture the "conversations" of demography with other disciplines. Our goals are to (1) identify the primary topics of demography since the discipline first gained prominence as an organized field; (2) assess changes in the field's intellectual cohesion and the topical areas that have grown or shrunk; and (3) examine how demographers place their work in relationship to other disciplines, the visibility and influence of demographic research in the broader scientific literature, and the cross-disciplinary translational reach of demographic research. Results provide a dynamic view of the field's scientific development in the second half of the twentieth century and the first two decades of the twenty-first century.

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The global rise of the COVID-19 pandemic has been accompanied by an increase in anti-Asian discrimination with potentially deleterious effects on individuals of Asian descent. In the present study, we examine how two types of COVID-19-related anti-Asian discrimination and other contemporaneous stressors independently contribute to perceptions of stress in a population-representative sample of Chinese immigrants in North Carolina, as well as the moderating role of ethnic identity on the association between COVID-related discrimination and stress. Analyses rely on data collected among participants ages 18+ in the Chinese Immigrants in Raleigh-Durham (ChIRDU) study who completed surveys in 2018 and during the COVID-19 pandemic (July-September 2020). We utilize ordinary least squares regressions to examine associations of two types of COVID-related discrimination (measured by changes in perceptions of being feared by others and racism-related vigilance) and contemporaneous stressors (measured by general COVID-19-related stressors and acculturative stressors) with perceptions of stress by respondents' pre-pandemic reports of ethnic identity. Controlling for sociodemographic predictors and other stressors, racism-related vigilance is significantly associated with higher perceived stress for Chinese immigrants who identify as completely Chinese. For those who identify as at least partly American, new perceptions of being feared by others during the pandemic are significantly associated with higher perceived stress. Acculturative and COVID-related stressors are independently associated with higher perceived stress for both groups. These results suggest that COVID-related anti-Asian discrimination aggravates the psychological burden of multiple stressors in Chinese immigrants' lives by uniquely contributing to perceptions of stress alongside contemporaneous stressors. The results also highlight the heterogeneous mental health needs of Chinese immigrants and hold important implications for intervention development in the community studied here as well as in other Chinese communities in the US.

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IMPORTANCE: Primary cutaneous lymphomas (PCL) are rare diseases, but the indolent course makes their prevalence high. Although there are many treatment options, no hierarchy is recommended. OBJECTIVE: To identify the burden of PCL and describe clinical-pathologic features; associated comorbidities; analyse treatment approaches in real-life and the parameters associated with the achievement of complete response (CR). DESIGN, SETTING AND PARTICIPANTS: In this study, all the PCL patients (384 patients) consecutively seen at the Dermatologic Clinic of the University of Turin from January 1, 2019 to December 31, 2019, with follow-up updated to December 2020, were included. MAIN OUTCOMES AND MEASURES: Subtype of PCL, demographic data, time elapsed between first lesions and diagnosis, associated symptoms, comorbidities, staging at diagnosis, high-grade transformation, blood involvement, stage progression, therapies used and response were assessed. RESULTS: 247 were cutaneous T-cell lymphomas (CTCL, 64.3%), 137 cutaneous B-cell lymphomas (CBCL, 35.7%) and the most frequent subtype was MF (48.4%). 62.3% of CTCL patients showed at least one comorbidity, mainly cardiovascular (28.7%), 20.2% show other not cutaneous neoplasms. The main approaches were skin-directed therapies (topical steroids 65.6%; phototherapy 50.2%). 39.3% patients achieved a CR during the disease course. Pruritus, the presence of comorbidities and high-grade transformation were factors associated with failure to achieve CR, whereas stage IA of MF was associated with greater achievement of CR. CONCLUSIONS AND RELEVANCE: The Th2 cytokine related development of pruritus could justify increased resistance to treatment, while the presence of associated comorbidities could reduce treatment options as well as treatment compliance.

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We test the effectiveness of a link-tracing sampling approach-network sampling with memory (NSM)-to recruit samples of rare immigrant populations with an application among Chinese immigrants in the Raleigh-Durham area of North Carolina. NSM uses the population network revealed by data from the survey to improve the efficiency of link-tracing sampling and has been shown to substantially reduce design effects in simulated sampling. Our goals are to (1) show that it is possible to recruit a probability sample of a locally rare immigrant group using NSM and achieve high response rates; (2) demonstrate the feasibility of the collection and benefits of new forms of network data that transcend kinship networks in existing surveys and can address unresolved questions about the role of social networks in migration decisions, the maintenance of transnationalism, and the process of social incorporation; and (3) test the accuracy of the NSM approach for recruiting immigrant samples by comparison with the American Community Survey. Our results indicate feasibility, high performance, cost-effectiveness, and accuracy of the NSM approach to sample immigrants for studies of local immigrant communities. This approach can also be extended to recruit multisite samples of immigrants at origin and destination.

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Introducción: la Guía Práctica se basa en la actual guía científica de la ESPEN sobre nutrición clínica en las enfermedades hepáticas. Métodos: se ha reducido y transformado en diagramas de flujo para facilitar su uso en la práctica clínica. La guía está dedicada a todos los profesionales, incluidos médicos, dietistas, Nutriciónistas y enfermeras, que trabajan con pacientes con enfermedad hepática crónica. Resultados: la guía presenta un total de 103 pronunciamientos y recomendaciones con breves comentarios para el manejo Nutricional y metabólico de pacientes con (i) insuficiencia hepática aguda grave, (ii) esteatohepatitis alcohólica, (iii) enfermedad hepática grasa no alcohólica, (iv) cirrosis hepática, y (v) cirugía o trasplante de hígado. Conclusión: las recomendaciones relacionadas con enfermedades están precedidas por recomendaciones generales sobre el diagnóstico del estado Nutricional en los pacientes hepáticos y sobre las complicaciones hepáticas asociadas a la nutrición médica (AU)

Background: the Practical Guideline is based on the current scientific ESPEN guide on Clinical Nutrition in Liver Disease Methods: it has been shortened and transformed into flow charts for easier use in clinical practice. The guideline is dedicated to all professionals including physicians, dieticians, nutritionists and nurses working with patients with chronic liver disease. Results: a total of 103 statements and recommendations are presented with short commentaries for the nutritional and metabolic management of patients with (i) acute liver failure, (ii) alcoholic steatohepatitis, (iii) non-alcoholic fatty liver disease, (iv) liver cirrhosis, and (v) liver surgery/transplantation. Disease-related recommendations are preceded by general recommendations on the diagnosis of nutritional status in liver patients and on liver complications associated with medical nutrition. Conclusion: this Practical Guideline gives guidance to health care providers involved in the management of liver disease on how to offer optimal nutritional care (AU)

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Although local policies aimed at reducing childhood health inequities can benefit from local data, sample size constraints in population representative health surveys often prevent rigorous evaluations of child health disparities and health care patterns at local levels. Electronic Health Records (EHRs) offer a possible solution as they contain large amounts of information on pediatric patients within a health system. In this paper, we consider the suitability of using EHRs from a large health system to study local children's health by evaluating the extent to which the EHRs capture the county's child population. First, we compare the demographic characteristics of Duke University Health System pediatric patients who live in Durham County, NC (USA) to the child population estimates in the 2015-2019 American Community Survey. We then examine geographic variation in census tract rates of children captured in the EHR data and estimate negative binomial models to assess how tract characteristics are associated with these rates. We also perform these analyses for the subset of pediatric patients who have a well-child encounter. We find that the demographic characteristics of pediatric patients captured by the EHRs are similar to those of the county's child population. Although the county rate of children captured in the EHRs is high, there is variation across census tracts. On average, census tracts with higher concentrations of non-Hispanic Black residents have lower capture rates and tracts with higher concentrations of poverty have higher capture rates, with the poorest tracts showing the largest racial gap in rates of children captured by EHRs. Our findings suggest that EHRs from a large health system can be used to assess children's population health, but that EHR-based evaluations of children's health disparities and health care patterns should account for differences in who is captured by the EHRs based on census tract characteristics.

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Halite is an important mineral for industry, agriculture and food production. It crystallises during water evaporation, and the progressive increase of dissolved metal ions in the brine occurs simultaneously. Thus, halite exploitation may deliver metal ions into the environment and the mechanism of this trace element accumulation has to be studied. In this work, we investigate the distribution of lanthanides and Y (hereafter called rare earth elements, REE), Zr and Hf between crystallising halite and brines in the Dead Sea as geochemical tools for recognising the mechanism of metal ion removal from brines and accumulation in halite. Halite forms cubic crystals where octahedral planes sometimes occur under particular thermal gradient conditions. Our findings indicate that crystal morphology influences the mechanism of metal ion removal from brines because octahedral surfaces are polar unlike those that are cubic. Accordingly, octahedra preferentially fractionate aqueous charged species such as [Hf(OH)5]-, compared to neutral species such as [Zr(OH)4]0. Cubic surfaces do not fractionate aqueous species. In crystal cores, positive Eu anomalies occur suggesting Eu substitution for Na in the lattice. This substitution is energetically justified by ab initio calculations. Hf enrichment relative to Zr also occurs in primary halite-rich evaporites. It is not found in cubic halite from saltworks. The results of this study suggest that primary halite kinetically crystallised from brines can concentrate dissolved metal ions onto crystal surfaces where dissolved charged species are adsorbed. Accordingly, the dissolution of halite due to human activity can release these metal ions to the environment.

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BACKGROUND: Identifying the mechanisms responsible for the development of food allergy in liver transplant recipients is more complex as there are several different clinical scenarios related to the immunological function of the liver. CASE PRESENTATION: We describe the first case of Transplant Acquired Food Allergy (TAFA) to cow milk in an adult following LT from a donor dead because of anaphylactic shock. A 67-year-old woman with primary biliary cirrhosis was referred to the Transplant Center of our hospital because of an acute-on-chronic liver failure. The donor was a 15-year-old girl deceased for anoxic encephalopathy due to food induced anaphylaxis after eating a biscuit. In the donor's history food allergies to cow milk and eggs were present. CONCLUSION: This case emphasizes the need for a standardized assessment of both solid-organ donors and recipients including donor allergy history in order to detect recipients at risk for anaphylaxis due to passive IgE transfer. Despite several reports of TAFA after solid organ, especially liver, an appropriate protocol to avoid risk for the recipient doesn't exist at the moment. The SPT (skin prick test) or specific IgE level are not enough to ensure a correct management in these cases and a correct education of the patients and the medical staff involved is absolutely necessary. It is the first case of milk allergy sensitization after solid organ transplant by passive transfer of IgE.

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Coupled with the social practice of female hypergamy, the male surplus within the never-married population means that today's Chinese marriage market is extremely tight in particular for men from a rural background and the least privileged socio-economic categories. Drawing on quantitative data from a survey conducted in 2014-2015, this article sheds light on the situation of single men who are past prime marriage age in three rural districts of Shaanxi particularly affected by this phenomenon. It compares single men's characteristics to those of their married counterparts and offers insights into the heterogeneity of single men with the aim of challenging some commonly accepted assumptions about bachelorhood in rural China. Results suggest a strong internalization of the various characteristics, centred on being able to offer social mobility to a potential wife, that a man is expected to have to be attractive to women in a context where women have more choice in mate selection. We conclude that mate selection is highly marked by class, social norms, social interactions, health, generation and age, and requires the mobilization of certain amounts of individual, social and economic resources. Unwanted bachelorhood would thus be better understood using an intersectional approach rather than mainly in numeric terms.

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OBJECTIVES: To compare the effects of two similar 6-month protocols of high-intensity exercise training, in water and on land, in patients with chronic obstructive pulmonary disease (COPD). DESIGN: Randomised controlled trial. SETTING: University-based outpatient clinic. PARTICIPANTS: Thirty-six patients with predominantly moderate-to-severe COPD completed the study. INTERVENTION: Patients were evaluated at baseline, at 3 months and at the end of the programme (i.e. 6 months). For both groups, the 6-month protocol consisted of high-intensity endurance and strength exercises with gradual increase in time and/or workload, totalling 60 sessions. MAIN OUTCOMES: Objective monitoring of physical activity in daily life (PADL, primary outcome), lung function, peripheral and respiratory muscle strength, body composition, maximal and submaximal exercise capacity, functional status, quality of life, and symptoms of anxiety and depression. RESULTS: After 6 months of training, a significant improvement in PADL was seen for both groups [mean difference (95% confidence interval): land group 993 (358 to 1628) steps/day; water group 1669 (404 to 2934) steps/day]. Significant improvements were also seen in inspiratory, expiratory and peripheral muscle strength; maximal and submaximal exercise capacity; quality of life and functional status for both groups. There were no significant improvements in lung function, body composition, and symptoms of anxiety and depression for either group. No difference was found in the magnitude of improvement between the two types of training for any outcome. CONCLUSION: High-intensity exercise training in water generates similar effects compared with training on land in patients with moderate-to-severe COPD, rendering it an equally beneficial therapeutic option for this population. CLINICAL TRIAL REGISTRATION NUMBER: NCT01691131.

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OBJECTIVES: The aim of the study was to investigate whether the rs35761398 variants of the cannabinoid receptor 2 (CB2) gene may influence the acquisition of HIV infection and the clinical presentation of HIV/hepatitis C virus (HCV) coinfection. METHODS: We compared 166 HIV/HCV-coinfected patients with 186 HCV-monoinfected patients, all with biopsy-proven chronic hepatitis (using the Ishak scoring system), naïve for anti-HCV treatment and tested for the CB2 rs35761398 polymorphism (using the TaqMan assay). RESULTS: The HIV/HCV-coinfected patients were more frequently male (P < 0.002), were younger (P < 0.001), and had lower median BMI (P < 0.001) and HCV RNA (P < 0.05) and higher median aspartate aminotransferase (AST; P < 0.001), alanine aminotransferase (ALT; P < 0.001) and gamma glutamyl transferase (GGT; P < 0.001) levels than the HCV-monoinfected patients. The CB2 RR variant predominated in HIV/HCV-coinfected patients (45.8% vs. 31.2% in HCV-monoinfected patients; P < 0.001) and the CB2 QR variant in HCV-monoinfected patients (57.5% vs. 38.6% in HIV/HCV-coinfected patients; P < 0.00001), and the CB2 QQ variant was equally distributed. Focusing on patients with the CB2 QQ variant, the 26 HIV/HCV-coinfected patients, compared with the 21 HCV-monoinfected patients, showed less severe liver necroinflammation [lower histological activity index (HAI)] (P < 0.05). Of the patients with the CB2 RR variant, the 76 HIV/HCV-coinfected patients, compared with the 58 HCV-monoinfected patients, were more frequently male (P < 0.05), were younger (P < 0.001), and had a lower median body mass index (BMI; P < 0.001), a higher median AST level (P < 0.001), a higher mean HAI score (P < 0.05) and a higher rate of cases with severe steatosis (P = 0.05). In an analysis of variance (anova) of HCV/HIV-coinfected and HCV-monoinfected patient data, those with the CB2 RR variant (P = 0.003) and of male sex (P = 0.002) were more prevalent in the HCV/HIV-coinfected group. CONCLUSIONS: There is the suggestion of a positive effect of the CB2 RR variant on HIV acquisition and/or spread, which is in accordance with previous in vitro observations.

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OBJECTIVES: To describe the current epidemiology of bloodstream infection (BSI) in patients with cirrhosis; and to analyse predictors of 30-day mortality and risk factors for antibiotic resistance. METHODS: Cirrhotic patients developing a BSI episode were prospectively included at 19 centres in five countries from September 2014 to December 2015. The discrimination of mortality risk scores for 30-day mortality were compared by area under the receiver operator risk and Cox regression models. Risk factors for multidrug-resistant organisms (MDRO) were assessed with a logistic regression model. RESULTS: We enrolled 312 patients. Gram-negative bacteria, Gram-positive bacteria and Candida spp. were the cause of BSI episodes in 53%, 47% and 7% of cases, respectively. The 30-day mortality rate was 25% and was best predicted by the Sequential Organ Failure Assessment (SOFA) and Chronic Liver Failure-SOFA (CLIF-SOFA) score. In a Cox regression model, delayed (>24 hours) antibiotic treatment (hazard ratio (HR) 7.58; 95% confidence interval (CI) 3.29-18.67; p < 0.001), inadequate empirical therapy (HR 3.14; 95% CI 1.93-5.12; p < 0.001) and CLIF-SOFA score (HR 1.35; 95% CI 1.28-1.43; p < 0.001) were independently associated with 30-day mortality. Independent risk factors for MDRO (31% of BSIs) were previous antimicrobial exposure (odds ratio (OR) 2.91; 95% CI 1.73-4.88; p < 0.001) and previous invasive procedures (OR 2.51; 95% CI 1.48-4.24; p 0.001), whereas spontaneous bacterial peritonitis as BSI source was associated with a lower odds of MDRO (OR 0.30; 95% CI 0.12-0.73; p 0.008). CONCLUSIONS: MDRO account for nearly one-third of BSI in cirrhotic patients, often resulting in delayed or inadequate empirical antimicrobial therapy and increased mortality rates. Our data suggest that improved prevention and treatment strategies for MDRO are urgently needed in the liver cirrhosis patients.

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