Miracle-dz/UniFAR-FTUs huggingface dataset:
Influence of oncogenic mutations and tumor microenvironment alterations on extranodal invasion in diffuse large B‐cell lymphoma

Abstract Background Diffuse large B‐cell lymphoma (DLBCL) is an aggressive subtype of lymphoma, and multiple extranodal involvement (ENI) indicates adverse clinical outcomes. The aim of this study was to investigate the influence of oncogenic mutations and tumor microenvironment alterations on ENI in DLBCL. Methods The clinical features of 1960 patients with newly diagnosed DLBCL were analyzed, and DNA and RNA sequencing was performed on 670 and 349 patients, respectively. Oncogenic mutations and tumor microenvironment alterations were compared according to ENI and evaluated in zebrafish patient‐derived tumor xenograft models. Results Multiple ENI was significantly associated with poor performance status, advanced stage, elevated serum lactate dehydrogenase, low response rate, and inferior prognosis. Lymphoma invasion of the bones, spleen, bone marrow, liver, and central nervous system were independent unfavorable prognostic factors. MYD88 was frequently mutated in patients with multiple ENI, co‐occurred with mutations in CD79B, PIM1, TBL1XR1, BTG1, MPEG1, and PRDM1, and correlated with invasion of the bones, kidney/adrenal glands, breasts, testes, skin, and uterus/ovaries. For tumor microenvironment alterations, patients with multiple ENI showed higher regulatory T‐cell (Treg)‐recruiting activity, but lower extracellular matrix‐encoding gene expression, than those without ENI and with single ENI. Elevated Treg‐recruiting activity was related to mutations in B2M, SGK1, FOXO1, HIST1H1E, and ARID1A, and correlated with invasion of the bone marrow and thyroid. Additionally, mutations in MYD88, PIM1, TBL1XR1, SGK1, FOXO1, HIST1H1E, and ARID1A were associated with decreased major histocompatibility complex class I expression. Zebrafish models further revealed relationships between MYD88 mutations and invasion of the kidneys and gonads, as well as B2M mutations and invasion of the bone marrow. Increased CXCR4 expression is linked to bone marrow invasion in an organotropic way. Conclusions Our findings thus contribute to an improved understanding of the biological behavior of multiple ENI and provide a clinical rationale for targeting ENI in DLBCL.
A highly efficient multi-step methodology for the quantification of micro-(bio)plastics in sludge

The present study develops a multi-step methodology for identification and quantification of microplastics and micro-bioplastics (together called in the current work micro-(bio)plastics) in sludge. In previous studies, different methods for the extraction of microplastics were devised for traditional plastics, while the current research tested the methodology on starch-based micro-bioplastics of 0.1–2 mm size. Compostable bioplastics are expected to enter the anaerobic or aerobic biological treatments that lead to end-products applicable in agriculture; some critical conditions of treatments (e.g. low temperature and moisture) can slow down the degradation process and be responsible for the presence of microplastics in the end-product. The methodology consists of an initial oxidation step, with hydrogen peroxide 35% concentrated to clear the sludge and remove the organic fraction, followed by a combination of flotation with sodium chloride and observation of the residues under a fluorescence microscope using a green filter. The workflow revealed an efficacy of removal from 94% to 100% and from 92% to 96% for plastic fragments, 0.5–2 mm and 0.1–0.5 mm size, respectively. The methodology was then applied to samples of food waste pulp harvested after a shredding pre-treatment in an anaerobic digestion (AD) plant in Italy, where polyethylene, starch-based Mater-Bi® and cellophane microplastics were recovered in amounts of 9 ± 1.3/10 g <2 mm and 4.8 ± 1.2/10 g ⩾2 mm. The study highlights the need to lower the threshold size for the quantification of plastics in organic fertilizers, which is currently set by legislations at 2 mm, by improving the background knowledge about the fate of the micro-(bio)plastics in biological treatments for the organic waste.
Physiology of intra‐abdominal volume during pregnancy

Abstract A total of 580 pregnant and 50 puerperal women were included in this cross-sectional study to assess the physiological changes that allow women to adapt to a chronic increase in intra-abdominal pressure during pregnancy. The volume of the uterus, intra‐abdominal volume (IAV), visceral and subcutaneous fat was calculated. During pregnancy, the IAV increases up to 1.5 times. Changes in IAV until 24 weeks present a linear relationship (5.2%); thereafter, changes become exponential and, at 40 weeks, IAV increases by 61%. This fact is exclusively related to the progressive growth of the foetus and to the increase in uterine size. At term, the IAV reserve is exhausted, becoming equal the anteroposterior and transverse diameters of the abdomen. In conclusion, the adaptive capabilities of IAV related to the foetal growth are limited by the IAV reserve. The reserve capacity of the IAV and tensile properties of the abdominal wall can be estimated by the dynamics of the anteroposterior and transverse abdominal diameters. IMPACT STATEMENT What is already known on this subject? A causal relationship between intra-abdominal hypertension and the development of adverse obstetric and perinatal outcomes has been suggested. Nevertheless, the role of this condition as a leading cause of systemic dysfunction during pregnancy remains unrecognised and underestimated. What do the results of this study add? This study assesses the dynamics of IAV in uncomplicated singleton pregnancies. What are the implications of these findings for clinical practice and/or further research? The study of abdominal pressure indicators such as intra-abdominal volume and compliance will help to a better understand the aetiology, pathophysiology, prognosis and treatment strategies for pregnant women with intra-abdominal hypertension.
Biopolymer-based nanocomposite films and coatings: recent advances in shelf-life improvement of fruits and vegetables

Abstract Consumers increasingly prefer healthy and nutritious diet worldwide, and demands for fresh fruits and vegetables are rapidly growing. Fresh produce are perishable commodities, and physical damage, moisture loss, biochemical changes, and postharvest microbial decay are primary causes of quality loss and reduced shelf-life. Packaging, including plastic films and coatings is an effective strategy to improve postharvest-life of whole and cut fruits and vegetables. However, plastic packaging is a significant environmental concern globally. Biopolymer based films and/or coatings are environment-friendly alternative packaging for food. But, these biopolymers, derived from plant, animal and microbial sources, lack some of the primary physico-chemical and mechanical properties compared to conventional plastic packaging. Reinforcement of biopolymer with nanomaterials addresses these shortcomings, and adds functional properties such as antimicrobial and/or antioxidant activities to the nanocomposites. Organic (e.g. nanocellulose fibrils), and inorganic (e.g. montmorillonite, zinc oxide, silver) nanomaterials are effective in achieving these improvements in biopolymer based nanocomposite. Plant-extracts and compounds derived from plant (e.g. essential oil) are also effective in imparting antimicrobial and antioxidant properties to biopolymer based nanocomposites. This is an extensive review of research works on effectiveness of biopolymer based nanocomposite films and coatings used for packaging of whole and cut fruits and vegetables to extend their shelf-life. Numerous reports have demonstrated effectiveness of biopolymer based nanocomposites in improvement in shelf-life of packaged and/or coated whole and cut fruits and vegetables by at least 4–5 days to as much as a few months. Highlights Fresh produce are perishable commodities requiring package or coating. Conventional plastics and waxes are major environmental and health concerns. Biopolymer based nanocomposites are environment-friendly alternatives. These nanocomposite films and coatings are effective in enhancing shelf-life.
The impact of repeat fine‐needle aspiration in thyroid nodules categorized as atypia of undetermined significance or follicular lesion of undetermined significance: A single center experience

Atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS) is the most controversial category of the Bethesda System. The present study was conducted to compare the histological findings in a series of thyroid nodules diagnosed with AUS/FLUS after single or repeat fine needle aspiration (FNA) cytology.
Clinical Usefulness of the HFA-PEFF Diagnostic Scoring System in Identifying Late Elderly Heart Failure With Preserved Ejection Fraction Patients.

BACKGROUND Diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging in elderly. This study investigated the diagnostic ability of the HFA-PEFF scoring system in elderly patients (>75 years of age). Methods and Results:This study enrolled 286 subjects aged >75 years (130 men; mean [± SD] age 81.5±5.1 years): 95 healthy controls, 98 with hypertension (HT), and 93 with HFpEF. The HFA-PEFF score was calculated as a sum of points in functional, morphological, and biomarker domains. In the HFpEF group, 84%, 84%, and 70% of subjects met the major functional, morphological, and biomarker criteria for HFpEF, respectively. Thus, 73 subjects with HFpEF (78%) were diagnosed as having HFpEF using the HFA-PEFF scoring system. In contrast, among the healthy controls and subjects with HT, 52% and 72%, respectively, met the major functional criteria for HFpEF, 28% and 53%, respectively, met the morphological criteria, and 0% and 24%, respectively, met the biomarker criteria. As such, 32 subjects with HT (33%) were diagnosed with HFpEF. Even in the healthy control group, 72% were classified as having an intermediate probability of HFpEF, and 3 were diagnosed with HFpEF. CONCLUSIONS In the late elderly, the HFA-PEFF scoring system diagnosed subjects with HFpEF precisely. In addition, this scoring system may be able to detect early stage HFpEF in the subclinical population.
Haemodynamic optimisation of a dialysis graft design using a global optimisation approach

Disturbed flow and the resulting non‐physiological wall shear stress (WSS) at the graft‐vein anastomosis play an important role in arteriovenous graft (AVG) patency loss. Modifying graft geometry with helical features is a popular approach to minimise the occurrence of detrimental haemodynamics and to potentially increase graft longevity. Haemodynamic optimisation of AVGs typically requires many computationally expensive computational fluid dynamics (CFD) simulations to evaluate haemodynamic performance of different graft designs. In this study, we aimed to develop a haemodynamically optimised AVG by using an efficient meta‐modelling approach. A training dataset containing CFD evaluations of 103 graft designs with helical features was used to develop computationally low‐cost meta‐models for haemodynamic metrics related to graft dysfunction. During optimisation, the meta‐models replaced CFD simulations that were otherwise needed to evaluate the haemodynamic performance of possible graft designs. After optimisation, haemodynamic performance of the optimised graft design was verified using a CFD simulation. The obtained optimised graft design contained both a helical graft centreline and helical ridge. Using the optimised design, the magnitude of flow disturbances and the size of the anastomotic areas exposed to non‐physiological WSS was successfully reduced compared to a regular straight graft. Our meta‐modelling approach allowed to reduce the total number of CFD model evaluations required for our design optimisation by approximately a factor 2000. The applied efficient meta‐modelling technique was successful in identifying an optimal, helical graft design at relatively low computational costs. Future studies should evaluate the in vivo benefits of the developed graft design.
A follow‐up study of patients with natural rubber latex allergy

Natural rubber latex (NRL) allergy is an important occupational health concern, particularly among healthcare professionals (HCPs). Numerous studies have demonstrated a significant decline in latex sensitization among HCPs since the introduction of low-allergen (often powder-free) latex gloves. There are limited data available on the long-term outcomes of latex-allergic patients. The aims of our study were to evaluate the long-term outcomes of latex-allergic patients and to ascertain the proportion of patients whose investigations remain consistent with a diagnosis of latex allergy following a period of latex avoidance. Patients with a diagnosis of type I hypersensitivity to latex were identified using a hospital database and invited to participate.
Norovirus elimination on the surface of fresh foods

Abstract Fresh foods like fruits, vegetables and shellfish are potential sources for viral infections such as human norovirus (NoV). Chemical treatment like chlorination is a well-known process for food pathogens and virus elimination. However, with the increase of the consumer demand for less toxic treatment, the use of natural antimicrobials like essential oils from spice or plants, fruit extracts, and cold pasteurization treatments (fermentation, irradiation, ozonation and high pressure) could be considered. The aim of this review is to discuss these technologies and their efficacy to eliminate NoV on the surface of fresh food.
Improving the treatment of patients with diabetes using insulin analogues: current findings and future directions

ABSTRACT Introduction: The aim of insulin replacement in insulin-deficient people (type 1 diabetes, pancreatic causes of diabetes, long-standing type 2 diabetes) is to approximate the physiologic insulin action profile as closely as possible. However, short-acting human insulins start too slow and act too long, causing postprandial hyperglycemia and delayed hypoglycemia, while the insulin action profile of long-acting human insulins is too variable in duration and strength of action, leading to insufficient basal insulin covering and peak insulin levels after injection causing early nocturnal hypoglycemia. Insulin analogues were designed to overcome these shortcomings. In insulin-resistant people (type 2 diabetes), insulin analogues contribute to more efficient and safer insulin supplementation. Areas covered: In this review, we describe the unmet needs for insulin therapy, the currently available short- and long-acting insulin analogues and some considerations on cardiovascular outcomes, use in special populations, and cost-effectiveness. Finally, we discuss what is new in the field of insulin analogues. Expert opinion: The development of insulin analogues is an important step in diabetes treatment. Despite many patients meeting their glycemic targets with the newest analogues, hypoglycemic episodes remain a major problem. More physiologic insulin regimens, with glucose-sensitive or organ-targeting insulin analogues may be the answer to these issues.
The Potential Contribution of Chronic Pain and Common Chronic Pain Conditions to Subsequent Cognitive Decline, New Onset Cognitive Impairment, and Incident Dementia: A Systematic Review and Conceptual Model for Future Research.

BACKGROUND Growing evidence suggests that chronic pain and certain chronic pain conditions may increase risk for cognitive decline and dementia. OBJECTIVE In this systematic review, we critically evaluate available evidence regarding the association of chronic pain and specific common chronic pain conditions to subsequent decline in cognitive function, new onset cognitive impairment (CI), and incident Alzheimer's disease and related dementias (ADRD); outline major gaps in the literature; and provide a preliminary conceptual model illustrating potential pathways linking pain to cognitive change. METHODS To identify qualifying studies, we searched seven scientific databases and scanned bibliographies of identified articles and relevant review papers. Sixteen studies met our inclusion criteria (2 matched case-control, 10 retrospective cohort, 2 prospective cohort), including 11 regarding the association of osteoarthritis (N = 4), fibromyalgia (N = 1), or headache/migraine (N = 6) to incident ADRD (N = 10) and/or its subtypes (N = 6), and 5 investigating the relation of chronic pain symptoms to subsequent cognitive decline (N = 2), CI (N = 1), and/or ADRD (N = 3). RESULTS Studies yielded consistent evidence for a positive association of osteoarthritis and migraines/headaches to incident ADRD; however, findings regarding dementia subtypes were mixed. Emerging evidence also suggests chronic pain symptoms may accelerate cognitive decline and increase risk for memory impairment and ADRD, although findings and measures varied considerably across studies. CONCLUSION While existing studies support a link between chronic pain and ADRD risk, conclusions are limited by substantial study heterogeneity, limited investigation of certain pain conditions, and methodological and other concerns characterizing most investigations to date. Additional rigorous, long-term prospective studies are needed to elucidate the effects of chronic pain and specific chronic pain conditions on cognitive decline and conversion to ADRD, and to clarify the influence of potential confounding and mediating factors.
Release of Chemicals from Contaminated Soils

At sites that contain contaminated soils, there can be questions about the magnitude of risk posed by the chemicals in the soils and about the cleanup levels that should be achieved. Knowledge about the rate of release of chemicals is important to answers to such questions. This article: (1) describes a laboratory protocol to obtain rate of release information for chemicals in soils, and (2) provides estimates of the rate of release of individual polyaromatic hydrocarbon (PAH) compounds from several manufactured gas plant (MGP) site soils. The data were analyzed using an empirical two-site model. Different fractions of PAH were released rapidly from these soils. For one soil, this fraction was less than 20%, for others, the fraction ranged from 36 to 85%. The first-order rate constant (k2) of PAH released during the slow phase of chemical release ranged from 0.0001 to 0.01 per hour.
Serum miR-185 Is a Diagnostic and Prognostic Biomarker for Non-Small Cell Lung Cancer

Objective: MicroRNAs (miRNAs) have been found to play important roles in the development of non-small cell lung carcinoma (NSCLC). The aim of this study was to analyze the expression and clinical value of serum miR-185 in NSCLC. Methods: Serum miR-185 levels were detected in 146 NSCLC patients, 50 patients with carcinoma in situ, 25 patients with non-malignant lung diseases (NMLD), and 80 healthy controls using quantitative reverse transcription PCR. The correlation between serum miR-185 level and clinical status of NSCLC was explored. Results: The results revealed that serum miR-185 expression was progressively decreased in healthy controls, patients with NMLD, patients with carcinoma in situ and NSCLC patients. In addition, compared to carcinoembryonic antigen (CEA), serum miR-185 demonstrated better diagnostic accuracy for discriminating patients with carcinoma from healthy controls, NSCLC patients from healthy controls and NSCLC patients from patients with carcinoma in situ. In addition, serum miR-185 levels were significantly elevated in post-treated samples compared to the pre-treated samples. Moreover, reduced serum miR-185 was closely associated with unfavorable clinicopathological parameters and worse survival. Univariate and multivariate cox regression analysis confirmed that serum miR-185 was an independent prognostic indicator for NSCLC. Conclusions: Collectively, our findings have demonstrated that serum miR-185 might serve as a promising and robust biomarker for the early detection and prognosis prediction of NSCLC.
Mucosa-Associated Lymphoid Tissue and Tertiary Lymphoid Structures of the Eye and Ear in Laboratory Animals

Mucosa-associated lymphoid tissue (MALT) of special senses is poorly described and can be confused with nonspecific mononuclear cell infiltrates and tertiary lymphoid structures (TLS). In the eye, MALT consists mostly of conjunctiva-associated lymphoid tissue (CALT) and lacrimal drainage-associated lymphoid tissue (LDALT). In humans, CALT and LDALT are important components of the normal eye-associated lymphoid tissue (EALT), but EALT is less frequently described in ocular tissues of animals. The EALT are acquired postnatally in preferential mucosal sites, expand with antigenic exposure, form well-developed lymphoid follicles, and are reported to senesce. Lymphoid follicles that are induced concurrently with chronic inflammation are more appropriately considered TLS but must be differentiated from inflammation in MALT. Less understood is the etiology for formation of lymphoid tissue aggregates in the ciliary body, limbus, or choroid of healthy eyes in animals and humans. In the healthy eustachian tube and middle ear of animals and humans, MALT may be present but is infrequently described. Concurrent with otitis media, lymphoid follicles in the eustachian tube are probably expanded MALT, but lymphoid follicles in the middle ear may be TLS. The purpose of this comparative review is to familiarize toxicologic pathologists with MALT in the special senses and to provide considerations for differentiating and reporting eye and ear MALT from immune or inflammatory cell infiltrates or inflammation in nonclinical studies, and the circumstances for reporting TLS in compartments of the eye and ear.
Simulation of a detoxifying organ function: Focus on hemodynamics modeling and convection‐reaction numerical simulation in microcirculatory networks

When modeling a detoxifying organ function, an important component is the impact of flow on the metabolism of a compound of interest carried by the blood. We here study the effects of red blood cells (such as the Fahraeus‐Lindqvist effect and plasma skimming) on blood flow in typical microcirculatory components such as tubes, bifurcations and entire networks, with particular emphasis on the liver as important representative of detoxifying organs. In one of the plasma skimming models, under certain conditions, oscillations between states are found and analyzed in a methodical study to identify their causes and influencing parameters. The flow solution obtained is then used to define the velocity at which a compound would be transported. A convection‐reaction equation is studied to simulate the transport of a compound in blood and its uptake by the surrounding cells. Different types of signal sharpness have to be handled depending on the application to address different temporal compound concentration profiles. To permit executing the studied models numerically stable and accurate, we here extend existing transport schemes to handle converging bifurcations, and more generally multi‐furcations. We study the accuracy of different numerical schemes as well as the effect of reactions and of the network itself on the bolus shape. Even though this study is guided by applications in liver micro‐architecture, the proposed methodology is general and can readily be applied to other capillary network geometries, hence to other organs or to bioengineered network designs.