Miracle-dz/UniFAR-FTUs huggingface dataset:
Monoclonal Antibodies and Antibody Drug Conjugates in Multiple Myeloma

Simple Summary Monoclonal antibodies represent a major therapeutic progress in multiple myeloma during the last decade. The use of antibodies as well as antibody drug conjugates has changed the treatment landscape rapidly. The intent of this paper is to summarize the current major results of monoclonal antibody treatments in multiple myeloma. Abstract Multiple myeloma is the second most common hematologic malignancy. Current treatment strategies are mainly based on immunomodulatory drugs, proteasome inhibitors or combination of both. Novel agents added to these backbone treatments represent a promising strategy in treatment of newly diagnosed as well as relapsed and refractory multiple myeloma patients. In this respect, the incorporation of monoclonal antibodies into standard-of-care regimens markedly improved prognosis of myeloma patients during the last years. More specifically, monoclonal anti-CD38 antibodies, daratumumab and isatuximab, have been implemented into treatment strategies from first-line treatment to refractory disease. In addition, the monoclonal anti-SLAM-F7 antibody elotuzumab in combination with immunomodulatory drugs has improved the clinical outcomes of patients with relapsed/refractory disease. Belantamab mafodotin is the first approved antibody drug conjugate directed against B cell maturation antigen and is currently used as a monotherapy for patients with advanced disease. This review focuses on clinical efficacy and safety of monoclonal antibodies as well as antibody drug conjugates in multiple myeloma.
A Method for Repeated, Longitudinal Sampling of Individual Aedes aegypti for Transmission Potential of Arboviruses

Simple Summary Mosquito-borne viruses, such as Zika virus (ZIKV), remain a major public health concern worldwide. Vector competence is defined by the ability of a vector (mosquito) to become infected by and subsequently transmit a virus. Not all species of mosquitoes will transmit the same viruses; therefore, it is imperative that we continue to study mosquito–virus pairings in order to assess risk of transmission in different areas. Traditionally, a competent vector is determined by a high proportion of infectious saliva at terminal time points. However, a multitude of factors, such as mosquito biting habits and time, will have an impact on vector competence. We herein present a novel method for measuring biting habits and ZIKV transmission over time. To do this, we offered individual mosquitoes a bloodmeal (180 μL) every other day from 9 to 24 days post-exposure. Biting behavior was recorded as either probing, blood fed, or no bite; the bloodmeal was then collected and tested for the presence of ZIKV. Our results were successful in measuring behavior and viral transmission over time, and demonstrated variation among individual mosquitoes for both biting behavior and the amount of virus expectorated over time. Our results highlight the need for continued investigation into the complexity of vector competence, and we offer a method to aid in such investigations. Abstract Mosquito-borne viruses are the cause of significant morbidity and mortality worldwide, especially in low- and middle-income countries. Assessing risk for viral transmission often involves characterization of the vector competence of vector–virus pairings. The most common determination of vector competence uses discreet, terminal time points, which cannot be used to investigate variation in transmission aspects, such as biting behavior, over time. Here, we present a novel method to longitudinally measure individual biting behavior and Zika virus (ZIKV) transmission. Individual mosquitoes were exposed to ZIKV, and from 9 to 24 days post-exposure, individuals were each offered a 180 μL bloodmeal every other day. Biting behavior was observed and characterized as either active probing, feeding, or no bite. The bloodmeal was then collected, spun down, serum collected, and tested for ZIKV RNA via qRT-PCR to determine individuals’ vector competence over time. This included whether transmission to the bloodmeal was successful and the titer of expectorated virus. Additionally, serum was inoculated onto Vero cells in order to determine infectiousness of positive recovered sera. Results demonstrate heterogeneity in not only biting patterns but expectorated viral titers among individual mosquitoes over time. These findings demonstrate that the act of transmission is a complex process governed by mosquito behavior and mosquito–virus interaction, and herein we offer a method to investigate this phenomenon.
Effects of n-3 Polyunsaturated Fatty Acid Supplementation in the Prevention and Treatment of Depressive Disorders—A Systematic Review and Meta-Analysis

N-3 polyunsaturated fatty acids (PUFAs) have been suggested to affect depressive disorders. This review aims to determine the effect of n-3 PUFAs on depressive symptoms in people with or without diagnosed depression. Medline, PsycINFO, and Cochrane CENTRAL databases were searched for randomized controlled trials (RCTs) assessing the association between n-3 PUFAs and depressive symptoms or disorders as outcomes. A random-effects meta-analysis of standardized mean difference (SMD) with 95% confidence intervals (CI) was performed. Twenty-five studies (7682 participants) were included. Our meta-analysis (20 studies) indicated that n-3 PUFA supplementation lowered depressive symptomology as compared with placebo: SMD = −0.34, 95% CI: −0.55, −0.12, I2 = 86%, n = 5836, but a possible publication bias cannot be ruled out. Subgroup analyses indicated no statistically significant difference by treatment duration of <12 vs. ≥12 weeks, presence of comorbidity, or severity of depressive symptoms. Nevertheless, beneficial effects were seen in the subgroups of studies with longer treatment duration and with no depression and mild to moderate depression. Subgroup analysis by eicosapentaenoic acid (EPA) dosage revealed differences in favor of the lower EPA dosage. Sensitivity analysis including studies with low risk of bias seems to confirm the overall result. Supplementation of n-3 PUFA appears to have a modest beneficial effect on depressive symptomology, although the quality of evidence is still insufficient.
Patient and Parent Experiences with Group Telerehabilitation for Child Survivors of Acute Lymphoblastic Leukemia

Background: Acute Lymphoblastic Leukemia (ALL) is the most common pediatric cancer. ALL and its treatment cause altered bone-mineral homeostasis, which can contribute to musculoskeletal late adverse effects (LAEs). With the increasing number of childhood cancer survivors, LAEs are reported often, and are aggravated by inactive lifestyles. A telerehabilitation program is proposed to strengthen the muscle–bone complex and prevent future impairment. Objective: This study aimed to explore and better understand patient and parent experience of a telerehabilitation program after completion of ALL treatment. Methods: ALL survivors (n = 12), 75% girls, 7.9 to 14.7 years old, within six months to five years of treatment, were recruited to participate in the proposed study, along with a parent. The 16-week group program included 40 potential home-based physical activities, with monthly progression, supervised by a kinesiologist, through an online telerehabilitation platform. Patients could be included in the study if they joined during the first month of intervention of their group (minimum 12 weeks of intervention). A semi-structured post-intervention interview was conducted with the patients and their parent during the final assessment, along with a review of the kinesiologist’s clinical notes, to obtain a portrait of the participants’ experience with the telerehabilitation program. Overarching themes were identified by one author and confirmed by two senior authors before extracting the various aspects of each theme. Results: Of the 12 patients recruited, three were excluded from the analysis because they did not complete the minimum 12 weeks of intervention (one = relapse, one = failure to meet technical requirements, and one = abandoned due to parent’s disinterest). The nine patients who completed the program (six girls; 10.93 ± 2.83 years) had a mean adherence of 89%. The overarching themes identified were the program modalities (group approach with patient–parent paired training, supervised by a kinesiologist), the telerehabilitation system, the participants’ perception of the benefits, and recommendations and suggestions from the families. Both patients and parents expressed very high satisfaction with the program and perceived benefits. Conclusion: Participants appreciated the program and reported they would all recommend it to other families in similar situations. The telerehabilitation method of service delivery was perceived by some as decisive in choosing to participate, while the supervision and intra- and inter-family interactions were the motivating factors that were key to program adherence.
Biological Rhythm and Chronotype: New Perspectives in Health

The circadian rhythm plays a fundamental role in regulating biological functions, including sleep–wake preference, body temperature, hormonal secretion, food intake, and cognitive and physical performance. Alterations in circadian rhythm can lead to chronic disease and impaired sleep. The circadian rhythmicity in human beings is represented by a complex phenotype. Indeed, over a 24-h period, a person’s preferred time to be more active or to sleep can be expressed in the concept of morningness–eveningness. Three chronotypes are distinguished: Morning, Neither, and Evening-types. Interindividual differences in chronotypes need to be considered to reduce the negative effects of circadian disruptions on health. In the present review, we examine the bi-directional influences of the rest–activity circadian rhythm and sleep–wake cycle in chronic pathologies and disorders. We analyze the concept and the main characteristics of the three chronotypes.
Importance of EPA and DHA Blood Levels in Brain Structure and Function

Brain structure and function depend on a constant and sufficient supply with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) by blood. Blood levels of EPA and DHA reflect dietary intake and other variables and are preferably assessed as percentage in erythrocytes with a well-documented and standardized analytical method (HS-Omega-3 Index®). Every human being has an Omega-3 Index between 2 and 20%, with an optimum of 8–11%. Compared to an optimal Omega-3 Index, a lower Omega-3 Index was associated with increased risk for total mortality and ischemic stroke, reduced brain volume, impaired cognition, accelerated progression to dementia, psychiatric diseases, compromises of complex brain functions, and other brain issues in epidemiologic studies. Most intervention trials, and their meta-analyses considered EPA and DHA as drugs with good bioavailability, a design tending to produce meaningful results in populations characterized by low baseline blood levels (e.g., in major depression), but otherwise responsible for many neutral results and substantial confusion. When trial results were evaluated using blood levels of EPA and DHA measured, effects were larger than comparing EPA and DHA to placebo groups, and paralleled epidemiologic findings. This indicates future trial design, and suggests a targeted use EPA and DHA, based on the Omega-3 Index.
Cytokine-Induced Memory-Like NK Cells with High Reactivity against Acute Leukemia Blasts and Solid Tumor Cells Suitable for Adoptive Immunotherapy Approaches

Simple Summary Several strategies have been under investigation on how to enhance anti-tumor responses in patients with poor prognosis. Considering the heterogeneity of antigens expressed by different hematological and solid neoplasia, it is difficult to develop specific immunotherapy approaches. The capacity of Natural Killer (NK) cells to kill tumor cells without specific Ag recognition provides an advantage over T cells and makes them appealing candidate effectors for immunotherapy, even if the effectiveness of their therapeutic use is limited by short-term persistence in vivo. After providing proof of concept regarding the feasibility of inducing NK cells endowed with anti-tumor activity and ability to persist for a protracted period in vivo, considering the relatively short period of in vitro activation, this approach could easily be translated into clinical practice to control tumor growth in high-risk patients. Abstract The limited efficacy of Natural Killer (NK) cell-based immunotherapy results in part from the suboptimal expansion and persistence of the infused cells. Recent reports suggest that the generation of NK cells with memory-like properties upon in vitro activation with defined cytokines might be an effective way of ensuring long-lasting NK cell function in vivo. Here, we demonstrate that activation with IL-12, IL-15 and IL-18 followed by a one-week culture with optimal doses of Interleukin (IL-2) and IL-15 generates substantial numbers of memory-like NK cells able to persist for at least three weeks when injected into NOD scid gamma (NSG) mice. This approach induces haploidentical donor-derived memory-like NK cells that are highly lytic against patients’ myeloid or lymphoid leukemia blasts, independent of the presence of alloreactive cell populations in the donor and with negligible reactivity against patients’ non-malignant cells. Memory-like NK cells able to lyse autologous tumor cells can also be generated from patients with solid malignancies. The anti-tumor activity of allogenic and autologous memory-like NK cells is significantly greater than that displayed by NK cells stimulated overnight with IL-2, supporting their potential therapeutic value both in patients affected by high-risk acute leukemia after haploidentical hematopoietic stem cell transplantation and in patients with advanced solid malignancies.
Ghrelin Receptors Enhance Fat Taste Responsiveness in Female Mice

Ghrelin is a major appetite-stimulating neuropeptide found in circulation. While its role in increasing food intake is well known, its role in affecting taste perception, if any, remains unclear. In this study, we investigated the role of the growth hormone secretagogue receptor’s (GHS-R; a ghrelin receptor) activity in the peripheral taste system using feeding studies and conditioned taste aversion assays by comparing wild-type and GHS-R-knockout models. Using transgenic mice expressing enhanced green fluorescent protein (GFP), we demonstrated GHS-R expression in the taste system in relation phospholipase C ß2 isotype (PLCβ2; type II taste cell marker)- and glutamate decarboxylase type 67 (GAD67; type III taste cell marker)-expressing cells using immunohistochemistry. We observed high levels of co-localization between PLCβ2 and GHS-R within the taste system, while GHS-R rarely co-localized in GAD67-expressing cells. Additionally, following 6 weeks of 60% high-fat diet, female Ghsr−/− mice exhibited reduced responsiveness to linoleic acid (LA) compared to their wild-type (WT) counterparts, while no such differences were observed in male Ghsr−/− and WT mice. Overall, our results are consistent with the interpretation that ghrelin in the taste system is involved in the complex sensing and recognition of fat compounds. Ghrelin-GHS-R signaling may play a critical role in the recognition of fatty acids in female mice, and this differential regulation may contribute to their distinct ingestive behaviors.
“Let Food Be Thy Medicine”: Gluten and Potential Role in Neurodegeneration

Wheat is a most favored staple food worldwide and its major protein is gluten. It is involved in several gluten dependent diseases and lately was suggested to play a role in non-celiac autoimmune diseases. Its involvement in neurodegenerative conditions was recently suggested but no cause-and-effect relationship were established. The present narrative review expands on various aspects of the gluten-gut-brain axes events, mechanisms and pathways that connect wheat and gluten consumption to neurodegenerative disease. Gluten induced dysbiosis, increased intestinal permeabillity, enteric and systemic side effects, cross-reactive antibodies, and the sequence of homologies between brain antigens and gluten are highlighted. This combination may suggest molecular mimicry, alluding to some autoimmune aspects between gluten and neurodegenerative disease. The proverb of Hippocrates coined in 400 BC, “let food be thy medicine,” is critically discussed in the frame of gluten and potential neurodegeneration evolvement.
Enzymatic and Chemical Cross-Linking of Bacterial Cellulose/Fish Collagen Composites—A Comparative Study

This article compares the properties of bacterial cellulose/fish collagen composites (BC/Col) after enzymatic and chemical cross-linking. In our methodology, two transglutaminases are used for enzymatic cross-linking—one recommended for the meat and the other proposed for the fish industry—and pre-oxidated BC (oxBC) is used for chemical cross-linking. The structure of the obtained composites is characterized by scanning electron microscopy, thermogravimetric analysis, X-ray diffraction, and Fourier transform infrared spectroscopy, and their functional properties by mechanical and water barrier tests. While polymer chains in uncross-linked BC/Col are intertwined by H-bonds, new covalent bonds in enzymatically cross-linked ones are formed—resulting in increased thermal stability and crystallinity of the material. The C2–C3 bonds cleavage in D-glucose units, due to BC oxidation, cause secondary alcohol groups to vanish in favor of the carbonyl groups’ formation, thus reducing the number of H-bonded OHs. Thermal stability and crystallinity of oxBC/Col remain lower than those of BC/Col. The BC/Col formation did not affect tensile strength and water vapor permeability of BC, but enzymatic cross-linking with TGGS improved them significantly.
The Contribution of Neighborhood Tree and Greenspace to Asthma Emergency Room Visits: An Application of Advanced Spatial Data in Los Angeles County

This paper aims to investigate the role of neighborhood tree and greenspace on asthma morbidity, especially asthma emergency room visits. We employed advanced spatial data which allow for precisely capturing both the quantity and the features of tree and greenspace within a neighborhood environment. The results from the spatial regression models in Los Angeles County revealed that the features of trees and greenspace, such as the configuration of the tree canopy, the level of tree clustering, and private neighborhood greenspaces contribute to decreasing asthma morbidity, in addition to the quantity of tree and greenspace acreages. Notably, however, large scale greenspace, such as golf courses, school playgrounds, and parks fails to reduce the number of asthma emergency room visits at the statistically significant level. These findings imply that the creation of dense or clustered tree patches and small-scale neighborhood greenspaces might play a substantial role in mitigating air quality and consequently reducing asthma emergency room visits.
Bamboo Fiber Based Cellulose Nanocrystals/Poly(Lactic Acid)/Poly(Butylene Succinate) Nanocomposites: Morphological, Mechanical and Thermal Properties

The purpose of this work was to investigate the effect of cellulose nanocrystals (CNC) from bamboo fiber on the properties of poly (lactic acid) (PLA)/poly (butylene succinate) (PBS) composites fabricated by melt mixing at 175 °C and then hot pressing at 180 °C. PBS and CNC (0.5, 0.75, 1, 1.5 wt.%) were added to improvise the properties of PLA. The morphological, physiochemical and crystallinity properties of nanocomposites were analysed by field emission scanning electron microscope (FESEM), Fourier-transform infrared spectroscopy (FTIR) and X-ray diffractometry (XRD), respectively. The thermal and tensile properties were analysed by thermogravimetic analysis (TGA), Differential scanning calorimetry (DSC) and Universal testing machine (UTM). PLA-PBS blend shows homogeneous morphology while the composite shows rod-like CNC particles, which are embedded in the polymer matrix. The uniform distribution of CNC particles in the nanocomposites improves their thermal stability, tensile strength and tensile modulus up to 1 wt. %; however, their elongation at break decreases. Thus, CNC addition in PLA-PBS matrix improves structural and thermal properties of the composite. The composite, thus developed, using CNC (a natural fiber) and PLA-PBS (biodegradable polymers) could be of immense importance as they could allow complete degradation in soil, making it a potential alternative material to existing packaging materials in the market that could be environment friendly.
Configuration of Gut Microbiota Structure and Potential Functionality in Two Teleosts under the Influence of Dietary Insect Meals

Insect meals are considered promising, eco-friendly, alternative ingredients for aquafeed. Considering the dietary influence on establishment of functioning gut microbiota, the effect of the insect meal diets on the microbial ecology should be addressed. The present study assessed diet- and species-specific shifts in gut resident bacterial communities of juvenile reared Dicentrarchus labrax and Sparus aurata in response to three experimental diets with insect meals from three insects (Hermetia illucens, Tenebrio molitor, Musca domestica), using high-throughput Illumina sequencing of the V3–V4 region of the 16S rRNA gene. The dominant phyla were Firmicutes, Proteobacteria and Actinobacteria in all dietary treatments. Anaerococcus sp. , Cutibacterium sp. and Pseudomonas sp. in D. labrax, and Staphylococcus sp. , Hafnia sp. and Aeromonas sp. in S. aurata were the most enriched shared species, following insect-meal inclusion. Network analysis of the dietary treatments highlighted diet-induced changes in the microbial community assemblies and revealed unique and shared microbe-to-microbe interactions. PICRUSt-predicted Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were significantly differentiated, including genes associated with metabolic pathways. The present findings strengthen the importance of diet in microbiota configuration and underline that different insects as fish feed ingredients elicit species-specific differential responses of structural and functional dynamics in gut microbial communities.