Miracle-dz/UniFAR-FTUs huggingface dataset:
Monoclonal Antibody Therapies in Multiple Myeloma: A Challenge to Develop Novel Targets

The treatment options in multiple myeloma (MM) has changed dramatically over the past decade with the development of novel agents such as proteasome inhibitors (PIs); bortezomib and immunomodulatory drugs (IMiDs); thalidomide, and lenalidomide which revealed high efficacy and improvement of overall survival (OS) in MM patients. However, despite these progresses, most patients relapse and become eventually refractory to these therapies. Thus, the development of novel, targeted immunotherapies has been pursued aggressively. Recently, next-generation PIs; carfilzomib and ixazomib, IMiD; pomalidomide, histone deacetylase inhibitor (HDADi); panobinostat and monoclonal antibodies (MoAbs); and elotuzumab and daratumumab have emerged, and especially, combination of mAbs plus novel agents has led to dramatic improvements in the outcome of MM patients. The field of immune therapies has been accelerating in the treatment of hematological malignancies and has also taken center stage in MM. This review focuses on an overview of current status of novel MoAb therapy including bispecific T-cell engager (BiTE) antibody (BsAb), antibody-drug conjugate (ADC), and chimeric antigen receptor (CAR) T cells, in relapsed or refractory MM (RRMM). Lastly, investigational novel MoAb-based therapy to overcome immunotherapy resistance in MM is shown.
Hypoxic Preconditioning Enhances Survival and Proangiogenic Capacity of Human First Trimester Chorionic Villus-Derived Mesenchymal Stem Cells for Fetal Tissue Engineering

Prenatal stem cell-based regenerative therapies have progressed substantially and have been demonstrated as effective treatment options for fetal diseases that were previously deemed untreatable. Due to immunoregulatory properties, self-renewal capacity, and multilineage potential, autologous human placental chorionic villus-derived mesenchymal stromal cells (CV-MSCs) are an attractive cell source for fetal regenerative therapies. However, as a general issue for MSC transplantation, the poor survival and engraftment is a major challenge of the application of MSCs. Particularly for the fetal transplantation of CV-MSCs in the naturally hypoxic fetal environment, improving the survival and engraftment of CV-MSCs is critically important. Hypoxic preconditioning (HP) is an effective priming approach to protect stem cells from ischemic damage. In this study, we developed an optimal HP protocol to enhance the survival and proangiogenic capacity of CV-MSCs for improving clinical outcomes in fetal applications. Total cell number, DNA quantification, nuclear area test, and cell viability test showed HP significantly protected CV-MSCs from ischemic damage. Flow cytometry analysis confirmed HP did not alter the immunophenotype of CV-MSCs. Caspase-3, MTS, and Western blot analysis showed HP significantly reduced the apoptosis of CV-MSCs under ischemic stimulus via the activation of the AKT signaling pathway that was related to cell survival. ELISA results showed HP significantly enhanced the secretion of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) by CV-MSCs under an ischemic stimulus. We also found that the environmental nutrition level was critical for the release of brain-derived neurotrophic factor (BDNF). The angiogenesis assay results showed HP-primed CV-MSCs could significantly enhance endothelial cell (EC) proliferation, migration, and tube formation. Consequently, HP is a promising strategy to increase the tolerance of CV-MSCs to ischemia and improve their therapeutic efficacy in fetal clinical applications.
The Effect of Shear Force on Skin Viability in Patients with Type 2 Diabetes

Background Shear is a major risk factor in the development of diabetic foot ulcers, but its effect on the skin of patients with type 2 diabetes mellitus (DM) remains to be elucidated. The aim was to determine skin responses to shear in DM patients with and without diabetic polyneuropathy (DNP). Methods The forearm skin was loaded with 14.5 N shear (+2.4 kPa pressure) and with 3.5 kPa pressure for 30 minutes in 10 type 2 DM patients without DNP, 10 type 2 DM patients with DNP, and 10 healthy participants. A Sebutape collected IL-1α (measure of tissue damage). A laser Doppler flowmeter measured cutaneous blood cell flux (CBF) as a measure of the reactive hyperaemic skin response. Findings Reactive hyperaemia and IL-1α release was significantly increased after shear loading in all three groups and was higher compared to the responses to pressure loading. The reactive hyperaemic response after shear loading was impaired in patients with type 2 DM compared to healthy participants but did not differ between patients with and without DNP. The reactive hyperaemic response was negatively correlated with the blood glucose level but did not correlate with the DNP severity score. Interpretation Shear is important in the development of tissue damage, but the reparative responses to shear are impaired in patients with type 2 DM. DNP was not associated with altered skin responses, suggesting that the loss of protective sensation to sense shear to skin remains a key factor in the development of diabetic foot ulcers in patients with DNP.
Comparison of i-Gel as a Conduit for Intubation between under Fiberoptic Guidance and Blind Endotracheal Intubation during Cardiopulmonary Resuscitation: A Randomized Simulation Study

Purpose This study aimed to compare intubation performances among i-gel blind intubation (IGI), i-gel bronchoscopic intubation (IBRI), and intubation using Macintosh laryngoscope (MCL) applying two kinds of endotracheal tube during chest compressions. We hypothesized that IGI using wire-reinforced silicone (WRS) tube could achieve endotracheal intubation most rapidly and successfully. Methods In 23 emergency physicians, a prospective randomized crossover manikin study was conducted to examine the three intubation techniques using two kinds of endotracheal tubes. The primary outcome was the intubation time. The secondary outcome was the cumulative success rate for each intubation technique. A significant difference was considered when identifying p < 0.05 between two devices or p < 0.017 in post hoc analysis of the comparison among three devices. Results The mean intubation time using IGI was shorter (p < 0.017) than that of using IBRI and MCL in both endotracheal tubes (17.6 vs. 29.3 vs. 20.2 in conventional polyvinyl chloride (PVC) tube; 14.6 vs. 27.4 vs. 19.9 in WRS tube; sec). There were no significant (p < 0.05) differences between PVC and WRS tubes for each intubation technique. The intubation time to reach 100% cumulative success rate was also shorter in IGI (p < 0.017) than that in IBRI and MCL in both PVC and WRS tubes. Conclusions IGI was an equally successful and faster technique compared with IBRI or MCL regardless of the use of PVC or WRS tube. IGI might be an appropriate technique for emergent intubation by experienced intubators during chest compressions.
Occupational Therapy for Parkinsonian Patients: A Retrospective Study

Background Hand functionality and finger dexterity are impaired in patients with Parkinson's disease (PD). These disturbances lead to a dependency in activities of daily living (ADL) and poor quality of life (QoL). Objective We aimed to evaluate whether a specific occupational therapy (OT) program is effective in improving finger and hand dexterity and its impact on ADL in PD patients. Methods We retrospectively studied PD patients, hospitalized for a 4-week multidisciplinary intensive rehabilitation treatment (MIRT) between January 2015 and June 2018. All patients underwent 1 h/day OT treatment, 5 days a week. The primary outcome measure was the O'Connor finger dexterity test; secondary outcome measures were the Minnesota dexterity test, UPDRS II, and Self-Assessment Parkinson's Disease Disability Scale (SPDDS). These measures were assessed at admission (T0) and discharge (T1). Results Based on the Hoehn and Yahr scale (H&Y), patients were divided into two groups: 262 subjects in H&Y stage <3 (early-stage PD patients) and 220 in H&Y stage ≥3 (medium-advanced stage PD patients). As expected, at baseline, all measures were worse in higher H&Y stages. After treatment, both groups experienced significant improvements in all outcomes. Significant differences between early-stage and medium-advanced stage PD patients were observed only for the changes in UPDRS II, with a better improvement in patients in H&Y stage ≥3. Conclusions We showed that PD patients who underwent a rehabilitation protocol including OT experienced improvements in finger dexterity and hand functionality. Our results underline the relevance of OT in improving autonomy and QoL in PD patients.
Machine Learning to Study Social Interaction Difficulties in ASD

Autism Spectrum Disorder (ASD) is a spectrum of neurodevelopmental conditions characterized by difficulties in social communication and social interaction as well as repetitive behaviors and restricted interests. Prevalence rates have been rising, and existing diagnostic methods are both extremely time and labor consuming. There is an urgent need for more economic and objective automatized diagnostic tools that are independent of language and experience of the diagnostician and that can help deal with the complexity of the autistic phenotype. Technological advancements in machine learning are offering a potential solution, and several studies have employed computational approaches to classify ASD based on phenomenological, behavioral or neuroimaging data. Despite of being at the core of ASD diagnosis and having the potential to be used as a behavioral marker for machine learning algorithms, only recently have movement parameters been used as features in machine learning classification approaches. In a proof-of-principle analysis of data from a social interaction study we trained a classification algorithm on intrapersonal synchrony as an automatically and objectively measured phenotypic feature from 29 autistic and 29 typically developed individuals to differentiate those individuals with ASD from those without ASD. Parameters included nonverbal motion energy values from 116 videos of social interactions. As opposed to previous studies to date, our classification approach has been applied to non-verbal behavior objectively captured during naturalistic and complex interactions with a real human interaction partner assuring high external validity. A machine learning approach lends itself particularly for capturing heterogeneous and complex behavior in real social interactions and will be essential in developing automatized and objective classification methods in ASD.
Gut Bacteriophage: Current Understanding and Challenges

The gut microbiome is widely accepted to have a significant impact on human health yet, despite years of research on this complex ecosystem, the contributions of different forces driving microbial population structure remain to be fully elucidated. The viral component of the human gut microbiome is dominated by bacteriophage, which are known to play crucial roles in shaping microbial composition, driving bacterial diversity, and facilitating horizontal gene transfer. Bacteriophage are also one of the most poorly understood components of the human gut microbiome, with the vast majority of viral sequences sharing little to no homology to reference databases. If we are to understand the dynamics of bacteriophage populations, their interaction with the human microbiome and ultimately their influence on human health, we will depend heavily on sequence based approaches and in silico tools. This is complicated by the fact that, as with any research field in its infancy, methods of analyses vary and this can impede our ability to compare the outputs of different studies. Here, we discuss the major findings to date regarding the human virome and reflect on our current understanding of how gut bacteriophage shape the microbiome. We consider whether or not the virome field is built on unstable foundations and if so, how can we provide a solid basis for future experimentation. The virome is a challenging yet crucial piece of the human microbiome puzzle. In order to develop our understanding, we will discuss the need to underpin future studies with robust research methods and suggest some solutions to existing challenges.
A Comparison of 16S rRNA Profiles Through Slaughter in Australian Export Beef Abattoirs

Microbial contamination of beef cattle carcases and subsequent cross-contamination during processing is inevitable and virtually impossible to prevent. The understanding of microbial contamination in the beef industry is currently limited to hypotheses based on traditional microbiological tools. Additionally, the complex structural and functional responses of beef cattle microbial communities to the fragmentation in the supply chain remain unknown. This study used 16S rRNA gene sequencing in combination with traditional microbiology to monitor and compare changes in the microbiota throughout slaughter in an integrated (abattoir A) and a fragmented (abattoir B) beef abattoir in Australia. Briefly, the primary difference between an integrated and a fragmented abattoir is that fragmented abattoirs receive cattle from multiple sources, whereas integrated abattoirs typically receive cattle that has been produced using the same production system and from a limited number of sources. The composition in the bacterial communities varied between the abattoirs, though the presence of the most predominant bacterial species within the microbiota at each abattoir was similar. Lactobacillales (2.4–56.2%) and Pseudomonadales (2.4–59.4%) most notably dominated hides, carcases, and the environment in abattoir B. In abattoir A, Bacteroidales (3.9–43.8%), Lactobacillales (0.0–61.9%), and Pseudomonadales (0.5–72.1%) fluctuated but generally shared the dominance over the rest. Combined results of total viable count (TVC) and 16S rRNA gene profiling indicated that an upward hide pulling system adopted by abattoir B may lead to increased transmission of hide contaminants to post-hide pull carcases. Abattoir B had 3.2 log10CFU/cm2 reduction from hide to carcase, where abattoir A had 4.5 log10CFU/cm2 reduction. The findings from this study indicated that common beef-associated microbiota exist in varying composition in Australian abattoirs, and 16S rRNA amplicon sequencing is a powerful tool to understand in-depth movement of microbial contaminants.
Intestinal Bacteroides sp. Imbalance Associated With the Occurrence of Childhood Undernutrition in China

Undernutrition (UN) is a worldwide concern affecting morbidity and mortality among children, but the safety and long-term efficacy of its current treatments remain controversial. Recent evidence showing the roles of the gut microbiome (GM) in nutrient absorption indicates its usefulness in alternative interventions to treat UN safely with sustainable amelioration. To enhance our understanding of the GM and childhood undernutrition, we deep sequenced the gut metagenomes of 65 children with moderate or severe undernutrition (UN group) and 61 healthy children (HC group) to identify associated taxa and genes using a two-stage validation scheme. At stage I, 54 UN patients and 51 healthy children were enrolled for the discovery of GM markers in UN children. The accuracy of the markers was then tested in an additional 11 UN patients and 10 healthy children at stage II. Compared to the HC group, the UN group had lower richness in microbial genes (P = 0.005, FDR = 0.005) and species (P = 0.002, FDR = 0.002). The distributions of bacterial genes enable the identification of 16 gene markers with which to discriminate UN patients with high accuracy [averaged areas under the receiver operating curve (AUC) = 0.87], including three Bacteroides uniformis genes that are responsible for the synthesis of iron transporters. We also identified four species markers that enable the UN patients to be confidently discriminated from the HC children (averaged AUC = 0.91), namely Bacteroides ovatus, Bacteroides uniformis, Bacteroides uniformis, and Bacteroides vulgatus. In addition, metabolic comparison showed significantly decreased isobutyric acid (P = 0.005, FDR = 0.017) and increased isovaleric acid (P = 0.006, FDR = 0.017) in UN patients. We also identified notable correlations between microbial species and short-chain fatty acids (SCFAs) and several nutritional indicators, including acetic acid and iron (r = 0.436, P = 0.029), butyric acid and iron (r = 0.422, P = 0.036), butyric acid and lymphocyte (r = −0.309, P = 0.011), and acetic acid and total protein (r = −0.303, P = 0.043). Taken together, the distinct features of gut microbiota in UN patients highlight the taxonomic and functional shift during the development of UN and provide a solid theoretical basis for intervention in childhood undernutrition through gut microbes.
Attractiveness Ratings for Musicians and Non-musicians: An Evolutionary-Psychology Perspective

From an evolutionary perspective, musical behavior such as playing an instrument can be considered as part of an individual’s courting behavior. Playing a musical instrument or singing might fulfill a function similar to that of a bird’s colored feathers: attracting attention. Therefore, musicians may be rated as more attractive than non-musicians. In an online survey, 137 volunteers (95 female) with ages ranging from 16 to 39 years rated the attractiveness of fictitious persons of the opposite sex described in short verbal profiles. These profiles differed with respect to whether the described person made music or not. Additionally, the musicians’ profiles varied with regard to whether the described person played music or sang in public or in private only. Results show that musicians’ profiles were not generally rated as more attractive than non-musicians’, but attractiveness did vary according to setting: private musicians were rated as most attractive, followed by non-musicians and public musicians. Furthermore, results indicate that participants who played a musical instrument or sang themselves gave higher ratings to profiles of musicians. But for participants who do not make music themselves, higher attractiveness ratings for musicians playing instruments or sing in private settings were found. These results indicate that the impression of sharing a common interest (making music) and furthermore making music in private instrumental settings seems to make people attractive to other people. No additional support for the sexual selection hypotheses for the evolution of music was provided by the current results. The musical status of the rater affected his or her judgements, with musicians rating other people as more attractive if they share the common interest in making music. Not the display of being a musician seems to be critical for attractiveness ratings but the perceived or imagined similarity by the rater created by information on musicality, fostering the theoretical significance of the communication aspect of music.
High-Salt Diet Causes Sleep Fragmentation in Young Drosophila Through Circadian Rhythm and Dopaminergic Systems

Salt (sodium chloride) is an essential dietary requirement, but excessive consumption has long-term adverse consequences. A high-salt diet (HSD) increases the risk of chronic diseases such as cardiovascular conditions and diabetes and is also associated with poor sleep quality. Little is known, however, about the neural circuit mechanisms that mediate HSD-induced sleep changes. In this study, we sought to identify the effects of HSD on the sleep and related neural circuit mechanisms of Drosophila. Strikingly, we found that HSD causes young Drosophila to exhibit a fragmented sleep phenotype similar to that of normal aging individuals. Importantly, we further showed that HSD slightly impairs circadian rhythms and that the HSD-induced sleep changes are dependent on the circadian rhythm system. In addition, we demonstrated that HSD-induced sleep changes are dopaminergic-system dependent. Together, these results provide insight into how elevated salt in the diet can affect sleep quality.
Assessing Knowledge Gaps of Women and Healthcare Providers Concerning Cardiovascular Risk After Hypertensive Disorders of Pregnancy—A Scoping Review

Background: A history of a Hypertensive Disorder of Pregnancy (HDP) at least doubles a woman's risk of cardiovascular disease (CVD). The risk increases within 10 years after HDP and continues for life, making long-term health after HDP of major public health importance. Understanding knowledge gaps in health care professionals and women regarding cardiovascular health after HDP is an important component in addressing these risks. Objectives: The primary aim was to examine what women and healthcare providers (HCP) know about cardiovascular risks after HDP. The secondary aims were to identify enablers and barriers to knowledge and action on knowledge. Methods: A scoping review was conducted. This was a narrative synthesis, using PRISMA-ScR guidelines, of English-language full text articles that included assessment of knowledge of women, and/or HCP, on long term cardiovascular risk after HDP. The databases Embase, Medline, Scopus, ProQuest, Cochrane, and PsycInfo were searched from 01 January 2005 to 31 May 2019. Results: Twelve studies were included, six addressing women's knowledge, five addressing HCP knowledge, and one addressing both. The studies included 402 women and 1,215 HCP from seven countries. Regarding women's knowledge, six of seven studies found women had limited or no knowledge about the link between HDP and CVD. Where women were aware of the link, the majority had sourced their own information, rather than obtaining it through their HCP. In five of six studies, HCP also mostly had limited knowledge about HDP-CVD links. Primary enablers for HCP acquisition of knowledge and counseling were the availability and knowledge of guidelines. Where comparisons between HCP groups were made, obstetricians had greater knowledge than family physicians, internal medical specialists, or midwives. Conclusion: There was a low level of knowledge amongst HCP and women about increased CVD risk after HDP. Where women had higher levels of knowledge, the information was often obtained informally rather than from HCP. There were variations in knowledge of HCP, with obstetricians generally more aware than other professions. Further country and context-specific research on current status of women's and HCP's knowledge is therefore necessary when creating educational strategies to address knowledge gaps after HDP.