Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficient and gentle delivery of molecules into cells with different elasticity via Progressive Mechanoporation†

Intracellular delivery of cargo molecules such as membrane-impermeable proteins or drugs is crucial for cell treatment in biological and medical applications. Recently, microfluidic mechanoporation techniques have enabled transfection of previously inaccessible cells. These techniques create transient pores in the cell membrane by shear-induced or constriction contact-based rapid cell deformation. However, cells deform and recover differently from a given extent of shear stress or compression and it is unclear how the underlying mechanical properties affect the delivery efficiency of molecules into cells. In this study, we identify cell elasticity as a key mechanical determinant of delivery efficiency leading to the development of “progressive mechanoporation” (PM), a novel mechanoporation method that improves delivery efficiency into cells of different elasticity. PM is based on a multistage cell deformation, through a combination of hydrodynamic forces that pre-deform cells followed by their contact-based compression inside a PDMS-based device controlled by a pressure-based microfluidic controller. PM allows processing of small sample volumes (about 20 μL) with high-throughput (>10 000 cells per s), while controlling both operating pressure and flow rate for a reliable and reproducible cell treatment. We find that uptake of molecules of different sizes is correlated with cell elasticity whereby delivery efficiency of small and big molecules is favoured in more compliant and stiffer cells, respectively. A possible explanation for this opposite trend is a different size, number and lifetime of opened pores. Our data demonstrates that PM reliably and reproducibly delivers impermeable cargo of the size of small molecule inhibitors such as 4 kDa FITC-dextran with >90% efficiency into cells of different mechanical properties without affecting their viability and proliferation rates. Importantly, also much larger cargos such as a >190 kDa Cas9 protein–sgRNA complex are efficiently delivered high-lighting the biological, biomedical and clinical applicability of our findings.
Structural recognition of the MYC promoter G-quadruplex by a quinoline derivative: insights into molecular targeting of parallel G-quadruplexes

Abstract DNA G-Quadruplexes (G4s) formed in oncogene promoters regulate transcription. The oncogene MYC promoter G4 (MycG4) is the most prevalent G4 in human cancers. However, the most studied MycG4 sequence bears a mutated 3′-residue crucial for ligand recognition. Here, we report a new drug-like small molecule PEQ without a large aromatic moiety that specifically binds MycG4. We determined the NMR solution structures of the wild-type MycG4 and its 2:1 PEQ complex, as well as the structure of the 2:1 PEQ complex of the widely used mutant MycG4. Comparison of the two complex structures demonstrates specific molecular recognition of MycG4 and shows the clear effect of the critical 3′-mutation on the drug binding interface. We performed a systematic analysis of the four available complex structures involving the same mutant MycG4, which can be considered a model system for parallel G4s, and revealed for the first time that the flexible flanking residues are recruited in a conserved and sequence-specific way, as well as unused potential for selective ligand-G4 hydrogen-bond interactions. Our results provide the true molecular basis for MycG4-targeting drugs and new critical insights into future rational design of drugs targeting MycG4 and parallel G4s that are prevalent in promoter and RNA G4s.
How pharmacists perceive their professional identity: a scoping review and discursive analysis.

OBJECTIVES The objectives of this scoping review were to (a) explore how pharmacists perceive their professional roles and identities and (b) describe factors impacting which professional roles or identities pharmacists embody in different pharmacy practice settings. METHODS A scoping review using a deductive approach was undertaken for this study. Systematic searches were conducted in five databases: Ovid MEDLINE, Ovid EMBASE, Ovid PsycINFO, EBSCO Cumulative Index to Nursing and Allied Health and Scopus (Elsevier). Key words searched included pharmacist, identity, professional role and one variations of these. Results were double-blind screened for relevance by two authors. Data extraction was facilitated by the web-based software platform COVIDENCE. Foucauldian critical discourse analysis was used to deconstruct how pharmacists perceive their professional roles and identities. KEY FINDINGS In total, 21 701 articles were retrieved in the search. Following de-duplication and screening, 23 studies from 11 different countries were included. Five major identity themes were identified: Clinician, Dispenser, Business Person, Patient Counsellor and Physician Supporter. The dispenser identity was the most widespread, but it was viewed by many pharmacists as undesirable. The clinician identity also had a strong presence but was viewed as an identity that pharmacists aspire to embody. CONCLUSIONS This scoping review illustrates that pharmacists do not uniformly perceive themselves to be clinicians. A significant gap exists between the profession's desired identity and that embodied by practicing pharmacists. The resulting dissonance may be a contributing factor to the lack of wide-scale practice change that the profession has been seeking for decades.
How we decide what to eat: Toward an interdisciplinary model of gut–brain interactions

Abstract Everyday dietary decisions have important short‐term and long‐term consequences for health and well‐being. How do we decide what to eat, and what physiological and neurobiological systems are involved in those decisions? Here, we integrate findings from thus‐far separate literatures: (a) the cognitive neuroscience of dietary decision‐making, and (b) growing evidence of gut–brain interactions and especially influences of the gut microbiome on diet and health outcomes. We review findings that suggest that dietary decisions and food consumption influence nutrient sensing, homeostatic signaling in the gut, and the composition of the gut microbiome. In turn, the microbiome can influence host health and behavior. Through reward signaling pathways, the microbiome could potentially affect food and drink decisions. Such bidirectional links between gut microbiome and the brain systems underlying dietary decision‐making may lead to self‐reinforcing feedback loops that determine long‐term dietary patterns, body mass, and health outcomes. This article is categorized under: Economics > Individual Decision‐Making Psychology > Brain Function and Dysfunction Psychology > Reasoning and Decision Making
Will medical schools offer healthcare assistantships as a permanent part of the curriculum? We need more evidence. A students’ perspective

Huang F, Mu Z. 2021. Response to: mindfulness–based mobile app reduces anxiety and increases self-compassion in healthcare students: a randomised controlled trial. Med Teach. DOI:10.1080/ 0142159X.2021. 1918657. Morrison AS, Mateen MA, Brozovich FA, Zaki J, Goldin PR, Heimberg RG, Gross JJ. 2019. Changes in empathy mediate the effects of cognitive-behavioral group therapy but not mindfulness-based stress reduction for social anxiety disorder. Behav Ther. 50(6): 1098–1111. Orosa-Duarte A, Mediavilla R, Mu~ noz-Sanjose A, Palao A, Garde J, L opez-Herrero V, Rodr ıguez-Vega B, Bay on C. 2021. Mindfulnessbased mobile app reduces anxiety and increases self-compassion in healthcare students: a randomised controlled trial. Med Teach. DOI: 10.1080/0142159X.2021. 1887835. Alvaro Orosa-Duarte Psychiatry, Clinical Psychology and Mental Health Department, La Paz University Hospital, Madrid, Spain Psychiatry Department, Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain
Maternal soy protein isolate diet during lactation programs deleterious effects on hepatic lipid metabolism, atherogenic indices, and function of adrenal in adult rat offspring

Abstract The benefits of consuming soy and its protein have been reported in many studies. However, its phytoestrogen content raises concerns about consumption during lactation and gestation We therefore examined the effects of soybean or soy protein isolate on the parameters-related cardiovascular pathophysiology in lactating mothers and their offsprings at weaning and adulthood. Lactating rats were divided: casein control (C); soy protein isolate (SPI); and soybean (S). At weaning, half of the litter received commercial ration up to 150 days. The levels of 17-β-estradiol and superoxide dismutase were low in the S mothers. For the SPI mothers, we observed a reduction of thiobarbituric acid reactive substances (TBARS). At weaning, atherogenic indices [1 = total cholesterol (TC)/HDL; 2 = LDL/HDL; 3 = TC-HDL/HDL)] decreased in the S and SPI offsprings compared to the casein control group; TBARS and antioxidant enzymes increased in the S offspring, while reduced/oxidized glutathione ratio increased in the SPI offspring, indicating lower oxidative stress. In adulthood, the SPI offspring showed an increase in liver cholesterol and atherogenic index 1 and 3 (vs. C and S) and 2 (vs. S). In addition, we found a decrease in catecholamines in the adrenal medulla and an increase in caffeine-stimulated secretion, but tyrosine hydroxylase expression remained constant. Maternal consumption of SPI during lactation worsened atherogenic indices of the offsprings in adulthood, which was associated with increased liver cholesterol and decreased catecholamines in the adrenal medulla. Soy consumption had no consistent long-term effects on the evaluated parameters compared to casein consumption. The data suggest that the consumption of SPI during lactation should be done with caution.
Comparison of coach-athlete perceptions on internal and external training loads in trained cyclists

ABSTRACT The aim was to compare the rating of perceived exertion (RPE), duration and session-RPE (S-RPE) prescribed by the coaches to those perceived by the cyclists in training sessions. The classification of RPE, duration and S-RPE of 14 male road cycling and mountain biking athletes were compared with the planned values of five coaches. The results revealed no differences for average RPE (P = 0.586), duration (P = 0.717) and S-RPE (P = 0.738) between coaches and cyclists. When comparing the three categories of effort, the results of the intensity of training sessions designed to be easy were perceived as significantly harder by cyclists compared to coaches (3.0 [2.0] vs. 2.0 [0.0] a.u.; P = 0.013). In addition, the correlations between coaches and cyclists on RPE (r = 0.73), duration (r = 0.95) and S-RPE (r = 0.87) were large, almost perfect and very large (P < 0.0001) respectively. In conclusion, our results indicate a mismatch between coaches (prescription) and cyclists (perception) of easy RPE training sessions, where the cyclists perceived the session harder. However, the S-RPE can be used to prescribe and quantifying the internal training load of trained cyclists.
Comparison of Human Interpretation and a Rule-Based Algorithm for Instrumented Sit-to-Stand Test

Background The five times sit-to-stand test (5STS) is one of the most commonly used tests to assess the physical performance of lower extremities. This study assessed the correlation between human interpretation (5STShuman) and a rule-based algorithm (5STSrule) using instrumented 5STS with two sensors. Methods We analyzed clinical records of 148 patients who visited the geriatric outpatient clinic of Asan Medical Center between December 2020 and March 2021 and underwent physical performance assessment using the electronic Short Physical Performance Battery (eSPPB) protocol. For STS, time-weight and time-distance curves were constructed using a loadcell and light detection and ranging (LiDAR). We manually assessed the grids of these curves to calculate 5STShuman, while 5STSrule used an empirical rule-based algorithm. Results In the study population, the mean 5STShuman and 5STSrule times, i.e., 12.2±0.4 and 11.4±0.4 seconds, respectively, did not differ significantly (p=0.232). Linear regression analysis showed that 5STShuman and 5STSrule were positively correlated (β=0.99, R2=0.99). The measures also did not differ (p=0.381) in classifying sarcopenia according to the Asian Working Group Society criteria, with C-indices of 0.826 for 5STShuman and 0.820 for 5STSrule. Conclusion An empirical rule-based algorithm correlated with human-interpreted 5STS and had comparable classification ability for sarcopenia.
Lifestyle-based mental health care in psychiatry: Translating evidence into practice

There is a large and growing body of evidence that supports the efficacy and cost-effectiveness of lifestylebased mental health care, targeting physical activity, diet, smoking and sleep, in the prevention and management of mental disorders. The new paradigm for understanding the relevance of lifestyle in both the aetiology and treatment of mood disorders is considered somewhat revolutionary in mental health and expands our traditional understanding of primary risk factors such as genetic, early life, socioeconomic and personality factors. The evidence is now such that lifestyle behaviours are given serious recognition as modifiable prevention and treatment targets. This is concomitant with the increasing focus on mitigating the substantial mortality gap arising from the cardiometabolic conditions so prevalent in people living with mental disorders (Firth et al., 2019b). Given the burden of mental disorders and limitations of existing approaches to prevention and treatment in mental health care, we urgently need to bridge the evidence–practice gap to bring lifestyle-based mental health care to people living with mental illness. The recent 2020 Royal Australian and New Zealand College of Psychiatrists (RANZCP) clinical practice guidelines for mood disorders represents a significant milestone in this process (Malhi et al., 2021). These guidelines recommend that dietary, exercise and sleep improvement, alongside smoking, alcohol and other substance use cessation, should form the foundation of mood disorder management, describing it as ‘essentially non-negotiable’ (Malhi et al., 2021). Here, we discuss the future directions needed to translate and firmly embed lifestyle-based mental health care into practice.
Intangible features extraction in the processing of abstract concepts: Evidence from picture-word priming

Over the last decade, hypotheses ranging from linguistic symbol processing to embodiment have been formulated to account for the content and mechanisms responsible for the representation of abstract concepts. Results of recent studies have suggested that abstract concepts, just like concrete ones, can benefit from knowledge of real-world situational context, but that they can also be processed based on abstract pictures devoid of such situational features. This paper presents two semantic priming experiments to explore such mechanisms further. The first experiment replicates Kuipers, Jones, and Thierry (2018) in a cross-linguistic setting which shows that abstract concepts can be processed from abstract pictures devoid of tangible features. In the second experiment, we studied extraction mechanisms that come into play when participants are presented with abstract and concrete pictures that provide situational information to illustrate target abstract concepts. We expected this facilitatory effect to be limited to concrete picture primes. Our data analysed with both Bayesian and Frequentist tests showed however that even when presented with tangible situational information, the extraction of features still occurred for abstract pictures. We discuss the implications of this with respect to future avenues for studying the processing of abstract concepts.
Microbial Selection and Survival in Subseafloor Sediment

Many studies have examined relationships of microorganisms to geochemical zones in subseafloor sediment. However, responses to selective pressure and patterns of community succession with sediment depth have rarely been examined. Here we use 16S rDNA sequencing to examine the succession of microbial communities at sites in the Indian Ocean and the Bering Sea. The sediment ranges in depth from 0.16 to 332 m below seafloor and in age from 660 to 1,300,000 years. The majority of subseafloor taxonomic diversity is present in the shallowest depth sampled. The best predictor of sequence presence or absence in the oldest sediment is relative abundance in the near-seafloor sediment. This relationship suggests that perseverance of specific taxa into deep, old sediment is primarily controlled by the taxonomic abundance that existed when the sediment was near the seafloor. The operational taxonomic units that dominate at depth comprise a subset of the local seafloor community at each site, rather than a grown-in group of geographically widespread subseafloor specialists. At both sites, most taxa classified as abundant decrease in relative frequency with increasing sediment depth and age. Comparison of community composition to cell counts at the Bering Sea site indicates that the rise of the few dominant taxa in the deep subseafloor community does not require net replication, but might simply result from lower mortality relative to competing taxa on the long timescale of community burial.
Knowledge of Sleep Disorders Among Physicians at a Tertiary Care Hospital in Qatar: Cross-sectional Study

Background Sleep disorders constitute a major health problem because of their relatively high and rising prevalence. Several studies worldwide have analyzed health care providers’ knowledge of sleep disorders. Objective In this study, we aimed to assess the knowledge of sleep disorders among physicians in Qatar. Methods A total of 250 physicians were surveyed regarding their knowledge of sleep medicine by using the validated 30-item Assessment of Sleep Knowledge in Medical Education (ASKME) Survey. The participants included residents, fellows, and consultants in medicine and allied subspecialties. A high score was defined as ≥60% of correctly answered questions, implying the respondent has adequate knowledge of sleep disorders. Results Responses were received from 158 of the 250 physicians, with a response rate of 63.2%. This included responses from 34 residents, 74 clinical fellows, and 50 consultants. The overall mean score was 15.53 (SD 4.42), with the highest possible score of 30. Only 57 of 158 (36.1%) respondents were able to answer ≥60% of the questions correctly. No statistically significant difference was found in the scores of participants with regard to their ranks (ie, residents, fellows, or consultants) or years of medical training. Conclusions This study demonstrates that health care providers in Qatar have decreased awareness and knowledge about sleep medicine, which may reflect reduced emphasis on sleep disorders during medical school and training. Increasing awareness regarding sleep medicine among nonspecialist physicians will allow early detection and treatment of sleep disorders, thereby reducing the morbidity associated with these disorders.
Low-dose aspirin can downregulate progesterone resistance and increase the expression of LIF in endometriosis during the implantation window

Abstract Aim Study the effect of low-dose aspirin on the endometrial receptivity in endometriosis rat models. Materials and methods This study is to explore the expressions of progesterone receptor and LIF among three groups of endometriosis rat models: control group (n = 12), EMs group (n = 15), and aspirin group (n = 17). The expressions of progesterone receptor (PR), PRA, PRB, and leukemia inhibitory factor receptor (LIFR) in eutopic endometrium were determined using immunohistochemistry technology, western blot, and qRT-PCR. The levels of LIF in eutopic endometrium and serum were detected by western blot, qRT-PCR, and ELISA. Results The expressions of PR, PRA, and PRB protein were significantly increased in the eutopic endometrium after low-dose aspirin treatment, and the level of PRB mRNA was also increased while the ratio of PRA/PRB mRNA was decreased in the eutopic endometrium. The levels of LIF in eutopic endometrium and serum were increased compared with the untreated endometriosis rats. However, the expression of LIFR was not statistically different among the three groups. Conclusions The results suggest that the low-dose aspirin treatment could downregulate progesterone resistance and increase the expression of LIF of endometriosis rats during the implantation window, which could improve endometrial receptivity and enhance the pregnant rate of endometriosis. It may provide a potential treatment method for endometriosis-related infertility.
Atomic-scale insights into quantum-order parameters in bismuth-doped iron garnet

Significance Substituted iron garnets, with a complex and diverse range of substitutional lattice sites, are widely used in magneto-optical devices. Atomic-scale investigations of local variations due to such substituents can give insights into the specific effects of elemental substitution, thereby helping to improve the functionality of magneto-optical materials. Here, via advanced electron microscopy techniques and theoretical calculations, we reveal how variations in the microstructure of Bi-substituted lutetium iron garnet are coupled to modulations in the lattice, electron, and spin structure. Our comprehensive approach provides a template for further improvement of materials through compositional design and shows how cooperative measurement of correlation characteristics between multiple quantum order parameters at the atomic scale can be beneficial for a wide range of functional materials. Bismuth and rare earth elements have been identified as effective substituent elements in the iron garnet structure, allowing an enhancement in magneto-optical response by several orders of magnitude in the visible and near-infrared region. Various mechanisms have been proposed to account for such enhancement, but testing of these ideas is hampered by a lack of suitable experimental data, where information is required not only regarding the lattice sites where substituent atoms are located but also how these atoms affect various order parameters. Here, we show for a Bi-substituted lutetium iron garnet how a suite of advanced electron microscopy techniques, combined with theoretical calculations, can be used to determine the interactions between a range of quantum-order parameters, including lattice, charge, spin, orbital, and crystal field splitting energy. In particular, we determine how the Bi distribution results in lattice distortions that are coupled with changes in electronic structure at certain lattice sites. These results reveal that these lattice distortions result in a decrease in the crystal-field splitting energies at Fe sites and in a lifted orbital degeneracy at octahedral sites, while the antiferromagnetic spin order remains preserved, thereby contributing to enhanced magneto-optical response in bismuth-substituted iron garnet. The combination of subangstrom imaging techniques and atomic-scale spectroscopy opens up possibilities for revealing insights into hidden coupling effects between multiple quantum-order parameters, thereby further guiding research and development for a wide range of complex functional materials.