Miracle-dz/UniFAR-FTUs huggingface dataset:
Current Techniques Used for Practical Blood Flow Restriction Training: A Systematic Review

Abstract Bielitzki, R, Behrendt, T, Behrens, M, and Schega, L. Current techniques used for practical blood flow restriction training: a systematic review. J Strength Cond Res 35(10): 2936–2951, 2021—The purpose of this article was to systematically review the available scientific evidence on current methods used for practical blood flow restriction (pBFR) training together with application characteristics as well as advantages and disadvantages of each technique. A literature search was conducted in different databases (PubMed, Web of Science, Scopus, and Cochrane Library) for the period from January 2000 to December 2020. Inclusion criteria for this review were (a) original research involving humans, (b) the use of elastic wraps or nonpneumatic cuffs, and (c) articles written in English. Of 26 studies included and reviewed, 15 were conducted using an acute intervention (11 in the lower body and 4 in the upper body), and 11 were performed with a chronic intervention (8 in the lower body, 1 in the upper body, and 2 in both the upper and the lower body). Three pBFR techniques could be identified: (a) based on the perceptual response (perceived pressure technique), (b) based on the overlap of the cuff (absolute and relative overlap technique), and (c) based on the cuffs' maximal tensile strength (maximal cuff elasticity technique). In conclusion, the perceived pressure technique is simple, valid for the first application, and can be used independently of the cuffs' material properties, but is less reliable within a person over time. The absolute and relative overlap technique as well as the maximal cuff elasticity technique might be applied more reliably due to markings, but require a cuff with constant material properties over time.
Accurate large-scale phylogeny-aware alignment using BAli-Phy

MOTIVATION BAli-Phy, a popular Bayesian method that co-estimates multiple sequence alignments and phylogenetic trees, is a rigorous statistical method, but due to its computational requirements, it has generally been limited to relatively small datasets (at most about 100 sequences). Here we repurpose BAli-Phy as a ``phylogeny-aware" alignment method: we estimate the phylogeny from the input of unaligned sequences, and then use that as a fixed tree within BAli-Phy. RESULTS We show that this approach achieves high accuracy, greatly superior to Prank, the current most popular phylogeny-aware alignment method, and is even more accurate than MAFFT, one of the top performing alignment methods in common use. Furthermore, this approach can be used to align very large datasets (up to 1000 sequences in this study). AVAILABILITY See https://doi.org/10.13012/B2IDB-7863273_V1 for datasets used in this study. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Differential optical absorption spectroscopy (DOAS)

The first € price and the £ and $ price are net prices, subject to local VAT. Prices indicated with * include VAT for books; the €(D) includes 7% for Germany, the €(A) includes 10% for Austria. Prices indicated with ** include VAT for electronic products; 19% for Germany, 20% for Austria. All prices exclusive of carriage charges. Prices and other details are subject to change without notice. All errors and omissions excepted. U. Platt, J. Stutz Differential Optical Absorption Spectroscopy
Antimicrobial Resistance Spectrum Conferred by pRErm46 of Emerging Macrolide (Multidrug)-Resistant Rhodococcus equi

Clonal multidrug resistance recently emerged in Rhodococcus equi, complicating the therapeutic management of this difficult-to-treat animal- and human-pathogenic actinomycete. The currently spreading multidrug-resistant (MDR) “2287” clone arose in equine farms upon acquisition, and coselection by mass macrolide-rifampin therapy, of the pRErm46 plasmid carrying the erm(46) macrolide-lincosamide-streptogramin resistance determinant and of an rpoBS531F mutation. ABSTRACT Clonal multidrug resistance recently emerged in Rhodococcus equi, complicating the therapeutic management of this difficult-to-treat animal- and human-pathogenic actinomycete. The currently spreading multidrug-resistant (MDR) “2287” clone arose in equine farms upon acquisition, and coselection by mass macrolide-rifampin therapy, of the pRErm46 plasmid carrying the erm(46) macrolide-lincosamide-streptogramin resistance determinant, and of an rpoBS531F mutation. Here, we screened a collection of susceptible and macrolide-resistant R. equi strains from equine clinical cases using a panel of 15 antimicrobials against rapidly growing mycobacteria (RGM) and nocardiae and other aerobic actinomycetes (NAA). R. equi isolates—including MDR ones—were generally susceptible to linezolid, minocycline, tigecycline, amikacin, and tobramycin according to Staphylococcus aureus interpretive criteria, plus imipenem, cefoxitin, and ceftriaxone based on Clinical and Laboratory Standards Institute (CLSI) guidelines for RGM/NAA. Susceptibility to ciprofloxacin and moxifloxacin was borderline according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. Molecular analyses linked pRErm46 to significantly increased MICs for trimethoprim-sulfamethoxazole and doxycycline, in addition to clarithromycin, within the RGM/NAA panel, and to streptomycin, spectinomycin, and tetracycline resistance. pRErm46 variants with spontaneous deletions in the class 1 integron (C1I) region, observed in ≈30% of erm(46)-positive isolates, indicated that the newly identified resistances were attributable to the C1I’s sulfonamide (sul1) and aminoglycoside (aaA9) resistance cassettes and adjacent tetRA(33) determinant. Most MDR isolates carried the rpoBS531F mutation of the 2287 clone, while different rpoB mutations (S531L, S531Y) detected in two cases suggest the emergence of novel MDR R. equi strains.
The impact of face masks on the communication of adults with hearing loss during COVID-19 in a clinical setting

Abstract Objective The aim of the study was to investigate the effect of surgical masks and face shields on speech intelligibility of adults with moderate to severe hearing loss. Design This study measured speech tracking scores in quiet for life speech in three different conditions: without a mask, with a surgical mask and with a face shield. Acoustic effects of the masks and face shields on the speech signal were also investigated. Study sample: The study sample consists of 42 patients with moderate to severe hearing loss, 23 cochlear implant users and 19 hearing aid users. Results A significant average difference in speech perception scores was found for the use of a surgical mask compared to the listening situation “without mask”. The worse the speech understanding in quiet, the larger the impact of the surgical mask. For the worse performers even the face shield had a negative impact on speech perception. The sound distortion for the face shield compared to the surgical mask was greater. Conclusion This study shows that even for speech perception in quiet, surgical face masks, and face shields to a lesser extent, have a negative effect for patients with moderate to severe hearing loss.
RhoA/ROCK Signaling Regulates TGF-β1-Induced Fibrotic Effects in Human Pterygium Fibroblasts through MRTF-A

ABSTRACT Purpose The overexpression of transforming growth factor-beta1 (TGF-β1) after surgical excision often leads to excessive fibrosis, indicating the recurrence of pterygium. The aims of the present in vitro study were to investigate the role of RhoA/ROCK signaling in regulating fibrotic effects of primary human pterygium fibroblasts (HPFs), as well as to explore the possible mechanisms of these effects. Methods Pterygium samples were obtained from surgery, and profibrotic activation was induced by TGF-β1. Cell proliferation was detected by CCK-8 assay; cell migration was detected by wound healing assay; quantitative real-time PCR and Western blot were used to detect the effects of TGF-β1 and the role of RhoA/ROCK signaling in the synthesis of alpha-smooth muscle actin (a-SMA), type I and III collagen (COL1 and COL3), and matrix metalloproteinase-9 (MMP9) in HPFs. The changes of signaling pathways were detected by Western blot; and pharmaceutical inhibition of RhoA/ROCK signaling and its downstream MRFT-A/SRF transcription pathway were used to assess their possible mechanism in HPFs fibrosis. Results ROCK inhibitor Y-27632 decreased TGF-β1-induced cell proliferation and migration, reduced the TGF-β1-induced expression of profibrotic markers in HPFs, and suppressed TGF-β1-induced nuclear accumulation of Myocardin-related transcription factor A (MRTF-A) as well as accompanied elevation of F/G-actin ratio in HPFs. MRTF-A/Serum response factor (SRF) inhibitor CCG-100602 attenuated the TGF-β1-induced α-SMA expression and reduced myofibroblast activation in HPFs. Conclusions RhoA/ROCK signaling played a pivotal role in TGF-β1-induced fibrosis and myofibroblast activation in HPFs at least in part by inactivating the downstream MRTF-A/SRF transcriptional pathway.
Child abuse and automatic emotion regulation in children and adolescents

Abstract Child abuse is associated with elevated risk for psychopathology. The current study examined the role of automatic emotion regulation as a potential mechanism linking child abuse with internalizing psychopathology. A sample of 237 youth aged 8–16 years and their caregivers participated. Child abuse severity was assessed by self-report questionnaires, and automatic emotion regulation was assessed using an emotional Stroop task designed to measure adaptation to emotional conflict. A similar task without emotional stimuli was also administered to evaluate whether abuse was uniquely associated with emotion regulation, but not cognitive control applied in a nonemotional context. Internalizing psychopathology was assessed concurrently and at a 2-year longitudinal follow-up. Child abuse severity was associated with lower emotional conflict adaptation but was unrelated to cognitive control. Specifically, the severity of emotional and physical abuse, but not sexual abuse, were associated with lower emotional conflict adaptation. Emotional conflict adaptation was not associated with internalizing psychopathology prospectively. These findings suggest that childhood emotional and physical abuse, in particular, may influence automatic forms of emotion regulation. Future work exploring the socioemotional consequences of altered automatic emotion regulation among youth exposed to child abuse is clearly needed.
Learning embedding features based on multisense-scaled attention architecture to improve the predictive performance of anticancer peptides

MOTIVATION Anticancer peptides (ACPs) have recently emerged as effective anticancer drugs in cancer therapy. Machine-learning-based predictors have been developed to identify ACPs and achieve satisfactory performance. However, existing methods suffer from experience-based feature engineering, which not only restricts the representation ability of the models to a certain extent but also lacks adaptivity for different data, limiting the further improvement of the predictive performance and impacting the robustness of the predictive models. To alleviate the above problems, we propose a novel deep-learning-based predictor named ACPred-LAF, in which we propose a novel multi-sense and multi-scaled embedding algorithm to automatically learn and extract context sequential characteristics of ACPs. RESULTS Through the feature comparative analysis, we demonstrate that our learnable and self-adaptive embedding features are better than hand-crafted features in capturing discriminative information, which can effectively benefit the performance improvement for ACP prediction. In addition, benchmarking comparison results demonstrate that our ACPred-LAF outperforms the state-of-the-art methods both on existing benchmark datasets and our newly constructed dataset. Furthermore, we also prove and validate the robustness of the model via the data interference experiment. To avoid potential evaluation bias, here we construct a new ACP benchmark dataset named ACP-Mixed by integrating existing datasets. We expect our newly constructed dataset to be a golden standard benchmark dataset in this field. To facilitate the use of our model, we develop a web server as the implementation of ACPred-LAF. AVAILABILITY Our proposed ACPred-LAF, newly constructed benchmark dataset ACP-Mixed are open source collaborative initiatives available in the GitHub repository (https://github.com/TearsWaiting/ACPred-LAF). Besides, a webserver as the implementation of ACPred-LAF that can be accessed via: http://server.malab. cn/ACPred-LAF. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Self-affirmation inductions to reduce defensive processing of threatening health risk information

Abstract Objective Self-affirmation reduces defensiveness toward threatening health messages. In this study, we compared several possible self-affirmation inductions in order to identify the most effective strategy. Design Women at increased risk for breast cancer (i.e. who drink 7+ drinks per week) were recruited through Amazon Mechanical Turk (N = 1,056), randomly assigned to one of 11 self-affirmation conditions, and presented with an article about the link between alcohol intake and breast cancer risk. Main Outcome Measures Participants answered questions that measured key indices of message acceptance (risk perception, message endorsement), future alcohol consumption intentions, and action plans to reduce alcohol intake. Results Participants who affirmed health vs. non-health values did not differ in behavioral intentions or action plans to reduce alcohol intake. General values vs. health essay affirmations led to higher odds of reporting some vs. no action plans to reduce alcohol consumption. Essay- vs. questionnaire-based inductions led to higher breast cancer worry and intentions to reduce alcohol consumption. Conclusion Overall, self-affirmation inductions that include an explicit focus on values (general or health-related) and self-generation of affirming thoughts through essay writing, are most potent in changing behavioral intentions and action plans to change future health behavior.
Muscle-tendon Crosstalk During Muscle Wasting.

In organisms from flies to mammals, the initial formation of a functional tendon is completely dependent on chemical signals from muscle (myokines). However, how myokines affect the maturation, maintenance, and regeneration of tendons as a function of age is completely unstudied. Here we discuss the role of four myokines - fibroblast growth factors (FGF), myostatin, the secreted protein acidic and rich in cysteine (SPARC), and miR-29 - in tendon development and hypothesize a role for these factors in the progressive changes in tendon structure and function as a result of muscle wasting (disuse, aging and disease). Because of the close relationship between mechanical loading and muscle and tendon regulation, disentangling muscle-tendon crosstalk from simple mechanical loading is experimentally quite difficult. Therefore, we propose an experimental framework that hopefully will be useful in demonstrating muscle-tendon crosstalk in vivo. Though understudied, the promise of a better understanding of muscle-tendon crosstalk is the development of new interventions that will improve tendon development, regeneration, and function throughout the lifespan.
Registered report protocol: Developing an artifact index for capacitive electrocardiography signals acquired with an armchair

Continuous monitoring of an electrocardiogram (ECG) in private diagnostic spaces such as vehicles or apartments allows early detection of cardiovascular diseases. We will use an armchair with integrated capacitive electrodes to record the capacitive electrocardiogram (cECG) during everyday activities. However, movements and other artifacts affect the signal quality. Therefore, an artifact index is needed to detect artifacts and classify the cECG. The unavailability of cECG data and reliable ground truth information requires new recordings to develop an artifact index. This study is designed to test the hypothesis: an artifact index can be devised, which intends to estimate the signal quality of segments and classify signals. In a single-arm study with 44 subjects, we will record two activities of 11-minute duration: reading and watching television. During recording, we will capture cECG, ECG, and oxygen saturation (SpO2) with time synchronization as well as keypoint-based movement indicators obtained from a video camera. SpO2 provides additional information on the subject’s health status. The keypoint-based movements indicate artifacts in the cECG. We will combine all ground truth data to evaluate the index. In the future, we aim at using the artifact index to exclude cECG segments with artifacts from further analysis. This will improve cECG technology for the measurement of cardiovascular parameters.
Metabolic map of the antiviral drug podophyllotoxin provides insights into hepatotoxicity

Abstract Podophyllotoxin (POD) is a natural compound with antiviral and anticancer activities. The purpose of the present study was to determine the metabolic map of POD in vitro and in vivo. Mouse and human liver microsomes were employed to identify POD metabolites in vitro and recombinant drug-metabolizing enzymes were used to identify the mono-oxygenase enzymes involved in POD metabolism. All in vitro incubation mixtures and bile samples from mice treated with POD were analysed with ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry. A total of 38metabolites, including six phase-I metabolites and 32 phase-II metabolites, of POD were identified from bile and faeces samples after oral administration, and their structures were elucidated through interpreting MS/MS fragmentation patterns. Nine metabolites, including two phase-I metabolites, five glucuronide conjugates, and two GSH conjugates were detected in both human and mouse liver microsome incubation systems and the generation of all metabolites were NADPH-dependent. The main phase-I enzymes involved in metabolism of POD in vitro include CYP2C9, CYP2C19, CYP3A4, and CYP3A5. POD administration to mice caused hepatic and intestinal toxicity, and the cellular damage was exacerbated when 1-aminobenzotriazole, a broad-spectrum inhibitor of CYPs, was administered with POD, indicating that POD, but not its metabolites, induced hepatic and intestinal toxicities. This study elucidated the metabolic map and provides important reference basis for the safety evaluation and rational for the clinical application of POD.
Evolution of Renal-Disease Factor APOL1 Results in Cis and Trans Orientations at the Endoplasmic Reticulum That Both Show Cytotoxic Effects

Abstract The recent and exclusively in humans and a few other higher primates expressed APOL1 (apolipoprotein L1) gene is linked to African human trypanosomiasis (also known as African sleeping sickness) as well as to different forms of kidney diseases. Whereas APOL1’s role as a trypanolytic factor is well established, pathobiological mechanisms explaining its cytotoxicity in renal cells remain unclear. In this study, we compared the APOL family members using a combination of evolutionary studies and cell biological experiments to detect unique features causal for APOL1 nephrotoxic effects. We investigated available primate and mouse genome and transcriptome data to apply comparative phylogenetic and maximum likelihood selection analyses. We suggest that the APOL gene family evolved early in vertebrates and initial splitting occurred in ancestral mammals. Diversification and differentiation of functional domains continued in primates, including developing the two members APOL1 and APOL2. Their close relationship could be diagnosed by sequence similarity and a shared ancestral insertion of an AluY transposable element. Live-cell imaging analyses showed that both expressed proteins show a strong preference to localize at the endoplasmic reticulum (ER). However, glycosylation and secretion assays revealed that—unlike APOL2—APOL1 membrane insertion or association occurs in different orientations at the ER, with the disease-associated mutants facing either the luminal (cis) or cytoplasmic (trans) side of the ER. The various pools of APOL1 at the ER offer a novel perspective in explaining the broad spectrum of its observed toxic effects.
Neuro-Oncology Clinicians’ Attitudes and Perspectives on Medical Assistance in Dying

ABSTRACT: Background: Medical assistance in dying (MAiD), also known as physician-assisted death, is currently legal in several locations across the globe. Brain cancer or its treatments can lead to cognitive impairment, which can impact decision-making capacity for MAiD. Objective: We sought to explore neuro-oncology clinicians’ attitudes and perspectives on MAiD, including interpretation of decision-making capacity for patient MAiD eligibility. Methods: An online survey was distributed to members of national and international neuro-oncology societies. We asked questions about decision-making capacity and MAiD, in part using hypothetical patient scenarios. Multiple choice and free-text responses were captured. Results: There were 125 survey respondents. Impaired cognition was identified as the most important factor that would signal a decline in patient capacity. At least 26% of survey respondents had moral objections to MAiD. Respondents thought that different hypothetical patients had capacity to make a decision about MAiD (range 18%–58%). In other hypothetical scenarios, fewer clinicians were willing to support a MAiD decision for a patient with an oligodendroglioma (26%) vs. glioblastoma (41%–70%, depending on the scenario). Time since diagnosis, performance status, and patient age seemed to affect support for MAiD decisions (Fisher’s exact P-values 0.007, < 0.001, and 0.049, respectively). Conclusion: While there are differing opinions on the moral permissibility of MAiD in general and for neuro-oncology patients, most clinicians agree that capacity must be assessed carefully before a decision is made. End-of-life discussions should happen early, before the capacity is lost. Our results can inform assessments of patient capacity in jurisdictions where MAiD is legal.
Genetic vulnerabilities upon inhibition of DNA damage response

Abstract Because of essential roles of DNA damage response (DDR) in the maintenance of genomic integrity, cellular homeostasis, and tumor suppression, targeting DDR has become a promising therapeutic strategy for cancer treatment. However, the benefits of cancer therapy targeting DDR are limited mainly due to the lack of predictive biomarkers. To address this challenge, we performed CRISPR screens to search for genetic vulnerabilities that affect cells’ response to DDR inhibition. By undertaking CRISPR screens with inhibitors targeting key DDR mediators, i.e. ATR, ATM, DNAPK and CHK1, we obtained a global and unbiased view of genetic interactions with DDR inhibition. Specifically, we identified YWHAE loss as a key determinant of sensitivity to CHK1 inhibition. We showed that KLHL15 loss protects cells from DNA damage induced by ATM inhibition. Moreover, we validated that APEX1 loss sensitizes cells to DNAPK inhibition. Additionally, we compared the synergistic effects of combining different DDR inhibitors and found that an ATM inhibitor plus a PARP inhibitor induced dramatic levels of cell death, probably through promoting apoptosis. Our results enhance the understanding of DDR pathways and will facilitate the use of DDR-targeting agents in cancer therapy.