Miracle-dz/UniFAR-FTUs huggingface dataset:
OptiFlex: video-based animal pose estimation using deep learning enhanced by optical flow

Deep learning based animal pose estimation tools have greatly improved animal behaviour quantification. However, those tools all make predictions on individual video frames and do not account for variability of animal body shape in their model designs. Here, we introduce the first video-based animal pose estimation architecture, referred to as OptiFlex, which integrates a flexible base model to account for variability in animal body shape with an optical flow model to incorporate temporal context from nearby video frames. This approach can be combined with multi-view information, generating prediction enhancement using all four dimensions (3D space and time). To evaluate OptiFlex, we adopted datasets of four different lab animal species (mouse, fruit fly, zebrafish, and monkey) and proposed a more intuitive evaluation metric - percentage of correct key points (aPCK). Our evaluations show that OptiFlex provides the best prediction accuracy amongst current deep learning based tools, and that it can be readily applied to analyse a wide range of behaviours.
Revealing Cellular Heterogeneity and In Vitro Differentiation Trajectory of Cultured Human Endometrial Mesenchymal-like Stem Cells Using Single-cell RNA Sequencing

Endometrial mesenchymal-like stem cells (eMSCs) are adult stem cells contributing to endometrial regeneration. One set of perivascular markers (CD140b+CD146+) have been widely used to enrich eMSCs. Although eMSCs are easily accessible for regenerative medicine and have long been studied, their cellular heterogeneity and molecular program controlling their expansion and differentiation in vitro remains largely unclear. In this study, we applied 10X genomics single-cell RNA sequencing to eMSCs cultured in vitro after microbeading from 7 donors to investigate cellular heterogeneity in an unbiased manner. Corresponding clonogenic progenies of eMSCs after culture for 14 days were also sequenced to construct the in vitro differentiation trajectory of eMSCs. Transcriptomic expression based clustering revealed several subpopulations in eMSCs. Each subpopulation manifested distinct functional characteristics associated with immunomodulation, proliferation, extracellular matrix organization and cell differentiation. Pseudotime trajectory analysis on eMSCs and their differentiated progenies identified in vitro differentiation hierarchy of eMSCs. Further ligand-receptor pair analysis found that WNT signaling, NOTCH signaling, TGF-beta signaling and FGF signaling were important regulatory pathways for eMSC self-renewal and differentiation. By comparing eMSCs to Wharton’s Jelly MSCs and adipose-derived MSCs, we found these 3 kinds of MSCs expressed largely overlapping differentiation (CD) genes and highly variable genes. In summary, we reveal for the first time high molecular and cellular heterogeneity in cultured eMSCs, and identify the key signaling pathways that may be important for eMSC differentiation.
Coordinated Postnatal Maturation of Striatal Cholinergic Interneurons and Dopamine Release Dynamics in Mice

Dynamic changes in motor abilities and motivated behaviors occur during the juvenile and adolescent periods. The striatum is a subcortical nucleus critical to action selection, motor learning, and reward processing. Its tonically active cholinergic interneuron (ChI) is an integral regulator of the synaptic activity of other striatal neurons, as well as afferent axonal projections of midbrain dopamine (DA) neurons; however, little is known about its development. Here, we report that ChI spontaneous activity increases during postnatal development of male and female mice, concomitant with a decreased afterhyperpolarization (AHP). We characterized the postnatal development of four currents that contribute to the spontaneous firing rate of ChIs, including ISK, IA, Ih, and INaP. We demonstrated that the developmental increase in INaP drives increased ChI firing rates during the postnatal period and can be reversed by the INaP inhibitor, ranolazine. We next addressed whether immature cholinergic signaling may lead to functional differences in DA release during the juvenile period. In the adult striatum, nicotinic acetylcholine receptors (nAChRs) prevent linear summation of DA release in response to trains of high-frequency stimuli. We show that, in contrast, during the second postnatal week, DA release linearly sums with trains of high-frequency stimuli. Consistently, nAChR antagonists exert little effect on dopamine release at postnatal day (P)10, but enhance the summation of evoked DA release in mice older than postnatal day P28. Together, these results reveal that postnatal maturation of ChI activity is due primarily to enhanced INaP and identify an interaction between developing cholinergic signaling and DA neurotransmission in the juvenile striatum. SIGNIFICANCE STATEMENT Motor skills and motivated behavior develop rapidly in juvenile rodents. Recent work has highlighted processes that contribute to the postnatal maturation of striatal principal neurons during development. The functional development of the striatal cholinergic interneuron (ChI), however, has been unexplored. In this study, we tracked the ontogeny of ChI activity and cellular morphology, as well as the developmental trajectory of specific conductances that contribute to the activity of these cells. We further report a link between cholinergic signaling and dopamine (DA) release, revealing a change in the frequency-dependence of DA release during the early postnatal period that is mediated by cholinergic signaling. This study provides evidence that striatal microcircuits are dynamic during the postnatal period and that they undergo coordinated maturation.
EXPRESSION OF Mycobacterium tuberculosis RpsA IN Mycobacterium smegmatis INCREASES SUSCEPTIBILITY TO PYRAZINAMIDE

Pyrazinamide (PZA) is one of the most important drugs used in combined antituberculous therapy. After the drug enters Mycobacterium tuberculosis it is hydrolyzed by pyrazinamidase (PZAse) to the bactericidal molecule pyrazinoic acid (POA). Ribosomal protein S1 (RpsA) was recently identified as a possible target of PZA based on its binding activity to POA and capacity to inhibit trans-translation. However, its role is not completely understood. It has been proposed that Mycobacterium smegmatis RpsA is not capable of binding POA, unlike M. tuberculosis RpsA. This may be due to the different amino acid sequence in the carboxy-terminal region of the two molecules: in M. smegmatis RpsA it is much closer to the sites that may interact with POA than in M. tuberculosis RpsA. These differences could be contributing, along with the presence of highly active POA efflux, to the natural resistance to PZA in M. smegmatis. To further understand the mechanisms of action of PZA and the role of RpsA in PZA susceptibility, we evaluated the effect of complementing M. tuberculosis RpsA expression in M. smegmatis using pNIT mycobacterial non-integrative expression vector and then performed a PZA susceptibility test determining the minimum inhibitory concentration (MIC) of PZA. It was expected that chimeric ribosomes comprising M. tuberculosis RpsA may be present and may affect PZA susceptibility. Our results showed a reduction in PZA MIC in M. smegmatis complemented with overexpressed M. tuberculosis RpsA compared to non-overexpressed M. smegmatis (468 µg/mL and >7500 µg/mL respectively).
Borrelia afzelii does not suppress the development of anti-tick immunity in bank voles

Vector-borne pathogens manipulate their vertebrate hosts to enhance their transmission to arthropod vectors. The ability of vertebrate hosts to develop acquired immunity against arthropod vectors represents an existential threat for both the vector and the pathogen. The purpose of the study was to test whether the tick-borne spirochete bacterium Borrelia afzelii could suppress the development of acquired immunity to its tick vector Ixodes ricinus in the bank vole Myodes glareolus, which is an important host for both the tick and the pathogen. We created a group of B. afzelii-infected bank voles and an uninfected control group by exposing lab-reared animals to infected or uninfected ticks. At 1, 2, and 3 months post-infection, all bank voles were infested with larval I. ricinus ticks. The bank voles developed a strong antibody response against tick salivary gland extract proteins. This anti-tick immunity had negative effects on tick fitness traits including engorged larval weight, unfed nymphal weight, larva-to-nymph molting time and larva-to-nymph molting success. Infection with B. afzelii did not suppress the development of acquired immunity against I. ricinus ticks. The development of anti-tick immunity was strongly correlated with a dramatic temporal decline in both the bacterial abundance in the host ear tissues and the host-tick transmission success of B. afzelii. Our study suggests that the development of anti-tick immunity in bank voles has important consequences for the density of infected ticks and the risk of Lyme borreliosis. Importance Many pathogens enhance their persistence and transmission by suppressing the immune system of their host. We used an experimental infection approach to test whether the Lyme disease pathogen, Borrelia afzelii, could suppress the development of acquired immunity against its tick vector (Ixodes ricinus) in the bank vole (Myodes glareolus), but found no evidence for this phenomenon. Uninfected and B. afzelii-infected bank voles both developed a strong IgG antibody response against tick salivary gland extract following repeated infestations with I. ricinus ticks. The development of anti-tick immunity was negatively correlated with the abundance of B. afzelii in ear tissue biopsies and with host-to-tick transmission to I. ricinus ticks. Our study suggests that anti-tick immunity in the bank vole reduces the prevalence of this important tick-borne pathogen.
Post-synaptic morphology of mouse neuromuscular junctions is linked to muscle fibre type

The neuromuscular junction (NMJ) is the highly specialised peripheral synapse formed between lower motor neuron terminals and muscle fibres. Post-synaptic acetylcholine receptors (AChRs), which are found in high density in the muscle membrane, bind to acetylcholine released into the synaptic cleft of the NMJ, ultimately facilitating the conversion of motor action potentials to muscle contractions. NMJs have been studied for many years as a general model for synapse formation, development and function, and are known to be early sites of pathological changes in many neuromuscular diseases. However, information is limited on the diversity of NMJs in different muscles, whether muscle fibre type impacts NMJ morphology and growth, and the relevance of these parameters to neuropathology. Here, this crucial gap was addressed using a robust and standardised semi-automated workflow called NMJ-morph to quantify features of pre- and post-synaptic NMJ architecture in an unbiased manner. Five wholemount muscles from wild-type mice were dissected and compared at immature (post-natal day, P7) and early adult (P31-32) timepoints. Post-synaptic AChR morphology was found to be more variable between muscles than that of the motor neuron terminal and there were greater differences in the developing NMJ than at the mature synapse. Post-synaptic architecture, but not neuronal morphology or post-natal synapse growth, correlates with fibre type and is largely independent of muscle fibre diameter. Counter to previous observations, this study indicates that smaller NMJs tend to innervate muscles with higher proportions of fast twitch fibres and that NMJ growth rate is not conserved across all muscles. Furthermore, healthy pre- and post-synaptic NMJ morphological parameters were collected for five anatomically and functionally distinct mouse muscles, generating reference data that will be useful for the future assessment of neuromuscular disease models. Graphical Abstract
Pseudomonas aeruginosa Aggregate Formation in an Alginate Bead Model System Exhibits In Vivo-Like Characteristics

ABSTRACT Alginate beads represent a simple and highly reproducible in vitro model system for diffusion-limited bacterial growth. In this study, alginate beads were inoculated with Pseudomonas aeruginosa and followed for up to 72 h. Confocal microscopy revealed that P. aeruginosa formed dense clusters similar in size to in vivo aggregates observed ex vivo in cystic fibrosis lungs and chronic wounds. Bacterial aggregates primarily grew in the bead periphery and decreased in size and abundance toward the center of the bead. Microsensor measurements showed that the O2 concentration decreased rapidly and reached anoxia ∼100 μm below the alginate bead surface. This gradient was relieved in beads supplemented with NO3− as an alternative electron acceptor allowing for deeper growth into the beads. A comparison of gene expression profiles between planktonic and alginate-encapsulated P. aeruginosa confirmed that the bacteria experienced hypoxic and anoxic growth conditions. Furthermore, alginate-encapsulated P. aeruginosa exhibited a lower respiration rate than the planktonic counterpart and showed a high tolerance toward antibiotics. The inoculation and growth of P. aeruginosa in alginate beads represent a simple and flexible in vivo-like biofilm model system, wherein bacterial growth exhibits central features of in vivo biofilms. This was observed by the formation of small cell aggregates in a secondary matrix with O2-limited growth, which was alleviated by the addition of NO3− as an alternative electron acceptor, and by reduced respiration rates, as well as an enhanced tolerance to antibiotic treatment. IMPORTANCE Pseudomonas aeruginosa has been studied intensively for decades due to its involvement in chronic infections, such as cystic fibrosis and chronic wounds, where it forms biofilms. Much research has been dedicated to biofilm formation on surfaces; however, in chronic infections, most biofilms form small aggregates of cells not attached to a surface, but embedded in host material. In this study, bacteria were encapsulated in small alginate beads and formed aggregates similar to what is observed in chronic bacterial infections. Our findings show that aggregates are exposed to steep oxygen gradients, with zones of oxygen depletion, and that nitrate may serve as an alternative to oxygen, enabling growth in oxygen-depleted zones. This is important, as slow growth under low-oxygen conditions may render the bacteria tolerant toward antibiotics. This model provides an alternative to surface biofilm models and adds to the comprehension that biofilms do not depend on a surface for formation.
Preferences for Hearing Aid Attributes Among People with Moderate or Greater Hearing Loss in Rural China: A Discrete Choice Experiment

Purpose Hearing loss has not received sufficient attention, especially in low- and middle-income countries where more than 80% of the people with hearing loss reside. Little is known about the preference for hearing aids among people with hearing loss in developing countries. The aim of this study is to elicit the preferences for hearing aid attributes among rural Chinese adults with moderate or greater hearing loss and examine how preferences vary across different individual socioeconomic characteristics. Patients and Methods We interviewed 125 adults in two rural counties in Shandong province in China. A discrete choice experiment (DCE) with eight attributes, comprising out-of-pocket (OOP) costs, hearing aid style, effective in quiet settings and noisy settings, feedback (whistling), connectivity, water/sweat resistance and battery life, were employed to examine participants’ preference for hearing aids. Mixed logit models were used for the statistical analyses. Results While OOP costs, effectiveness in quiet settings, water/sweat resistance and battery life were significantly associated with choosing a hearing aid, rural Chinese adults with moderate or greater hearing loss valued effectiveness in noisy settings above other attributes of hearing aids, followed closely by lack of feedback. The preference of the attributes of OOP costs, in the canal hearing aids, effectiveness in noisy settings, connectivity and battery life varied across individual socioeconomic characteristics including sex, marriage, employment, income and education level. Conclusion Our study supported the view that the development of noise suppression and feedback cancellation systems remained the main challenge for the hearing aid industry. Since OOP costs were also associated with choosing a hearing aid, the policy advice is to improve reimbursements from insurance schemes and/or reduce the costs of hearing aids.
Understanding and Remediating Social-Cognitive Dysfunctions in Patients with Serious Mental Illness Using Relational Frame Theory

Impairments in social cognition and perspective-taking play an important role in the psychopathology and social functioning of individuals with social anxiety, autism, or schizophrenia-spectrum disorders, among other clinical presentations. Perspective-taking has mostly been studied using the concept of Theory of Mind (ToM), which describes the sequential development of these skills in young children, as well as clinical populations experiencing perspective-taking difficulties. Several studies mention positive results of ToM based training programs; however, the precise processes involved in the achievement of these improvements are difficult to determine. Relational Frame Theory (RFT) is a modern behavioral account of complex cognitive functions, and is argued to provide a more precise approach to the assessment and training of perspective-taking, among other relational skills. Results of RFT-based studies of perspective-taking in developmental and clinical settings are discussed. The development of training methods targeting perspective-taking deficits from an RFT point of view appears to provide promising applications for the enhancement of current treatments of people with social-cognitive dysfunctions.
Assessment of Venographic Abnormalities during Replacement of Dysfunctional Tunneled Hemodialysis Catheters and Outcome of Endovascular Salvage Techniques

Although the native arteriovenous fistula (AVF) is recommended as the first choice dialysis access for most patients with better outcomes (1-3), the usage of hemodialysis catheter is unavoidable in some patients; these include using catheter as a bridge before maturation of AVF or waiting for renal transplantation, and in elderly and diabetic patients having unsuitable vessels for AVF. The National Kidney Foundation-Kidney Disease Outcome Quality Initiative issued Clinical Practice Guidelines for Vascular Access in 2006 recommend that less than 10% of prevalent hemodialysis patients should be maintained on central catheters as their permanent dialysis access. However, catheter usage in prevalent hemodialysis was reported from 2% to 45% among 20 countries in 2013, in which most countries except Japan reported more than 10% usage of catheter as prevalent hemodialysis access (4). There are several complications associated with tunneled heAssessment of Venographic Abnormalities during Replacement of Dysfunctional Tunneled Hemodialysis Catheters and Outcome of Endovascular Salvage Techniques 기능부전 터널식 투석용 도관의 교체 시 시행한 정맥조영술 결과의 분석과 혈관 내 치료 기술의 결과
Reproductive biology of the pearl oyster, Pinctada radiata (Mollusca: Pteriidae), in northern Kerkennah Island (Gulf of Gabes).

La reproduction de l'huitre perliere Pinctada radiata (Mollusca: Pteriidae) dans l'Ile de Kerkennah (Golfe de Gabes). Le cycle de reproduction de l'huitre perliere, Pinctada radiata, dans l'Ile de Kerkennah (golfe de Gabes) a ete etudie mensuellement entre janvier et decembre 2007. Le total des echantillons presente un sexe ratio desequilibre. Cependant, si les mâles predominent dans les petites tailles (hauteur de la coquille SH 65 mm). Un phenomene d'hermaphrodisme protandrique a ete observe a une taille comprise entre 41 et 75 mm SL. Les mâles deviennent matures a partir de la taille 23 mm SL et la taille L 50% est estimee a 28 mm SL. Les femelles sont matures a partir de la taille de 33 mm SL. Leur L 50% est estimee a 38 mm SL pour une taille superieure a 33 mm SL. L'observation macro et microscopique des gonades a montre que l'huitre perliere P radiata est une espece qui se reproduit presque toute l'annee. En effet, le repos sexuel n'est accuse que de fin decembre a debut fevrier et le cycle de reproduction s'etale sur onze mois avec deux pics prononces en ete et en automne.
Knowledge, attitude and barriers to hands hygiene practice: a study of Kampala International University undergraduate medical students

Background: Hand hygiene is the simplest method that is effective in terms of cost with its importance in preventing transmission of microorganisms and infections. Though this being the case, it has been found to be clumsy and faulty in most healthcare settings. What has been done on assessing the medical students’ knowledge, attitude and practice and comparisons of these factors between the medical disciplines is not exhaustive.Methods: A descriptive cross sectional study was conducted among the undergraduate medical students to assess the knowledge in medical students, their attitude and barriers to hand hygiene practice where simple random sampling technique was applied to obtain a sample size. A questionnaire on alcohol-based hand rubs and WHO recommendations on hand hygiene was used for data collection.Results: A total of 392 respondents were interviewed. The respondents comprised of 232 males and 160 females. The overall mean score for individual knowledge was 49.4%. The study revealed that more than half of the respondents 203 had poor knowledge on hand hygiene while 43.1% had average and 5.1% were consider to have good knowledge. Most of the respondents had good attitude on hand hygiene on most of the aspects that were assessed. Several barriers to effective hand hygiene practice were highlighted by the respondent.Conclusions: The study concluded that more sensitization was needed to increase awareness and knowledge of the practice in medical students which could be achieved by adding a course on hand hygiene practice to the undergraduate medical students’ curriculum amongst others.
Clinical Aspects of Periungual Desquamation in Kawasaki Disease

Objectives: To assess the relationship between coronary artery changes and periungual desquamation in Kawasaki disease (KD) and non - KD patients. Methods: This retrospective descriptive study was conducted through a review of records of children with KD from March 2011 to February 2016. We also analyzed non - KD subjects with desquamation. Results: Among 329 patients with KD, 177 (53.8%) had periungual desquamation. Subjects with desquamation had longer duration of fever(6.75 ± 2.43vs. 5.63 ± 1.78days),morefrequenterythemaandedemaof hands/feet(72.9% vs. 51.9%),andmorefrequentrash (94.4% vs. 74.3%)thansubjectswithoutdesquamation. Theyalsohadahigherplateletcount(470420 ± 127163vs. 351240 ± 105836,P =0.042)andhigherlevelsof aspartateaminotransferase(AST;91.58 ± 62.89vs. 55.5 ± 44.72IU/L,P=0.031),alanineaminotransferase (ALT; 105.39 ± 71.54 vs. 76.7 ± 91.25 IU/L, P = 0.029), and pro - brain natriuretic peptide (BNP; 1738.24 ± 584.26 vs. 1034.65 ± 754.25 pg/mL,P=0.042). Therewasnodiﬀerencebetweenthetwogroupsindevelopmentof coronaryarterychanges. Wealsoanalyzed47 non - KD subjects with desquamation. These patients had fewer clinical signs (87% had one sign of KD) and shorter fever duration according to parents’ reported history, and had a lower platelet count, AST, ALT, and BNP than patients with KD. These patients had no coronary artery lesions. Conclusions: Presenceof periungualdesquamationisnothelpfulforanearlydiagnosisof KDandisnotanindependentpredictor of coronary artery changes in patients with or without KD.