Miracle-dz/UniFAR-FTUs huggingface dataset:
GDF11 promotes osteogenesis as opposed to MSTN, and follistatin, a MSTN/GDF11 inhibitor, increases muscle mass but weakens bone

Significance MSTN, a member of the TGF-β family, has been widely shown to suppress muscle growth, leading to an intense effort being directed at targeting MSTN to treat patients with muscle loss. GDF11 is another TGF-β family member closely related to MSTN, but its postnatal function is less clear. Using conditional knockout techniques, we show that GDF11 enhances bone mass in contrast to MSTN, emphasizing that MSTN/GDF11 inhibitors, such as FST, can induce adverse effects on bone through GDF11 inhibition. Because most MSTN inhibitors also inhibit GDF11 due to the high sequence similarity between MSTN and GDF11, our findings suggest that their opposing roles must be carefully considered when developing MSTN inhibitors for clinical applications. Growth and differentiation factor 11 (GDF11) and myostatin (MSTN) are closely related transforming growth factor β (TGF-β) family members, but their biological functions are quite distinct. While MSTN has been widely shown to inhibit muscle growth, GDF11 regulates skeletal patterning and organ development during embryogenesis. Postnatal functions of GDF11, however, remain less clear and controversial. Due to the perinatal lethality of Gdf11 null mice, previous studies used recombinant GDF11 protein to prove its postnatal function. However, recombinant GDF11 and MSTN proteins share nearly identical biochemical properties, and most GDF11-binding molecules have also been shown to bind MSTN, generating the possibility that the effects mediated by recombinant GDF11 protein actually reproduce the endogenous functions of MSTN. To clarify the endogenous functions of GDF11, here, we focus on genetic studies and show that Gdf11 null mice, despite significantly down-regulating Mstn expression, exhibit reduced bone mass through impaired osteoblast (OB) and chondrocyte (CH) maturations and increased osteoclastogenesis, while the opposite is observed in Mstn null mice that display enhanced bone mass. Mechanistically, Mstn deletion up-regulates Gdf11 expression, which activates bone morphogenetic protein (BMP) signaling pathway to enhance osteogenesis. Also, mice overexpressing follistatin (FST), a MSTN/GDF11 inhibitor, exhibit increased muscle mass accompanied by bone fractures, unlike Mstn null mice that display increased muscle mass without fractures, indicating that inhibition of GDF11 impairs bone strength. Together, our findings suggest that GDF11 promotes osteogenesis in contrast to MSTN, and these opposing roles of GDF11 and MSTN must be considered to avoid the detrimental effect of GDF11 inhibition when developing MSTN/GDF11 inhibitors for therapeutic purposes.
Polymorphisms of the MTHFR gene in mothers of children with trisomy 21 (Down syndrome) in a Polish population.

BACKGROUND Down syndrome (DS) is the most frequent cause of intellectual disability. In 95% of cases, it is caused by simple trisomy of chromosome 21 resulting from nondisjunction of chromosomes in meiotic division. Currently, the molecular and cellular mechanisms responsible for the phenomenon of nondisjunction are unknown. OBJECTIVES To investigate the incidence of 5 single-nucleotide polymorphisms (SNPs) of the MTHFR gene in a population of Polish mothers who had given birth to children with trisomy 21 in comparison with a control group of women with healthy offspring. MATERIAL AND METHODS The test material comprised venous blood collected from mothers who had given birth to a child with DS (study group, n = 130) as well as from women who had given birth to children without trisomy 21 (control group, n = 88). DNA was isolated using a kit manufactured by Qiagen. Amplification was carried out using a Qiagen Multiplex PCR Kit (Qiagen); genotyping was performed using SNaPshot Genotyping MasterMix (Applied Biosystems). RESULTS No statistically significant differences were observed in the frequency of genotypes between the examined groups in terms of the polymorphisms of the MTHFR gene. CONCLUSIONS In the Polish population studied, no relationship was found between the occurrence of particular genotypes of the MTHFR gene, i.e., 677CT, 1298AC, rs3737964, rs4846048, and rs1994798, in women and the birth of children with trisomy 21. The results contradict the validity of research on polymorphisms of the MTHFR gene as potential predisposing factors for the occurrence of trisomy 21 in children.
Reliability and Minimum Important Difference of Sputum Weight in Bronchiectasis

BACKGROUND: Despite the widespread use of sputum weight to assess the effect of airway clearance interventions, its psychometric properties have not been evaluated. The purpose of this ad hoc analysis was to determine the test-retest reliability of 24-h sputum weight in clinically stable individuals with bronchiectasis. This study also aimed to estimate the minimum important difference of 24-h sputum weight after an airway clearance session in subjects with bronchiectasis. METHODS: Sixty subjects were included in the 24-h test-retest cohort, 42 of whom were part of the airway clearance cohort. For the 24-h test-retest cohort, spontaneously expectorated sputum was collected over 24 h on 2 different days without any airway clearance interventions. For the airway clearance cohort, sputum expectoration was also collected during 3 airway clearance sessions and over the 24 h following these interventions. Intraclass correlation coefficient (ICC3,1) and Bland-Altman analysis were used to assess reliability. The minimum important difference was calculated using distribution-based and anchor-based methods, with cough impact as assessed with the Leicester Cough Questionnaire and the global rating of change as anchors. RESULTS: The reliability was acceptable (ICC3,1 = 0.75) for sputum weight over 24 h without any intervention. The agreement level was wide, particularly for high levels of sputum expectoration. The minimum important difference of the sputum collected in the 24 h after the intervention from baseline was −6.4 g (about −17%), determined using distribution-based methods. There was no correlation between sputum weight and the anchors, thus the anchor-based methodology could not be used. CONCLUSIONS: Multiple measurements should be considered to increase the agreement when sputum weight is used as an outcome measure for short periods in people with bronchiectasis. A reduction of 6.4 g (or 17% from baseline) in sputum collected during the 24 h after the airway clearance intervention may be considered the minimum important difference in people with bronchiectasis. (ClinicalTrials.gov registration NCT02392663; NCT01854788; NCT02614300.)
Evidence that Criegee intermediates drive autoxidation in unsaturated lipids

Significance Autoxidation leads to the slow persistent destruction of organic molecules causing oxidative stress and associated disease. The prevailing autoxidation mechanism of unsaturated lipids involves chain reactions initiated and propagated by H-atom abstraction, mediated by peroxy radicals and other reactive oxygen species. Here we report experimental evidence for an autoxidation mechanism initiated by OH, which is unanticipated and proceeds by OH addition followed by pathways involving Criegee intermediates (CIs). Although CIs are routinely encountered in atmospheric and synthetic organic chemistry, their role in autoxidation is unexpected. Our results suggest that in all likelihood these exotic species play a much more prominent and general role in the chemistry of cells, food, petrochemicals, and the environment beyond what is currently believed. Autoxidation is an autocatalytic free-radical chain reaction responsible for the oxidative destruction of organic molecules in biological cells, foods, plastics, petrochemicals, fuels, and the environment. In cellular membranes, lipid autoxidation (peroxidation) is linked with oxidative stress, age-related diseases, and cancers. The established mechanism of autoxidation proceeds via H-atom abstraction through a cyclic network of peroxy–hydroperoxide-mediated free-radical chain reactions. For a series of model unsaturated lipids, we present evidence for an autoxidation mechanism, initiated by hydroxyl radical (OH) addition to C=C bonds and propagated by chain reactions involving Criegee intermediates (CIs). This mechanism leads to unexpectedly rapid autoxidation even in the presence of water, implying that as reactive intermediates, CI could play a much more prominent role in chemistries beyond the atmosphere.
Targeting Melanoma Hypoxia with the Food-Grade Lactic Acid Bacterium Lactococcus Lactis

Melanoma is the most aggressive form of skin cancer. Hypoxia is a feature of the tumor microenvironment that reduces efficacy of immuno- and chemotherapies, resulting in poor clinical outcomes. Lactococcus lactis is a facultative anaerobic gram-positive lactic acid bacterium (LAB) that is Generally Recognized as Safe (GRAS). Recently, the use of LAB as a delivery vehicle has emerged as an alternative strategy to deliver therapeutic molecules; therefore, we investigated whether L. lactis can target and localize within melanoma hypoxic niches. To simulate hypoxic conditions in vitro, melanoma cells A2058, A375 and MeWo were cultured in a chamber with a gas mixture of 5% CO2, 94% N2 and 1% O2. Among the cell lines tested, MeWo cells displayed greater survival rates when compared to A2058 and A375 cells. Co-cultures of L. lactis expressing GFP or mCherry and MeWo cells revealed that L. lactis efficiently express the transgenes under hypoxic conditions. Moreover, multispectral optoacoustic tomography (MSOT), and near infrared (NIR) imaging of tumor-bearing BALB/c mice revealed that the intravenous injection of either L. lactis expressing β-galactosidase (β-gal) or infrared fluorescent protein (IRFP713) results in the establishment of the recombinant bacteria within tumor hypoxic niches. Overall, our data suggest that L. lactis represents an alternative strategy to target and deliver therapeutic molecules into the tumor hypoxic microenvironment.
Live Semantic 3D Perception for Immersive Augmented Reality

Semantic understanding of 3D environments is critical for both the unmanned system and the human involved virtual/augmented reality (VR/AR) immersive experience. Spatially-sparse convolution, taking advantage of the intrinsic sparsity of 3D point cloud data, makes high resolution 3D convolutional neural networks tractable with state-of-the-art results on 3D semantic segmentation problems. However, the exhaustive computations limits the practical usage of semantic 3D perception for VR/AR applications in portable devices. In this paper, we identify that the efficiency bottleneck lies in the unorganized memory access of the sparse convolution steps, i.e., the points are stored independently based on a predefined dictionary, which is inefficient due to the limited memory bandwidth of parallel computing devices (GPU). With the insight that points are continuous as 2D surfaces in 3D space, a chunk-based sparse convolution scheme is proposed to reuse the neighboring points within each spatially organized chunk. An efficient multi-layer adaptive fusion module is further proposed for employing the spatial consistency cue of 3D data to further reduce the computational burden. Quantitative experiments on public datasets demonstrate that our approach works 11× faster than previous approaches with competitive accuracy. By implementing both semantic and geometric 3D reconstruction simultaneously on a portable tablet device, we demo a foundation platform for immersive AR applications.
Post-operative functional neurological symptom disorder after anesthesia

A rare manifestation during the post-anesthetic period may include the occurrence of functional neurological symptom disorder (FNSD). FNSD is described as neurological symptoms that are not consistently explained by neurological or medical conditions. We report a case series consisting of six patients who underwent a general anesthetic at a tertiary referral hospital and experienced FNSD in the immediate post-anesthetic period. Life-threatening causes were excluded based on benign physical exam findings and knowledge of past history. Five of six cases manifested with FNSD only in the immediate post-operative setting after exposure to anesthesia, and never otherwise experienced these symptoms during their normal daily lives. MEDLINE and Google Scholar were searched through October 2019 using a highly-sensitive search strategy and identified 38 published cases of post-anesthetic FNSD. Meta-analysis of pooled clinical data revealed that a significant proportion of patients were females (86%), reported a history of psychiatric illness (49%), reported a prior history of FNSD (53%), and underwent general anesthesia as the primary anesthetic (93%). The majority of patients were exposed to diagnostic studies (66% received radiographic tests and 52% received electroencephalogram) as well as pharmacologic therapy (57%). While no deaths occurred, many patients had unanticipated admission to the hospital (53%) or to the intensive care unit (25%). These data may help inform the anesthesia literature on presentation, risk factors, and treatment outcomes of FNSD in the context of anesthetic administration. We contemplate whether anesthetic agents may predispose a vulnerable brain to manifest with involuntary motor and sensory control seen in FNSD.
The Effect of Kinesiotape on Flexion-Extension of the Thoracolumbar Back in Horses at Trot

Simple Summary Weak back muscles and back pain are commonly seen in horses today; these problems are often caused by poor training techniques and lead to other problems such as poor performance, lameness, and pain. Veterinary treatment and/or rehabilitation is a necessity. Kinesiotaping is a commonly used treatment method in equine physiotherapy sand veterinary rehabilitation. The method theoretically stimulates the sensory pathways from the taped region that in turn modulates the neuromuscular activity and locomotor function to improve locomotion and/or range of motion (ROM). The aim of this study was to determine if kinesiotape applied to the abdominal muscles, with the intention of activating them as back flexors, would affect the ROM in flexion-extension (sagittal plane) of the thoracolumbar back of the trotting horse. Eight horses, aged 5–15 years, were included and were trotted on a straight line, 2 × 30 m, with and without kinesiotape. The differences between the two conditions were measured by an optical motion capture using reflective markers placed along the thoracolumbar spine. No statistical significance was shown between the two groups of horses; although some horses showed individual changes indicating that kinesiotape may have affected those horses. The evidence base for rehabilitation and training methods is essential, and more research is needed to understand whether there is any potential benefit of the kinesiotape. Abstract Kinesiotape theoretically stimulates mechanoreceptive and proprioceptive sensory pathways that in turn may modulate the neuromuscular activity and locomotor function, so alteration of activation, locomotion and/or range of motion (ROM) can be achieved. The aim of this study was to determine whether kinesiotape applied to the abdominal muscles would affect the ROM in flexion-extension (sagittal plane) in the thoracolumbar back of horses at trot. The study design was a paired experimental study, with convenient sample. Each horse was randomly placed in the control or the intervention group and then the order reversed. Eight horses trotted at their own preferred speed in hand on a straight line, 2 × 30 m. Optical motion capture was used to collect kinematic data. Paired t-tests, normality tests and 1-Sample Wilcoxon test were used to assess the effects of the kinesiotape. No statistical significance (p < 0.05) for changes in flexion-extension of the thoracolumbar back in trot was shown in this group of horses. Some changes were shown indicating individual movement strategies in response to stimuli from the kinesiotape. More research in this popular and clinically used method is needed to fully understand the reacting mechanisms in horses.
Understanding Public Attitudes to Hate: Developing and Testing a U.K. Version of the Hate Crime Beliefs Scale

Against the backdrop of an increase in reported hate crimes, we present the development of a U.K.-focussed instrument designed to evaluate the nature of public beliefs about hate crime, legislation, offenders and victims. In Study 1, 438 participants completed an Anglicized version of the Hate Crime Beliefs Scale (HCBS). Factor analyses revealed three subfactors: Denial (high scores represent a denial of hate crime severity and need for legislation), Compassion (high score reflect compassion toward victims and affected communities) and Sentencing (higher scores reflect more punitive attitudes). In Study 2 (N = 134) we show that scores on Denial are positively associated with those on Right-Wing Authoritarianism (RWA) and Social Dominance Orientation (SDO), ideologies known to be associated with prejudice. Compassion was negatively associated with these ideologies. Mediation analyses showed that Big Five personality traits Openness to Experience and Conscientiousness predicted Denial and Compassion via RWA, whereas Agreeableness and Openness predicted scores via SDO, consistent with a dual-process motivation model of hate crime beliefs. Results are discussed in terms of the nature of hate crime beliefs and the importance of understanding public attitudes which may support undesirable social norms and influence jury decision making in trials of hate related offenses.
Reforming teaching methods by integrating dental theory with clinical practice for dental students

Background Transitioning from theoretical medicine to clinical practice is both an important and difficult process in dental education. Thus, there is an urgent need for teaching methods that can improve the ability of dental students to integrate dental theory with clinical practice. Methods First, we conducted training for problem-based learning based on real clinical cases for dental students. The students were then assigned to dentist/patient roles to rehearse and perform simulated clinical scenarios. Finally, questionnaires, clinical patient care scores, and performance assessments were utilized to evaluate and compare the effectiveness of this training with that of traditional teaching methods. Results Students’ abilities to treat and communicate with patients markedly improved after using this reformed teaching method. Among the 30 enrolled students, 29 liked the method, found it time-efficient, and believed that it could help enhance their problem-solving confidence and interest in prosthodontics. They also believed that this teaching method could help them gain a good understanding of related theoretical material, generally thought that the reformed teaching method was more valuable than the traditional approach, and would like to introduce it to others. Conclusion After the reformed teaching method was implemented, the students not only achieved better scholastically, but also demonstrated greater accuracy in diagnosing the conditions of patients and formulating treatment plans. They were also more frequently acknowledged by patients, indicating that this method is effective for dental students.
Variables Associated with Missed Nursing Care in Alabama: A Cross-Sectional Analysis.

AIM To discover the extent of and factors associated with missed nursing care in Alabama. BACKGROUND Missed nursing care is a well-documented phenomenon. However, it has not been studied in US Southern states that consistently rank poorly in health outcomes, such as Alabama. METHODS The Perceived Implicit Rationing of Nursing Care Instrument was administered as part of the Alabama Hospital Staff Nurse Survey. Analyses were run on 950 surveys completed by inpatient registered nurses. RESULTS Overall missed nursing care scores vary significantly by gender, unit type, job satisfaction, and quality of nursing care. Overall missed nursing care scores are correlated with the work environment and number of patients assigned to each nurse. Unit type, quality of nursing care, and the work environment are important factors associated with missed nursing care. CONCLUSION The results of this study advance nursing science by adding to the growing body of knowledge surrounding missed nursing care. The results reveal opportunities where nurses may need support in their bedside practice. IMPLICATIONS FOR NURSING MANAGEMENT Nursing management must monitor the nursing work environment, periodically measure missed nursing care to assess for improvement opportunities, and watch for interventions that could decrease missed nursing care.
The Ashodaya PrEP project: Lessons and implications for scaling up PrEP from a community-led demonstration project among female sex workers in Mysore, India

ABSTRACT To inform PrEP roll out, Ashodaya Samithi, a sex workers’ collective, conducted a community-led prospective demonstration project among female sex workers in Mysore and Mandya, India. Following a community preparedness phase and pre-screening, participants were recruited for clinical screening and enrolment, provided PrEP as part of combination HIV prevention, and followed for 16 months. Adherence was measured by self-reported pill intake and by tenofovir blood level testing among a subset of participants. Of the 647 participants enrolled, 640 completed follow-up. Condom use remained stable and no HIV seroconversions occurred. Self-reported daily PrEP intake over the last month was 97.97% at the end of the study. Tenofovir blood levels >40 ng/mL (consistent with steady state dosing) were detected among 80% (n = 68/85) and 90.48% (n = 76/84) of participants at month 3 and 6, respectively. Our study holds important insights for rolling out PrEP in community settings as part of targeted HIV prevention interventions.
Qualification and Clinical Validation of an Immunodiagnostic Assay for Detecting 11 Additional Streptococcus pneumoniae Serotype–specific Polysaccharides in Human Urine

Abstract Background Identifying Streptococcus pneumoniae serotypes by urinary antigen detection (UAD) assay is the most sensitive way to evaluate the epidemiology of nonbacteremic community-acquired pneumonia (CAP). We first described a UAD assay to detect the S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F, covered by the licensed 13-valent S. pneumoniae conjugate vaccine. To assess the substantial remaining pneumococcal disease burden after introduction of several pneumococcal vaccines, a UAD-2 assay was developed to detect 11 additional serotypes (2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20, 22F, and 33F) in individuals with radiographically confirmed CAP. Methods The specificity of the UAD-2 assay was achieved by capturing pneumococcal polysaccharides with serotype-specific monoclonal antibodies, using Luminex technology. Assay qualification was used to assess accuracy, precision, and sample linearity. Serotype positivity was based on cutoffs determined by nonparametric statistical evaluation of urine samples from individuals without pneumococcal disease. The sensitivity and specificity of the positivity cutoffs were assessed in a clinical validation, using urine samples obtained from a large study that measured the proportion of radiographically confirmed CAP caused by S. pneumoniae serotypes in hospitalized US adults. Results The UAD-2 assay was shown to be specific and reproducible. Clinical validation demonstrated assay sensitivity and specificity of 92.2% and 95.9% against a reference standard of bacteremic pneumonia. In addition, the UAD-2 assay identified a S. pneumoniae serotype in 3.72% of nonbacteremic CAP cases obtained from hospitalized US adults. When combined with bacteremic CAP cases, the proportion of pneumonias with a UAD-2 serotype was 4.33%. Conclusions The qualified/clinically validated UAD-2 method has applicability in understanding the epidemiology of nonbacteremic S. pneumoniae CAP and for assessing the efficacy of future pneumococcal conjugate vaccines that are under development.