Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Testing for Mycoplasma genitalium in the United States: Results from the AMES Prospective Multicenter Clinical Study

A prospective multicenter clinical study involving subjects from 21 sites across the United States was conducted to validate the performance of a new in vitro diagnostic nucleic acid amplification test (NAAT) for the detection of Mycoplasma genitalium. ABSTRACT A prospective multicenter clinical study involving subjects from 21 sites across the United States was conducted to validate the performance of a new in vitro diagnostic nucleic acid amplification test (NAAT) for the detection of Mycoplasma genitalium. Seven urogenital specimen types (n = 11,556) obtained from 1,778 females, aged 15 to 74 years, and 1,583 males, aged 16 to 82 years, were tested with the Aptima Mycoplasma genitalium assay, an investigational transcription-mediated amplification (TMA) NAAT for the detection of M. genitalium 16S rRNA. Infected status for enrolled subjects was established using results obtained from testing either self-collected vaginal swab or clinician-collected male urethral swab specimens with a composite reference method consisting of three transcription-mediated amplification NAATs targeting unique regions of M. genitalium 16S or 23S rRNA. M. genitalium prevalence was 10.2% in females and 10.6% in males; prevalence was high in both symptomatic and asymptomatic subjects for both sexes. Compared to the subject infected status standard, the investigational test had sensitivity and specificity estimates, respectively, of 98.9% and 98.5% for subject-collected vaginal swabs, 92.0% and 98.0% for clinician-collected vaginal swabs, 81.5% and 98.3% for endocervical swabs, 77.8% and 99.0% for female urine, and 98.2% and 99.6% for male urethral swabs, 88.4% and 97.8% for self-collected penile meatal swabs, and 90.9% and 99.4% for male urine specimens. For all seven specimen types, within-specimen positive and negative agreements between the investigational test and the composite reference standard ranged from 94.2% to 98.3% and from 98.5 to 99.9%, respectively. These results provide clinical efficacy evidence for the first FDA-cleared NAAT for M. genitalium detection in the United States.
Heteroaryl phosphonates as non-covalent inhibitors of both serine and metallo-carbapenemases.

Gram-negative pathogens expressing serine β-lactamases (SBLs) and metallo-β-lactamases (MBLs), especially those with carbapenemase activity, threaten the clinical utility of almost all β-lactam antibiotics. Here we describe the discovery of a heteroaryl phosphonate scaffold that exhibits non-covalent cross-class inhibition of representative carbapenemases, specifically the SBL KPC-2 and the MBLs NDM-1 and VIM-2. The most potent lead, compound 16, exhibited low nM to low µM inhibition of KPC-2, NDM-1, and VIM-2. Compound 16 potentiated imipenem efficacy against resistant clinical and laboratory bacterial strains expressing carbapenemases, while showing some cytotoxicity toward human HEK293T cells only at concentrations above 100 µg/mL. Complex structures with KPC-2, NDM-1, and VIM-2 demonstrate how these inhibitors achieve high binding affinity to both enzyme classes. These findings provide a structurally and mechanistically new scaffold for drug discovery targeting multidrug resistant Gram-negative pathogens, and more generally highlight the active site features of carbapenemases that can be leveraged for lead discovery.
Differential requirements for FcγR engagement by protective antibodies against Ebola virus

Significance In recent years, systematic research efforts have led to the preclinical development of antibody-based therapeutics that confer potent antiviral activity against Ebola virus (EBOV). Immunoglobulin G (IgG) antibodies against virus pathogens depend on their interaction with specialized leukocyte receptors (Fcγ receptors [FcγRs]) to confer antiviral functions. FcγR engagement by IgG antibodies induces leukocyte activation and mediates pleiotropic effector functions to control virus infection. Here, we examined the contribution of FcγR engagement to the antibody-mediated protection against EBOV infection in unique animal models of EBOV infection. Our findings suggest that anti-EBOV antibodies exhibit differential requirements for FcγR engagement to confer protection from EBOV infection, guiding the design of optimized antibody-based therapeutics with maximal protective efficacy. Ebola virus (EBOV) continues to pose significant threats to global public health, requiring ongoing development of multiple strategies for disease control. To date, numerous monoclonal antibodies (mAbs) that target the EBOV glycoprotein (GP) have demonstrated potent protective activity in animal disease models and are thus promising candidates for the control of EBOV. However, recent work in a variety of virus diseases has highlighted the importance of coupling Fab neutralization with Fc effector activity for effective antibody-mediated protection. To determine the contribution of Fc effector activity to the protective function of mAbs to EBOV GP, we selected anti-GP mAbs targeting representative, protective epitopes and characterized their Fc receptor (FcγR) dependence in vivo in FcγR humanized mouse challenge models of EBOV disease. In contrast to previous studies, we find that anti-GP mAbs exhibited differential requirements for FcγR engagement in mediating their protective activity independent of their distance from the viral membrane. Anti-GP mAbs targeting membrane proximal epitopes or the GP mucin domain do not rely on Fc–FcγR interactions to confer activity, whereas antibodies against the GP chalice bowl and the fusion loop require FcγR engagement for optimal in vivo antiviral activity. This complexity of antibody-mediated protection from EBOV disease highlights the structural constraints of FcγR binding for specific viral epitopes and has important implications for the development of mAb-based immunotherapeutics with optimal potency and efficacy.
Investigating the Prevalence and Predictors of Injury Occurrence in Competitive Hip Hop Dancers: Prospective Analysis

Hip hop is a popular form of competitive and recreational sport worldwide, but studies rarely investigate injury prevalence and factors associated with injury occurrence in this sport. This study aimed to prospectively examine injury occurrence in hip hop dancers in a three-month period and to evaluate potential predictors of injury occurrence in hip hop dancers. The participants were 129 competitive hip hop dancers (114 females, 17.95 ± 4.15 years of age). Study predictors were obtained at study baseline and included sociodemographic factors, sport-related factors, previous injury status, anthropometric and body build indices (body height, mass, body mass index, and body composition variables), and dynamic balance performance (obtained by the Star Excursion Balance Test—SEBT). The outcome was injury occurrence, which was prospectively observed once a week by the Oslo Sports Trauma Research Center Overuse Injury Questionnaire (OSTRC). During the course of the study, 101 injuries occurred, equating to an annual injury incidence of 312%. On average, each dancer suffered 0.78 injuries (95% Confidence Interval (95% CI): 0.61–0.97) across a study period of three months (0.76 (95% CI: 0.60–0.95) and 0.93 (95% CI: 0.75–1.13), in females and males, respectively; Mann Whitney Z-value: 0.68, p = 0.52). Seventeen percent of dancers suffered multiple injuries, and 49% of all injuries were time-loss injuries. The knee was the most frequently injured body location (42% of all reported injuries), followed by the back region (32%) and the ankle (15%). Previous injury was a strong predictor of injury occurrence (Odds Ratio: 3.76, 95% CI: 1.87–4.59). Lower injury risk was evidenced among those participants who achieved better scores on several SEBT variables, irrespective of gender and previous injury status; with no significant influence of anthropometric and body build variables on injury occurrence. This study highlighted a high injury rate in hip hop dancers. Dancers and coaches should be informed about the certain protective effects of dynamic balance on the prevention of musculoskeletal injury in hip hop in order to assure safe and effective practices. The usage of SEBT as a convenient and cheap testing procedure is encouraged in other dance disciplines.
Target-Derived Neurotrophic Factor Deprivation Puts Retinal Ganglion Cells on Death Row: Cold Hard Evidence and Caveats

Glaucoma and other optic neuropathies are characterized by axonal transport deficits. Axonal cargo travels back and forth between the soma and the axon terminus, a mechanism ensuring homeostasis and the viability of a neuron. An example of vital molecules in the axonal cargo are neurotrophic factors (NTFs). Hindered retrograde transport can cause a scarcity of those factors in the retina, which in turn can tilt the fate of retinal ganglion cells (RGCs) towards apoptosis. This postulation is one of the most widely recognized theories to explain RGC death in the disease progression of glaucoma and is known as the NTF deprivation theory. For several decades, research has been focused on the use of NTFs as a novel neuroprotective glaucoma treatment. Until now, results in animal models have been promising, but translation to the clinic has been highly disappointing. Are we lacking important knowledge to lever NTF therapies towards the therapeutic armamentarium? Or did we get the wrong end of the stick regarding the NTF deprivation theory? In this review, we will tackle the existing evidence and caveats advocating for and against the target-derived NTF deprivation theory in glaucoma, whilst digging into associated therapy efforts.
"Side Effects" Observed within ~1-90 Days after Cannabis Onset: Epidemiological Estimates for the United States, 2004-2014.

BACKGROUND AND OBJECTIVES Among newly incident cannabis users, fewer than 4% develop cannabis dependence syndromes within 12 to 24 months, but earlier cannabis side effect (SE) incidence and early syndrome formation remains understudied. We estimate cannabis SE incidence within ~1 to 90 days after first use, and estimate odds ratios (OR) for SE pairs to quantify potential syndromic "running together. " METHODS Each year, 2004 to 2014, the US populations under study consisted of noninstitutionalized civilian residents age 12-years-and-older, sampled for National Surveys on Drug Use and Health. Computerized self-interviews identified 3710 newly incident cannabis users and asked about SEs. Analysis-weighted year-specific SE and SE-SE pair incidence proportions were estimated. Analysis-weighted odds ratio (OR) estimates quantify SE-SE co-occurrences, judged as "greater than chance" when lower bounds (LB) of 95% confidence intervals (CIs) exceed 1.0. Meta-analysis is used to summarize and to check reproducibility. RESULTS Illustrative of estimates on 17 SEs, roughly 1/2 of cannabis initiates experienced "wanting or trying to cut down or stop using," but 80% of these cut back, such that less than 7% had symptom-like inability to cut back or stop. An estimated 25% had "spent a lot of time getting or using cannabis. " The SE-SE paired estimate is 2.8% for those who had spent a lot of time and also had wanted/tried to cut down (95% CI = 2.0, 4.0). OR estimation suggests no syndromic co-occurrence of this SE-SE pair (OR = 0.9; 95% CI = 0.5, 1.6). In contrast, "cannabis causing serious problems at home/work/school" and "continuing to use despite physical problems" were more rare, but had strong SE-SE co-occurrence (OR = 14.8, LB = 2.4). For 78 of 136 possible SE-SE pairs, meta-analysis LB estimates exceeded the 1.0 threshold. CONCLUSION AND SCIENTIFIC SIGNIFICANCE In these US community samples of cannabis initiates studied soon after first use, the vast majority were free of individual SE experiences counted toward Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition cannabis use disorder diagnoses. For a minority, SE-SE pairs might indicate syndrome formation. These epidemiological meta-analysis estimates might find use in refinement of clinical practice guidelines for fast effective syndrome screens when primary care patients are seen soon after cannabis onset, akin to clinical screening guides designed for newly incident drinkers (Am J Addict 2019;00:1-9).
Minimum Number of MRI Ultrasound Fusion Targeted Biopsy Cores Needed for Prostate Cancer Detection: Multivariable Retrospective Lesion-Based Analyses of Patients Treated with Radical Prostatectomy.

OBJECTIVE To analyze the number of mpMRI targeted biopsy (TBx) cores per lesion needed for PCa detection in patients treated with radical prostatectomy (RP). MATERIAL AND METHODS Analyses focus on TBx of PCa suspicious MRI lesions (PI-RADS ≥3) with consecutive RP. Descriptive statistics included frequencies/proportions and interquartile ranges (IQR). Multivariable logistic regression analyses (MVA) on per lesion level predicted the number of TBx with PCa. RESULTS In the total cohort of 771 RP patients, 437 (57%) and 334 (43%) were either systematic transrectal ultrasound-guided biopsy (SBx) naïve or had ≥1 prior negative SBx. A maximum PI-RADS score of 3, 4 and 5 was present in 67 (8.7%), 567 (74%) and 137 (18%) patients. A total of 1,459 of tumor suspicious mpMRI lesions PCa were identified for analyses. PCa detection was made based on initial, second, third or ≥ fourth TBx in 79%, 92%, 98% and 100%, respectively. PCa detection on first TBx core only increased with higher PI-RADS score (3, 4 and 5) from 67%, 79% and 87%. Number of prior negative SBx and pathological tumor stage emerged as independent predictors in MVA addressing the need of ≥2 TBx cores necessary for csPCa detection. CONCLUSIONS RP based analyses demonstrate that the majority of cancers can be detected by two TBx only and in minority of cases three and more TBx are necessary. Such findings might indicate that TBx procedure and related technology have improved, especially in intermediate/high-risk PCa patients.
Inactivation of the pgmA Gene in Streptococcus mutans Significantly Decreases Biofilm-Associated Antimicrobial Tolerance

Screening of a Streptococcus mutans mutant library indicated that pgmA mutants displayed a reduced biofilm-associated tolerance toward gentamicin. The biofilms formed by the S. mutans pgmA mutant also displayed decreased tolerance towards linezolid and vancomycin compared to wild-type biofilms. On the contrary, the resistance of planktonic S. mutans pgmA cells to gentamycin, linezolid, and vancomycin was more similar to wild-type levels. Investigations of biofilms grown in microtiter trays and on submerged glass slides showed that pgmA mutants formed roughly the same amount of biofilm as the wild type, indicating that the reduced antimicrobial tolerance of these mutants is not due to diminished biofilm formation. The pgmA gene product is known to be involved in the synthesis of precursors for cell wall components such as teichoic acids and membrane glycolipids. Accordingly, the S. mutans pgmA mutant showed increased sensitivity to Congo Red, indicating that it has impaired cell wall integrity. A changed cell wall composition of the S. mutans pgmA mutant may play a role in the increased sensitivity of S. mutans pgmA biofilms toward antibiotics.
Joint Audio-Ultrasound Food Recognition for Noisy Environments

Continuous recognition of ingested foods without user intervention is very useful for the pre-screening of obesity and diet-related disease. An automatic food recognition method that combines the two modalities of audio and ultrasonic signals (US) is proposed in this study. Under a noise-free environment, classification accuracy of an audio-only recognizer is generally higher than that of US-only recognizers, but the performance of US recognizers is unaffected by acoustic noise levels. In the recognition system presented herein, the likelihood score of the audio-US feature was given by a linear combination of class-conditional observation log-likelihoods for two classifiers, using the appropriate weights. We developed a weighting process adaptive to signal-to-noise ratios (SNRs). The main objective here involves determining the optimal SNR classification boundaries and constructing a set of optimum stream weights for each SNR class. A feasibility test was conducted to verify the usefulness of the proposed method by conducting recognition experiments on seven types of food. The performance was compared with conventional methods that use in-ear and throat microphones. The proposed method yielded remarkable levels of recognition performance of 90.13% for artificially added noise and 89.67% under actual noisy environments, when the SNR ranged from 0 to 20 dB.
NanoTouch: intracellular recording using transmembrane conductive nanoparticles

Observations of the electrophysiological properties of cells are important for understanding cellular functions and their underlying mechanisms. Short action potentials in axons are essential to rapidly deliver signals from the neuronal cell body to the terminals, whereas longer action potentials are required for sufficient calcium influx for transmitter release at the synaptic terminals and for cardiomyocyte and smooth muscle contractions. To accurately observe the shape and timing of depolarizations, it is essential to measure changes in the intracellular membrane potential. The ability to record action potentials and intracellular membrane potentials from mammalian cells and neurons was made possible by Ling and Gerard’s discovery in 1949, when they introduced sharp glass electrode with a submicron sized tip. Because of the small tip size, the sharp glass electrode could penetrate the cell membrane with little damage, which was one of the major breakthroughs in cellular electrophysiology and is the basic principle of the intracellular recording technique to date, providing the basis for further innovation of patch-clamp electrophysiology. I report a proof-of-principle demonstration of a novel method for recording intracellular potentials without penetrating the cell membrane using glass electrodes. We discovered that magnetically held transmembrane conductive nanoparticles can function as an intracellular electrode to detect transmembrane membrane potentials similar to those obtained by the conventional patch-clamp recording method. NEW & NOTEWORTHY To accurately observe the shape of action potentials, it is essential to perform intracellular recordings. I present a method to record intracellular potentials using magnetically held magnetic conductive nanoparticles in the membrane as an electrode. These nanoparticles function similarly to a conventional intracellular microelectrode. This is the first report to apply conductive nanoparticles to detect action potentials in the form of electrical signals.
Peer‐to‐peer connections: Perceptions of a social support app designed for young adults with cancer

Social support is a critical, yet frequently unmet, need among young adults (YAs) with cancer. YAs desire age‐appropriate resources to connect with peers. Peer‐to‐peer mobile apps are promising interventions to provide social support. Peer‐to‐peer apps will be more effective if development incorporates users' input for whether app designs (look and function) afford meaningful connections.
Implementation of two different experimental designs for screening and optimization of process parameters for metformin-loaded carboxymethyl chitosan formulation

Abstract Metformin (MET) was effectively encapsulated into O-carboxymethyl chitosan (O-CMC) polymeric formulation using an experimental design method. Six factors Plackett–Burman (PB) design was utilized to find the significant process parameters. Linear equations used to study the effect of each process parameters on particle size (PS), encapsulation efficiency (EE), and zeta potential (ZP) and the most influential three factors decided for further optimization. Optimization was carried out by implementing three-factor three-level Box–Behnken (BB) design. Mathematical models were generated by regression analysis for responses of PS, EE, and ZP. Two-step experimental design took into account for the preparation of optimized formulation with maximum %EE (72.78 ± 9.7%) and minimum PS (225.67 ± 5.53 nm) at optimum process conditions with a ZP of –5.22 mV for the nano-polymeric formulation in an economical matter by reduction chemical use and formulation time. Furthermore, the biological activity of the final formulation was determined by in vitro cytotoxicity study compared to free MET. The cytotoxicity result reveals that both pure drug and nano-formulation biocompatible with MCF10A non-tumorigenic cell line and lethal for the MCF7 cell line. These in vitro results were the first helpful step to further investigate O-CMC loaded MET nanoparticles in diagnostic and therapeutic applications of breast cancer.
A unifying model for the accretion of chondrules and matrix

Significance An impasse exists between chemical and astrophysical models that explore the accretion of the Solar System’s building blocks, the chondrites. To resolve this issue means to gain an understanding of the dimensions of mass transport in the early Solar System and, hence, a crucial insight into the volatile inventory of the terrestrial planets. Here, we use element volatility patterns of chondrules and their dust rims to show that these main constituents of chondrites are not complementary to each other and did not form in the same chemical reservoirs. We propose a unifying chondrule and matrix accretion model that necessitates significant mass transport in the protoplanetary disk and an inward flux of volatile-rich CI-like (Ivuna-type carbonaceous chondrite) dust. The so far unique role of our Solar System in the universe regarding its capacity for life raises fundamental questions about its formation history relative to exoplanetary systems. Central in this research is the accretion of asteroids and planets from a gas-rich circumstellar disk and the final distribution of their mass around the Sun. The key building blocks of the planets may be represented by chondrules, the main constituents of chondritic meteorites, which in turn are primitive fragments of planetary bodies. Chondrule formation mechanisms, as well as their subsequent storage and transport in the disk, are still poorly understood, and their origin and evolution can be probed through their link (i.e., complementary or noncomplementary) to fine-grained dust (matrix) that accreted together with chondrules. Here, we investigate the apparent chondrule–matrix complementarity by analyzing major, minor, and trace element compositions of chondrules and matrix in altered and relatively unaltered CV, CM, and CR (Vigarano-type, Mighei-type, and Renazzo-type) chondrites. We show that matrices of the most unaltered CM and CV chondrites are overall CI-like (Ivuna-type) (similar to solar composition) and do not reflect any volatile enrichment or elemental patterns complementary to chondrules, the exception being their Fe/Mg ratios. We propose to unify these contradictory data by invoking a chondrule formation model in which CI-like dust accreted to so-called armored chondrules, which are ubiquitous in many chondrites. Metal rims expelled during chondrule formation, but still attached to their host chondrule, interacted with the accreted matrix, thereby enriching the matrix in siderophile elements and generating an apparent complementarity.
Physiologically based pharmacokinetic evaluation of cefuroxime in perioperative antibiotic prophylaxis

Adequate plasma concentrations of antibiotics during surgery are essential for the prevention of surgical site infections. We examined the pharmacokinetics of 1.5 g cefuroxime administered during induction of anaesthesia with follow‐up doses every 2.5 hours until the end of surgery. We built a physiologically based pharmacokinetic model with the aim to ensure adequate antibiotic plasma concentrations in a heterogeneous population.