Miracle-dz/UniFAR-FTUs huggingface dataset:
A multistate assessment of population normalization factors for wastewater-based epidemiology of COVID-19

Wastewater-based epidemiology (WBE) has become a valuable tool for monitoring SARS-CoV-2 infection trends throughout the COVID-19 pandemic. Population biomarkers that measure the relative human fecal contribution to normalize SARS-CoV-2 wastewater concentrations are needed for improved analysis and interpretation of community infection trends. The Centers for Disease Control and Prevention National Wastewater Surveillance System (CDC NWSS) recommends using the wastewater flow rate or human fecal indicators as population normalization factors. However, there is no consensus on which normalization factor performs best. In this study, we provided the first multistate assessment of the effects of flow rate and human fecal indicators (crAssphage, F+ Coliphage, and PMMoV) on the correlation of SARS-CoV-2 wastewater concentrations and COVID-19 cases using the CDC NWSS dataset of 182 communities across six U.S. states. Flow normalized SARS-CoV-2 wastewater concentrations produced the strongest correlation with COVID-19 cases. The correlation from the three human fecal indicators were significantly lower than flow rate. Additionally, using reverse transcription droplet digital polymerase chain reaction (RT-ddPCR) significantly improved correlation values over samples that were analyzed with real-time reverse transcription quantitative polymerase chain reaction (rRT-qPCR). Our assessment shows that utilizing flow normalization with RT-ddPCR generate the strongest correlation between SARS-CoV-2 wastewater concentrations and COVID-19 cases.
Stimulus Onset Asynchrony Affects Weighting-related Event-related Spectral Power in Self-motion Perception

Abstract Self-motion perception relies primarily on the integration of the visual, vestibular, proprioceptive, and somatosensory systems. There is a gap in understanding how a temporal lag between visual and vestibular motion cues affects visual–vestibular weighting during self-motion perception. The beta band is an index of visual–vestibular weighting, in that robust beta event-related synchronization (ERS) is associated with visual weighting bias, and robust beta event-related desynchronization is associated with vestibular weighting bias. The present study examined modulation of event-related spectral power during a heading judgment task in which participants attended to either visual (optic flow) or physical (inertial cues stimulating the vestibular, proprioceptive and somatosensory systems) motion cues from a motion simulator mounted on a MOOG Stewart Platform. The temporal lag between the onset of visual and physical motion cues was manipulated to produce three lag conditions: simultaneous onset, visual before physical motion onset, and physical before visual motion onset. There were two main findings. First, we demonstrated that when the attended motion cue was presented before an ignored cue, the power of beta associated with the attended modality was greater than when visual–vestibular cues were presented simultaneously or when the ignored cue was presented first. This was the case for beta ERS when the visual-motion cue was attended to, and beta event-related desynchronization when the physical-motion cue was attended to. Second, we tested whether the power of feature-binding gamma ERS (demonstrated in audiovisual and visual–tactile integration studies) increased when the visual–vestibular cues were presented simultaneously versus with temporal asynchrony. We did not observe an increase in gamma ERS when cues were presented simultaneously, suggesting that electrophysiological markers of visual–vestibular binding differ from markers of audiovisual and visual–tactile integration. All event-related spectral power reported in this study were generated from dipoles projecting from the left and right motor areas, based on the results of Measure Projection Analysis.
Determination of complex refractive index of thin metal films from terahertz time-domain spectroscopy

Thin metal films alone or incorporated in a multilayer stack structure with dielectric films are good candidates of terahertz absorbers necessary for achieving the maximum responsivity in microbolometer devices. However, the design and optimization of these absorber structures depend on the knowledge of the complex refractive index of metal films in the terahertz frequency range, which is not easy to measure or determine from experiment. This paper presents a novel method that allows fast and reliable extraction of the complex refractive index from terahertz time-domain spectroscopy. It starts with terahertz time-domain transmission measurements, followed by Fourier transforms to obtain the transmission spectrum in the frequency range of 0.1–3 THz, and finally an extraction process using the enhanced “on-the-downhill” algorithm. Some experimental examples are given, all of which show good agreement with theoretical calculations. This extraction method, combined with the scattering matrix model, can help d.
Ceftobiprole medocaril for the treatment of pneumonia

ABSTRACT Introduction Ceftobiprole, a fifth-generation cephalosporin, exhibits a broad-spectrum activity against common pathogens causing pneumonia, including multidrug-resistant organisms (MDROs), such as penicillin-resistant S. pneumoniae (PRSP) and methicillin-resistant Staphylococcus aureus (MRSA) and non-extended-spectrum β -lactamase (non-ESBL) producing Enterobacterales strains. Therefore, ceftobiprole should be considered as a potential alternative for the empirical treatment of pneumonia in patients with high risk for MDROs. Area covered In this review, we discussed the role of ceftobiprole in the treatment of patients with pneumonia. Expert opinion Ceftobiprole has several advantages in the treatment of pneumonia. First, ceftobiprole exerts its bactericidal activity by inhibiting transpeptidases, especially showing strong affinities to penicillin-binding protein (PBP) 2a, PBP2× and PBP3. Second, its plasma protein binding is minimal, allowing it to penetrate lung tissue and achieve high concentrations in epithelial lung fluid. Third, ceftobiprole exhibits potent in vitro activity against a wide range of susceptible pathogens, including S. aureus, S. pneumoniae, Viridans streptococci, H. influenzae, M. catarrhalis, Enterobacterales, and particularly, MRSA and P. aeruginosa. Finally, several randomized controlled trials have demonstrated the clinical efficacy and safety of ceftobiprole in the treatment of pediatric and adult patients with community-acquired pneumonia and hospital-acquired pneumonia (excluding ventilator-associated pneumonia).
Bilateral risk-reducing mastectomy and reconstruction–A 12-year review of methodological trends and outcomes at a tertiary referral centre

Introduction Bilateral risk-reducing mastectomy (BRRM) involves removal of healthy breast tissue to substantially decrease the risk of developing breast cancer in individuals with greater susceptibility due to a strong family history or genetic mutation. This retrospective study evaluates cases of BRRM and associated reconstruction performed at a tertiary centre, with emphasis on mastectomy and reconstructive trends. Methods A retrospective review of all BRRM cases performed between January 2010 and May 2022 was conducted, with two separate cohorts corresponding to the earlier (group 1) and later (group 2) portion of the time-period. Data collected included demographics, genetic test results, family history of breast/ovarian cancer, co-morbidities, mastectomy type, reconstruction type, surgical histopathology findings and post-operative complications. Results A total of 82 patients (group 1 = 41, group 2 = 41) underwent BRRM. The proportion of nipple-sparing mastectomy increased from 14.6% to 56.1% between the two time periods with a reduction in skin-sparing mastectomies from 75.6% to 20.3% (p<0.001). Of the 80 patients who opted to undergo reconstruction, there was a significant decrease in combined flap-implant reconstructions (19.51% to 0%, p<0.01). Importantly, for implant-only reconstruction, there were significant increases in prepectoral approaches (p = 0.0267) and use of acellular dermal matrix (ADM) (48.15% to 90.63%, p<0.001). Conclusion This study documents recent increases in nipple-sparing techniques for BRRM compared to more traditional skin-sparing methods. Concurrently, reconstruction following RRM has become predominantly implant-based without a flap, coinciding with more widespread usage of ADM. This is consistent with national trends towards fewer complex autologous procedures.
Predicting opioid use disorder before and after the opioid prescribing peak in the United States: A machine learning tool using electronic healthcare records

Existing predictive models of opioid use disorder (OUD) may change as the rate of opioid prescribing decreases. Using Veterans Administration’s EHR data, we developed machine-learning predictive models of new OUD diagnoses and ranked the importance of patient features based on their ability to predict a new OUD diagnosis in 2000–2012 and 2013–2021. Using patient characteristics, the three separate machine learning techniques were comparable in predicting OUD, achieving an accuracy of >80%. Using the random forest classifier, opioid prescription features such as early refills and length of prescription consistently ranked among the top five factors that predict new OUD. Younger age was positively associated with new OUD, and older age inversely associated with new OUD. Age stratification revealed prior substance abuse and alcohol dependency as more impactful in predicting OUD for younger patients. There was no significant difference in the set of factors associated with new OUD in 2000–2012 compared to 2013–2021. Characteristics of opioid prescriptions are the most impactful variables that predict new OUD both before and after the peak in opioid prescribing rates. Predictive models should be tailored to age groups. Further research is warranted to determine if machine learning models perform better when tailored to other patient subgroups.
Effect of accessibility of a genetic counselor on uptake of preimplantation genetic testing for aneuploidy (PGT‐A) and carrier screening for patients undergoing in vitro fertilization

This retrospective cohort study assessed the accessibility of a genetic counselor on uptake of preimplantation genetic testing for aneuploidy (PGT‐A) and carrier screening in a single academic Reproductive Endocrinology and Infertility (REI) clinic. A total of 420 patients were evaluated with 219 patients counseled by a REI physician only and 201 patients after the addition of a genetic counselor (GC) to the REI clinic team. Cycles initiated before hiring of a GC (pre‐GC) were assessed from June 2018 to December 2018 and after integration of a GC (post‐GC) from March 2019 to August 2019. Additionally, information regarding carrier screening was collected if available in the medical record. Results showed more patients utilized PGT‐A post‐GC (9.5% vs. 5.5%), although the difference between groups did not reach statistical significance (p = 0.12). Individuals who were screened post‐GC or who started screening pre‐GC and continued screening post‐GC were screened for a larger number of conditions than if they were only screened pre‐GC (median pre‐GC = 3, post‐GC = 27, pre‐ and post‐GC = 274; p < 0.0001). The change in practice from using physician‐only counseling to counseling with accessibility to a GC did not change the utilization of PGT‐A in a single clinic.
Confidence limits for stress-strength models with explanatory variables

A lower confidence bound is obtained for Pr(Y > X|z 1, z 2), where X and Y are independent normal variables, with explanatory variables z 1 and z 2, respectively. For equal residual variances, an exact solution is obtained, but for the unequal variance case, an approximate lower confidence bound is developed. Examples of the use of these procedures are given.
Neurite Orientation Dispersion and Density Imaging in Multiple Sclerosis: A Systematic Review

Diffusion‐weighted imaging has been applied to investigate alterations in multiple sclerosis (MS). In the last years, advanced diffusion models were used to identify subtle changes and early lesions in MS. Among these models, neurite orientation dispersion and density imaging (NODDI) is an emerging approach, quantifying specific neurite morphology in both grey (GM) and white matter (WM) tissue and increasing the specificity of diffusion imaging. In this systematic review, we summarized the NODDI findings in MS. A search was conducted on PubMed, Scopus, and Embase, which yielded a total number of 24 eligible studies. Compared to healthy tissue, these studies identified consistent alterations in NODDI metrics involving WM (neurite density index), and GM lesions (neurite density index), or normal‐appearing WM tissue (isotropic volume fraction and neurite density index). Despite some limitations, we pointed out the potential of NODDI in MS to unravel microstructural alterations. These results might pave the way to a deeper understanding of the pathophysiological mechanism of MS.
MR imaging in the evaluation of (deep infiltrating) endometriosis: the value of diffusion-weighted imaging

Materials and Methods: In a prospective single center study, DWI was added to the standard MR imaging protocol in 56 consecutive patients with known or suspected endometriosis. Endometriotic lesions as well as (functional) ovarian cysts were analysed for location, size, and signal intensity on T1-, T2-, and DWI. Signal intensity ratios were calculated, using the obturatorius muscle. Apparent diffusion coefficient (ADC) values were calculated using b-values of 50, 400, 800 and 1200 s/mm. Statistical analysis included the Spearman correlation coefficient, Mann Whitney U and Kruskall-Wallis tests.
Monoclonal antibodies for the treatment of squamous cell carcinoma: A literature review

Squamous cell carcinoma (SCC) is a relatively common and heterogenous malignancy of different organs, such as the skin, esophagus, and lungs. Although most cases experience good survival with surgical methods, management of advanced types of the disease remains challenging. Several modalities, including different chemotherapy regimens and immunotherapies, have been investigated in this matter, among which Monoclonal antibodies (Mabs) are one of the most promising ones. Since the development of Mabs, they have been widely used to treat different diseases. Mabs have shown significant efficacy with high specificity along with acceptable safety, which makes them a favorable option in cancer therapy. In this article, we aimed to review the different aspects of using Mabs in SCC therapy.
Disposition effect and reference points: An experimental study

This study calls into question the default computation of the disposition effect that uses the average purchase price as a reference point. We show, through a lab experiment, that the reference price of participants can change depending on the experimental behavioral design that is used. Our results show that for the control group, different reference prices do not show significant differences in the computation of the disposition effect, thus supporting the use of the average purchase price as a reference. However, this is not the case for participants in the treatment group. With the addition of experimental treatment concerning the disclosure of the final balance of the participants, the reference prices to compute the disposition effect showed statistically significant differences. The need to display their results caused these participants to use the first purchase price as a reference point when selling their assets.
Dissemination of Pseudomonas aeruginosa blaNDM-1-Positive ST308 Clone in Singapore

P. aeruginosa is a Gram-negative opportunistic pathogen ubiquitously found in the environment and a major cause of nosocomial infections. While the P. aeruginosa ST308 clone has been known to bear blaIMP and blaVIM among global isolates, reports of blaNDM-1-positive P. aeruginosa ST308 are rare. ABSTRACT Pseudomonas aeruginosa ST308 clone has been reported to carry carbapenemase genes such as blaIMP and blaVIM but has been rarely associated with blaNDM-1. A total of 199 P. aeruginosa ST308 clinical and environmental isolates obtained between April 2019 and November 2020 from a tertiary-care hospital in Singapore were characterized using whole-genome sequencing. In addition, 71 blaNDM-1-positive ST308 whole-genome sequences from two other local tertiary-care hospitals in Singapore and 83 global blaNDM-1-negative ST308 whole-genome sequences in public databases were included to assess phylogenetic relationships and perform genome analyses. Phylogenetic analysis and divergent time estimation revealed that blaNDM-1-positive P. aeruginosa ST308 was introduced into Singapore in 2005 (95 % highest posterior density: 2001 to 2008). Core genome, resistome, and analyses of all local blaNDM-1-positive ST308 isolates showed chromosomal integration of multiple antibiotic resistance genes (ARGs) [aac(3)-Id, aac(6′)-Il, aadA6, aadA11, dfrB5, msr(E), floR, sul2, and qnrVC1], which was absent in global blaNDM-1-negative ST308 sequences. Most ARGs and virulence genes were conserved across isolates originating from the three different local hospitals. Close genetic relatedness of the blaNDM-1-positive ST308 clinical and environmental isolates suggests cocirculation between the hospital environment and human hosts with the hospital environment as a potential reservoir. Core genome single nucleotide polymorphism analyses revealed possible clonal transmission of blaNDM-1-positive ST308 isolates between the three hospitals over 7 years. Bloodstream isolates accounted for six of 95 (6.3%) clinical isolates. This study reports the introduction of a pathogenic blaNDM-1-positive P. aeruginosa ST308 more than a decade ago in Singapore and warrants surveillance for wider dissemination. IMPORTANCE P. aeruginosa is a Gram-negative opportunistic pathogen ubiquitously found in the environment and a major cause of nosocomial infections. While the P. aeruginosa ST308 clone has been known to bear blaIMP and blaVIM among global isolates, reports of blaNDM-1-positive P. aeruginosa ST308 are rare. The local blaNDM-1-positive P. aeruginosa ST308 isolates detected in this study appear to be unique to this region, with evidence of chromosomal acquisition of multiple ARGs compared to global blaNDM-1-negative P. aeruginosa ST308 isolates. Surveillance in Singapore and beyond for dissemination is essential to determine whether existing measures are sufficient to control the spread of this ST308 clone.
Edaravone promotes viability of random skin flaps via activating PI3K/Akt/mTOR signalling pathway‐mediated enhancement of autophagy

Random skin flap transplantation is a commonly used technique. However, ischemia and ischemia–reperfusion injury always impair its therapeutic effectiveness through acclerating oxidative stress, apoptosis and suppressing angiogenesis. To survive, cells rely on mediating autophagy, DNA repair, immunoregulation to resist these cellular injuries. Thus, mediating autophagy may affect the survival of random skin flaps. The edaravone (EDA), a oxygen radicals scavenger, also possesses autophagy mediator potential, we investigated the effects of EDA on skin flap survival and its autophagy‐related mechanisms. In vivo, mice were administered EDA or saline intraperitoneally for 7 days postoperatively. We found that EDA ameliorated the viability of random skin flaps, promoted autophagy and angiogenesis, attenuated apoptosis and oxidative stress. In vitro, mouse umbilical vascular endothelial cells (MUVECs) were administered EDA or 3‐methyladenine (3‐MA, an autophagy inhibitor) or rapacymin (Rapa, an autophagy activator) at the beginning of oxygen glucose deprivation (OGD). We found that EDA promoted cell viability, activated autophagy, enhanced angiogenesis, alleviated apoptosis and oxidative stress. On one hand, 3‐MA reversed the effects of EDA on cell viability, oxidative stress and apoptosis via inhibiting autophagy. On the other hand, Rapa had the similar effects of EDA. Furthermore, EDA‐induced autophagy was mediated through downregulating PI3K/Akt/mTOR signalling pathway. The findings showed that EDA ameliorated viability of random skin flaps by promoting angiogenesis, suppressing oxidative stress and apoptosis, which may be mediated by autophagic activation through downregulating PI3K/AKT/mTOR signalling pathway.
Genotoxicity evaluation of orally administered styrene monomer in mice using comet, micronucleus, and Pig‐a endpoints

Male B6C3F1 mice were administered styrene monomer by oral gavage for 29 consecutive days at dose levels of 0, 75, 150, or 300 mg/kg/day. The highest dose level represented the maximum tolerated dose based on findings in a 28‐day dose range‐finding study, in which the bioavailability of orally administered styrene was also confirmed. The positive control group received ethyl nitrosourea (ENU; 51.7 mg/kg/day) on Study Days 1–3 and ethyl methanesulfonate (EMS; 150 mg/kg/day) on Study Days 27–29 by oral gavage. Approximately 3 h following the final dose, blood was collected to assess erythrocyte Pig‐a mutant and micronucleus frequencies. DNA strand breakage was assessed in glandular stomach, duodenum, kidney, liver, and lung tissues using the alkaline comet assay. The %tail DNA for stomach, liver, lung, and kidney in the comet assay among the styrene‐treated groups was neither significantly different from the respective vehicle controls nor was there any dose‐related increasing trend in any of the tissues; results for duodenum were interpreted to be inconclusive because of technical issues. The Pig‐a and micronucleus frequencies among styrene‐treated groups also did not show significant increases relative to the vehicle controls and there was also no evidence for a dose‐related increasing trend. Thus, orally administered styrene did not induce DNA damage, mutagenesis, or clastogenesis/aneugenesis in these Organization of Economic Co‐operation and Development test guideline‐compliant genotoxicity studies. Data from these studies can contribute to the overall assessment of genotoxic hazard and risk posed to humans potentially exposed to styrene.
The association between early traumatic experiences and the five domains of negative symptoms in participants at clinical high risk for psychosis

Youth at clinical high risk (CHR) for psychosis have high rates of early life trauma, but it is unclear how trauma exposure impacts later negative symptom severity in CHR. The current study examined the association between early childhood trauma and the five domains of negative symptoms (anhedonia, avolition, asociality, blunted affect, alogia).
Device profile of Nerivio for the acute and preventive treatment of episodic or chronic migraine in patients 12 years and older

ABSTRACT Introduction Migraine is a prevalent, inherited and disabling brain disease with multiple symptoms and a variety of treatment options. Nerivio, utilizing remote electrical neuromodulation (REN) a wearable device, offers users good efficacy, tolerability and safety. It is user-friendly, affordable, non-addictive and cleared by the FDA and the European Conformity. Areas covered The device structure, mechanism of action, indications for use, application instructions, efficacy, adverse events, tolerability, safety, patient satisfaction, associated application and the research highlights are discussed herein. Expert opinion The device works well for most people living with migraine, often without concomitant medication, is tolerable, safe and causes minimal and mild adverse effects. It expands our migraine treatment options and improves patient adherence to treatment. Nerivio is easy-to-use and can be worn at any time of the day; it provides a non-pharmacologic option for the optimization of migraine treatment without significant adverse events.