Miracle-dz/UniFAR-FTUs huggingface dataset:
Asymptotic hypothesis test to simultaneously compare the weighted kappa coefficients of multiple binary diagnostic tests in the presence of ignorable missing data

The weighted kappa coefficient of a binary diagnostic test is a measure of the beyond-chance agreement between the diagnostic test and the gold standard, and is a measure that allows us to assess and compare the performance of binary diagnostic tests. In the presence of partial disease verification, the comparison of the weighted kappa coefficients of two or more binary diagnostic tests cannot be carried out ignoring the individuals with an unknown disease status, since the estimators obtained would be affected by verification bias. In this article, we propose a global hypothesis test based on the chi-square distribution to simultaneously compare the weighted kappa coefficients when in the presence of partial disease verification the missing data mechanism is ignorable. Simulation experiments have been carried out to study the type I error and the power of the global hypothesis test. The results have been applied to the diagnosis of coronary disease.
Understanding perinatal mental illness as a governance concern in South Africa through health provider perspectives

ABSTRACT Women in South Africa experience a disproportionately high prevalence of common perinatal mental disorders (CPMDs). These disorders often remain a silent burden and a complex health, social, and policy concern, both nationally and globally. Moreover, policy efforts to address this concern have been fragmented. Greater understanding of the governance of perinatal mental illness is needed to address this complex issue. No research to date has focused explicitly on the importance of ‘issue framing’ to advance governance for perinatal mental health. We sought to achieve a more nuanced understanding of clinical governance and issue framing for perinatal mental health in South Africa by interviewing 24 key informants with expertise in perinatal mental illness. Dominant themes encompassed: framing of perinatal mental health determines its priority; perinatal mental health is not prioritised due to competition from other health concerns; and, screening policy responses are shaped by the framing. We found that understanding the varying views influencing perinatal mental illness provides insights into how experts frame the problem. Findings suggest that a better understanding of policy implementation and responses in South Africa is important in guiding research, policy, and practice, while improving the governance of perinatal mental illness.
Signaling Network Response to α-Particle–Targeted Therapy with the 225Ac-Labeled Minigastrin Analog 225Ac-PP-F11N Reveals the Radiosensitizing Potential of Histone Deacetylase Inhibitors

Visual Abstract α-particle emitters have recently been explored as valuable therapeutic radionuclides. Yet, toxicity to healthy organs and cancer radioresistance limit the efficacy of targeted α-particle therapy (TAT). Identification of the radiation-activated mechanisms that drive cancer cell survival provides opportunities to develop new points for therapeutic interference to improve the efficacy and safety of TAT. Methods: Quantitative phosphoproteomics and matching proteomics followed by the bioinformatics analysis were used to identify alterations in the signaling networks in response to TAT with the 225Ac-labeled minigastrin analog 225Ac-PP-F11N (DOTA-(dGlu)6-Ala-Tyr-Gly-Trp-Nle-Asp-Phe) in A431 cells, which overexpress cholecystokinin B receptor (CCKBR). Western blot analysis and microscopy verified the activation of the selected signaling pathways. Small-molecule inhibitors were used to validate the potential of the radiosensitizing combinatory treatments both in vitro and in A431/CCKBR tumor–bearing nude mice. Results: TAT-induced alterations were involved in DNA damage response, cell cycle regulation, and signal transduction, as well as RNA transcription and processing, cell morphology, and transport. Western blot analysis and microscopy confirmed increased phosphorylations of the key proteins involved in DNA damage response and carcinogenesis, including p53, p53 binding protein 1 (p53BP1), histone deacetylases (HDACs), and H2AX. Inhibition of HDAC class II, ataxia-telangiectasia mutated (ATM), and p38 kinases by TMP269, AZD1390, and SB202190, respectively, sensitized A431/CCKBR cells to 225Ac-PP-F11N. As compared with the control and monotherapies, the combination of 225Ac-PP-F11N with the HDAC inhibitor vorinostat (suberoylanilide hydroxamic acid, SAHA) significantly reduced the viability and increased the DNA damage of A431/CCKBR cells, led to the most pronounced tumor growth inhibition, and extended the mean survival of A431/CCKBR xenografted nude mice. Conclusion: Our study revealed the cellular responses to TAT and demonstrated the radiosensitizing potential of HDAC inhibitors to 225Ac-PP-F11N in CCKBR-positive tumors. This proof-of-concept study recommends development of novel radiosensitizing strategies by targeting TAT-activated and survival-promoting signaling pathways.
Monopulse estimation with subarray-adaptive arrays and arbitrary sum and difference beams

The shape of the sum and difference beams can be severely distorted if nulls in jammer directions are formed. The usual monopulse estimation can then show a large bias, especially for mainbeam jammers. In the paper the previously developed correction formulas for the monopulse ratio are generalised to antennas with low sidelobe patterns and digital beamforming at subarray outputs. The low sidelobe sum beam is assumed to be formed by suitable element tapering and the low sidelobe difference beams by subarray output weighting. The new correction values are simply calculated from scalar products of the adapted beamforming vectors with planewave or steering vectors. The bias can be further reduced by switching the beams at subarray level to the estimated direction and repeating the procedure, which is called the multistep monopulse procedure.
Outcomes of surgical versus nonsurgical treatment for multiple rib fractures: A US hospital matched cohort database analysis

Treatment for multiple rib fractures include surgical stabilization of rib fractures (SSRF) or non-operative management (NOM). Our study showed that SSRF had greater odds of home discharge and lower rates of lung-related readmissions compared to NOM at 12 months follow-up. BACKGROUND Treatment for multiple rib fractures includes surgical stabilization of rib fractures (SSRF) or nonoperative management (NOM). Meta-analyses have demonstrated that SSRF results in faster recovery and lower long-term complication rates versus NOM. Our study evaluated postoperative outcomes for multiple rib fracture patients following SSRF versus NOM in a real-world, all-comer study design. METHODS Multiple rib fracture patients with inpatient admissions in the PREMIER hospital database from October 1, 2015, to September 30, 2020, were identified. Outcomes included discharge disposition, and 3- and 12-month lung-related readmissions. Demographics, comorbidities, concurrent injuries at index, Abbreviated Injury Scale and Injury Severity Scores, and provider characteristics were determined for all patients. Patients were excluded from the cohort if they had a thorax Abbreviated Injury Scale score of <2 (low severity patient) or a Glasgow Coma Scale score of ≤8 (extreme high severity patient). Stratum matching between SSRF and NOM patients was performed using fine stratification and weighting so that all patient data were kept in the final analysis. Outcomes were analyzed using generalized linear models with quasinormal distribution and logit links. RESULTS A total of 203,450 patients were included, of which 200,580 were treated with NOM and 2,870 with SSRF. Compared to NOM, patients with SSRF had higher rates of home discharge (62% SSRF vs. 58% NOM) and lower rates of lung-related readmissions (3 months, 3.1% SSRF vs. 4.0% NOM; 12 months, 6.2% SSRF vs. 7.6% NOM). The odds ratio (OR) for home or home health discharge in patients with SSRF versus NOM was 1.166 (95% confidence interval [CI], 1.073–1.266; p = 0.0002). Similarly, ORs for lung-related readmission at 3- and 12-month were statistically lower in the patients treated with SSRF versus NOM (OR [3 months], 0.764 [95% CI, 0.606–0.963]; p = 0.0227 and OR [12 months], 0.799 [95% CI, 0.657–0.971]; p = 0.0245). CONCLUSION Surgical stabilization of rib fractures results in greater odds of home discharge and lower rates of lung-related readmissions compared with NOM at 12 months of follow-up. LEVEL OF EVIDENCE Therapeutic/Care Management; Level III.
Volatile compounds for biotechnological applications produced during competitive interactions between yeasts and fungi

Fungi, yeasts and bacteria produce volatile compounds during their metabolism. In this study, the volatile compounds produced by yeast strains (Saccharomyces cerevisiae and Rhodotorula mucilaginosa) and fungal strains (Aspergillus carbonarius and Aspergillus ochraceus) during competitive interactions were investigated by solid‐phase microextraction coupled with gas chromatography–mass spectrometry. Fifty‐six volatile compounds were identified representing alcohols, aldehydes, esters, ketones, aromatic compounds, acids, furans, phenols, and nitrogen compounds, being the largest amount in the class of esters and alcohols. Eight compounds were identified only in interactive culture conditions such as 2‐amino‐1‐propanol, isopropylamine, dimethylamine, pentyl propanoate, ethyl‐2‐aminopropanoate, acetone, oxalic acid, and β‐elemene and five of these were produced in cocultures including A. carbonarius. These will be developed for future biotechnological applications such as in the pharmaceutical and biological industry to produce drugs. Antimicrobial and antifungal activities; Solvent and herbicide; flavoring ingredient; solvent, plastic synthesis, nail polish remover and thinner, pesticide and herbicide; important in the complexation of minerals in the soil; and plant‐environment interactions, defending predators, pathogens, and competitors.
The uncertainty of a selected graphical model

Graphical models are useful to detect multivariate association structures in terms of conditional independencies and to represent these structures in a graph. When fitting graphical models to multivariate data, the uncertainty of a selected graphical model cannot be directly assessed. In this paper, we therefore propose various descriptive measures to assess the uncertainty of a graphical model based on the nonparametric bootstrap. We also introduce a so-called mean graphical model. Simulations and one real data example illustrate the application and interpretation of the newly proposed measures and demonstrate that the mean graphical model performs better than a single selected graphical model.
Creating a Self-management Mobile Application for People With Chronic Low Back Pain

Mobile health can fulfill the unmet needs of patients with chronic low back pain by recommending individualized management plans. Limited mobile applications have been developed based on the needs, preferences, and values relative to self-management of patients with chronic low back pain. This study aimed to explore the experience of patients with chronic low back pain and the desired content, designs, and features of a self-management application. We conducted five focus groups (N = 24). Participants provided feedback on draft contents and they also discussed the desired designs and features of an application while reviewing a low-fidelity prototype. Data were audio-recorded, transcribed verbatim, and analyzed using qualitative content analysis. Three categories and eight subcategories emerged. Participants: (1) confronted difficulties of their pain experience along with vicious cycles of pain and unmet needs; (2) acknowledged the importance of self-management as they lived with chronic low back pain and realized how to self-manage their pain; and (3) suggested ways to fulfill needs and preferences among patients with chronic low back pain. The nature of chronic low back pain causes disruptions well-being and requires constant management. Developing user-centered strategies to enhance knowledge and promote self-management among chronic low back pain patients is required.
Versatile strategy using vaccinia virus-capping enzyme to synthesize functional 5′ cap-modified mRNAs

Abstract The potential of synthetic mRNA as a genetic carrier has increased its application in scientific fields. Because the 5′ cap regulates the stability and translational activity of mRNAs, there are concerted efforts to search for and synthesize chemically-modified 5′ caps that improve the functionality of mRNA. Here, we report an easy and efficient method to synthesize functional mRNAs by modifying multiple 5′ cap analogs using a vaccinia virus-capping enzyme. We show that this enzyme can introduce a variety of GTP analogs to the 5′ end of RNA to generate 5′ cap-modified mRNAs that exhibit different translation levels. Notably, some of these modified mRNAs improve translation efficiency and can be conjugated to chemical structures, further increasing their functionality. Our versatile method to generate 5′ cap-modified mRNAs will provide useful tools for RNA therapeutics and biological research.
Loss of dyskerin facilitates the acquisition of metastatic traits by altering the mevalonate pathway

Cholesterol metabolism may be involved in the early steps of tumor dissemination. Epigenetic regulation of cholesterol synthesis and uptake is of great importance in this process and may constitute a vulnerability of the cancer cell that could be exploited pharmacologically. The initial dissemination of cancer cells from many primary tumors implies intravasation to lymphatic nodes or blood vessels. To investigate the mechanisms involved, we analyzed the expression of small non-coding RNAs in cutaneous squamous cell carcinoma (cSCC), a prevalent tumor that mainly spreads to lymph nodes. We report the reduced expression of small nucleolar RNAs in primary cSCCs that metastasized when compared to non-metastasizing cSCCs, and the progressive loss of DKC1 (dyskerin, which stabilizes the small nucleolar RNAs) along the metastasis. DKC1 depletion in cSCC cells triggered lipid metabolism by altering the mevalonate pathway and the acquisition of metastatic traits. Treatment of DKC1-depleted cells with simvastatin, an inhibitor of the mevalonate pathway, blocked the expression of proteins involved in the epithelial-to-mesenchymal transition. Consistently, the expression of the enzyme 3-hydroxy-3-methylglutaryl-CoA synthase 1 was associated with pathological features of high metastatic risk in cSCC patients. Our data underpin the relevance of the mevalonate metabolism in metastatic dissemination and pave the possible incorporation of therapeutic approaches among the antineoplastic drugs used in routine patient care. Graphical Abstract
Real-time image fusion and adaptive exposure control for smart surveillance systems

A smart surveillance system that performs image fusion for extending dynamic range and adaptively adjusts exposure for enhancing regions of interest (ROIs) is proposed. It keeps good colour constancy and better contrast for image details of ROIs. The system performance of image fusion and object tracking can achieve 4 and 10 frames/s, respectively.
Modular Morphing Lattices for Large-Scale Underwater Continuum Robotic Structures

In this study, we present a method to construct meter-scale deformable structures for underwater robotic applications by discretely assembling mechanical metamaterials. We address the challenge of scaling up nature-like deformable structures while remaining structurally efficient by combining rigid and compliant facets to form custom unit cells that assemble into lattices. The unit cells generate controlled local anisotropies that architect the global deformation of the robotic structure. The resulting flexibility allows better unsteady flow control that enables highly efficient propulsion and optimized force profile manipulations. We demonstrate the utility of this approach in two models. The first is a morphing beam snake-like robot that can generate thrust at specific anguilliform swimming parameters. The second is a morphing surface hydrofoil that, when compared with a rigid wing at the same angles of attack (AoAs), can increase the lift coefficient up to 0.6. In addition, in lower AoAs, the L∕D ratio improves by 5 times, whereas in higher angles it improves by 1.25 times. The resulting hydrodynamic performance demonstrates the potential to achieve accessible, scalable, and simple to design and assemble morphing structures for more efficient and effective future ocean exploration and exploitation.
Dantrolene and ryanodine receptors in COVID‐19: The daunting task and neglected warden

Dantrolene (DTN) is a ryanodine receptor (RyR) antagonist that inhibits Ca2+ release from stores in the sarcoplasmic reticulum. DTN is mainly used in the management of malignant hyperthermia. RyRs are highly expressed in immune cells and are involved in different viral infections, including severe acute respiratory syndrome coronavirus type 2 (SARS‐CoV‐2), because Ca2+ is necessary for viral replication, maturation and release. DTN can inhibit the proliferation of SARS‐CoV‐2, indicating its potential role in reducing entry and pathogenesis of SARS‐CoV‐2. DTN may increase clearance of SARS‐CoV‐2 and promote coronavirus disease 2019 (COVID‐19) recovery by shortening the period of infection. DTN inhibits N‐methyl‐D‐aspartate (NMDA) mediated platelets aggregations and thrombosis. Therefore, DTN may inhibit thrombosis and coagulopathy in COVID‐19 through suppression of platelet NMDA receptors. Moreover, DTN has a neuroprotective effect against SARS‐CoV‐2 infection‐induced brain injury through modulation of NMDA receptors, which are involved in excitotoxicity, neuronal injury and the development of neuropsychiatric disorders. In conclusion, DTN by inhibiting RyRs may attenuate inflammatory disorders in SARS‐CoV‐2 infection and associated cardio‐pulmonary complications. Therefore, DNT could be a promising drug therapy against COVID‐19. Preclinical and clinical studies are warranted in this regards.
Positioning and Position Error of Petroleum Wells

Positioning and Position Error of Petroleum Wells We present a new model for the estimation of positional uncertainty of petroleum wells. The model uses a heavy tailed normal inverse Gaussian distribution for the errors in Earth's magnetic field reference values. These references are required for calculating the position of a well using magnetic directional surveying. The results show that the normal inverse Gaussian distribution gives a more realistic fit to the Earth's magnetic field reference values than the normal distribution, which is the current state of art. Errors in surveying sensors and reference errors are propagated along the well path to obtain the positioning uncertainty. The positional uncertainty is important for the probability of collisions between wells and for drilling accurate relief wells when an eventual collision has resulted in a blow-out situation. We compare results of the normal model used in the petroleum industry with our proposed model. The comparison is made for anti-collision calculations between drilled wells and a planned well. The results indicate a higher risk of collisions for certain well geometries when using the normal distribution, while a collision is avoided in the normal inverse Gaussian situation. We find clear differences between an approximate normal test and a Monte Carlo test.
IMPORTANCE OF THE INNATE IMMUNE RESPONSE IN SKELETAL MUSCLE TO SEPSIS-INDUCED ALTERATIONS IN PROTEIN BALANCE

ABSTRACT There is growing appreciation that skeletal muscle is a fully functional component of the body's innate immune system with the potential to actively participate in the host response to invading bacteria as opposed to being a passive target. In this regard, skeletal muscle in general and myocytes specifically possess an afferent limb that recognizes a wide variety of host pathogens via their interaction with multiple classes of cell membrane–bound and intracellular receptors, including toll-like receptors, cytokine receptors, NOD-like receptors, and the NLRP inflammasome. The efferent limb of the innate immune system in muscle is equally robust and with an increased synthesis and secretion of a variety of myocyte-derived cytokines (i.e., myokines), including TNF-α, IL-1, IL-6, and NO as well as multiple chemokines in response to appropriate stimulation. Herein, the current narrative review focuses primarily on the immune response of myocytes per se as opposed to other cell types within whole muscle. Moreover, because there are important differences, this review focuses specifically on systemic infection and inflammation as opposed to the response of muscle to direct injury and various types of muscular dystrophies. To date, however, there are few definitive muscle-specific studies that are necessary to directly address the relative importance of muscle-derived immune activation as a contributor to either the systemic immune response or the local immune microenvironment within muscle during sepsis and the resultant downstream metabolic disturbances.
Filamentous bacteriophages are associated with chronic Pseudomonas lung infections and antibiotic resistance in cystic fibrosis

Pseudomonas strains that produce filamentous bacteriophage are associated with chronic infection and increased antibiotic resistance in patients with cystic fibrosis. Infection-boosting phage Chronic Pseudomonas aeruginosa infection is common in patients with cystic fibrosis (CF). Filamentous bacteriophage (Pf phage) can infect P. aeruginosa and has been shown to contribute to the virulence of infection in animal models. However, whether Pf phage plays a role in the pathogenicity of P. aeruginosa in CF is unknown. Now, Burgener et al. showed that Pf phage was abundantly expressed in sputum samples from two large cohorts of patients with CF. The presence of Pf phage was associated with increased antibiotic resistance and reduced lung function. The results suggest that Pf phage might play a role in the pathogenicity of P. aeruginosa infection in CF. Filamentous bacteriophage (Pf phage) contribute to the virulence of Pseudomonas aeruginosa infections in animal models, but their relevance to human disease is unclear. We sought to interrogate the prevalence and clinical relevance of Pf phage in patients with cystic fibrosis (CF) using sputum samples from two well-characterized patient cohorts. Bacterial genomic analysis in a Danish longitudinal cohort of 34 patients with CF revealed that 26.5% (n = 9) were consistently Pf phage positive. In the second cohort, a prospective cross-sectional cohort of 58 patients with CF at Stanford, sputum qPCR analysis showed that 36.2% (n = 21) of patients were Pf phage positive. In both cohorts, patients positive for Pf phage were older, and in the Stanford CF cohort, patients positive for Pf phage were more likely to have chronic P. aeruginosa infection and had greater declines in pulmonary function during exacerbations than patients negative for Pf phage presence in the sputum. Last, P. aeruginosa strains carrying Pf phage exhibited increased resistance to antipseudomonal antibiotics. Mechanistically, in vitro analysis showed that Pf phage sequesters these same antibiotics, suggesting that this mechanism may thereby contribute to the selection of antibiotic resistance over time. These data provide evidence that Pf phage may contribute to clinical outcomes in P. aeruginosa infection in CF.