Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparing in-person, blended and virtual training interventions; a real-world evaluation of HIV capacity building programs in 16 countries in sub-Saharan Africa

We sought to evaluate the impact of transitioning a multi-country HIV training program from in-person to online by comparing digital training approaches implemented during the pandemic with in-person approaches employed before COVID-19. We evaluated mean changes in pre-and post-course knowledge scores and self-reported confidence scores for learners who participated in (1) in-person workshops (between October 2019 and March 2020), (2) entirely asynchronous, Virtual Workshops [VW] (between May 2021 and January 2022), and (3) a blended Online Course [OC] (between May 2021 and January 2022) across 16 SSA countries. Learning objectives and evaluation tools were the same for all three groups. Across 16 SSA countries, 3023 participants enrolled in the in-person course, 2193 learners participated in the virtual workshop, and 527 in the online course. The proportions of women who participated in the VW and OC were greater than the proportion who participated in the in-person course (60.1% and 63.6%, p<0.001). Nursing and midwives constituted the largest learner group overall (1145 [37.9%] vs. 949 [43.3%] vs. 107 [20.5%]). Across all domains of HIV knowledge and self-perceived confidence, there was a mean increase between pre- and post-course assessments, regardless of how training was delivered. The greatest percent increase in knowledge scores was among those participating in the in-person course compared to VW or OC formats (13.6% increase vs. 6.0% and 7.6%, p<0.001). Gains in self-reported confidence were greater among learners who participated in the in-person course compared to VW or OC formats, regardless of training level (p<0.001) or professional cadre (p<0.001). In this multi-country capacity HIV training program, in-person, online synchronous, and blended synchronous/asynchronous strategies were effective means of training learners from diverse clinical settings. Online learning approaches facilitated participation from more women and more diverse cadres. However, gains in knowledge and clinical confidence were greater among those participating in in-person learning programs.
Free vibration analysis of coupled sloshing-flexible membrane system in a liquid container

A finite element model is developed to study free vibration of a liquid in a tank of arbitrary geometry with a flexible membrane constraining the liquid free-surface. A variational formulation is initially developed using the Galerkin method, assuming inviscid, incompressible and irrotational flow. The resulting generalized eigenvalue problem is then reduced by considering only the elements on the liquid free-surface, which significantly reduces the computational time. The proposed physical model is subsequently implemented into the FEniCS framework to obtain coupled hydroelastic liquid-membrane frequencies and modes. The coupled frequencies are compared with those reported for rectangular and upright cylindrical tanks using analytical methods in order to illustrate the validity of the finite element model. The results are subsequently presented for a horizontal cylindrical tank with an elastic free-surface membrane for different fill ratios and tank lengths. The effects of the membrane tension on the free vibration of the liquid in the tank are further investigated by comparing the coupled liquid-membrane frequencies with slosh frequencies of the liquid alone. It is shown that sloshing frequencies can be effectively shifted to higher values to prevent resonance in partially filled moving containers.
Applied Factor Analysis in the Natural Sciences.

This graduate-level text aims to introduce students of the natural sciences to the powerful technique of factor analysis and to provide them with the background necessary to be able to undertake analyses on their own. A thoroughly updated and expanded version of the authors' successful textbook on geological factor analysis, this book draws on examples from botany, zoology, ecology, and oceanography, as well as geology. Applied multivariate statistics has grown into a research area of almost unlimited potential in the natural sciences. The methods introduced in this book, such as classical principal components, principal component factor analysis, principal coordinate analysis, and correspondence analysis, can reduce masses of data to manageable and interpretable form. Q-mode and Q-R-mode methods are also presented. Special attention is given to methods of robust estimation and the identification of atypical and influential observations. Throughout the book, the emphasis is on application rather than theory.
Evaluation of the feasibility of a multisource CBCT for maxillofacial imaging

Objective. The aim of this study was to investigate the feasibility of improving the image quality and accuracy of cone beam computed tomography (CBCT) by replacing the conventional wide cone angle x-ray tube with a distributed x-ray source array positioned in the axial direction. Approach. The multisource CBCT (ms-CBCT) design was experimentally simulated using a benchtop scanner with a carbon nanotube x-ray tube and a flat-panel detector. The source was collimated and translated in the axial direction to simulate a source array with a reduced cone angle for each beam. An adjacent scatter ratio subtraction (ASRS) method was implemented for residual scatter reduction. Several phantoms were imaged using the ms-CBCT and conventional CBCT configurations under otherwise similar conditions. The Requirements of the ms-CBCT design on the x-ray source and detector were evaluated. Main results. Compared to the conventional CBCT, the ms-CBCT design with 8 sources and ASRS significantly improved the image quality and accuracy, including: (1) reducing the cupping artifact from 15% to 3.5%; (2) reducing the spatial nonuniformity of the CT Hounsfield unit values from 38.0 to 9.2; (3) improving the contrast-to-noise ratio of the low contrast objects (acrylic and low density polyethylene inserts) against the water-equivalent background by ∼20% and (4) reducing the root-mean-square error of the HU values by 70%, from 420.1 to 124.4. The imaging dose and scanning time used by the current clinical CBCT for maxillofacial imaging can be achieved by current source and detector technologies. Significance. The ms-CBCT design significantly reduces the scatter and improves the image quality and accuracy compared to the conventional CBCT.
Reduced Mortality and Radiation Necrosis After Surgery With Postoperative Stereotactic Radiation in Patients With Multiple Brain Metastases

BACKGROUND AND OBJECTIVES: Although stereotactic radiation has frequently supplanted whole-brain radiation therapy (WBRT) in treating patients with multiple brain metastases, the role of surgery for these patients remains unresolved. No randomized trials have compared surgical resection with postoperative stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) to SRS/SRT alone. Previous studies addressing surgery for patients with multiple brain metastases are often limited by small sample sizes, a lack of appropriate comparison groups, or a focus on patients treated before recent advances in targeted therapy and immunotherapy. We compared outcomes in patients with multiple brain metastases treated with surgical resection and postoperative SRS/SRT to those treated with SRS/SRT alone. METHODS: We studied 734 patients with multiple newly diagnosed brain metastases (surgery with SRS/SRT, n = 228; SRS/SRT alone, n = 506) from 2011 to 2022 in a retrospective, single-institution cohort. Patients who received upfront whole-brain radiotherapy were excluded. Cox proportional hazards models were constructed for overall survival and additional intracranial outcomes. RESULTS: After adjustment for potential confounders, surgery with postoperative SRS/SRT was associated with decreased all-cause mortality compared with SRS/SRT alone (hazard ratio [HR]: 0.67, 95% CI [0.50-0.89], P = 5.56 × 10−3). The association between surgical resection and overall survival was replicated in a subset of the cohort after cardinality matching (HR: 0.64, 95% CI [0.46-0.88], P = 6.68 × 10−3). Patients with melanoma benefited significantly less from surgical resection compared with patients with other tumor types, most notably non–small-cell lung cancer. Compared with definitive SRS/SRT, cavity SRS/SRT was associated with a significantly reduced risk of both symptomatic radiation necrosis (HR: 0.22, 95% CI [0.08-0.59], P = 2.70 × 10−3) and radiographic radiation necrosis (HR: 0.23, 95% CI [0.09-0.57], P = 1.43 × 10−3) in multivariable models. CONCLUSION: In patients with multiple brain metastases, surgical resection before SRS/SRT is associated with reduced mortality and radiation necrosis. Prospective studies may further delineate patient populations that benefit from aggressive local, brain-directed treatment even with significant intracranial disease burden.
Effect of immune responses on breath methane dynamics

Methane (CH4) which can be detected in human breath has long been exclusively associated with anaerobic microbial activity (methanogenesis) in the gastrointestinal tract. However, recent studies challenge this understanding by revealing that CH4 might also be produced endogenously in cells through oxidative–reductive stress reactions. Consequently, variations in breath CH4 levels compared to an individual’s baseline level might indicate enhanced oxidative stress levels, and, therefore, monitoring breath CH4 levels might offer great potential for ‘in vivo’ diagnostics such as disease diagnosis, monitoring the efficacy of treatments, or during the application of personalized medicine. To evaluate the effects from immune responses triggered by infections, inflammations, and induced perturbation by vaccination on CH4 dynamics in breath, two subjects were monitored over a period of almost 2 years. Breath CH4 levels were measured by gas chromatography equipped with a flame-ionization detector. Both subjects exhibited significant deviations (positive and negative, respectively) from their normal CH4 breath levels during periods of potential enhanced immune activity. Deviations from the ‘healthy state’ were indicated by the exceeding of individual CH4 ranges. Moreover, for the first time we could clearly prove CH4 degradation induced through vaccination by measuring stable carbon isotopes of CH4 using gas chromatograph–combustion–isotope ratio mass spectrometry. Hence, breath CH4 concentration and isotopic analyses may be used as a biomarker to evaluate specific immune responses and individual immune states.
Unbiased whole genome detection of ultrarare off‐target mutations in genome‐edited cell populations by HiFi sequencing

DNA base editors (BEs) composed of a nuclease‐deficient Cas9 fused to a DNA‐modifying enzyme can achieve on‐target mutagenesis without creating double‐strand DNA breaks (DSBs). As a result, BEs generate far less DNA damage than traditional nuclease‐proficient Cas9 systems, which do rely on the creation of DSBs to achieve on‐target mutagenesis. The inability of BEs to create DSBs makes the detection of their undesired off‐target effects very difficult. PacBio HiFi sequencing can efficiently detect ultrarare mutations resulting from chemical mutagenesis in whole genomes with a sensitivity ~1 × 10−8 mutations per base pair. In this proof‐of‐principle study, we evaluated whether this technique could also detect the on‐ and off‐target mutations generated by a cytosine‐to‐thymine (C>T) BE targeting the LacZ gene in Escherichia coli (E. coli). HiFi sequencing detected on‐target mutant allele fractions ranging from ~7% to ~63%, depending on the single‐guide RNA (sgRNA) used, while no on‐target mutations were detected in controls lacking the BE. The presence of the BE resulted in a ~3‐fold increase in mutation frequencies compared to controls lacking the BE, irrespective of the sgRNA used. These increases were mostly composed of C:G>T:A substitutions distributed throughout the genome. Our results demonstrate that HiFi sequencing can efficiently identify on‐ and off‐target mutations in cell populations that have undergone genome editing.
Identification of the nuclear localization signal in the Saccharomyces cerevisiae Pif1 DNA helicase

Saccharomyces cerevisiae Pif1 is a multi-functional DNA helicase that plays diverse roles in the maintenance of the nuclear and mitochondrial genomes. Two isoforms of Pif1 are generated from a single open reading frame by the use of alternative translational start sites. The Mitochondrial Targeting Signal (MTS) of Pif1 is located between the two start sites, but a Nuclear Localization Signal (NLS) has not been identified. Here we used sequence and functional analysis to identify an NLS element. A mutant allele of PIF1 (pif1-NLSΔ) that lacks four basic amino acids (781KKRK784) in the carboxyl-terminal domain of the 859 amino acid Pif1 was expressed at wild type levels and retained wild type mitochondrial function. However, pif1-NLSΔ cells were defective in four tests for nuclear function: telomere length maintenance, Okazaki fragment processing, break-induced replication (BIR), and binding to nuclear target sites. Fusing the NLS from the simian virus 40 (SV40) T-antigen to the Pif1-NLSΔ protein reduced the nuclear defects of pif1-NLSΔ cells. Thus, four basic amino acids near the carboxyl end of Pif1 are required for the vast majority of nuclear Pif1 function. Our study also reveals phenotypic differences between the previously described loss of function pif1-m2 allele and three other pif1 mutant alleles generated in this work, which will be useful to study nuclear Pif1 functions.
A nonlinear problem for the Laplace equation with a degenerating Robin condition

We investigate the behavior of the solutions of a mixed problem for the Laplace equation in a domain Ω. On a part of the boundary ∂Ω, we consider a Neumann condition, whereas in another part, we consider a nonlinear Robin condition, which depends on a positive parameter δ in such a way that for δ = 0 it degenerates into a Neumann condition. For δ small and positive, we prove that the boundary value problem has a solution u(δ,·). We describe what happens to u(δ,·) as δ→0 by means of representation formulas in terms of real analytic maps. Then, we confine ourselves to the linear case, and we compute explicitly the power series expansion of the solution.
Addressing the psychology of weight loss and maintenance: A feasibility study of the Skills for weight loss and Maintenance weight management programme.

OBJECTIVES Building on prior theory, we aimed to evaluate the feasibility and acceptability of integrating novel, weight loss maintenance strategies into existing weight management programmes. We also piloted recruitment and data collection procedures for future research. DESIGN Two phases of action research nested within a single-arm feasibility study. The intervention was refined between phases using feedback from intervention fidelity analysis and qualitative exploration of patient and provider experiences. Changes in outcomes were assessed up to 18 months post-baseline. METHODS One hundred adults with a mean body mass index of 37 kg/m2 were offered the Skills for weight loss and Maintenance (SkiM) intervention. This included existing weight management programme content and additional weight loss maintenance techniques delivered fortnightly for 6 months in local community centres to groups of 11-15 people. RESULTS Of the 100 participants, 65%, 58% and 56% provided data at 7, 12 and 18 months. Across both phases, the mean initial weight loss was 4.2 kg (95% CI: 2.4-5.9) and 3.1 kg at 18 months (95% CI: .8-5.5). In Phase 2, we observed better weight loss maintenance (.5 kg [13.2%] regain from 7 to 18 months, vs. 1.7 kg [36.2%] in Phase 1). Variation in outcomes, high early dropout rates and qualitative feedback indicated that, although delivery of the intervention and trial procedures was feasible and acceptable, there was scope to refine the intervention to engage a wider range of participants. Intervention fidelity was acceptable, particularly in Phase 2. CONCLUSIONS The SkiM intervention seems promising, but more research is needed to improve recruitment and retention prior to further evaluation.
Reducing safety behaviors to prevent anxious symptoms: a pre-registered prevention intervention study

ABSTRACT The purpose of this pre-registered study was to test the efficacy of a simple, low-impact safety behavior prevention intervention for anxiety. The intervention was delivered online using a 4-week workbook format. Participants (n = 130) were a non-clinical sample of American college students; they were randomly assigned to one of two intervention conditions: safety-behavior reduction or active control condition (academic skills). Results showed that participants in the safety behavior workbook condition did not report fewer safety behaviors or lower levels of anxiety compared to the active control condition post-intervention. Exploratory analyses found that fidelity mattered; participants who completed all the workbook activities reported a significant decrease in the safety-behaviors relative to the control condition. However, those who reduced their use of safety behaviors reported greater levels of anxiety compared to participants in the control condition who reduced their safety behaviors. These results suggest that encouraging safety behavior reduction in non-clinical samples may have the unintended consequence of maintaining anxiety.
The Emerging Role of Senotherapy in Cancer: A Comprehensive Review

Senotherapy, a promising therapeutic strategy, has drawn a lot attention recently due to its potential for combating cancer. Senotherapy refers to the targeting of senescent cells to restore tissue homeostasis and mitigate the deleterious effects associated with senescence. Senolytic drugs represent a promising avenue in cancer treatment, with the potential to target and modulate senescent cells to improve patient outcomes. The review highlights the intricate interplay between the senescence-associated secretory phenotype (SASP) and the tumor microenvironment, emphasizing the role of senescent cells in promoting chronic inflammation, immune evasion, and tumor-cell proliferation. It then explores the potential of senotherapy as a novel strategy for cancer therapy. This review addresses the emerging evidence on the combination of senotherapy with conventional cancer treatments, such as chemotherapy and immunotherapy.
Full-length transcript alterations in human bronchial epithelial cells with U2AF1 S34F mutations

Using long-read Nanopore cDNA sequencing, this study identifies full-length transcripts associated with U2AF1 S34F mutations revealing effects on translation regulation of specific genes. U2AF1 is one of the most recurrently mutated splicing factors in lung adenocarcinoma and has been shown to cause transcriptome-wide pre-mRNA splicing alterations; however, the full-length altered mRNA isoforms associated with the mutation are largely unknown. To better understand the impact U2AF1 has on full-length isoform fate and function, we conducted high-throughput long-read cDNA sequencing from isogenic human bronchial epithelial cells with and without a U2AF1 S34F mutation. We identified 49,366 multi-exon transcript isoforms, more than half of which did not match GENCODE or short-read–assembled isoforms. We found 198 transcript isoforms with significant expression and usage changes relative to WT, only 68% of which were assembled by short reads. Expression of isoforms from immune-related genes is largely down-regulated in mutant cells and without observed splicing changes. Finally, we reveal that isoforms likely targeted by nonsense-mediated decay are down-regulated in U2AF1 S34F cells, suggesting that isoform changes may alter the translational output of those affected genes. Altogether, our work provides a resource of full-length isoforms associated with U2AF1 S34F in lung cells.
A New Robust Multi-station Direction Finding Cross Algorithm

During the multi-station direction finding cross positioning, instable or divergent positioning evaluation result, even invalid situation will occur caused by unreasonable sensor allocation, and analyzes the causes of ill-condition in traditional localization algorithm Therefore, this paper puts forward a kind of stable positioning method based on singular value decomposition modification. The method doesn’t require the station allocation greatly and could consider the resolution and variance assessed by positioning parameter effectively. It realizes effective inhibition to the random observation noise in the observation equation and has better engineering application value. The value simulation result indicates the positioning result is more precise and stable than traditional calculating method.
Epigenetic Regulation in Heterosis and Environmental Stress: The Challenge of Producing Hybrid Epigenomes to Face Climate Change

Epigenetic regulation has the potential to revolutionize plant breeding and improve crop yields by regulating gene expression in plants. DNA methylation and histone modifications are key epigenetic modifications that can impact plant development, stress responses, productivity, and yields. Higher-yielding crops not only generate greater profits for farmers and seed producers, but also require less land, water, fuel, and fertilizer than traditional crops for equivalent yields. The use of heterosis in crops can influence productivity and food quality, but producing hybrids with superior agronomic traits to their parents remains challenging. However, epigenetic markers, such as histone methylation and acetylation, may help select parental and hybrid combinations with better performances than the parental plants. This review assesses the potential applications of epigenetics in crop breeding and improvement, rendering agriculture more efficient, sustainable, and adaptable to changing environmental conditions.
Whole Body Substrate Metabolism during Different Exercise Intensities with Special Emphasis on Blood Protein Changes in Trained Subjects—A Pilot Study

Contrary to carbohydrate and fat metabolism, the influence of a single exercise dose on protein metabolism has not been adequately explored yet. We assessed the effects of different exercise intensities and durations on blood protein changes and their association with carbohydrate (CHO) and fat metabolism in six eligible trained subjects. Subjects performed maximal incremental (IE100: at 100%VO2max) and submaximal continuous exercise (CE) at 75%VO2max for 30 min (CE75) and at 50%VO2max for 90 min (CE50). Blood samples were collected at rest (R), end of exercise (EE), and 1 h after recovery to assess blood urea nitrogen (BUN), plasma amino acids (AA), glucose, lactate, FFA, and glycerol. In IE100 blood lactate, CHO-oxidation (g/min), energy expenditure (kcal/min), and RER were significantly increased during rest (p < 0.05). CE50 induced significantly higher BUN, FFA, glycerol, and fat oxidation (g/min) (p < 0.05). At recovery, the mean sum of the free AA pool (µmol/L) reduced by 8% (p < 0.03) during CE50. Values for CE75 were between IE100 and CE50. Beside lipolysis, also proteolysis (BUN) was an important source of fuel for low-to-moderate intensity CE50. An increased uptake of AA from the plasma bed during CE50 suggests the importance for oxidation and synthesis of other metabolic sources such as gluconeogenesis necessary for recovery. Therefore, one needs to be cautious of protein diet following prolonged cycle exercise training.