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Activity impairment, work productivity, health-related quality-of-life, and costs associated with uncomplicated urinary tract infection among females in Germany

Uncomplicated urinary tract infections (uUTIs) represent a sizable healthcare burden with a substantial negative impact on patients’ health-related quality-of-life (HRQoL). However, the HRQoL impact of uUTI from the patient perspective is under-represented in research. A cross-sectional online survey assessed activity impairment and work productivity, HRQoL, costs, and treatment satisfaction of female patients with uUTIs in the US; the current study applies this earlier methodology to Germany to provide a European perspective. We examined: activity impairment and work productivity using Activity Impairment Assessment (AIA), and Work Productivity and Activity Impairment (WPAI) questionnaires, respectively; HRQoL using a modified Short Form-36, and participants completed the treatment satisfaction questionnaire for medication. Participants (≥ 12 years) self-reported a uUTI treated with oral antibiotics in the last 60 days, had no evidence of complicated UTI, and were recruited via a consumer panel. In the patient (N = 200) survey, bladder pain (70%), dysuria (69%), and frequent urination (66%) were the most common uUTI symptoms reported. Activities frequently affected by uUTI were sexual activity (56%) and exercise (48%), resulting in an overall AIA score of 8.2 indicating that activities among patients were impaired ‘most of the time’ during their recent uUTI. Absenteeism was 29% (of a 40-hour work week); presenteeism, 34%; and overall work impairment, 41%. Indirect costs due to impact of uUTI were €7.62/hour/participant, representing a loss for the employer. The lowest HRQoL scores were for mental (44%) and physical components (43%); emotional and physical functioning scores were 71% and 70%, respectively. Mean direct costs of €20.10 for medical treatments and €11.30 for other treatment costs were reported. Overall, most participants were satisfied with the uUTI treatment (76% satisfaction score). Results demonstrate the patient-reported burden of uUTI for patients and employers, with activities and ability to work impacted, resulting in a notable indirect burden in Europe.

Two-year follow-up of gait and postural control following initiation of recombinant human tripeptidyl intracerebroventricular enzyme replacement therapy in two atypical CLN2 patients

AbstractNeuronal ceroid lipofuscinosis type 2 (CLN2) is a rapidly progressive neurodegenerative disorder leading to premature mortality. Ambulatory CLN2 patients typically receive standard of care treatment through biweekly intracerebroventricular (ICV) enzyme replacement therapy (ERT) involving recombinant human tripeptidyl peptidase 1, known as cerliponase alfa (Brineura®, Biomarin Pharmaceuticals). This study longitudinally assessed the impact of ICV cerliponase alfa ERT on gait, and postural control across a two-year span in two siblings diagnosed with atypical CLN2 disease. Both participants, ID01 (18 years and 8 months old at enrollment) and ID02 (13 years and 3 months old at enrollment), exhibited symptomatic characteristics which were studied longitudinally over three years. Their evaluations assessed postural sway variability, potential for slips and trips, gait metrics, sit-to-stand durations, scores from the sensory organization test (SOT), and gross motor function measure (GMFM) scores. Findings indicated a decline in postural complexity and stability in the medial-lateral (ML) axis, a reduction in toe clearance, and an augmented risk of stumbling for the participants. Over the two-year period of ERT, both siblings exhibited a progressive decline in walking velocity, characterized by reductions in step length and prolonged gait cycle time. The elder sibling demonstrated a notable increase in double support duration, indicative of heightened reliance on proprioceptive input to maintain stability during ambulation. Additionally, sit-to-stand times lengthened for siblings, further reflecting declines in motor function. Despite these challenges, SOT scores showed improvement after two years of ERT, suggesting some preservation of sensory integration. These findings in SOT scores indicate that cerliponase alfa treatment in patients with atypical CLN2 disease may confer benefits in postural stability, lower extremity strength, and ankle stiffness. However, declines in more complex motor functions, including sit-to-stand performance and postural complexity, persist, underscoring the progressive nature of the disease despite ongoing therapeutic intervention.

Time evolution of a pumped molecular magnet—A time-resolved inelastic neutron scattering study

Introducing an experimental technique of time-resolved inelastic neutron scattering (TRINS), we explore the time-dependent effects of resonant pulsed microwaves on the molecular magnet Cr 8 F 8 Piv 16 . The octagonal rings of magnetic Cr 3+ atoms with antiferromagnetic interactions form a singlet ground state with a weakly split triplet of excitations at 0.8 meV. A 4.6 tesla field was applied to tune the splitting between two members of the triplet excited level | 1 ⟩ ↔ | 2 ⟩ to resonance with 105 GHz (0.434 meV) microwaves. The time-dependent occupations of the ground state | 0 ⟩ , lower lying levels | 1 ⟩ and | 2 ⟩ , and higher energy states | λ ≥ 3 ⟩ were extracted during and after 20 s long microwave pulses incident along the (101) direction of a Cr 8 F 8 Piv 16 crystal held at 1.9 K. At significantly elevated spin temperatures, we found underpopulation relative to thermal equilibrium of | 2 ⟩ and spin-lattice thermalization time scales ranging from 1.6(2) s to 5.7(2) s depending on the power level. This contrasts with the relaxation time τ 1 ( T → 0 ) = 27 ( 5 ) μ s inferred for | 2 ⟩ from in situ Electron Spin Resonance measurements. By probing a broad range of excited states during intense microwave pumping, TRINS thus provides a first view of long lived excited states in a molecular antiferromagnet.

Avoiding catastrophic overfitting in fast adversarial training with adaptive similarity step size

Adversarial training has become a primary method for enhancing the robustness of deep learning models. In recent years, fast adversarial training methods have gained widespread attention due to their lower computational cost. However, since fast adversarial training uses single-step adversarial attacks instead of multi-step attacks, the generated adversarial examples lack diversity, making models prone to catastrophic overfitting and loss of robustness. Existing methods to prevent catastrophic overfitting have certain shortcomings, such as poor robustness due to insufficient strength of generated adversarial examples, and low accuracy caused by excessive total perturbation. To address these issues, this paper proposes a fast adversarial training method—fast adversarial training with adaptive similarity step size (ATSS). In this method, random noise is first added to the input clean samples, and the model then calculates the gradient for each input sample. The perturbation step size for each sample is determined based on the similarity between the input noise and the gradient direction. Finally, adversarial examples are generated based on the step size and gradient for adversarial training. We conduct various adversarial attack tests on ResNet18 and VGG19 models using the CIFAR-10, CIFAR-100 and Tiny ImageNet datasets. The experimental results demonstrate that our method effectively avoids catastrophic overfitting. And compared to other fast adversarial training methods, ATSS achieves higher robustness accuracy and clean accuracy, with almost no additional training cost.

Exposing the obscured influence of state-controlled media via causal inference of quotation propagation

Abstract Reporting by major media outlets influences news coverage by other outlets, resulting in an outsized impact on public opinion. Understanding this inter-outlet influence, known as intermedia agenda setting, is important for assessing the impact of state media and strategic communications. We demonstrate a novel method to quantify inter-outlet influence using causal inference on “quote following,” where one outlet uses the same quote as another outlet at a later date. By applying our methodology to a dataset of quotes from over 100,000 articles published in European media between May 2018 and October 2019, we reveal obscured influence by Russian state-affiliated media over other outlets and the general dynamics of European media. We find that Russian state-controlled media have a strong influence on the coverage of other Russian outlets, including independent outlets. Moreover, this influence extends to media ecosystems of other countries. Finally, we demonstrate quantifying inter-outlet influence on the specific topic of nuclear forces treaty, as an example of precision study of intermedia agenda setting on specific issues. Overall, our methodology quantifies sources and channels of influence between news outlets with important implications for strategic communication, influence operations, and media independence.

A phase transition in diffusion models reveals the hierarchical nature of data

Understanding the structure of real data is paramount in advancing modern deep-learning methodologies. Natural data such as images are believed to be composed of features organized in a hierarchical and combinatorial manner, which neural networks capture during learning. Recent advancements show that diffusion models can generate high-quality images, hinting at their ability to capture this underlying compositional structure. We study this phenomenon in a hierarchical generative model of data. We find that the backward diffusion process acting after a time t is governed by a phase transition at some threshold time, where the probability of reconstructing high-level features, like the class of an image, suddenly drops. Instead, the reconstruction of low-level features, such as specific details of an image, evolves smoothly across the whole diffusion process. This result implies that at times beyond the transition, the class has changed, but the generated sample may still be composed of low-level elements of the initial image. We validate these theoretical insights through numerical experiments on class-unconditional ImageNet diffusion models. Our analysis characterizes the relationship between time and scale in diffusion models and puts forward generative models as powerful tools to model combinatorial data properties.

Health status correlates of malnutrition diagnosed based on the GLIM criteria in older Polish adults—Results of the PolSenior 2 study

Introduction Older individuals are at risk of malnutrition resulting from chronic diseases-related body and muscle mass reduction. In turn, nutritional deficiencies may enhance catabolic processes, leading to accelerated aging and comorbidity, thus creating a vicious cycle. Our study aimed to assess the prevalence of malnutrition using the Global Leadership Initiative on Malnutrition (GLIM) criteria and to determine the health correlates of malnutrition in a representative sample of community-dwelling older adults. Methods We used the GLIM criteria to diagnose malnutrition in 5,614 participants of the PolSenior2 study. The PolSenior2 study was a population-based survey designed to assess the medical, psychological, social, and economic characteristics of community-dwelling older adults. Results Malnutrition was diagnosed in 13.4% of the participants using the GLIM criteria. Results of multiple logistic regression showed that the risk of depression [OR 4.18, p<0.001], peptic ulcer disease [OR 2.73, p<0.001], past stroke [OR 1.71, p<0.001], cognitive impairment [OR 1.34, p = 0.015], and chronic pain [OR 1.23, p = 0.046] were independent correlates of malnutrition. Conclusion Due to the high risk of malnutrition, special attention should be paid to individuals in late old age. Suspected malnutrition should also be considered in people at risk of depression, with peptic ulcer disease, past stroke, and cognitive impairment. Chronic pain should also prompt the diagnosis for malnutrition.

Examination of the requirements for powered air-purifying respirator (PAPR) utilization as an alternative to lockdown

Abstract With the emergence of COVID-19 variants and new viruses, it remains uncertain when the next pandemic will occur. A lockdown is considered the last resort to halt the spread of infection; however, it causes significant economic and social damage. Therefore, exploring less harmful alternatives during such scenarios is crucial. This study explores the feasibility of using a powered air-purifying respirator (PAPR) as an alternative to lockdowns and as a strategy for infection control. Specifically, the study examines the potential impact of the PAPR wearing rate and PAPR aerosol shielding performance on the controllability of the spread of infections. The study investigated the necessary PAPR wearing rate and aerosol shielding performance to control infections as an alternative to the lockdown, using a simple simulation under limited conditions. When using a PAPR with 100% aerosol shielding capability in air supply, only 55% of the population needs to consistently wear the PAPR to reduce the effective reproduction number from a critical level ( R t  = 2) to a target level ( R t  = 0.9). Furthermore, if everyone consistently wears PAPR, only 55% the reduction ratio in the probability of becoming infected by PAPR supplying air I r_in is enough for reducing the effective reproduction number from a critical level ( R t  = 2) to a target level ( R t  = 0.9). This study demonstrates the potential for utilizing PAPR as an alternative to lockdowns.

PhiSiCal-Checkup: A Bayesian framework to validate amino acid conformations within experimental protein structures

As structural biology and drug discovery depend on high-quality protein structures, assessment tools are essential. We describe a new method for validating amino-acid conformations: “PhiSiCal ( ϕ ψ χ al) Checkup.” Twenty new joint probability distributions in the form of statistical mixture models explain the empirical distributions of dihedral angles ω , ϕ , ψ , χ 1 , χ 2 , … of canonical amino acids in experimental protein structures. Marginal and conditional probability distributions for subsets of dihedral angles are derived from these joint mixture models. Together, these distributions are employed to measure rapidly the information-theoretic “favorability” of any proposed experimental protein structure. The inferred statistical models and measures overcome several shortcomings and afford improvements over the current state of the art in amino-acid conformation verification. Experimental comparisons are made against current protein conformation verification software. In a number of examples, we pick up outliers that are invisible to current methods. We also calculate, as part of verification, the sensitivity of favorability to small changes in a proposed structure accounting for the precision of coordinates. In some cases a near neighbor of a proposed amino-acid conformation may be either less or more favorable. This raises the question, is the current reliance on fixed “thresholds” for validation a good thing? PhiSiCal-Checkup is freely available for online and offline (open-source) use from https://lcb.infotech.monash.edu.au/phisical/checkup .

Woody species composition and diversity of agroforestry homegardens along altitudinal gradient in southwest Ethiopia

Homegarden agroforestry systems that integrate trees with agricultural practices are usually valued for the conservation of farm biodiversity. Despite the system having a significant conservation role, litle is known on woody species composition and diversity following the elevation belt of southwest Ethiopia. A complete enumeration of 72 homegardens (24 each from altitudinal gradient) was purposively selected for woody species inventory. A total of 55 woody species belonging to 31 families and 45 genera were recorded. Of which, 56.4% of woody species are indigenous and two are endemic to Ethiopia. Family Fabaceae was the most represented family with eight species. The highest species richness (42) was observed at high altitudes followed by 39 species at middle and 31 species at low altitudes but no significant difference between them. Species richness significantly (P < 0.001) increased with increasing wealth status. The overall richness distribution was 46, 40, and 27 across rich, medium, and poor wealth classes respectively. Shannon diversity index differed significantly between poor and rich households. Pearson correlation result shows a strong positive and significant correlation between richness and wealth status. The mean woody species density was 89.06±9.25 and 1236.22±131.42 per garden and hectare, respectively. Stem density was significantly higher (P < 0.001) in wealthier farms. We found that, in southwestern Ethiopia wealthier agroforestry farms can support more woody species diversity in homegardens.

Kinematics of balance controls in people with chronic ankle instability during unilateral stance on a moving platform

AbstractBalance control deficits resulting from ankle sprains are central to chronic ankle instability (CAI) and its persistent symptoms. This study aimed to identify differences in balance control between individuals with CAI and healthy controls (HC) using challenging single-leg balance tasks. Twenty-three CAI and 23 HC participants performed balance tasks on a force plate that either remained static or moved mediolaterally. Force and kinematic data were recorded to measure balance and joint movements. The CAI group showed significantly shorter time-to-boundary during static conditions but no significant differences during moving conditions compared to HC. During moving conditions, CAIs exhibited greater proximal compensations, with greater range of motion and higher angular velocity in the knee, hip, and torso. while no significant differences were observed in these parameters during static conditions. Principal component analysis indicated specific kinetic chain in CAI during one-leg balance under both static and moving conditions compared to HC. These findings suggest an altered movement strategy in CAI, that ankle injuries impair the ability to stabilize both distal and proximal joints, and an altered kinetic chain from ankle to torso. Rehabilitation programs for CAI might benefit from considering the integration of the entire kinetic chain, addressing both distal and proximal joint dynamics to support effective recovery and prevent secondary injuries.

Development and validation of the Iranian Minimum Data Set for Epidermolysis Bullosa: A mixed method approach

Minimum Data Set (MDS) enables integration in data collection, uniform data reporting, and data exchange across clinical and research information systems. The current study was conducted to determine a comprehensive national MDS for the Epidermolysis Bullosa (EB) information management system in Iran. This cross-sectional descriptive study consists of three steps: systematic review, focus group discussion, and the Delphi technique. A systematic review was conducted using relevant databases. Then, a focus group discussion was held to determine the extracted data elements with the help of contributing multidisciplinary experts. Finally, MDSs were selected through the Delphi technique in two rounds. The collected data were analyzed using Microsoft Excel 2019. In total, 103 data elements were included in the Delphi survey. The data elements, based on the experts’ opinions, were classified into two main categories: administrative data and clinical data. The final categories of data elements consisted of 11 administrative items and 92 clinical items. The national MDS, as the core of the EB surveillance program, is essential for enabling appropriate and informed decisions by healthcare policymakers, physicians, and healthcare providers. In this study, a MDS was developed and internally validated for EB. This research generated new knowledge to enable healthcare professionals to collect relevant and meaningful data for use. The use of this standardized approach can help benchmark clinical practice and target improvements worldwide.

Impact of bariatric surgery on liver fibrosis indices among type 2 diabetes patients in a national cohort

Optimizing power grids: A valley-filling heuristic for energy-efficient electric vehicle charging

The expansion of electric vehicles (EVs) challenges electricity grids by increasing charging demand, thereby making Demand-Side Management (DSM) strategies essential to maintaining balance between supply and demand. Among these strategies, the Valley-Filling approach has emerged as a promising method to optimize renewable energy utilization and alleviate grid stress. This study introduces a novel heuristic, Load Conservation Valley-Filling (LCVF), which builds on the Classical and Optimistic Valley-Filling approaches by incorporating dynamic load conservation principles, enabling better alignment of EV charging with grid capacity. We conducted a comprehensive analysis of the heuristic across five EV charging scenarios. In both the Original and Flexible scenarios, LCVF reduced energy demand by up to 10.65%, demonstrating its adaptability and effectiveness. Notably, in the 24-hour Availability scenario, LCVF achieved a reduction of over 20% in energy demand compared to CVF. These findings indicate that LCVF could play a crucial role in enhancing real-world EV charging infrastructure, boosting energy efficiency and grid stability. By integrating DSM strategies like LCVF, energy grids can better accommodate renewable energy sources, promoting more sustainable operations.

Qualitative comparison of decalcifiers for mouse bone cryosections for subsequent biophotonic analysis

AbstractBone tissue, with its complex structure, often necessitates decalcification of the hard tissue for ex vivo morphological studies. The choice of a suitable decalcification method plays a crucial role in preserving desired features and ensuring compatibility with diverse imaging techniques. The search for a universal decalcification method that is suitable for a range of biophotonic analyses remains an ongoing challenge. In this study, we systematically assessed five standard bone decalcification protocols, encompassing strong mineralic acids (3% and 5% nitric acid), a commercially available formulation of hydrochloric and formic acid), as well as weak organic acids (5% trichloroacetic acid and 8% formic acid), and a chelating agent (25% ethylenediamine-tetraacetic acid) with varying decalcification durations, using mouse long bones as our experimental model. Our imaging analysis panel included classical histological staining (Hematoxylin and Eosin, H&E), immunofluorescence staining, and label-free Raman microspectroscopic imaging. We used cryosections instead of paraffin sections since paraffin interferes with tissue Raman signals. This approach is not as commonly used as it is more prone to handling artifacts, but is the preferred method for subsequent Raman analysis. Decalcification efficacy was evaluated based on various qualitative and some quantitative imaging parameters by 2–3 independent observers. Our systematic approach revealed that the chelating agent, when used for 24 h, optimally preserved bone features and, thus, would be the ideal decalcifying agent for comprehensive subsequent analysis. However, the choice of decalcifier and the ideal decalcification duration may vary depending on the type and thickness of bone, necessitating tailored adjustments to meet specific experimental requirements.

Effectiveness of menstrual hygiene management training to enhance knowledge, attitude, and practice among adolescents in Sindhupalchowk, Nepal

Background Menstrual Health (MH) knowledge, attitude and practice (KAP) are highly affected by access to information regarding menstruation. Despite being included in the school curriculum, Sexual and Reproductive Health (SRH) education is often not delivered in practice. School-based educational interventions have been shown to be effective in promoting MH. Methods A school-based study was conducted in Indrawati rural municipality of Sindhupalchowk district in Nepal. 427 participants (175 boys and 252 girls), aged 11–13, completed a questionnaire evaluating MH KAP before receiving a structured training module on MH provided by experienced trainers from Putali Nepal using the Menstrupedia tool. The questionnaire was repeated one month after the training. Pre and post intervention scores were compared to determine the effect of the intervention. Focus group discussions were also conducted to understand the perceptions of participants toward SRH teaching. Association of independent socio-demographic with dependent variables knowledge and attitude towards menstrual health were analyzed using MANOVA test. The Wilcoxon signed-rank test was used to compare the median outcome of the pre and post-test attitude and knowledge. The maximum possible score was 6 for MH knowledge. The total attitude score ranged 14 to 70. Results The median knowledge score increased by 1 point (p = <0.001) and the median attitude score by 5 points (p = <0.001), one month after delivery of the intervention. Higher knowledge scores were significantly associated with Hindu religion, female gender, higher father’s literacy, and mothers in an informal occupation on multivariate analysis. Higher attitude scores were significantly associated with Hindu religion while lower attitude scores were associated with a mother in an informal occupation. Conclusion The Menstrupedia comic educational intervention improved knowledge and attitude towards menstruation among Nepali adolescents. A scale-up of the Menstrupedia based intervention would significantly change knowledge and attitude towards menstruation in Nepali adolescents.

Analyzing the association of critical illness and cardioversion success in patients with atrial fibrillation at the emergency department

Hypermethylation at 45S rDNA promoter in cancers

The ribosomal genes (rDNA genes) encode 47S rRNA which accounts for up to 80% of all cellular RNA. At any given time, no more than 50% of rDNA genes are actively transcribed, and the other half is silent by forming heterochromatin structures through DNA methylation. In cancer cells, upregulation of ribosome biogenesis has been recognized as a hallmark feature, thus, the reduced methylation of rDNA promoter has been thought to support conformational changes of chromatin accessibility and the subsequent increase in rDNA transcription. However, an increase in the heterochromatin state through rDNA hypermethylation can be a protective mechanism teetering on the brink of a threshold where cancer cells rarely successfully proliferate. Hence, clarifying hypo- or hypermethylation of rDNA will unravel its additional cellular functions, including organization of genome architecture and regulation of gene expression, in response to growth signaling, cellular stressors, and carcinogenesis. Using the bisulfite-based quantitative real-time methylation-specific PCR (qMSP) method after ensuring unbiased amplification and complete bisulfite conversion of the minuscule DNA amount of 1 ng, we established that the rDNA promoter was significantly hypermethylated in 107 breast, 65 lung, and 135 colon tumour tissue samples (46.81%, 51.02% and 96.60%, respectively) as compared with their corresponding adjacent normal samples (26.84%, 38.26% and 77.52%, respectively; p < 0.0001). An excessive DNA input of 1 μg resulted in double-stranded rDNA remaining unconverted even after bisulfite conversion, hence the dramatic drop in the single-stranded DNA that strictly required for bisulfite conversion, and leading to an underestimation of rDNA promoter methylation, in other words, a faulty hypomethylation status of the rDNA promoter. Our results are in line with the hypothesis that an increase in rDNA methylation is a natural pathway protecting rDNA repeats that are extremely sensitive to DNA damage in cancer cells.

Mechanical properties and mechanisms of soda residue and fly ash stabilized soil

Affinity maturation endows potent activity onto class 6 SARS-CoV-2 broadly neutralizing antibodies

The emergence of SARS-CoV-2 variants of concern (VOCs) has greatly diminished the neutralizing activity of previously FDA-approved monoclonal antibodies (mAbs), including that of antibody cocktails and of first-generation broadly neutralizing antibodies such as S309 (Sotrovimab). In contrast, antibodies targeting cryptic conformational epitopes of the receptor binding domain (RBD) have demonstrated broad activity against emerging variants, but exert only moderate neutralizing activity, which has so far hindered clinical development. Here, we utilize in vitro display technology to identify and affinity-mature antibodies targeting the cryptic class 6 epitope, accessible only in the “up” conformation of the SARS-CoV-2 spike trimer. Increasing antibody affinity into the low picomolar range endowed potent neutralization of VOCs and protection of hACE2 mice from viral challenge. Cryoelectron microscopy and crystal structures of two affinity-matured antibodies (4C12-B12 and 4G1-C2) in complex with RBD highlighted binding modes and epitopes distal from mutational hotspots commonly overserved in VOCs, providing direct structural insights into the observed mutational resistance. Moreover, we further demonstrate that antibodies targeting the class 6 epitope, rather than being an artifact of in vitro selection, are common in the IgG1 + memory B cell repertoire of convalescent patients and can be induced in human antibody V-gene transgenic mice through immunization. Our results highlight the importance of very high (picomolar) affinity in the development of neutralizing antibodies and vaccines and suggest an affinity threshold in the provision of broad and long-lasting immunity against SARS-CoV-2.