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Physicists unleashed the power of the atom — but to what end?

Development and characterization of pramipexole dihydrochloride buccal films for Parkinson’s disease treatment

Parkinson’s disease is one of the most common neurodegenerative diseases worldwide. Swallowing difficulties present a significant challenge in the treatment of Parkinson’s disease patients. Our current experimental work aimed to produce and assess a buccal polymer film containing pramipexole as the active pharmaceutical agent. This dosage form addresses the swallowing difficulties faced by Parkinson’s patients, potentially eliminating inappropriate drug application and thereby improving therapeutic success. For the preparation of polymer films, chitosan was used as the film-forming agent, and pramipexole dihydrochloride was the active pharmaceutical ingredient. The physical properties of the prepared polymer films, such as thickness, tensile strength, mass, and disintegration time were examined, along with in vitro mucoadhesivity. The chemical interactions between the different components of the films were analyzed using FTIR spectroscopy. Additionally, the dissolution of pramipexole from the polymer film and the permeation of the active ingredient through the TR146 buccal cell line were investigated. Finally, the biocompatibility of the prepared polymer films was also tested on a buccal cell line. The results indicate that increasing the concentration of glycerol reduced the tensile strength and mucoadhesion of the films to 12 kPa and 7 N, respectively. Interactions between the components of films were confirmed by FTIR analysis. All formulations demonstrated biocompatibility higher than 80%. Based on different investigations, Sample 4 and Sample 5 are suitable for buccal application. These formulations exhibit promising attributes for treating Parkinson’s disease.

Why space foods aren’t just for space

Oral creatine in hemodialysis patients increases physical functional capacity and muscle mass, an open label study

Background and hypothesis Individuals undergoing chronic hemodialysis represent a population with high morbidity and mortality, primarily due to poor nutritional status, chronic inflammation, and cardiovascular disease. However, additional factors, such as low physical activity and impaired functionality, have also been identified as directly associated with increased mortality. Main objective This study was conceived as a pilot study to investigate whether creatine supplementation (5g/day) for eight weeks could provide benefits in terms of physical functionality, handgrip and body composition in a group of adult patients on chronic hemodialysis. On dialysis days, creatine was administered immediately post-dialysis, while on non-dialysis days, patients took the supplement at home. Measurements were taken using bioimpedance analysis, handgrip strength (via dynamometry), and the Short Physical Performance Battery (SPPB), both before starting creatine supplementation and at week 8 of treatment. Results After performing robust statistical analysis, following creatine supplementation, an increase in SPPB scores was observed, with a mean improvement of 0.78 points [95% CI: 0.17–1.44] and an effect size of 0.53. Skeletal muscle mass increased by an average of 1.31 kg [95% CI: 0.55 to 2.23], with an effect size of 0.66. Fat-free mass showed a mean increase of 2.11 kg [95% CI: 0.75 to 3.58] with an effect size of 0.64, while phase angle rose by 0.52 degrees [95% CI: 0.27 to 0.76], corresponding to an effect size of 0.90. Regarding volumetric estimates, total body water increased by 1.17 L [95% CI: 0.26 to 2.13] with an effect size of 0.54, and intracellular water increased by 0.97 L [95% CI: 0.48 to 1.51] with an effect size of 0.81. No significant differences were observed in extracellular water with change of 0.20 L [95% CI: −0.30 to 0.70] or handgrip strength with an increment of 0.67 kgF, [95% CI: −0.67 to 2.11]. Conclusion Oral creatine supplementation in HD patients for eight weeks improved muscular and functional outcomes and may be proposed as a strategy to mitigate the elevated morbidity observed in this group of patients.

Highly efficient enzymes designed from scratch

Renal cancer survival in clear cell renal cancer compared to other types of tumor histology: A population-based cohort study

Introduction Renal cancer (RC) presents a challenge with increasing incidence and mortality. This study compares RC cancer-specific survival (CSS) and overall survival (OS) based on histological type. Study design This population-based retrospective cohort study covers 1995–2017, utilizing cases from the Finnish Cancer Registry. Comorbidity, procedure and treatment information from 1995–2018 were obtained from the national health care registry, while death data originated from the national death certificate registry. RC cases were categorized by histology to analyze CSS and OS via Fine and Gray’s proportional sub-hazards model and Cox regression (adjusting for age, tumor extent, Charlson comorbidity index and treatment). Results The final cohort included 14,413 patients, predominantly ccRCC (75.5%), followed by papillary RCC (pRCC),5.8% and chromophobe RCC (chRCC) 2.1%. Univariate analysis showed better OS for non-ccRCC patients, with 5-year survival (5ySR) of 72.6% (95% CI 70.3–74.7%), compared to ccRCC (62.7%, 95%CI 61.8–63.5). Among non-ccRCC, the 5ySRs were as follows: pRCC 74.3% (95%CI 71.2–77.2), chRCC 82.2% (95% CI 77.2–86.1), sarcomatoid variants (sarcRC) 29.2% (95% CI 20.6–38.3), and collecting duct carcinoma (CDC) 23.5% (95%CI 7.3–44.9). Non-ccRCC showed improved CSS compared to ccRCC (sHR 0.69, 95% CI 0.60–0.78). Favorable CSS for chRCC (sHR 0.28, 95% CI 0.18–0.43) and pRCC (sHR 0.66, 95% CI 0.56–0.78), while sarcRC (sHR 1.83, 95% CI 1.36–2.46) and CDC (sHR 3.19, 95% CI 2.01–5.08) showed poorer CSS. Overall, non-ccRCC had a better prognosis, driven by pRCC and chRCC, whereas sarcRC and CDC had poor prognoses. CSS has improved over time, with a 62% reduction in death risk since 1995. Conclusion Our results demonstrate that the histological subtype is a powerful predictor of survival. Histology should be used more in clinical decision-making. Having a histological confirmation would tailor the selection of treatment: surgical management for aggressive and ccRCC and conservative management for less aggressive histological types.

How I’m helping to develop more-resilient food systems

The impact of demographic factors and personality traits on nurse compassion fatigue: A cross-sectional analysis

Background Compassion fatigue significantly impacts nurses’ work efficiency, care quality, and overall well-being. Consequently, the phenomenon of compassion fatigue among nurses has garnered considerable attention. Research from abroad indicates that demographic factors and the Big Five personality traits are closely related to the burnout dimension of compassion fatigue. This insight opens new avenues for studying compassion fatigue in nurses. Purpose This study aims to analyze the current state of compassion fatigue among nurses and its influencing factors. Furthermore, it seeks to explore the correlation between compassion fatigue and personality traits, providing valuable references for alleviating compassion fatigue among nurses. Methods A survey using general information, the Chinese Compassion Fatigue Short Scale, and the brief version of the Chinese Neuroticism Extraversion Openness Five-Factor Inventory was conducted on 332 nurses from a major tertiary hospital. Results The total score for nurse compassion fatigue was 51.83(SD=22.02). Factors such as years of service, professional title, monthly income, and department were identified as influencing compassion fatigue. The total score for compassion fatigue exhibited a negative correlation with extraversion, openness, agreeableness, and conscientiousness, while it showed a positive correlation with neuroticism. The Big Five personality traits accounted for 47.9%, 45.2%, and 50.2% of the variance in secondary trauma, burnout, and the overall compassion fatigue score, respectively. Conclusions/Implications for Practice Neuroticism and agreeableness are primary predictors of nurses’ compassion fatigue. Nursing managers can implement targeted measures to alleviate compassion fatigue based on the identified influencing factors and the predictive role of the Big Five personality traits.

Structure-based virtual screening, molecular docking, and MD simulation studies: An in-silico approach for identifying potential MBL inhibitors

The global rise of antibiotic-resistant infections has been driven in part by the spread of bacteria producing metallo-β-lactamase (MBL), particularly New Delhi metallo-β-lactamase-1 (NDM-1). Currently, there are no clinically approved inhibitors targeting NDM-1 or other MBLs, highlighting the urgent need for novel therapeutic agents. This study addresses this gap by identifying potential NDM-1 inhibitors through a comprehensive in silico workflow. A total of 4,561 natural product compounds were screened using a machine learning (ML)-based quantitative structure–activity relationship (QSAR) model. Molecular docking was then performed to prioritize hits, followed by Tanimoto similarity-based clustering to identify representative compounds. The three most promising compounds identified were S721-1034, S904-0022, and N118-0137. 300 ns molecular dynamics (MD) simulation was used to examine binding interactions and stability of a control molecule (meropenem (0RV)) and the three selected compounds (S721-1034, S904-0022, and N118-0137) with the target protein. Among the three compounds evaluated, S904-0022 demonstrated consistent root mean square deviation (RMSD) values throughout the molecular dynamics (MD) simulation compared to the other two ligands. Additionally, S904-0022 exhibited considerable affinity with key residues, including Gln123, His250, Trp93, and Val73, indicating robust interactions with NDM-1. The strength of this interaction was further validated by a significantly favorable binding free energy of −35.77 kcal/mol, markedly better than the control compound (−18.90 kcal/mol). The strength of this interaction was further validated by a significantly favorable binding free energy of −35.77 kcal/mol, markedly better than the control compound (−18.90 kcal/mol). The findings of this study provide valuable insights into the molecular interactions and stability of these compounds, which can be used to improve drug development and explore the interactions between proteins and ligands. The study concluded that S904-0022 exhibited substantial therapeutic potential and requires additional experimental exploration as a potential NDM-1 inhibitor.

Artificial diamonds are forever: 70 years of synthesizing these iconic gems

PairReg: A method for enhancing the learning of molecular structure representation in equivariant graph neural networks

The 3D structure of molecules contains a wealth of important information, but traditional 3DCNN-based methods fail to adequately address the transformations of rigid motions (rotation, translation, and mapping). Equivariant graph neural networks (EGNNs) emerge as efficient models to handle molecular 3D structures due to their unique mechanisms for capturing topological properties and equivariance to rigid motions. Historically, the optimization of EGNN models has been achieved by incorporating higher-order features to capture more complex topological properties. However, adding higher-order features incurs high computational costs. To address this issue, we explore the mechanism to mitigate the oversmoothing of equivariant graph neural networks and propose a new method (PairReg) to mitigate oversmoothing by utilizing equivariant information, such as coordinates, to enhance the model’s performance. We validate the performance of the model using the QM9 dataset and conduct ablation experiments on the rMD17 dataset. The results show that our approach enhances the model’s ability to characterize the 3D structure of molecules and offers new insights for enhancing the performance of EGNNs.

China reins in the spiralling construction costs of nuclear power — what can other countries learn?

Effects of microbial-derived long-chain polyunsaturated fatty acids from Aurantiochytrium limacinum BCC52274 and Mortierella sp. on growth and immunity in Litopenaeus vannamei post-larvae

The rapid growth of the aquaculture industry has increased the demand for feed ingredients, resulting in a shortage of fishmeal and fish oil, the latter of which serves as a source of essential fatty acids in aquaculture feed. As dietary supplementation of long-chain polyunsaturated fatty acids (LC-PUFA) improved growth and strengthened immunity in marine larvae, alternative sources for LC-PUFA are required to maintain sustainable aquaculture practice. This study explored the use of Aurantiochytrium limacinum BCC52274 (AL) and oil extracted from Mortierella sp. (ARASCO) as the source of LC-PUFA for the Pacific white shrimp Litopenaeus vannamei post-larvae (PLs) by using Artemia as a carrier. The Artemia were first enriched with combinations of AL and ARASCO with varying ratios of DHA:ARA at 100:0, 75:25, 50:50, 25:75, and 0:100, which were designated as Groups A, B, C, D, and E, respectively. The unenriched Artemia in Group R served as a control. The L. vannamei PL1 were fed with these Artemia for 18 days, revealing that the PL18 in Group A contained the highest biomass and average body weight among all feed groups. Meanwhile, other ratios of DHA:ARA supplementation were more beneficial to shrimp immunity, as the PL18 from Group D expressed the highest levels of prophenoloxidase II transcripts among all feed groups. The increasing proportion of ARA in the enriched Artemia also increased the levels of anti-inflammatory eicosanoids, including 15-deoxy-Δ12,14-prostaglandin J2, 11-hydroxyeicosatetraenoic acid (11-HETE), and 12-HETE. When these PLs were infected with white spot syndrome virus (WSSV), the PLs from Groups A, C, D, and E contained lower WSSV copy numbers compared with Group R, suggesting that the supplementation of LC-PUFAs from AL and ARASCO strengthened the immunity of these PLs against viral infection. However, the challenge with Vibrio harveyi resulted in no significant difference in the mean survival rates of PLs in all feed groups. Our results indicate that AL and ARASCO are more sustainable alternative sources of essential fatty acids that can be used strategically to enhance the growth and immunity of L. vannamei PLs.

Comparative evaluation of root canal morphology in mandibular first premolars with deep radicular grooves using direct vision, dental operating microscope, 2D radiographic visualisation and micro-computed tomography

Objectives The objective of this study was to evaluate the effectiveness of clinically applicable diagnostic methods such as Direct Vision (DV), Dental Operating Microscope (DOM), and two-dimensional (2D) radiographs in detecting canal orifices and root canal configurations in mandibular first premolars with deep radicular grooves. The study also aimed to compare these methods with micro-computed tomography (micro-CT) to better understand their diagnostic capabilities and to assess the applicability of the Ahmed et al. (2017) classification system across different imaging modalities. Methods A total of 133 mandibular first premolars with deep radicular grooves were scanned using micro-CT. After scanning, two examiners, blinded to micro-CT results, accessed and examined the root canal orifices of the study samples under DV, and DOM. Further evaluation of the root canal configurations was undertaken using exploration and 2D radiographic images. A second round of relocation of canals was undertaken if the radiographic view showed the presence of a missed canal. The data were then compared with the original reconstructed micro-CT images. Descriptive statistical analysis, Kappa and chi-square tests were performed to compare between methods and examiners, and the p-value was set at 0.05. Results Except for three teeth, all samples exhibited multiple canals. Micro-CT data revealed a wide range of root canal configurations, with the most common being 1MFP1-2 (19.54%), followed by 1MFP1-2-3 (15.78%), 1MFP1-2-3-2 (5.26%), and both 1MFP1-2-4 and 1MFP1-2-1 configurations, each at 4.51%. For both examiners, using the DOM resulted in detection of more canal orifices compared to DV (p < 0.001). A number of root canal configuration types including 1MFP1-2 and 1MFP1-2-1 was identified using exploration and radiographic imaging. Both examiners identified additional canals in the relocation phase. A significant difference was found when the radiographic method is compared with micro-CT results (p < 0.001), in which the latter method showed more complex root canal configuration types. Conclusions Mandibular first premolars with deep proximal grooves exhibit considerable variability and complexity in their root canal systems. The use of a dental operating microscope (DOM) significantly improves the detection of canal orifices compared to direct vision. The most frequently observed root canal configuration was 1MFP1-2. A high percentage of additional canals may be missed due to atypical locations of bifurcations along the root. While micro-CT imaging is not applicable in clinical settings, it remains a valuable reference tool in studies for enhancing our understanding of root canal morphology and guiding the development of clinically feasible diagnostic strategies.

Clinical and molecular characterization of hepatic glycogen storage disease in Saudi Arabia

Background and objectives The paucity of data on glycogen storage diseases (GSDs) from Arabs prompted us to report on hepatic GSD to characterize its clinical and molecular features and outcomes among Saudi children and to evaluate genotype‒phenotype correlations. Methods We retrospectively reviewed the charts of 65 children (37 females) with genetically confirmed hepatic GSD who presented between 2008 and 2020 and were followed up for a median duration of 9 years (range: 0.4–21 years). Results The most common hepatic GSD in our cohort was GSD Ia (37%), followed by GSD III (20%), GSD Ib (12.3%), and GSDVI (10.8%). Twenty-seven variants were identified (8 novel and 4 from the common ancestor, i.e., “founder in nature”). The most common founder variant is P.(Arg83Cys) in the G6PC1 gene (20% of the 65 GSD patients), clustering in Aseer Province. Six patients underwent liver transplantation (due to difficulty controlling hypoglycemia in 5 GSD Ia patients and severe portal hypertension in one GSD IV patient). One patient with GSD type 1b developed hepatic adenoma at the age of 17 years. A patient with GSD IXc developed portal hypertension at the age of 5 years, and one patient with GSD IXa developed cirrhosis. Renal complications developed in 18 patients. An echocardiogram was performed in 16 patients and revealed mild–moderate asymptomatic left ventricular hypertrophy in 5 patients. The majority of the hepatic GSD cases in our cohort manifested a severe phenotype (hepatomegaly, hypoglycemia, ± systemic involvement); only the 7 GSD VI patients manifested a mild phenotype (hepatomegaly without hypoglycemia). No “genotype‒phenotype correlations” could be observed when the two common G6PC1 gene variants [p.(Arg83Cys) versus p.(Gln20Arg)] were compared. Conclusion With the exception of GSD VI, all the hepatic GSD subtypes in Saudi Arabia are associated with a severe phenotype. Identification of the predominant gene variants and their geographic distribution in any population is likely to facilitate rapid molecular analysis by future targeting of that specific mutation.

Does an improved HDI trigger tourism outflows for China? New evidence from the ARDL cointegration approach

Extant studies have predominantly focused on understanding the effects of inbound tourism on economic growth. At the same time, it ignores the key factors that promote outbound tourism in a country. Outbound tourism not only plays a crucial role in the sustainable development of the host country but also helps foster an understanding of cross-cultural similarities and differences, promoting goodwill towards the home country. It also provides an opportunity to experience the cuisine, weather, and working habits of different geographical locations. Therefore, this study aims to investigate the relationship between the Human Development Index and tourism outflows in the context of China. We use data from the period 1995–2020 to estimate the relationship between the Human Development Index (HDI) and tourism outflows. The short-run and long-run Autoregressive Distributed Lag (ARDL) results indicate that improving China’s Human Development Index (HDI) has a positive impact on tourism outflows. More precisely, a 1 unit increase in the HDI index will increase tourism outflow by 5.25%. Furthermore, the results of individual HDI show that life expectancy, per capita income, and education considerably promote China’s tourism outflows. Policy prescriptions are outlined regarding the spillover effects of China’s human development on the tourism-led economic growth of recipient countries.

Comprehensive analysis of molecular characteristic and clinical prognosis of CD8+ T cell related genes in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive, life-threatening interstitial lung disease whose pathogenesis remains unclear. There is evidence showing the possible role of CD8+ T cells in the pathogenesis of IPF and the correlation with the clinical symptoms of IPF. In order to further explore the role of CD8+ T cells in IPF, we screened CD8+ T cell related genes (CRG) that are associated with IPF prognosis, and established the molecular typing characteristics of IPF. Subsequently, CXCR4, GPR56 and PAK1 were screened as independent prognostic factors. Expression profiles and multivariate analysis coefficients were used to establish and validate prognostic features of IPF. Immuno-infiltration characteristics of the established feature were also analyzed. Subsequent in vitro experiments verified the abnormal expressions of three independent prognostic factors in TGF-β1 treated IPF model at protein and mRNA levels. Our findings shed new light on the important role of CD8+ T cells in the pathogenesis of IPF and provide potential targets for predicting prognosis and possible future clinical applications.

An instrumented approach to quantify wrist and finger flexor spasticity: A study protocol

Spasticity in the upper limb is a common condition observed in individuals with Cerebral Palsy, post-stroke or following traumatic brain injury. Affected patients present with significant functional and care challenges. Advances in both conservative and surgical treatments necessitate improved assessment tools. This study aims to develop and validate an instrumented measurement procedure combining 3D motion analysis, surface electromyography (sEMG), and musculoskeletal modeling to assess wrist and finger spasticity and function. The goal is to create a preoperative assessment tool for surgical strategy determination and a postoperative outcome measurement. We hypothesize that this combination of technologies will offer superior assessment accuracy compared to traditional methods and provide predictive insights into therapeutical outcomes.

Expression of Concern: Atm inhibition decreases lens opacity in a rat model of galactose-induced cataract

Effect of tillage system on epigeal and foliar insect predation in an organic cropping system in Pennsylvania, USA

Organic growers rely largely on cultural and biological control to manage pest populations and often use soil disturbance with inversion tillage to manage pests and weeds, incorporate crop residues and fertility amendments, and create seedbeds. Reduced-tillage systems are often associated with greater populations of insect generalist predators, as tillage can directly and indirectly disrupt predators and their activity. We investigated the in-season and legacy effects of soil disturbance in three organic feed grain and one forage production systems that varied in frequency and intensity of disturbance on epigeal predation rates on larval waxworms, Galleria mellonella L., and foliar predation rates on eggs of the western bean cutworm, Striacosta albicosta Smith, and European corn borer, Ostrinia nubilalis (Hübner), by arthropod natural enemies. The experimental site included three annual feed grain production systems comprised of a corn, Zea mays L., soybean, Glycine max (L.) Merr., and wheat Triticum aestivum L. sequence and one forage production system represented by a biculture of alfalfa, Medicago sativa L. and orchardgrass, Dactylis glomerata L. We also measured damage to corn ears from naturally occurring lepidopteran pests and corn yield. The epigeal predation rate on sentinel waxworms in the system managed predominantly with reduced tillage (64 ± 6.4%) was significantly greater than in the systems managed predominantly with inversion tillage (44 ± 5.5%) or with a shallow high-speed disk (48 ± 5.1%). There was no effect of intensity or frequency of soil disturbance on foliar predation or foliar predator community composition in corn. Damage to corn ears from lepidopteran pests was greater in the system managed predominantly with a shallow high-speed disk (51 ± 4.4% damaged ears) compared to systems predominantly managed with inversion tillage (35 ± 4.3%) or no-till planting (31 ± 1.4%). There was no difference in corn yield across systems, but corn yield variability was greatest in the reduced tillage system. We suggest that the occasional use of inversion tillage with a moldboard plow may not have lasting detrimental effects on foliar or epigeal predation rates on arthropod pests in annual organic grain production systems.