Miracle-dz/UniFAR-FTUs huggingface dataset:
Aerosolizable Lipid-Nanovesicles Encapsulating Voriconazole Effectively Permeate Pulmonary Barriers and Target Lung Cells

The entire world has recently been witnessing an unprecedented upsurge in microbial lung infections. The major challenge encountered in treating the same is to ensure the optimum drug availability at the infected site. Aerosolization of antimicrobials, in this regard, has shown immense potential owing to their localized and targeted effect. Efforts, therefore, have been undertaken to systematically develop lung-phosphatidylcholine-based lipid nanovesicles of voriconazole for potential management of the superinfections like aspergillosis. LNVs, prepared by thin-film hydration method, exhibited a globule size of 145.4 ± 19.5 nm, polydispersity index of 0.154 ± 0.104 and entrapment efficiency of 71.4 ± 2.2% with improved in vitro antifungal activity. Aerodynamic studies revealed a microdroplet size of ≤5 μm, thereby unraveling its promise to target the physical barrier of lungs effectively. The surface-active potential of LNVs, demonstrated through Langmuir-Blodgett troughs, indicated their ability to overcome the biochemical pulmonary surfactant monolayer barrier, while the safety and uptake studies on airway-epithelial cells signified their immense potential to permeate the cellular barrier of lungs. The pharmacokinetic studies showed marked improvement in the retention profile of voriconazole in lungs following LNVs nebulization compared to pristine voriconazole. Overall, LNVs proved to be safe and effective delivery systems, delineating their distinct potential to efficiently target the respiratory fungal infections.
White Matter Abnormalities and Cognitive Deficit After Mild Traumatic Brain Injury: Comparing DTI, DKI, and NODDI

White matter (WM) disruption is an important determinant of cognitive impairment after mild traumatic brain injury (mTBI), but traditional diffusion tensor imaging (DTI) shows some limitations in assessing WM damage. Diffusion kurtosis imaging (DKI) and neurite orientation dispersion and density imaging (NODDI) show advantages over DTI in this respect. Therefore, we used these three diffusion models to investigate complex WM changes in the acute stage after mTBI. From 32 mTBI patients and 31 age-, sex-, and education-matched healthy controls, we calculated eight diffusion metrics based on DTI (fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity), DKI (mean kurtosis), and NODDI (orientation dispersion index, volume fraction of intracellular water (Vic), and volume fraction of the isotropic diffusion compartment). We used tract-based spatial statistics to identify group differences at the voxel level, and we then assessed the correlation between diffusion metrics and cognitive function. We also performed subgroup comparisons based on loss of consciousness. Patients showed WM abnormalities and cognitive deficit. And these two changes showed positive correlation. The correlation between Vic of the splenium of the corpus callosum and Digit Symbol Substitution Test scores showed the smallest p-value (p = 0.000, r = 0.481). We concluded that WM changes, especially in the splenium of the corpus callosum, correlate to cognitive deficit in this study. Furthermore, the high voxel count of NODDI results and the consistency of mean kurtosis and the volume fraction of intracellular water in previous studies and our study showed the functional complementarity of DKI and NODDI to DTI.
Bone Density and Structure in Overweight Men With and Without Diabetes

Objective Metabolic syndrome (MetS), type 1 diabetes (T1D), and type 2 diabetes, are associated with an increased risk of fractures; however, the impact of obesity on bone deficits in diabetes is unknown. We aimed to compare markers of bone structure, bone density, and bone turnover in non-diabetic overweight men with MetS and overweight men with T1D or T2D. Methods and Research Design In this cross-sectional study we included participants from two previously described study cohorts consisting of participants with diabetes and participants with MetS. Participants underwent dual-energy X-ray absorptiometry measuring areal bone mineral density (aBMD) at the hip and lumbar spine, High Resolution peripheral Quantitative (HRpQCT) scan of the tibia and radius and measurement of circulating bone turnover markers. We compared groups with unpaired t test and performed multiple linear regression with adjustment for age, body mass index, and smoking. Results We included 33 participants with T1D, 25 participants with T2D, and 34 participants with MetS. Bone turnover markers levels were comparable between T1D and MetS. aBMD at the hip was lower in T1D compared to MetS, also after adjustment. P1NP and Osteocalcin levels were lower among individuals with T2D compared to MetS, whereas aBMD were similar between the groups after multiple adjustments. We observed no difference in volumetric BMD at the tibia or radius between MetS and T1D and T2D, respectively. Participants with T2D had a higher trabecular number and lower trabecular separation compared to individuals with MetS at the tibia, which remained signficant after multiple adjustments. Conclusion In conclusion, we observed no clinically important differences in bone density or structure between men with T2D, T1D, or MetS. However, men with T2D displayed lower bone turnover compared to MetS highlighting that T2D per se and not obesity, is associated with low bone turnover.
Cytidine Triphosphate Synthase Four From Arabidopsis thaliana Attenuates Drought Stress Effects

Cytidine triphosphate synthase (CTPS) catalyzes the final step in pyrimidine de novo synthesis. In Arabidopsis, this protein family consists of five members (CTPS1–5), and all of them localize to the cytosol. Specifically, CTPS4 showed a massive upregulation of transcript levels during abiotic stress, in line with increased staining of CTPS4 promoter:GUS lines in hypocotyl, root and to lesser extend leaf tissues. In a setup to study progressive drought stress, CTPS4 knockout mutants accumulated less fresh and dry weight at days 5–7 and showed impaired ability to recover from this stress after 3 days of rewatering. Surprisingly, a thorough physiological characterization of corresponding plants only revealed alterations in assimilation and accumulation of soluble sugars including those related to drought stress in the mutant. Bimolecular fluorescence complementation (BiFC) studies indicated the interaction of CTPS4 with other isoforms, possibly affecting cytoophidia (filaments formed by CTPS formation. Although the function of these structures has not been thoroughly investigated in plants, altered enzyme activity and effects on cell structure are reported in other organisms. CTPS activity is required for cell cycle progression and growth. Furthermore, drought can lead to the accumulation of reactive oxygen species (ROS) and by this, to DNA damage. We hypothesize that effects on the cell cycle or DNA repair might be relevant for the observed impaired reduced drought stress tolerance of CTPS4 mutants.
Light Color and the Commercial Broiler: Effect on Ocular Health and Visual Acuity

Light is a critical management factor for broiler production, and the wavelength spectrum, one of its components, can affect bird physiology, behavior and production. Among all the senses, sight is important to birds, and their visual system possess several adaptations that allow them to perceive light differently from humans. Therefore, it is critical to consider whether the exposure to monochromatic light colors influences broiler visual ability, which could affect behavioral expression. The present study examined the effects of various light colors on the visual systems of broiler chickens. Ross 708 males were raised from 0 to 35 days under three wavelength programs [blue (dominant wavelengths near 455 nm), green (dominant wavelengths near 510 nm) or white]. Broilers were given a complete ophthalmic examination, including chromatic pupillary light reflex testing, rebound tonometry, anterior segment biomicroscopy and indirect ophthalmoscopy (n = 36, day 21). To assess ocular anatomy, broilers were euthanized, eyes were weighed, and dimensions were taken (n = 108, day 16 and day 24). An autorefractor was used to assess the refractive index and the corneal curvature (n = 18, day 26). To evaluate spatial vision, broilers underwent a grating acuity test at one of three distances–50, 75, or 100 cm (n = 24, day 29). Data were analyzed as a one-way ANOVA using the MIXED procedure or Proc Par1way for non-normally distributed data. Significant differences were observed for refractive index and spatial vision. Birds raised under blue light were slightly more hyperopic, or far-sighted, than birds raised under white light (P = 0.01). As for spatial vision, birds raised under blue light took less time to approach the stimulus at distances of 50 cm (P = 0.03) and 75 cm (P = 0.0006) and had a higher success rate (choosing the right feeder, P = 0.03) at 100 cm than birds raised under white light. Improvements in spatial vision for birds exposed to blue light can partially explain the behavioral differences resulting from rearing broilers under different wavelengths.
A Phase II Trial of a Personalized, Dose-Intense Administration Schedule of 177Lutetium-DOTATATE in Children With Primary Refractory or Relapsed High-Risk Neuroblastoma–LuDO-N

Background Half the children with high-risk neuroblastoma die with widespread metastases. Molecular radiotherapy is an attractive systemic treatment for this relatively radiosensitive tumor. 131I-mIBG is the most widely used form in current use, but is not universally effective. Clinical trials of 177Lutetium DOTATATE have so far had disappointing results, possibly because the administered activity was too low, and the courses were spread over too long a period of time, for a rapidly proliferating tumor. We have devised an alternative administration schedule to overcome these limitations. This involves two high-activity administrations of single agent 177Lu-DOTATATE given 2 weeks apart, prescribed as a personalized whole body radiation absorbed dose, rather than a fixed administered activity. “A phase II trial of 177Lutetium-DOTATATE in children with primary refractory or relapsed high-risk neuroblastoma - LuDO-N” (EudraCT No: 2020-004445-36, ClinicalTrials.gov Identifier: NCT04903899) evaluates this new dosing schedule. Methods The LuDO-N trial is a phase II, open label, multi-center, single arm, two stage design clinical trial. Children aged 18 months to 18 years are eligible. The trial is conducted by the Nordic Society for Pediatric Hematology and Oncology (NOPHO) and it has been endorsed by SIOPEN (https://www.siopen.net). The Karolinska University Hospital, is the sponsor of the LuDO-N trial, which is conducted in collaboration with Advanced Accelerator Applications, a Novartis company. All Scandinavian countries, Lithuania and the Netherlands participate in the trial and the UK has voiced an interest in joining in 2022. Results The pediatric use of the Investigational Medicinal Product (IMP) 177Lu-DOTATATE, as well as non-IMPs SomaKit TOC® (68Ga-DOTATOC) and LysaKare® amino acid solution for renal protection, have been approved for pediatric use, within the LuDO-N Trial by the European Medicines Agency (EMA). The trial is currently recruiting. Recruitment is estimated to be finalized within 3–5 years. Discussion In this paper we present the protocol of the LuDO-N Trial. The rationale and design of the trial are discussed in relation to other ongoing, or planned trials with similar objectives. Further, we discuss the rapid development of targeted radiopharmaceutical therapy and the future perspectives for developing novel therapies for high-risk neuroblastoma and other pediatric solid tumors.
Physicians' Perspective on Vaccine-Hesitancy at the Beginning of Israel's COVID-19 Vaccination Campaign and Public's Perceptions of Physicians' Knowledge When Recommending the Vaccine to Their Patients: A Cross-Sectional Study

Because public healthcare workers (HCWs) are at the forefront of the battle against COVID-19, they must be able to provide vaccination information to their patients and respond to their anxieties and concerns. This research objectives were to (1) examine physicians' perceptions of how they received information about the Pfizer COVID-19 vaccine, their attitudes toward hesitant colleagues, and their own knowledge and self-efficacy in communicating information to their patients, and (2) to examine the public's perceptions of physicians' knowledge when recommending the COVID-19 vaccine to their patients. At the beginning of the vaccination campaign, a survey examined the attitudes of physicians in the Israeli public healthcare system (n = 295) regarding the Pfizer vaccine. In addition, the attitudes of a representative sample (n = 500) of the Israeli adult population (age 18+) were examined through interviews. Most of the participating physicians (81%) reported they had already been vaccinated or intended to be vaccinated. When asked about their reasons for vaccine hesitancy, 27% cited concerns about long-term side effects and doubts about the vaccine's effectiveness in preventing contagion. They cited system pressure and departmental norms as explanations for their eventual compliance. Moreover, they saw the system as less tolerant of hesitant physicians, while they themselves tend to be more tolerant. The results of the survey of the public showed that mostly young people (under 44) who tend to be critical believe that physicians do not have sufficient knowledge to make recommendations about the COVID-19 vaccine. The findings indicate that the health system should employ complete transparency in conveying the advantages and disadvantages of the COVID-19 vaccine to physicians. The system should be more tolerant of physicians' worries and concerns and grant legitimacy to their reservations and misgivings. Moreover, medical studies should reinforce physicians' immunological knowledge regarding vaccinations so they can help their patients make informed decisions.
Effect of Obesity on Arithmetic Processing in Preteens With High and Low Math Skills: An Event-Related Potentials Study

Preadolescence is an important period for the consolidation of certain arithmetic facts, and the development of problem-solving strategies. Obese subjects seem to have poorer academic performance in math than their normal-weight peers, suggesting a negative effect of obesity on math skills in critical developmental periods. To test this hypothesis, event-related potentials (ERPs) were collected during a delayed-verification math task using simple addition and subtraction problems in obese [above 95th body mass index (BMI) percentile] and non-obese (between 5th and 90th BMI percentile) preteens with different levels of math skill; thirty-one with low math skills (14 obese, mean BMI = 26.40, 9.79 years old; 17 non-obese, BMI = 17.45, 9.76 years old) and thirty-one with high math skills (15 obese, BMI = 26.90, 9.60 years old; 16 non-obese, BMI = 17.13, 9.63 years old). No significant differences between weight groups were observed in task accuracy regardless of their mathematical skill level. For ERPs, electrophysiological differences were found only in the subtraction condition; participants with obesity showed an electrophysiologic pattern associated with a reduced ability to allocate attention resources regardless of their math skill level, these differences were characterized by longer P300 latency than their normal-weight peers. Moreover, the participants with obesity with high math skills displayed hypoactivity in left superior parietal lobule compared with their normal-weight peers. Additionally, obese preteens with low math skills displayed smaller arithmetic N400 amplitude than non-obese participants, reflecting difficulties in retrieving visual, semantic, and lexical information about numbers. We conclude that participants with obesity are less able than their normal-weight peers to deploy their attention regardless of their behavioral performance, which seems to have a greater effect on obese participants with low math skills because they also show problems in the retrieval of solutions from working memory, resulting in a delay in the development of mathematical skills.
How Has the Nationwide Public Health Emergency of the COVID-19 Pandemic Affected Older Chinese Adults' Health Literacy, Health Behaviors and Practices, and Social Connectedness? Qualitative Evidence From Urban China

Older Chinese adults' daily lives have been affected significantly during the outbreak phase of the COVID-19 pandemic since January 2020. They were confronted with activity restrictions due to strict pandemic prevention. The older population also had to get accustomed to widely-used modern technologies in community management, such as health codes and WeChat groups. By late 2021, mainland China had reduced the prevalence of COVID-19, and people's daily lives had primarily returned to pre-pandemic normality. Under China's systematic health management during the pandemic, older Chinese adults' responses to this nationwide public health emergency may have influenced their health in the long run. However, it remains unclear what specific health changes or improvements have occurred. Such a void in the literature is worrying, given that older adults are at high health risks due to the pandemic which, might still be with humankind for a while. Thus, it is of necessity to explore and report their health changes after this official, large-scale health intervention. In this study, 17 adults aged 55 and above were recruited as interviewees. All interviewees reside in a community located in Q district, N city of the People's Republic of China. According to the findings, many interviewees now have better literacy in health risk prevention. Information and Communication Technologies (ICTs) play a significant role in getting access to health information. Specifically, television, WeChat chatting groups, and TikTok could be valuable information sources for older adults. As for the understanding and evaluation of health information, although older participants can distinguish COVID-19 rumors, they may sometimes feel confused about the underlying scientific logic. Regarding changes in health behaviors and practices, many older adults can integrate health information and knowledge into their daily lives. Additionally, although interviewees can keep important social connections, not all of them are familiar with using new ICTs, such as online chatting group, for social participation and engagement. The empirical evidence suggests that both the communities and the local governments can offer specific training programs to older residents for the sake of enhancing their health literacy, health behaviors and practices, and social connectedness during and after the pandemic.
Experimental Study of Internally Mixed Twin-Fluid Liquid Atomizer

In this paper, the characterization of an internally-mixed twin-fluid atomizer is carried out in terms of SMD and spray cone angle for a wide range of gas-liquid ratio (GLR). The droplet size was measured which indicates that there is an decreases in SMD with gas-liquid ratios. For a particular GLR, mean droplet sizes were observed to increase with increasing axial distance which may be due to coagulation of droplets at higher axial distances as momentum of droplets might have attained low value. The spray cone angles were found to be in the range of 12-20°, which matches well with the reported data available in literature. The cone angle was observed to increase slightly with GLR that may be due to the increased turbulence level inside the mixing chamber. These studies are expected to aid in the development of atomizers for airbreathing engines.
How Advanced Is Our Understanding of the Role of Intestinal Barrier Dysfunction in the Pathogenesis of Recurrent Urinary Tract Infections

A comprehensive understanding of urinary tract infections (UTIs), one of the most common human infections, is required as they are complex and poorly understood diseases. Periurethral and vaginal colonization by rectal flora, with the constant presence of pathogens in the urethra, is the initial step of the recurrent UTIs pathway. Current scientific data describe the genetic, etiological, biological, and behavioral risk factors for recurring UTIs, but they do not include the effect of intestinal barrier function on the disease. Although gut microbiota has been proposed as the main source for UTIs, the cross-talk between intestinal barrier dysfunction and the recurrence of UTIs has not yet been supported by scientific data. In this opinion review, based on published data and the results of our clinical studies, I aimed to outline the possible contribution of intestinal barrier dysfunction to the pathogenesis of recurrent UTIs. I believe that the unanswered questions raised by this review can guide further experimental and controlled studies to clarify the mechanisms underlying the role of intestinal barrier dysfunction in the pathogenesis of recurrent UTIs.
Hollow CoS/C Structures for High-Performance Li, Na, K Ion Batteries

Alkali ion (Li, Na, and K) batteries as a new generation of energy storage devices are widely applied in portable electronic devices and large-scale energy storage equipment. The recent focus has been devoted to develop universal anodes for these alkali ion batteries with superior performance. Transition metal sulfides can accommodate alkaline ions with large radius to travel freely between layers due to its large interlayer spacing. Moreover, the composite with carbon material can further improve electrical conductivity of transition metal sulfides and reduce the electron transfer resistance, which is beneficial for the transport of alkali ions. Herein, we designed zeolitic imidazolate framework (ZIF)–derived hollow structures CoS/C for excellent alkali ion (Li, Na, and K) battery anodes. The porous carbon framework can improve the conductivity and effectively buffer the stress-induced structural damage. The ZIF-derived CoS/C anodes maintain a reversible capacity of 648.9, and 373.2, 224.8 mAh g−1 for Li, Na, and K ion batteries after 100 cycles, respectively. Its outstanding electrochemical performance is considered as a universal anode material for Li, Na, and K ion batteries.