julilili42/papers huggingface dataset:
Evaluation of Printability of PVA-Based Tablets from Powder and Assessment of Critical Rheological Parameters
2024-04-19

Fused deposition modeling (FDM) is a rather new technology in the production of personalized dosage forms. The melting and printing of polymer–active pharmaceutical ingredient (API)—mixtures can be used to produce oral dosage forms with different dosage as well as release behavior. This process is utilized to increase the bioavailability of pharmaceutically relevant active ingredients that are poorly soluble in physiological medium by transforming them into solid amorphous dispersions (ASD). The release from such ASDs is expected to be faster and higher compared to the raw materials and thus enhance bioavailability. Printing directly from powder while forming ASDs from loperamide in Polyvinylalcohol was realized. Different techniques such as a change in infill and the incorporation of sorbitol as a plastisizer to change release patterns as well as a non-destructive way for the determination of API distribution were shown. By measuring the melt viscosities of the mixtures printed, a rheological model for the printer used is proposed.
Evaluation of Tobacco heating system (THS) during closed lower limb fracture healing in trauma smokers’ patients
2024-04-19

<title>Abstract</title> Background Since 1976, it's been recognized that increased cigarette consumption correlates with decreased bone density, hindering fracture healing and leading to prolonged hospitalization. Although prior research has shown the relatively less harmful effects of electronic nicotine delivery systems (ENDS) on bone cells in lab settings and animal models, clinical evidence regarding their impact on fracture healing remains scarce. This study aims to investigate whether switching to a tobacco heating system (THS) post-orthopedic surgery improves outcomes for smoking patients during tibia or femur fracture healing over a 6-month period. Methods The study is a prospective, open-label, non-parallel, single-center trial involving 150 patients from a Level 1 Trauma center, Germany, diagnosed and treated for closed tibia, closed femur shaft, or closed distal femur fractures (according to AO/OTA: 41A2-41C3, 42A-C, 43A-C, 32A-C, 33A2-3, 33B-C). Participants will be categorized into three groups based on smoking behavior: smokers (no intervention), THS (participants switching from cigarettes to THS), and ex-smokers (participants abstaining from cigarettes or ENDS during the study). Clinical, radiological, and laboratory data will be collected during preoperative and postoperative assessments at 6, 12, 18, and 24 weeks. The primary outcome will be the serum concentration of N-terminal propeptide procollagen type 1, a bone formation marker. Secondary outcomes include bone metabolism, healing, immunological, blood count, and clinical parameters. Approval for the study protocol and consent declarations was obtained from the ethics committee of the medical faculty of Eberhard Karls University (724/2022BO1). Discussion The study results will provide evidence that switching to THS previous orthopedic intervention improves clinical outcomes during closed tibia or femur fracture healing in smokers’ patients due to reduced bone resorption rate consequent to the diminished activity of cigarette smoke-activated osteoclast. Trial registration: The study is registered on ClinicalTrials.gov (NCT05859451).
When less is more
2024-04-19

The grammatical ambition to distinguish well-formed from ill-formed structures very often leads to more complicated analyses, which in turn can impede the use of analyses in further studies. We argue thus that less ambitious and less complicated analyses can often provide more scientific insight. Two concrete cases are presented where less discriminating analyses enabled interesting investigations. In one case it was fortunate that the researchers could appeal an external, quantitative standard of quality to justify the simplification. At the risk of platitude, we conclude by confirming that the pursuit of simplicity shouldn’t be exaggerated.
Multiple dimensions of gender ideologies: How they relate to normative judgements of the gender division of parental leave
2024-04-19

Previous research found that gender ideologies are multidimensional. In addition, their influence on work-care practices depends on the context, including the life stage, presence of children and partners’ resources, which has received less attention. This study contributes to the understanding of the conditionality of gender ideologies by examining how dimensions of gender ideologies relate to more specific beliefs regarding the division of parental leave and testing whether the association depends on partners’ relative earnings. I draw on data from a vignette experiment implemented in the representative German GESIS Panel and apply OLS regression models with cluster-robust standard errors to 8,185 vignette evaluations of 2,249 respondents. More egalitarian ideologies regarding the division of employment and housework and less essentialist ideologies are associated with less traditional judgements of the division of parental leave. Support for individual choice is only associated with less traditional judgements on the condition that the mother earns more.
Elastogenesis Stimulation by Minoxidil or Nebivolol Reduces Premature Aging of the Aortic Wall in Diabetic Mice
2024-04-19

<title>Abstract</title> Background The approximately fifteen-year reduction in life expectancy observed in diabetic patients, compared to non-diabetic individuals, is believed to be attributed to the early onset of cardiovascular diseases. Among the molecular actors involved in the occurrence of cardiovascular complications, the remodeling of elastic fibers (EFs) in favor of degradation rather than neosynthesis is significant. Objective This study aims to modulate the elastogenesis/elastolysis balance in the arterial wall of diabetic db/db mice (a diabetic model where the leptin receptor is deficient) to limit the premature aging of their EFs and aortic stiffening. Methods Mice are treated with two antihypertensive agents: minoxidil (an ATP-sensitive potassium (KATP) channel opener) or nebivolol (a β-blocker also active on KATP channels). The degree of wear and functionality of EF are assessed after these treatments. We complement this analysis by identifying molecular actors from smooth muscle cell cultures. Results Our data show that by applying these antihypertensive agents in cultured vascular smooth muscle cells in vitro and in diabetic mice, we efficiently stimulate elastogenesis and inhibit elastolysis. Therefore, treatments restore functional EFs and limit their degradation. This brings blood pressure values of diseased mice close to normal ones (as in unaffected mice). Elastogenesis pathway stimulation and elastolysis inhibition are induced by the opening of sensitive KATP channels and the regulation of the forkhead box transcription factor (FOXO1). Conclusion Monitoring these two pathways could, therefore, be sufficient to limit the premature aging of the aorta and to reduce the occurrence of hypertension, atherosclerosis, and aneurysms in diabetic patients.
Assessing visual performance during intense luminance changes in virtual reality
2024-04-19

Summary During indoor-outdoor transitions humans encounter luminance changes beyond the functional range of the photoreceptors, leaving the individual at risk of overlooking harmful low-contrast objects until adaptation processes re-enable optimal vision. To study human visual performance during intense luminance changes, we propose a virtual reality based testbed. After linearization of the headset’s luminance output, detection times were recorded for ten participants. The small (FWHM = 0.6 degree) low-contrast stimuli appeared randomly in one of four corners (±10 degree) after luminance changes of three magnitudes within 1 or 3 seconds. Significantly decreased detection times were observed for the conditions with simulated self-tinting lenses compared to lenses with fixed transmission rates after luminance decreases. In cases of luminance increases all detection times were similar. In conclusion, the proposed virtual reality testbed allows for studying vision during or after steep luminance changes and helps to design technical aids like self-tinting lenses. Highlights The HTC Vive headset provides a practicable luminance range of 3 magnitudes, allowing the simulation of indoor-outdoor transitions. Visual performance after steep luminance decreases was significantly better with simulated self-tinting spectacles reducing the encountered luminance step. Different transmission rates of the simulated lenses did not affect the detection times for small low-contrast stimuli after luminance increases.
Facial magnetomyography using an array of optically pumped magnetometer
2024-04-19

Background The measurement of muscular activity in the face is a central component in the diagnosis of patients with facial nerve palsy. Magnetomyography (MMG) is a method for contactless measurement of magnetic muscle potentials. This study investigated whether non-invasive MMG using optically pumped magnetometers (OPM) is a feasible instrument for visualizing facial muscle activity.
Audiometric markers of cochlear Synaptopathy and speech in noise deficits in humans
2024-04-19

Background Cochlear synaptopathy has been shown to precede hair cell loss and threshold shift over age. Cochlear synaptopathy is assumed to alter auditory information processing, whether accompanied by threshold elevations or not, and is a predicted contributor to speech-in-noise difficulties. It is crucial to understand the impact of cochlear synaptopathy on speech coding to develop effective therapeutic interventions.
The development of a digital health application for central compensation of peripheral vertigo
2024-04-19

Introduction The effectiveness of vestibular exercises in the treatment of peripheral vertigo is evidence-based. However, their regular long-term implementation often fails due to insufficient adherence and compliance.
Otoscopy training on the Virtual Reality Otoscopy simulator &quot;Earsi&quot; for medical students – Effectiveness and transfer in oral-practical examinations. A prospective study in a control group design
2024-04-19

Background Otoscopy plays a crucial role in various medical disciplines. The aim of the study was to investigate to what extent the use of a low-fidelity (conventional) and a high-fidelity (virtual reality) otoscopy simulator improves the skills of otoscopy of medical students and whether a more objective assessment of the learned skills is possible. 7
Digital information and communication technology usage and prospects in Otolaryngology care: Insights from German patients
2024-04-19

Objective Digital information and communication technology in European healthcare is growing. Unlike the numerous technological possibilities, the present use and perspectives in otolaryngology care have been of less interest so far. This study evaluates the utilization and attitudes towards digital information and communication technology in cross-sectoral otolaryngology care among German patients.
Detection and quantification of Na,K-ATPase dimers in the plasma membrane of living cells by FRET-FCS
2024-04-20

The sodium potassium pump, Na,K-ATPase (NKA), is an integral plasma membrane protein, expressed in all eukaryotic cells. It is responsible for maintaining the transmembrane Na<sup>+</sup> gradient and is the major determinant of the membrane potential. Self-interaction and oligomerization of NKA in cell membranes has been proposed and discussed but is still an open question. Here, we have used a combination of FRET and Fluorescence Correlation Spectroscopy, FRET-FCS, to analyze NKA in the plasma membrane of living cells. Click chemistry was used to conjugate the fluorescent labels Alexa 488 and Alexa 647 to non-canonical amino acids introduced in the NKA α<sub>1</sub> and β<sub>1</sub> subunits. We demonstrate that FRET-FCS can detect an order of magnitude lower concentration of green-red labeled protein pairs in a single-labeled red and green background than what is possible with cross-correlation (FCCS). We show that a significant fraction of NKA is expressed as a dimer in the plasma membrane. We also introduce a method to estimate not only the number of single and double labeled NKA, but the number of unlabeled, endogenous NKA and estimate the density of endogenous NKA at the plasma membrane to 1400 ± 800 enzymes/μm<sup>2</sup>.
Effects of microbial groups on soil organic carbon accrual and mineralization during high- and low-quality litter decomposition
2024-04-21

Litter input regulates the mineralization and accrual of soil organic carbon (SOC), depending on microbial groups and litter quality. Stable isotope probing was used after the addition of 13C-labeled litter of different recalcitrance, including Populus davidiana (characterized by low quality, high C:N, and lignin content) and Quercus wutaishanica (characterized by high quality, low C:N, and lignin content). The flow of litter C to microbial biomass and necromass was followed by quantification of 13C incorporation into phospholipid fatty acids (13C-PLFAs) and amino sugars (13C-AS), and their respiration. The CO2 efflux and positive priming effects (PE) were higher, but the 13C-necromass was lower (8.5% vs. 10%) in the soil with P. davidiana than with Q. wutaishanica. The 13C-necromass continuously increased with P. davidiana litter decomposition, but reached a peak at day 14 after Q. wutaishanica litter addition. These results indicated that the decomposition of resistance compounds mainly resulted in necromass formation after low-quality litter addition. The P. davidiana-derived 13C in fungal PLFAs increased with decomposition, suggesting the importance of these microorganisms in decomposing resistance compounds in low-quality litter despite the bacterial-dominated decomposition process of both litters. Bacteria frequently exhibit versatility in utilizing C from different sources, whereas a larger proportion of fungi display specialization. SOC mineralization increased with the remaining litter but decreased with 13C-G- bacterial PLFAs and 13C-actinobacterial PLFAs after both types of litter addition because starving microbes need to invest more soil C in maintenance respiration vs. biomass formation. 13C-necromass increased with 13C-PLFA because microbial biomass is the primary precursor of necromass. Altogether, low-quality compounds are more readily respired, whereas C from high-quality biopolymers is relatively more assimilated into the necromass. This study further explains the effect of soil microbial groups on SOC under different qualities of litter decomposition and deepens our understanding of the mechanism of SOC sequestration.
Health insurance and height inequality: Evidence from European health insurance expansions
2024-04-21

Health insurance expansions can improve health outcomes by increasing access to healthcare. This is especially true among the poorer segments of the population, who may not be able to afford the cost of healthcare, or might lack the information about where to seek proper medical care. In this paper we examine whether increased access to health insurance has historically reduced height inequality by promoting body growth, particularly among poor individuals, and so enhanced their height, a widely used and well-established anthropometric health and well-being indicator. We draw on evidence from a large global panel of countries for which we could measure height inequality. Our evidence documents that indeed within-country differences in height inequality decreased following health insurance expansions towards near-universal coverage.
Fluorescence-Guided Laparoscopy after Oral Hypericin Administration for Staging of Locally Advanced Gastric Cancer—A Pilot Study
2024-04-21

(1) Background: Laparoscopic staging is essential in gastric cancer (GC) to rule out peritoneal metastasis (PM). Hypericin, a plant-derived fluorescent compound, has been suggested to improve laparoscopic visualization of PM from GC. This prospective, single-arm, open-label clinical trial aimed to assess the feasibility and safety of oral hypericin administration as well as the suitability of fluorescence-guided laparoscopy (FGL) for improving the sensitivity and specificity of staging in GC patients (EudraCT-Number: 2015-005277-21; clinicaltrials.gov identifier: NCT-02840331). (2) Methods: GC patients received Laif® 900, an approved hypericin-containing phytopharmaceutical, once orally two to four hours before white light and ultraviolet light laparoscopy. The peritoneal cancer index was evaluated, biopsies taken and hypericin concentrations in serum and peritoneal tissue were determined by mass spectrometry. (3) Results: Between 2017 and 2021, out of 63 patients screened for eligibility, 50 patients were enrolled and treated per protocol. The study intervention was shown to be feasible and safe in all patients. Standard laparoscopy revealed suspicious lesions in 27 patients (54%), among whom 16 (59%) were diagnosed with PM. FGL identified suspicious areas in 25 patients (50%), among whom PM was confirmed in 13 cases (52%). Although hypericin concentrations in serum reached up to 5.64 ng/mL, no hypericin was detectable in peritoneal tissue biopsies. (4) Conclusions: FGL in patients with GC was shown to be feasible but futile in this study. Sufficient levels of hypericin should be ensured in target tissue prior to reassessing FGL with hypericin.
The SPFH complex HflK-HflC regulates aerobic respiration in bacteria
2024-04-21

ABSTRACT The bacterial HflK-HflC membrane complex is a member of the highly conserved SPFH protein family, which is found throughout all domains of life and includes eukaryotic stomatins, flotillins, and prohibitins. These proteins organize cell membranes and are involved in various processes. However, the exact physiological functions of most bacterial SPFH proteins remain unclear. Here, we report that the HflK-HflC complex in Escherichia coli is required for growth under high aeration. The absence of this complex causes an aerobic growth defect due to a reduced abundance of IspG, a crucial enzyme in the isoprenoid biosynthetic pathway. This reduction leads to lower levels of ubiquinone, reduced respiration, lower ATP levels, and misregulated expression of respiratory genes. The regulation of aerobic respiration by the HflK-HflC complex resembles the mitochondrial respiratory defects caused by prohibitin mutations in mammalian and yeast cells, suggesting a functional commonality between these bacterial and eukaryotic SPFH proteins.
Middle Pleistocene Hippopotamuses from the Italian Peninsula: An Overview
2024-04-22

Our work presents an updated overview of the Italian Middle Pleistocene records of hippopotamuses, including the two species Hippopotamus antiquus and Hippopotamus amphibius. In addition to reviewing several well-known fossils in the literature, a large number of samples are described herein for the first time. Following the recent results published in the literature, where the skull from the Middle Pleistocene of Cava Montanari (ca. MIS 13) was confirmed to belong to H. amphibius, one of the aims of this work was to investigate the H. antiquus–H. amphibius transition. A morphological analysis applied to a large sample confirmed the validity of the arrangement of the enamel ridges of the external surfaces of the lower canines as a diagnostic character for specific identifications. Finally, biometric analyses allowed us to test the size variability during the Middle Pleistocene, which confirmed that H. antiquus was generally larger than H. amphibius. Nevertheless, the remains of H. antiquus dated to ca. 600 ka show a reduced size when compared to older fossils of the same taxon, probably as a response to severe glacial conditions that occurred during MIS 16.
Reverse N-Substituted Hydroxamic Acid Derivatives of Fosmidomycin Target a Previously Unknown Subpocket of 1-Deoxy-d-xylulose 5-Phosphate Reductoisomerase (DXR)
2024-04-22

Reverse analogs of the phosphonohydroxamic acid antibiotic fosmidomycin are potent inhibitors of the nonmevalonate isoprenoid biosynthesis enzyme 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR, IspC) of <i>Plasmodium falciparum</i>. Some novel analogs with large phenylalkyl substituents at the hydroxamic acid nitrogen exhibit nanomolar <i>Pf</i>DXR inhibition and potent <i>in vitro</i> growth inhibition of <i>P. falciparum</i> parasites coupled with good parasite selectivity. X-ray crystallographic studies demonstrated that the <i>N</i>-phenylpropyl substituent of the newly developed lead compound <b>13e</b> is accommodated in a subpocket within the DXR catalytic domain but does not reach the NADPH binding pocket of the <i>N</i>-terminal domain. As shown for reverse carba and thia analogs, <i>Pf</i>DXR selectively binds the <i>S</i>-enantiomer of the new lead compound. In addition, some representatives of the novel inhibitor subclass are nanomolar <i>Escherichia coli</i> DXR inhibitors, whereas the inhibition of <i>Mycobacterium tuberculosis</i> DXR is considerably weaker.
A 10-Year Longitudinal Study of Brain Cortical Thickness in People with First-Episode Psychosis using Normative Models
2024-04-22

ABSTRACT Background Clinical forecasting models have potential to optimize treatment and improve outcomes in psychosis, but predicting long-term outcomes is challenging and long-term follow up data are scarce. In this 10-year longitudinal study we aimed to characterize the temporal evolution of cortical correlates of psychosis and their associations with symptoms. Design Structural MRI from people with first-episode psychosis and controls (n=79 and 218) were obtained at enrollment, after 12 months (n=67 and 197), and 10 years (n=23 and 77), within the Thematically Organized Psychosis (TOP) study. Normative models for cortical thickness estimated on public MRI datasets (n=42983) were applied to TOP data to obtain deviation scores for each region and timepoint. Positive And Negative Syndrome Scale (PANSS) scores were acquired at each timepoint along with registry data. Linear mixed effects (LME) models assessed effects of diagnosis, time and their interactions on cortical deviations plus associations with symptoms. Results LMEs revealed conditional main effects of diagnosis and time x diagnosis interactions in a distributed cortical network, where negative deviations in patients attenuate over time. In patients, symptoms also attenuate over time. LMEs revealed effects of anterior cingulate on PANSS total, and insular and orbitofrontal regions on PANSS negative scores. Conclusions This long-term longitudinal study revealed a distributed pattern of cortical differences which attenuated over time together with a reduction in symptoms. These findings are not in line with a simple neurodegenerative account of schizophrenia, and deviations from normative models offer a promising avenue to develop biomarkers to track clinical trajectories over time.