Miracle-dz/UniFAR-FTUs huggingface dataset:
A Detailed View on the Proanthocyanidins in Ginkgo Extract EGb 761

Abstract The Ginkgo extract EGb 761® manufactured with leaves of Ginkgo biloba has been continuously produced over decades at a large scale and is used as a clinically proven remedy for, among other things, the improvement of age-associated cognitive impairment and quality of life in patients with mild dementia. It belongs to the class of extracts addressed as quantified extracts according to the European Pharmacopeia. Accordingly, several compounds (e.g., flavone glycosides and terpene trilactones) are acknowledged to contribute to its clinical efficacy. Covering only about 30% of the mass balance, these characterized compounds are accompanied by a larger fraction of additional compounds, which might also contribute to the clinical efficacy and safety of the extract. As part of our systematic research to fully characterize the constituents of Ginkgo extract EGb 761, we focus on the structural class of proanthocyanidins in the present study. Structural insights into the proanthocyanidins present in EGb 761 and a quantitative method for their determination using HPLC are shown. The proanthocyanidins were found to be of oligomeric to polymeric structure, which yield delphinidin and cyanidin as main building blocks after acidic hydrolysis. A validated HPLC method for quantification of the anthocyanidins was developed in which delphinidin and cyanidin were detected after hydrolysis of the proanthocyanidins. The content of proanthocyanidins in Ginkgo extract EGb 761 was found to be approximately 7%.
Inertial Cavitation Behaviors Induced by Nonlinear Focused Ultrasound Pulses

Inertial cavitation induced by pulsed high-intensity focused ultrasound (pHIFU) has previously been shown to successfully permeabilize tumor tissue and enhance chemotherapeutic drug uptake. In addition to HIFU frequency, peak rarefactional pressure (<inline-formula> <tex-math notation="LaTeX">${p}^{-}$ </tex-math></inline-formula>), and pulse duration, the threshold for cavitation-induced bioeffects has recently been correlated with asymmetric distortion caused by nonlinear propagation, diffraction and formation of shocks in the focal waveform, and therefore with the transducer <inline-formula> <tex-math notation="LaTeX">${F}$ </tex-math></inline-formula>-number. To connect previously observed bioeffects with bubble dynamics and their attendant physical mechanisms, the dependence of inertial cavitation behavior on shock formation was investigated in transparent agarose gel phantoms using high-speed photography and passive cavitation detection (PCD). Agarose phantoms with concentrations ranging from 1.5% to 5% were exposed to 1-ms pulses using three transducers of the same aperture but different focal distances (<inline-formula> <tex-math notation="LaTeX">${F}$ </tex-math></inline-formula>-numbers of 0.77, 1.02, and 1.52). Pulses had central frequencies of 1, 1.5, or 1.9 MHz and a range of <inline-formula> <tex-math notation="LaTeX">${p}^{-}$ </tex-math></inline-formula> at the focus varying within 1–18 MPa. Three distinct categories of bubble behavior were observed as the acoustic power increased: stationary near-spherical oscillation of individual bubbles, proliferation of multiple bubbles along the pHIFU beam axis, and fanned-out proliferation toward the transducer. Proliferating bubbles were only observed under strongly nonlinear or shock-forming conditions regardless of frequency, and only where the bubbles reached a certain threshold size range. In stiffer gels with higher agarose concentrations, the same pattern of cavitation behavior was observed, but the dimensions of proliferating clouds were smaller. These observations suggest mechanisms that may be involved in bubble proliferation: enhanced growth of bubbles under shock-forming conditions, subsequent shock scattering from the gel–bubble interface, causing an increase in the repetitive tension created by the acoustic wave, and the appearance of a new growing bubble in the proximal direction. Different behaviors corresponded to specific spectral characteristics in the PCD signals: broadband noise in all cases, narrow peaks of backscattered harmonics in the case of stationary bubbles, and broadened, shifted harmonic peaks in the case of proliferating bubbles. The shift in harmonic peaks can be interpreted as a Doppler shift from targets moving at speeds of up to 2 m/s, which correspond to the observed bubble proliferation speeds.
Physalin B attenuates liver fibrosis via suppressing LAP2α–HDAC1‐mediated deacetylation of the transcription factor GLI1 and hepatic stellate cell activation

Liver fibrosis is one of the leading causes of morbidity and mortality worldwide but lacks any acceptable therapy. The transcription factor glioma‐associated oncogene homologue 1 (GLI1) is a potentially important therapeutic target in liver fibrosis. This study investigates the anti‐fibrotic activities and potential mechanisms of the phytochemical, physalin B.
Institutional injustice: Implications for system transformation emerging from the mental health recovery narratives of people experiencing marginalisation

Background Institutional injustice refers to structures that create disparities in resources, opportunities and representation. Marginalised people experience institutional injustice, inequalities and discrimination through intersecting personal characteristics and social circumstances. This study aimed to investigate sources of institutional injustice and their effects on marginalised people with experience of mental health problems. Methods Semi-structured interviews were conducted with 77 individuals from marginalised groups with experience of mental health problems, including psychosis, Black, Asian and minority ethnic (BAME) populations, complex needs and lived experience as a work requirement. These were analysed inductively enabling sensitising concepts to emerge. Findings Three processes of institutional injustice were identified: not being believed because of social status and personal backgrounds; not being heard where narratives did not align with dominant discourses, and not being acknowledged where aspects of identity were disregarded. Harmful outcomes included disengagement from formal institutions through fear and mistrust, tensions and reduced affiliation with informal institutions when trying to consolidate new ways of being, and damaging impacts on mental health and wellbeing through multiple oppression. Conclusions Institutional injustice perpetuates health inequalities and marginalised status. Master status, arising from dominant discourses and heuristic bias, overshadow the narratives and experiences of marginalised people. Cultural competency has the potential to improve heuristic availability through social understandings of narrative and experience, whilst coproduction and narrative development through approaches such as communities of practice might offer meaningful avenues for authentic expression.
Individual calculation of perfusion activity based on ventilation efficiency for V/P-SPECT

Abstract Aim Implementation of the individual calculation of perfusion activity to ensure the guideline-compliant ratio of perfusion to ventilation (P/V-ratio) of ≥ 3 in the diagnosis of acute pulmonary embolism (PE) using V/P-SPECT. Material and Methods 50 consecutive V/P-SPECT examinations, in which a standard activity of 160 MBq was applied for perfusion imaging, are evaluated retrospectively. Based on this patient group an activity factor is determined, which provides a correlation between the applied perfusion activity and the expected perfusion counts of the gamma camera. Using the mean activity factor, the perfusion activity required for a P/V-ratio of four is calculated using the previously acquired ventilation count rate. This is applied prospectively to the 100 subsequent examinations. Results The mean perfusion activity factor is (54.56 ± 10.13) cps/MBq. The individually calculated perfusion activities range from 80 MBq to 200 MBq with an average value of (146.9 ± 35.3) MBq and a median of 140 MBq. The individual activity calculation thus reduced the mean perfusion activity by 8.2 % and the median by 12.5 %. In addition, the individual calculation reduced the proportion of P/V ratios < 3 from 14 % to 0 % and the proportion of P/V ratios > 5 from 24 % to 19 %. Conclusion The presented method for the individual calculation of perfusion activity offers a simple way to ensure a guideline-compliant P/V-ratio. Furthermore, unnecessarily high perfusion activity as a result of inadequate ventilation can be avoided.
Daily inpatient ertapenem therapy can be an alternative to hospitalization for the treatment of complicated urinary tract infections during the COVID‐19 pandemic

Physicians hospitalize the patients with complicated urinary tract infections (cUTIs) when they need intravenous antibiotics and outpatient parenteral antimicrobial therapy (OPAT) is unavailable. Daily inpatient antimicrobial therapy is an alternative to hospitalization, which is similar to OPAT; patients go home after they are administered antibiotics in a separate room in the hospital setting.
Ultrasound Evaluation of Gastric Emptying Time in Healthy Term Neonates after Formula Feeding

Background: The current American Society of Anesthesiologists fasting guideline for formula-fed infants in the periprocedural setting is 6 h. Prolonged fasting in very young infants is associated with an increased risk for hypoglycemia and dehydration as well as patient discomfort and patient/parental dissatisfaction. This study aimed to determine the time to gastric emptying in healthy neonates after formula feeding by serially evaluating the gastric antrum with ultrasound. The authors hypothesized that gastric emptying times in formula-fed neonates are significantly shorter than the current 6 h fasting recommendation. Methods: After institutional review board approval and written informed parental consent, ultrasound examination was performed in healthy full-term neonates before and after formula feeding at 15-min intervals until return to baseline. Ultrasound images of the gastric antrum were measured to obtain cross-sectional areas, which were then used to estimate gastric antral volumes. Results: Forty-six of 48 recruited neonates were included in the final analysis. Gastric emptying times ranged from 45 to 150 min and averaged 92.9 min (95% CI, 80.2 to 105.7 min; 99% CI, 76.0 to 109.8 min) in the overall study group. No significant differences were found in times to gastric emptying between male and female neonates (male: mean, 93.3 [95% CI, 82.4 to 104.2 min]; female: mean, 92.6 [95% CI, 82.0 to 103.2 min]; P = 0.930) or those delivered by vaginal versus cesarean routes (vaginal: mean, 93.9 [95% CI, 81.7 to 106.1 min]; cesarean: mean, 92.2 [95% CI, 82.5 to 101.9 min]; P = 0.819). Conclusions: These results demonstrate that gastric emptying times are substantially less than the current fasting guideline of 6 h for formula-fed, healthy term neonates. Serial ultrasound imaging of the gastric antrum in healthy term neonates after formula feeding reveals gastric emptying times ranging from 45 to 150 min. These observations suggest that preanesthesia fasting of healthy term neonates could be substantially shorter than is currently recommended.
Culture in the spotlight—cultural adaptation and content validity of the integrated palliative care outcome scale for dementia: A cognitive interview study

Background: Dementia is a life-limiting disease with high symptom burden. The Integrated Palliative Care Outcome Scale for Dementia (IPOS-Dem) is the first comprehensive person-centered measure to identify and measure palliative care needs of people with dementia. However, such a measure is missing in the German health care system. Aim: To develop a culturally adapted German version of the IPOS-Dem and determine its content validity as a foundation for comprehensive psychometric testing. Design: Cognitive interview study with intermittent analysis and questionnaire adaptation. Interview guide and coding frame followed thematic analysis according to Willis complemented by Tourangeau’s model of cognitive aspects of survey methodology: comprehension, retrieval, judgment, response. Participants: Purposive sample with professionals (n = 29) and family carers (n = 6) of people with advanced dementia in seven nursing homes and person’s own home care in four interview rounds (n = 11; 10; 7; 7). Results: IPOS-Dem was regarded as comprehensive and accessible. Cultural adaption pertained to issues of comprehension and judgment. Comprehension challenges referred to the person-centered concept of “being affected by” used in the POS-measures. Judgment problems related to persons with limited communication causing challenges in assessment. Conclusion: Most issues of cultural adaptation could be addressed by questionnaire modifications. However, interviews unveiled fundamental challenges for using proxy reported person-centered assessments. Continuous training on how to use the instrument is imperative to integrate the person-centered approach of palliative care into nursing homes as a key provider of generalist palliative care for people with dementia. The refined version is ready for psychometric testing.
Olinciguat, a stimulator of soluble guanylyl cyclase, attenuates inflammation, vaso‐occlusion and nephropathy in mouse models of sickle cell disease

Reduced bioavailability of NO, a hallmark of sickle cell disease (SCD), contributes to intravascular inflammation, vasoconstriction, vaso‐occlusion and organ damage observed in SCD patients. Soluble guanylyl cyclase (sGC) catalyses synthesis of cGMP in response to NO. cGMP‐amplifying agents, including NO donors and phosphodiesterase 9 inhibitors, alleviate TNFα‐induced inflammation in wild‐type C57BL/6 mice and in ‘humanised’ mouse models of SCD.
Estimating the reference interval from a fixed effects meta‐analysis

A reference interval provides a basis for physicians to determine whether a measurement is typical of a healthy individual. It can be interpreted as a prediction interval for a new individual from the overall population. However, a reference interval based on a single study may not be representative of the broader population. Meta‐analysis can provide a general reference interval based on the overall population by combining results from multiple studies. Methods for estimating the reference interval from a random effects meta‐analysis have been recently proposed to incorporate the within and between‐study variation, but a random effects model may give imprecise estimates of the between‐study variation with only few studies. In addition, the normal distribution of underlying study‐specific means, and equal within‐study variance assumption in these methods may be inappropriate in some settings. In this article, we aim to estimate the reference interval based on the fixed effects model assuming study effects are unrelated, which is useful for a meta‐analysis with only a few studies (e.g., ≤5). We propose a mixture distribution method only assuming parametric distributions (e.g., normal) for individuals within each study and integrating them to form the overall population distribution. This method is compared to an empirical method only assuming a parametric overall population distribution. Simulation studies have shown that both methods can estimate a reference interval with coverage close to the targeted value (i.e., 95%). Meta‐analyses of women daytime urination frequency and frontal subjective postural vertical measurements are reanalyzed to demonstrate the application of our methods.
Low glucose and high pyruvate reduce the production of 2-oxoaldehydes, improving mitochondrial efficiency, redox regulation, and stallion sperm function

Abstract Energy metabolism in spermatozoa is complex and involves the metabolism of carbohydrate fatty acids and amino acids. The ATP produced in the electron transport chain in the mitochondria appears to be crucial for both sperm motility and maintaining viability, whereas glycolytic enzymes in the flagella may contribute to ATP production to sustain motility and velocity. Stallion spermatozoa seemingly use diverse metabolic strategies, and in this regard, a study of the metabolic proteome showed that Gene Ontology terms and Reactome pathways related to pyruvate metabolism and the Krebs cycle were predominant. Following this, the hypothesis that low glucose concentrations can provide sufficient support for motility and velocity, and thus glucose concentration can be significantly reduced in the medium, was tested. Aliquots of stallion semen in four different media were stored for 48 h at 18°C; a commercial extender containing 67 mM glucose was used as a control. Stallion spermatozoa stored in media with low glucose (1 mM) and high pyruvate (10 mM) (LG-HP) sustained better motility and velocities than those stored in the commercial extender formulated with very high glucose (61.7 ± 1.2% in INRA 96 vs 76.2 ± 1.0% in LG-HP media after 48 h of incubation at 18°C; P < 0.0001). Moreover, mitochondrial activity was superior in LG-HP extenders (24.1 ± 1.8% in INRA 96 vs 51.1 ± 0.7% in LG-HP of spermatozoa with active mitochondria after 48 h of storage at 18°C; P < 0.0001). Low glucose concentrations may permit more efficient sperm metabolism and redox regulation when substrates for an efficient tricarboxylic acid cycle are provided. The improvement seen using low glucose extenders is due to reductions in the levels of glyoxal and methylglyoxal, 2-oxoaldehydes formed during glycolysis; these compounds are potent electrophiles able to react with proteins, lipids, and DNA, causing sperm damage. Summary sentence Hiigh glucose in the extender damages spermatozoa through formation of 2-oxoaldehydes. Graphical Abstract
Central amygdala inflammation drives pain hypersensitivity and attenuates morphine analgesia in experimental autoimmune encephalomyelitis.

ABSTRACT Chronic pain is a highly prevalent symptom associated with the autoimmune disorder multiple sclerosis (MS). The central nucleus of the amygdala plays a critical role in pain processing and modulation. Neuropathic pain alters nociceptive signaling in the central amygdala, contributing to pain chronicity and opioid tolerance. Here, we demonstrate that activated microglia within the central amygdala disrupt nociceptive sensory processing and contribute to pain hypersensitivity in experimental autoimmune encephalomyelitis (EAE), the most frequently used animal model of MS. Male and female mice with EAE exhibited differences in microglial morphology in the central amygdala, which was associated with heat hyperalgesia, impaired morphine reward and reduced morphine antinociception in females. EAE animals displayed a lack of morphine-evoked activity in cells expressing somatostatin within the central amygdala, which drive anti-nociception. Induction of focal microglial activation in naïve mice via injection of lipopolysaccharide into the central amygdala produced a loss of morphine analgesia in females, similar to as observed in EAE animals. Our data indicate that activated microglia within the central amygdala may contribute to the sexually dimorphic effects of morphine and may drive neuronal adaptations that lead to pain hypersensitivity in EAE. Our results provide a possible mechanism underlying the decreased efficacy of opioid analgesics in the management of MS-related pain, identifying microglial activation as a potential therapeutic target for pain symptoms in this patient population.
A clinical and biological review of keratoacanthoma *

Keratoacanthoma (KA) is a common skin tumour that remains controversial regarding classification, epidemiology, diagnosis, prognosis and management. Classically, a KA manifests as a rapidly growing, well‐differentiated, squamoid lesion with a predilection for sun‐exposed sites in elderly people and a tendency to spontaneously regress. Historically, KAs have been considered a variant of cutaneous squamous cell carcinoma (cSCC) and are often reported as KA‐type cSCC. However, the penchant for regression has led many to categorize KAs as biologically benign tumours with distinct pathophysiological mechanisms from malignant cSCC. The clinical and histopathological similarities between KA and cSCC, particularly the well‐differentiated variant of cSCC, have made definitive differentiation difficult or impossible in many cases. The ambiguity between entities has led to the general recommendation for surgical excision of KAs to ensure a potentially malignant cSCC is not left untreated. This current standard creates unnecessary surgical morbidity and financial strain for patients, especially the at‐risk elderly population. There have been no reports of death from a definitive KA to date, while cSCC has an approximate mortality rate of 1·5%. Reliably distinguishing cSCC from KA would shift management strategies for KAs towards less‐invasive treatment modalities, prevent unnecessary surgical morbidity, and likely reduce associated healthcare costs. Herein, we review the pathophysiology and clinical characteristics of KA, and conclude on the balance of current evidence that KA is a benign lesion and distinct from cSCC.
Frontal circuit specialisations for decision making

There is widespread consensus that distributed circuits across prefrontal and anterior cingulate cortex (PFC/ACC) are critical for reward‐based decision making. The circuit specialisations of these areas in primates were likely shaped by their foraging niche, in which decision making is typically sequential, attention‐guided and temporally extended. Here, I argue that in humans and other primates, PFC/ACC circuits are functionally specialised in two ways. First, microcircuits found across PFC/ACC are highly recurrent in nature and have synaptic properties that support persistent activity across temporally extended cognitive tasks. These properties provide the basis of a computational account of time‐varying neural activity within PFC/ACC as a decision is being made. Second, the macrocircuit connections (to other brain areas) differ between distinct PFC/ACC cytoarchitectonic subregions. This variation in macrocircuit connections explains why PFC/ACC subregions make unique contributions to reward‐based decision tasks and how these contributions are shaped by attention. They predict dissociable neural representations to emerge in orbitofrontal, anterior cingulate and dorsolateral prefrontal cortex during sequential attention‐guided choice, as recently confirmed in neurophysiological recordings.