Miracle-dz/UniFAR-FTUs huggingface dataset:
Antibacterial Effect of Caffeic Acid Phenethyl Ester on Cariogenic Bacteria and Streptococcus mutans Biofilms

Dental caries is the most common disease in the human mouth. Streptococcus mutans is the primary cariogenic bacterium. Propolis is a nontoxic natural product with a strong inhibitory effect on oral cariogenic bacteria. The polyphenol-rich extract from propolis inhibits S. mutans growth and biofilm formation, as well as the genes involved in virulence and adherence, through the inhibition of glucosyltransferases (GTF). However, because the chemical composition of propolis is highly variable and complex, the mechanism of its antimicrobial action and the active compound are controversial and not completely understood. ABSTRACT Dental caries is the most common disease in the human mouth. Streptococcus mutans is the primary cariogenic bacterium. Propolis is a nontoxic natural product with a strong inhibitory effect on oral cariogenic bacteria. The polyphenol-rich extract from propolis inhibits S. mutans growth and biofilm formation, as well as the genes involved in virulence and adherence, through the inhibition of glucosyltransferases (GTF). However, because the chemical composition of propolis is highly variable and complex, the mechanism of its antimicrobial action and the active compound are controversial and not completely understood. Caffeic acid phenethyl ester (CAPE) is abundant in the polyphenolic compounds from propolis, and it has many pharmacological effects. In this study, we investigated the antibacterial effects of CAPE on common oral cariogenic bacteria (Streptococcus mutans, Streptococcus sobrinus, Actinomyces viscosus, and Lactobacillus acidophilus) and its effects on the biofilm-forming and cariogenic abilities of S. mutans. CAPE shows remarkable antimicrobial activity against cariogenic bacteria. Moreover, CAPE also inhibits the formation of S. mutans biofilms and their metabolic activity in mature biofilms. Furthermore, CAPE can inhibit the key virulence factors of S. mutans associated with cariogenicity, including acid production, acid tolerance, and the bacterium’s ability to produce extracellular polysaccharides (EPS), without affecting bacterial viability at subinhibitory levels. In conclusion, CAPE appears to be a new agent with anticariogenic potential, not only via inhibition of the growth of cariogenic bacteria.
Deep learning applications in automatic needle segmentation in ultrasound-guided prostate brachytherapy.

PURPOSE High-Dose-Rate (HDR) brachytherapy is one of the most effective ways to treat the prostate cancer, which is the second most common cancer in men worldwide. This treatment delivers highly conformal dose through the transperineal needle implants and is guided by a real time ultrasound (US) imaging system. Currently, the brachytherapy needles in the US images are manually segmented by physicists during the treatment, which is time-consuming and error-prone. In this study, we propose a set of deep learning based algorithms to accurately segment the brachytherapy needles and locate the needle tips from the US images. METHODS Two deep neural networks are developed to address this problem. First, a modified deep U-Net is used to segment the pixels belonging to the brachytherapy needles from the US images. Second, an additional VGG-16 based deep convolutional network is combined with the segmentation network to predict the locations of the needle tips. The networks are trained and evaluated on a clinical US images dataset with labeled needle trajectories collected in our hospital (Institutional Review Board approval (IRB 41755)). RESULTS The evaluation results show that our method can accurately extract the trajectories of the needles with a resolution of 0.668 mm and 0.319 mm in x and y direction respectively. 95.4% of the x direction and 99.2% of the y direction have error ≤ 2 mm. Moreover, The position resolutions of the tips are 0.721 mm, 0.369 mm and 1.877 mm in x, y and z directions respectively, while 94.2%, 98.3% and 67.5% of the data have error ≤ 2 mm. CONCLUSIONS This paper proposed a neural network based algorithm to segment the brachytherapy needles from the US images and locate the needle tip. It can be used in the HDR brachytherapy to help improve the efficiency and quality of the treatments.
EDITORIAL

The concept of “Mania” is intimately linked to the evolution of psychiatry itself. The word Mania has two Proto-Indo-European roots, *mn ̥yoand *men-, meaning “to think” or “to remember”; however, many other IndoEuropean derivations are more akin to passion and desire [1]. Thinking and memory are central to cognition as passion and desire to motivation, likability, and reward anticipation, the centre of emotional life; their alterations constitute the core of all psychiatric disorders. The above roots gave birth in Greek to a range of words, among which μῆνις, fury, wrath or rage, that was in use since Homer’s times (interestingly, in Æolian it was μαῖνις and in Dorian μᾶνις, and referred to the wrath of Gods [2]); μαίνομαι, i.e., to rage, to move back and forth in restlessness and emotional activation, to rampage; μνήμη, memory; and μάντης, diviner, soothsayer or fortuneteller. Hence, the Greek words bound to the *mn ̥yo and *men roots cover a wide emotional and cognitive range. The word μανία refers to persistent rage, unrelenting desire and stubborn goal-directedness; it was used in common Ancient Greek language to refer to madness at least since the times of Æschylus (525-455 b.C.), who in “Prometheus bound” [3] puts in Io’s mouth the words “By the fanged insect, with a maniac leap I rushed on to Cenchrea's limpid stream”. Further on, in replying to Prometheus, Io states “. καὶ φρενοπληγεῖς μανίαι θάλπουσ ̓”, i.e., “. and mind-striking manias they kindle” [4]. We don’t mean to say by this that Æschylus had anticipated Bob Post, but it is astonishing how the words the Ancient Greeks used conveyed emotional meanings and a mentality akin to those of modern people, an interesting match to Julian Jaynes’ bicameral mind theory [5]. Socrates (470-469 b.C.–399 b.C.), in Plato’s (427 b.C.– 347 b.C.) Dialogue “Phædrus” initially endorsed Phædrus’ presentation of Lysias’ view of eros as incurable mania (madness, viewed like an irrational addiction) [6], but later in the Dialogue went on to idealise it and defend it. Around these times, mania often appeared not only in literature and philosophy, but also in Medicine. There are several recurrences in Hippocratic writings, not to mention an entire book dedicated to mania, Περί Μανίας Λόγος, which
The association of gene rearrangement and lymphoma diagnosis

Abstract Introduction: To investigate the gene rearrangement and mutation of lymphoma biomarkers including (Immunoglobulin H (IgH), Immunoglobulin kappa (IGK), Immunoglobulin lambda (IGL), and TCR) in the lymphoma diagnosis. Methods and analysis: Paraffin tissue samples from 240 cases diagnosed as suspected lymphoma in the department of pathology, Deyang City People's Hospital from June 2020 to June 2021 will be enrolled. Deoxyribonucleic acid extraction and Polymerase Chain Reaction (PCR) amplification will be performed in these paraffin tissue samples. Immunoglobulin and T cell receptor (TCR) rearrangement will be analyzed by hetero-double chain gel electrophoresis and BioMed-2 standardized immunoglobulin gene rearrangement detection system. In this study protocol IGH gene rearrangement, IGK gene rearrangement, both IGH and IGL gene rearrangement, both IGH and IGK gene rearrangement, both IGK and IGL gene rearrangement, both IGH, IGK and IGL gene rearrangement, TCR gene rearrangement and positive Ig/TCR rearrangement will be analyzed. Discussion: In this study, we will use B and T cell lymphoma analysis focusing on IgH, IGK, IGL, and TCR gene rearrangement, so as to provide early guidance for the diagnosis of lymphoma. Second generation sequencing technology is helpful in the differential diagnosis of lymphoma. Trial registration: Chinese Clinical trial registry: ChiCTR2000032366.
Roving: The causes of interference and re-enabled learning in multi-task visual training

People routinely perform multiple visual judgments in the real world, yet, intermixing tasks or task variants during training can damage or even prevent learning. This paper explores why. We challenged theories of visual perceptual learning focused on plastic retuning of low-level retinotopic cortical representations by placing different task variants in different retinal locations, and tested theories of perceptual learning through reweighting (changes in readout) by varying task similarity. Discriminating different (but equivalent) and similar orientations in separate retinal locations interfered with learning, whereas training either with identical orientations or sufficiently different ones in different locations released rapid learning. This location crosstalk during learning renders it unlikely that the primary substrate of learning is retuning in early retinotopic visual areas; instead, learning likely involves reweighting from location-independent representations to a decision. We developed an Integrated Reweighting Theory (IRT), which has both V1-like location-specific representations and higher level (V4/IT or higher) location-invariant representations, and learns via reweighting the readout to decision, to predict the order of learning rates in different conditions. This model with suitable parameters successfully fit the behavioral data, as well as some microstructure of learning performance in a new trial-by-trial analysis.
Intraoperative Ultrasound Elastography Is Useful for Determining the Pancreatic Texture and Predicting Pancreatic Fistula After Pancreaticoduodenectomy

Objectives Pancreatic fistula (PF) is one of the most common complications after pancreaticoduodenectomy (PD). The soft pancreatic texture is known to be an important predictive factor for PF after PD. However, its evaluation is dependent on the sense of touch by the operator during operation, thus not objective. The aim of this study was to investigate the relationship between mean elasticity via intraoperative ultrasound elastography and histological pancreatic hardness, as well as predictive factor of PF after PD. Methods Forty-eight patients who underwent ultrasound elastography during PD and had pancreatic parenchyma histologically evaluated were included. Results Pancreatic fistula was noted in 20 patients. There were significant differences in the histological pancreatic fibrosis rate between soft pancreas group (8.2%) and hard pancreas group (28.4%, P < 0.05) and in the mean elasticity between soft pancreas group (1.94 m/s) and hard pancreas group (3.17 m/s, P < 0.05). The mean elasticity was significantly correlated with pancreatic fibrosis rate (P < 0.05). A multivariate analysis revealed that the mean elasticity of less than 2.2 m/s was a significant predictor of PF after PD (P = 0.003). Conclusions Intraoperative ultrasound elastography could predict pancreatic texture objectively. The mean elasticity of less than 2.2 m/s was a significant predictor of PF after PD.
Global Frequencies of Clinically Important HLA Alleles and Their Implications For the Cost‐Effectiveness of Preemptive Pharmacogenetic Testing

Immune‐mediated drug hypersensitivity reactions are an important source of iatrogenic morbidity and mortality. Human leukocyte antigen (HLA)‐B*57:01, HLA‐B*15:02, HLA‐A*31:01, and HLA‐B*58:01 constitute established risk factors and preemptive genotyping of these HLA alleles in patients prior to the initiation of abacavir, carbamazepine, and allopurinol‐based therapies can prevent toxicity and improve patient outcomes. However, the cost‐effectiveness of preemptive HLA testing has only been evaluated in the United States and few countries in Europe and Asia. In this study, we consolidated HLA genotypes from 3.5–6.4 million individuals across up to 74 countries and modeled the country‐specific cost‐effectiveness of genetic testing. We find major ethnogeographic differences in risk allele prevalence, which translated into pronounced differences in the number of patients needed to test to prevent one case of severe hypersensitivity reactions between countries and populations. At incremental cost‐effectiveness ratio thresholds of $40,000, testing of HLA‐B*57:01 in patients initiating abacavir was cost‐effective in the majority of countries with potential exceptions of East Asia, Saudi Arabia, Ghana, and Zimbabwe. For carbamazepine, preemptive genotyping of HLA‐B*15:02 is only cost‐effective across most of East and South Asia, whereas HLA‐A*31:01 testing is likely to be cost‐effective globally. Testing of HLA‐B*58:01 is more likely to be cost‐effective throughout Africa and Asia compared with Europe and the Americas. We anticipate that this data set can serve as an important resource for clinicians and health economists to guide clinical decision making and inform public healthcare strategies.
Functional imaging evidence for task-induced deactivation and disconnection of a major default mode network hub in the mouse brain

Significance Our report first validates an imaging technique, functional ultrasound, an experimental approach providing significantly higher sensitivity and spatiotemporal resolution than fMRI, for the study of sensory stimulation-induced changes in activation and connectivity patterns in the awake mouse brain. Next, by using this approach in lightly sedated conscious mice, we provide functional evidence supporting an evolutionary preserved function of the default mode network, a set of highly connected brain areas, which is characteristically impaired in major neuropsychiatric diseases in humans. Uncovering the existence and function of the default mode network in mice, the main preclinical model organism for neuropsychiatric diseases, opens new avenues of high translational relevance for brain research and drug development. The default mode network (DMN) has been defined in functional brain imaging studies as a set of highly connected brain areas, which are active during wakeful rest and inactivated during task-based stimulation. DMN function is characteristically impaired in major neuropsychiatric diseases, emphasizing its interest for translational research. However, in the mouse, a major preclinical rodent model, there is still no functional imaging evidence supporting DMN deactivation and deconnection during high-demanding cognitive/sensory tasks. Here we have developed functional ultrasound (fUS) imaging to properly visualize both activation levels and functional connectivity patterns, in head-restrained awake and behaving mice, and investigated their modulation during a sensory-task, whisker stimulation. We identified reproducible and highly symmetric resting-state networks, with overall connectivity strength directly proportional to the wakefulness level of the animal. We show that unilateral whisker stimulation leads to the expected activation of the contralateral barrel cortex in lightly sedated mice, while interhemispheric inhibition reduces activity in the ipsilateral barrel cortex. Whisker stimulation also leads to elevated bilateral connectivity in the hippocampus. Importantly, in addition to functional changes in these major hubs of tactile information processing, whisker stimulation during genuine awake resting-state periods leads to highly specific reductions both in activation and interhemispheric correlation within the restrosplenial cortex, a major hub of the DMN. These results validate an imaging technique for the study of activation and connectivity in the lightly sedated awake mouse brain and provide evidence supporting an evolutionary preserved function of the DMN, putatively improving translational relevance of preclinical models of neuropsychiatric diseases.
Competitive Antagonism of Etomidate Action by Diazepam: In Vitro GABAA Receptor and In Vivo Zebrafish Studies.

BACKGROUND Recent cryo-electron microscopic imaging studies have shown that in addition to binding to the classical extracellular benzodiazepine binding site of the α1β3γ2L γ-aminobutyric acid type A (GABAA) receptor, diazepam also binds to etomidate binding sites located in the transmembrane receptor domain. Because such binding is characterized by low modulatory efficacy, the authors hypothesized that diazepam would act in vitro and in vivo as a competitive etomidate antagonist. METHODS The concentration-dependent actions of diazepam on 20 µM etomidate-activated and 6 µM GABA-activated currents were defined (in the absence and presence of flumazenil) in oocyte-expressed α1β3γ2L GABAA receptors using voltage clamp electrophysiology. The ability of diazepam to inhibit receptor labeling of purified α1β3γ2L GABAA receptors by [H]azietomidate was assessed in photoaffinity labeling protection studies. The impact of diazepam (in the absence and presence of flumazenil) on the anesthetic potencies of etomidate and ketamine was compared in a zebrafish model. RESULTS At nanomolar concentrations, diazepam comparably potentiated etomidate-activated and GABA-activated GABAA receptor peak current amplitudes in a flumazenil-reversible manner. The half-maximal potentiating concentrations were 39 nM (95% CI, 27 to 55 nM) and 26 nM (95% CI, 16 to 41 nM), respectively. However, at micromolar concentrations, diazepam reduced etomidate-activated, but not GABA-activated, GABAA receptor peak current amplitudes in a concentration-dependent manner with a half-maximal inhibitory concentration of 9.6 µM (95% CI, 7.6 to 12 µM). Diazepam (12.5 to 50 µM) also right-shifted the etomidate-concentration response curve for direct activation without reducing the maximal response and inhibited receptor photoaffinity labeling by [H]azietomidate. When administered with flumazenil, 50 µM diazepam shifted the etomidate (but not the ketamine) concentration-response curve for anesthesia rightward, increasing the etomidate EC50 by 18-fold. CONCLUSIONS At micromolar concentrations and in the presence of flumazenil to inhibit allosteric modulation via the classical benzodiazepine binding site of the GABAA receptor, diazepam acts as an in vitro and in vivo competitive etomidate antagonist. : WHAT WE ALREADY KNOW ABOUT THIS TOPIC: Diazepam binds to the γ-aminobutyric acid type A (GABAA) receptor high-affinity extracellular benzodiazepine siteDiazepam can also bind to the GABAA receptor transmembrane etomidate siteIt is unknown whether diazepam or similar compounds can antagonize etomidate WHAT THIS ARTICLE TELLS US THAT IS NEW: In vitro and in vivo zebrafish studies show that diazepam and other like compounds can competitively antagonize etomidate at the GABAA receptor etomidate binding siteThis provides proof-of-concept for development of competitive anesthetic antagonists.
Case Series: Deep Brain Stimulation for Facial Pain.

BACKGROUND Deep brain stimulation (DBS) has been used for chronic pain for decades, but its use is limited due to a lack of reliable data about its efficacy for specific indications. OBJECTIVE To report on 9 patients who underwent DBS for facial pain, with a focus on differences in outcomes between distinct etiologies. METHODS We retrospectively reviewed 9 patients with facial pain who were treated with DBS of the ventral posteromedial nucleus of the thalamus and periventricular gray. We report on characteristics including facial pain etiology, complications, changes in pain scores using the visual analog scale (VAS), and willingness to undergo DBS again. RESULTS Nine patients underwent DBS for either poststroke, post-traumatic, postherpetic, or atypical facial pain. Eight patients (89%) were permanently implanted. Seven patients had sufficient follow-up (mean 40.3 mo). Of these 7 patients, average VAS scores decreased from 9.4 to 6.1 after DBS. The average decrease in VAS was 55% for post-traumatic facial pain (2 patients), 45% for poststroke (2 patients), 15% for postherpetic neuralgia (2 patients), and 0% for atypical facial pain (1 patient). Three of the 8 implanted patients (38%) had complications which required removal of hardware. Only 2 of 7 (29%) patients met classical criteria for responders (50% decrease in pain scores). However, among 4 patients who were asked about willingness to undergo DBS again, all expressed that they would repeat the procedure. CONCLUSION There is a trend towards improvement in pain scores following DBS for facial pain, most prominently with post-traumatic pain.
Diffuse alveolar damage (DAD) resulting from coronavirus disease 2019 Infection is Morphologically Indistinguishable from Other Causes of DAD

Diffuse alveolar damage (DAD) is a ubiquitous finding in inpatient coronavirus disease 2019 (COVID‐19)‐related deaths, but recent reports have also described additional atypical findings, including vascular changes. An aim of this study was to assess lung autopsy findings in COVID‐19 inpatients, and in untreated severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐positive individuals who died in the community, in order to understand the relative impact of medical intervention on lung histology. Additionally, we aimed to investigate whether COVID‐19 represents a unique histological variant of DAD by comparing the pathological findings with those of uninfected control patients.
Androgens modify therapeutic response to cabazitaxel in models of advanced prostate cancer

Disruption of the phenotypic landscape via epithelial‐mesenchymal transition (EMT) enables prostate cancer cells to metastasize and acquire therapeutic resistance. Our previous studies demonstrated that cabazitaxel (CBZ) (second‐generation Food and Drug Administration‐approved taxane chemotherapy), used for the treatment of castration‐resistant prostate cancer (CRPC), causes reversal of EMT to mesenchymal‐epithelial transition (MET) and reduces expression of kinesin motor protein KIFC1 (HSET). The present study examined the effect of sequencing CBZ chemotherapy mediated MET on prostate tumor redifferentiation overcoming therapeutic resistance in models of advanced prostate cancer.
Important anatomical variations of the superior posterior alveolar artery: Studied by cone beam computed tomography

The knowledge of anatomical variations of the posterior superior alveolar artery (PSAA) is very important in surgeries for maxillary sinus (MS) elevation and subsequent insertion of dental implants, avoiding common and serious surgical complications. The main objective of this study was to analyse important anatomical variations of the PSAA by means of cone beam computed tomography (CBCT) examinations. 180 tomographic CBCT were analysed, and MS was divided into three equal regions: (I) anterior, (II) intermediate and (III) posterior. Variables evaluated were the visualisation of the artery, distance from the artery to the ridge crest, distance from the artery to the sinus floor, alveolar ridge height and arterial diameter. The PSAA visualisation was more prevalent in males and region III (76.7%). The distance from the artery to the sinus floor presented no significant difference between regions II and III, with both regions showing significantly lower values than region I. A significant difference was observed in the diameter of the arteries with higher prevalence of diameters >1.0 mm in males and <1.0 mm in females. The PSAA can be well visualised frequently with a CBCT, and differences in artery diameter were observed in relation to gender (males > females). Additional care is recommended when it is necessary to extend surgeries to the posterior MS region, avoiding haemorrhages that are associated with failures in these procedures.