Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of an Upper Limit of Tumor Burden for Downstaging in Candidates with Hepatocellular Cancer Waiting for Liver Transplantation: A West–East Collaborative Effort

Since the introduction of Milan Criteria, all scoring models describing the prognosis of hepatocellular cancer (HCC) after liver transplantation (LT) have been exclusively based on characteristics available at surgery, therefore neglecting the intention-to-treat principles. This study aimed at developing an intention-to-treat model through a competing-risk analysis. Using data available at first referral, an upper limit of tumor burden for downstaging was identified beyond which successful LT becomes an unrealistic goal. Twelve centers in Europe, United States, and Asia (Brussels, Sapienza Rome, Padua, Columbia University New York, Innsbruck, Medanta-The Medicity Dehli, Hong Kong, Kyoto, Kaohsiung Taiwan, Mainz, Fukuoka, Shulan Hospital Hangzhou) created a Derivation (n = 2318) and a Validation Set (n = 773) of HCC patients listed for LT between January 2000–March 2017. In the Derivation Set, the competing-risk analysis identified two independent covariables predicting post-transplant HCC-related death: combined HCC number and diameter (SHR = 1.15; p < 0.001) and alpha-fetoprotein (AFP) (SHR = 1.80; p < 0.001). WE-DS Model showed good diagnostic performances at internal and external validation. The identified upper limit of tumor burden for downstaging was AFP ≤ 20 ng/mL and up-to-twelve as sum of HCC number and diameter; AFP = 21–200 and up-to-ten; AFP = 201–500 and up-to-seven; AFP = 501–1000 and up-to-five. The WE-DS Model proposed here, based on morphologic and biologic data obtained at first referral in a large international cohort of HCC patients listed for LT, allowed identifying an upper limit of tumor burden for downstaging beyond which successful LT, following downstaging, results in a futile transplantation.
Characterization of Ocular Clinical Isolates of Pseudomonas aeruginosa from Non-Contact Lens Related Keratitis Patients from South India

P. aeruginosa is the most common Gram-negative organism causing bacterial keratitis. Pseudomonas utilizes various virulence mechanisms to adhere and colonize in the host tissue. In the present study, we examined virulence factors associated with thirty-four clinical P. aeruginosa isolates collected from keratitis patients seeking care at L V Prasad Eye Institute, Hyderabad. The virulence-associated genes in all the isolates were genotyped and characteristics such as antibiotic susceptibility, biofilm formation, swarming motility, pyoverdine production and cell cytotoxicity were analyzed. All the isolates showed the presence of genes related to biofilm formation, alkaline proteases and elastases; however, there was a difference in the presence of genes related to the type III secretion system (T3SS). A higher prevalence of exoU+ genotype was noted in the drug-resistant isolates. All the isolates were capable of forming biofilms and more than 70% of the isolates showed good swarming motility. Pyoverdine production was not associated with the T3SS genotype. In the cytotoxicity assay, the presence of exoS, exoU or both resulted in higher cytotoxicity compared to the absence of both the genes. Overall, our results suggest that the T3SS profile is a good indicator of P. aeruginosa virulence characteristics and the isolates lacking the effector genes may have evolved alternate mechanisms of colonization in the host.
Ethanol exposure during the brain growth spurt affects social behavior and increases susceptibility to acute ethanol effects during adolescence in male mice

The brain is particularly vulnerable to ethanol effects during its growth spurt. Outcomes of early ethanol exposure such as hyperactivity have been extensively investigated; however, persons with fetal alcohol spectrum disorder frequently have social impairments and are heavy drinkers. Despite that, scant information is available regarding the neurobiological basis of these latter behavioral issues. Here, Swiss mice exposed to ethanol (Etoh, 5 g/kg i.p., alternate days) or saline during the brain growth spurt [postnatal day (PN) 2 to 8] were used to assess social behavior after an ethanol challenging during adolescence. At PN39, animals were administered with a single ethanol dose (1 g/Kg) or water by gavage and were then evaluated in the three‐chamber sociability test. We also evaluated corticosterone serum levels and the frontal cerebral cortex serotoninergic system. Etoh males showed reductions in sociability. Ethanol challenging reverted these alterations in social behavior, reduced corticosterone levels, and increased the 5‐HT2 receptor binding of male Etoh mice. No alterations were observed in 5‐HT and 5‐HIAA contents. These data support the idea that ethanol exposure during the brain growth spurt impacts social abilities during adolescence, alters ethanol reexposure effects, and suggests that stress response and serotoninergic system play roles in this phenomenon.
Intravascular Ultrasound Imaging–Guided Versus Coronary Angiography–Guided Percutaneous Coronary Intervention: A Systematic Review and Meta‐Analysis

Background Intravascular ultrasound (IVUS) guidance during percutaneous coronary intervention (PCI) offers tomographic images of the coronary vessels, allowing optimization of stent implantation at the time of PCI. However, the long‐term beneficial effect of IVUS over PCI guided by coronary angiography (CA) alone remains under question. We sought to investigate the outcomes of IVUS‐guided compared with CA‐guided PCI. Methods and Results We performed a comprehensive search of PubMed, Medline, and Cochrane Central Register, looking for randomized controlled trials and observational studies that compared PCI outcomes of IVUS with CA. Data were aggregated for the primary outcome measure using the random‐effects model as pooled risk ratio (RR). The primary outcomes were the rate of cardiovascular death, need for target lesion revascularization, occurrence of myocardial infarction, and rate of stent thrombosis. A total of 19 studies met the inclusion criteria, comprising 27 610 patients divided into IVUS (n=11 513) and CA (n=16 097). Compared with standard CA‐guided PCI, we found that the risks of cardiovascular death (RR, 0.63; 95% CI, 0.54–0.73), myocardial infarction (RR, 0.71; 95% CI, 0.58–0.86), target lesion revascularization (RR, 0.81; 95% CI, 0.70–0.94), and stent thrombosis (RR, 0.57; 95% CI, 0.41–0.79) were all significantly lower using IVUS guidance. Conclusions Compared with standard CA‐guided PCI, the use of IVUS imaging guidance to optimize stent implantation is associated with a reduced risk of cardiovascular death and major adverse events, such as myocardial infarction, target lesion revascularization, and stent thrombosis.
Measles Immunization Policies and Vaccination Coverage in EU/EEA Countries over the Last Decade

Background: Starting from 2016, a major measles epidemic affected EU/EEA countries, after the measles incidence rate had progressively decreased from 2011 to 2015. Methods: This study describes measles incidences (ECDC reports), the vaccination coverages (VCs) (WHO/UNICEF reports) and the vaccination strategies, whether mandatory or recommended (ECDC Vaccine Scheduler), in 30 European countries over the last decade. Results: VCs were higher in countries with historically mandatory vaccination. However, in these countries, VCs declined between 2010 and 2018, in two cases to levels below 90% at the second dose. Instead, 9 and 12 countries with recommended vaccination increased their VCs, respectively, for the first and the second dose. Overall, the countries with VC ≥ 95% decreased from 20 to 15 for the first dose and from 10 to 7 for the second dose. This trend led Italy, France and Germany to make vaccination mandatory. In Italy this provision was introduced in 2017, and together with the catch-up campaigns on children between 1 and 15 years at school entry, led immediately to a strong effect: the first dose VC passed from 87% in 2016 to 93% in 2018, and from 82% to 89% for the second dose. Conclusions: Mandatory vaccination is certainly a policy producing positive effects; however, it seems to require additional strategies in order to reach the WHO goal of 95% of VC. Measures such as catch-up action on susceptible populations and communication strategies aimed at increasing awareness and acceptance should be considered.
Exploring BODIPY Derivatives as Singlet Oxygen Photosensitizers for PDT

This minireview is devoted to honoring the memory of Dr. Thomas Dougherty, a pioneer of modern photodynamic therapy (PDT). It compiles the most important inputs made by our research group since 2012 in the development of new photosensitizers based on BODIPY chromophore which, thanks to the rich BODIPY chemistry, allows a finely tuned design of the photophysical properties of this family of dyes to serve as efficient photosensitizers for the generation of singlet oxygen. These two factors, photophysical tuning and workable chemistry, have turned BODIPY chromophore as one of the most promising dyes for the development of improved photosensitizers for PDT. In this line, this minireview is mainly related to the establishment of chemical methods and structural designs for enabling efficient singlet oxygen generation in BODIPYs. The approaches include the incorporation of heavy atoms, such as halogens (iodine or bromine) in different number and positions on the BODIPY scaffold, and also transition metal atoms, by their complexation with Ir(III) center, for instance. On the other hand, low‐toxicity approaches, without involving heavy metals, have been developed by preparing several orthogonal BODIPY dimers with different substitution patterns. The advantages and drawbacks of all these diverse molecular designs based on BODIPY structural framework are described.
Assessing the role of membrane lipids in the action of ruthenium(III) anticancer compounds

This work addresses the possible role of the cell membrane in the molecular mechanism of action of two salan-type ruthenium complexes that were previously shown to be active against human tumor cells, namely [Ru(III)(L1)(PPh3)Cl] and [Ru(III)(L2)(PPh3)Cl] (where L1 is 6,6′-(1R,2R)-cyclohexane-1,2-diylbis(azanediyl)bis(methylene)bis(3-methoxyphenol); and L2 is 2,2′-(1R,2R)-cyclohexane-1,2-diylbis(azanediyl)bis(methylene)bis(4-methoxyphenol)). One-component membrane models were first used, a disordered fluid bilayer of dioleoylphosphatodylcholine (DOPC), and an ordered rigid gel bilayer of dipalmitoylphosphatidylcholine. In addition, two quaternary mixtures of phosphatidylcholine, phosphatidylethanolamine, sphingomyelin and cholesterol were used to mimic the lipid composition either of mammalian plasma membrane (1:1:1:1 mol ratio) or of a cancer cell line membrane (36.2:23.6:6.8:33.4 mol ratio). The results show that both salan ligands L1 and L2 bind relatively strongly to DOPC bilayers, but without significantly affecting their structure. The ruthenium complexes have moderate affinity for DOPC. However, their impact on the membranes was notable, leading to a significant increase in the permeability of the lipid vesicles. None of the compounds compromised liposome integrity, as revealed by dynamic light scattering. Fluorescence spectroscopy studies revealed changes in the biophysical properties of all membrane models analyzed in the presence of the two complexes, which promoted an increased fluidity and water penetration into the lipid bilayer in the one-component systems. In the quaternary mixtures, one of the complexes had an analogous effect (increasing water penetration), whereas the other complex reorganized the liquid ordered and liquid disordered domains. Thus, small structural differences in the metal ligands may lead to different outcomes. To better understand the effect of these complexes in cancer cells, the membrane dipole potential was also measured. For both Ru complexes, an increase in the dipole potential was observed for the cancer cell membrane model, while no alteration was detected on the non-cancer plasma membrane model. Our results show that the action of the Ru(III) complexes tested involves changes in the biophysical properties of the plasma membrane, and that it also depends on membrane lipid composition, which is frequently altered in cancer cells when compared to their normal counterparts.
Investigation of an Ultra Wideband Noise Sensor for Health Monitoring

Quick on-scene assessment and early intervention is the key to reduce the mortality of stroke and trauma patients, and it is highly desirable to develop ambulance-based diagnostic and monitoring devices in order to provide additional support to the medical personnel. We developed a compact and low cost ultra wideband noise sensor for medical diagnostics and vital sign monitoring in pre-hospital settings. In this work, we demonstrated the functionality of the sensor for respiration and heartbeat monitoring. In the test, metronome was used to manipulate the breathing pattern and the heartbeat rate reference was obtained with a commercial electrocardiogram (ECG) device. With seventeen tests performed for respiration rate detection, sixteen of them were successfully detected. The results also show that it is possible to detect the heartbeat rate accurately with the developed sensor.
Exercise May Ameliorate the Detrimental Side Effects of High Vitamin D Supplementation on Muscle Function in Mice

Vitamin D is commonly prescribed to normalize deficiencies and to treat osteoporosis. However, the effect vitamin D supplements have on skeletal muscle health is equivocal. Although vitamin D is known to play a role in the various processes that maintain muscle integrity and function, recent studies utilizing high bolus dose vitamin D supplementation has demonstrated an increased risk of falls. Thus, the aim of this study was to investigate the effects of high vitamin D supplementation on skeletal muscle function with and without exercise enrichment. Four‐week old C57BL/10 mice (n = 48) were separated into either normal vitamin D (1500 IU/kg diet; unsupplemented) or high vitamin D (20,000 IU/kg diet; supplemented) treatment groups. Each dietary group was further separated into interventional subgroups where mice either remained sedentary or received exercise‐enrichment for 8 weeks in the form of voluntary running. Following the intervention period, whole body in vivo and ex vivo contractile analysis were performed. High vitamin D supplementation decreased force production in the slow‐twitch soleus muscles of sedentary mice (p < .01); however, exercise normalized this effect. Eight weeks of exercise did not improve fatigue resistance of the extensor digitorum longus (EDL) or soleus muscles in unsupplemented mice, likely due to low levels of activation in these muscles. In contrast, fatigability was improved in the EDL (p < .01) and even more so in the soleus (p < .001) in the supplemented exercise‐enriched group. Our data highlights that increasing vitamin D levels above normal reduces postural muscle force as seen in the soleus. Thus, unnecessary vitamin D supplementation may contribute to the increased risk of falls observed in some studies. Interestingly, when vitamin D supplementation was combined with exercise, force production was effectively restored, and fatigue resistance improved, even in muscles lowly activated. Regular exercise may modulate the effects of vitamin D on skeletal muscle, and be recommended for individuals receiving vitamin D supplements. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.
Is there an association between Perceptual Ability Test scores and color vision acuity?

OBJECTIVE The purpose of this study was to determine if there is an association between Perceptual Ability Test (PAT) results and color vision deficiency (CVD). METHODS Three consecutive classes of first-year dental students (n = 291) voluntarily participated in the study. The Farnsworth-Munsell 100 Hue Color Vision test (FM-100) was administered to students beneath a Macbeth Judge II viewing booth that provided ideal lighting conditions to ascertain CVD. Results of FM-100 test were recorded as total error scores (TES). Color acuity was scored as superior (TES 0-16), average (TES 20-100), or poor (TES > 100). Additional information of age, sex, ethnicity, and time to complete the FM-100 was obtained. Multiple linear regression was used to determine the association between PAT and CVD while adjusting for age, sex, ethnicity, and time to complete the FM-100 test. RESULTS TES ranged from 0-244. There were 132 students with superior color acuity, 161 with average, and eight with poor acuity. Females performed better than males on the FM-100 test. Time to complete the FM-100 test ranged from 3:40 minutes to 25:12 minutes. There was a strong relationship between PAT scores and CVD (P = 0.0003). A 1-unit increase in PAT scores was found to result in a 9% decrease in TES; indicating that students with higher PAT scores are less likely to have CVD. CONCLUSION The PAT may be a preliminary screening instrument to identify students who may have CVD. The FM-100 test can then confirm the presence of CVD. Students with CVD may desire to improve dental shade matching skills through targeted training and education.
Cuminal Inhibits Trichothecium roseum Growth by Triggering Cell Starvation: Transcriptome and Proteome Analysis

Trichothecium roseum is a harmful postharvest fungus causing serious damage, together with the secretion of insidious mycotoxins, on apples, melons, and other important fruits. Cuminal, a predominant component of Cuminum cyminum essential oil has proven to successfully inhibit the growth of T. roseum in vitro and in vivo. Electron microscopic observations revealed cuminal exposure impaired the fungal morphology and ultrastructure, particularly the plasmalemma. Transcriptome and proteome analysis was used to investigate the responses of T. roseum to exposure of cuminal. In total, 2825 differentially expressed transcripts (1516 up and 1309 down) and 225 differentially expressed proteins (90 up and 135 down) were determined. Overall, notable parts of these differentially expressed genes functionally belong to subcellular localities of the membrane system and cytosol, along with ribosomes, mitochondria and peroxisomes. According to the localization analysis and the biological annotation of these genes, carbohydrate and lipids metabolism, redox homeostasis, and asexual reproduction were among the most enriched gene ontology (GO) terms. Biological pathway enrichment analysis showed that lipids and amino acid degradation, ATP-binding cassette transporters, membrane reconstitution, mRNA surveillance pathway and peroxisome were elevated, whereas secondary metabolite biosynthesis, cell cycle, and glycolysis/gluconeogenesis were down regulated. Further integrated omics analysis showed that cuminal exposure first impaired the polarity of the cytoplasmic membrane and then triggered the reconstitution and dysfunction of fungal plasmalemma, resulting in handicapped nutrient procurement of the cells. Consequently, fungal cells showed starvation stress with limited carbohydrate metabolism, resulting a metabolic shift to catabolism of the cell’s own components in response to the stress. Additionally, these predicaments brought about oxidative stress, which, in collaboration with the starvation, damaged certain critical organelles such as mitochondria. Such degeneration, accompanied by energy deficiency, suppressed the biosynthesis of essential proteins and inhibited fungal growth.
Anti–PD-1 treatment impairs opioid antinociception in rodents and nonhuman primates

PD-1 regulates opioid signaling in primary sensory and spinal cord neurons and plays a critical role in opioid antinociception. A checkpoint for pain Immune checkpoint blockade therapies using antibodies against programmed cell death protein–1 (PD-1) have been shown encouraging results for treating several tumors. Opioid treatment is frequently administered to patients with cancer for controlling disease-associated pain. PD-1 is expressed in sensory neurons and mediates pain sensitivity in mice. Now, Wang et al. studied the relationship between PD-1 expression and opioid effects in mice and nonhuman primates (NHPs). Morphine analgesic effect was diminished after PD-1 inhibition, and PD-1 blockade increased opioid-induced hyperalgesia in mice. In NHPs, immunotherapy targeting PD-1 inhibited morphine-induced antinociception. The results suggest that immunotherapies targeting PD-1 might reduce the sensitivity to opioids. Emerging immunotherapies with monoclonal antibodies against programmed cell death protein–1 (PD-1) have shown success in treating cancers. However, PD-1 signaling in neurons is largely unknown. We recently reported that dorsal root ganglion (DRG) primary sensory neurons express PD-1 and activation of PD-1 inhibits neuronal excitability and pain. Opioids are mainstay treatments for cancer pain, and morphine produces antinociception via mu opioid receptor (MOR). Here, we report that morphine antinociception and MOR signaling require neuronal PD-1. Morphine-induced antinociception after systemic or intrathecal injection was compromised in Pd1−/− mice. Morphine antinociception was also diminished in wild-type mice after intravenous or intrathecal administration of nivolumab, a clinically used anti–PD-1 monoclonal antibody. In mouse models of inflammatory, neuropathic, and cancer pain, spinal morphine antinociception was compromised in Pd1−/− mice. MOR and PD-1 are coexpressed in sensory neurons and their axons in mouse and human DRG tissues. Morphine produced antinociception by (i) suppressing calcium currents in DRG neurons, (ii) suppressing excitatory synaptic transmission, and (iii) inducing outward currents in spinal cord neurons; all of these actions were impaired by PD-1 blockade in mice. Loss of PD-1 also enhanced opioid-induced hyperalgesia and tolerance and potentiates opioid-induced microgliosis and long-term potentiation in the spinal cord in mice. Last, intrathecal infusion of nivolumab inhibited intrathecal morphine-induced antinociception in nonhuman primates. Our findings demonstrate that PD-1 regulates opioid receptor signaling in nociceptive neurons, leading to altered opioid-induced antinociception in rodents and nonhuman primates.
Efficient Structure for InP/ZnS based Electroluminescence Device by Embedding the Emitters in the Electron-Dominating Interface.

The charge carrier distribution has been an important parameter in determining the efficiency of quantum dots based light-emitting diodes (QLEDs). In this letter, we demonstrate a new inverted device structure of ITO/ZnO/polyethylenimine/quantum dots (QDs)/1,3,5-tris(N-phenylbenzimidazole-2-yl)benzene (TPBi)/ 4,4'-bis(9-carbazolyl)-2,2'-biphenyl (CBP)/MoO3/Al for improving the efficiency of InP-QDs based QLEDs. By introducing a thin layer of electron transport materials, the hole accumulation at hole transport layer and QD interface is largely reduced, which suppresses the quenching effect of holes on the QD emission. Compared with the conventional device structure with the emitters at ZnO/CBP pn junction, the peak current efficiency (external quantum efficiency) increases from 3.83% (5.17 cd/A) to 6.32% (8.54 cd/A) by imbedding the QDs at electron-dominating interface of ZnO/TPBi. The analysis reveals that an internal quantum efficiency of nearly 100% is achieved for the InP-QDs (with photoluminescence quantum yield of 32%) based device. This work provides alternative device structure for achieving high efficiency QLED devices.