Miracle-dz/UniFAR-FTUs huggingface dataset:
Nanogold Functionalized With Lipoamide-isoDGR: A Simple, Robust and Versatile Nanosystem for αvβ3-Integrin Targeting

Gold nanoparticles functionalized with isoDGR, a tripeptide motif that recognizes αvβ3 integrin overexpressed in tumor vessels, have been used as nano-vectors for the delivery of cytokines to tumors. Functionalization of nanogold with this peptide has been achieved by coating nanoparticles with a peptide-albumin conjugate consisting of heterogeneous molecules with a variable number of linkers and peptides. To reduce nanodrug heterogeneity we have designed, produced and preclinically evaluated a homogeneous and well-defined reagent for nanogold functionalization, consisting of a head-to-tail cyclized CGisoDGRG peptide (iso1) coupled via its thiol group to maleimide-PEG11-lipoamide (LPA). The resulting iso1-PEG11-LPA compound can react with nanogold via lipoamide to form a stable bond. In vitro studies have shown that iso1, after coupling to nanogold, maintains its capability to bind purified αvβ3 and αvβ3-expressing cells. Nanogold functionalized with this peptide can also be loaded with bioactive tumor necrosis factor-α (TNF) to form a bi-functional nanodrug that can be stored for three days at 37°C or >1 year at low temperatures with no loss αvβ3-binding properties and TNF-cytolytic activity. Nanoparticles functionalized with both iso1 and TNF induced tumor eradication in WEHI-164 fibrosarcoma-bearing mice more efficiently than nanoparticles lacking the iso1 targeting moiety. These results suggest that iso1-PEG11-LPA is an efficient and well-defined reagent that can be used to produce robust and more homogeneous nano-vectors for the delivery of TNF and other cytokines to αvβ3 positive cells.
EFFECTS OF ELECTROKINETIC TREATMENTS ON THE PROPERTIES OF A SALT AFFECTED SOIL

SUMMARY This paper presents experimental results of a study undertaken to investigate the effects of electroki netic treatments on selected chemical and physical properties of a salt contaminated (saline) soil. The study was conducte d as a laboratory scale pilot project using locally available saline soil samples. The soil was subjected to an electric gradient by passing a direct current between inserted electrodes. After c ertain electrokinetic treatment periods, the proper ties of the soil were evaluated. The experimental data reveals that elect rokinetic techniques could offer a low cost, rapid solution to treat saline soils. The removal efficiency of sodium ions was found to be greater than 90% within a relative ly short time period of 14 to 30 days, using low current and volt age systems. After 14 to 30 days, the degree of sal inity and sodicity decreased to a very low or negligible level. The un confined compression strength of the soil increased by between 30 % to 100% in 30 days of electrokinetic treatment indi cating the improvements in the physical properties, especially in the stress-strain characteristics of the soil. The liqu id limit (LL) and plastic limit (PL) increased at t he cathode.
Personality and Lockdown: A Study on Italian Undergraduates During the COVID-19 Pandemic

The current study aimed at increasing our understanding of the psychological impact of the COVID-19 lockdown on undergraduate students, particularly with respect to the association between personality traits; defense mechanisms (DMs); depression, anxiety, and stress symptoms (DASSs); and compliance with the government recommended health measures. A sample of 1,427 Italian undergraduate students were administered the Personality Inventory for the DSM-5—Brief Form; the Defense Style Questionnaire-40; and the Depression, Anxiety and Stress Scale-21. Compliance with the COVID-19 behavioral recommendations was measured through a 10-item survey measure. Results showed that immature DMs and internalizing personality traits (i.e., detachment, negative affect, psychoticism) were risk factors of DASSs. Furthermore, subjects with higher levels of DASSs appeared less compliant with the health measures recommended by the Italian government. Experts may use these results to identify and subsequently support (via the Internet) young subjects at greater risk of mental health problems as a result of the COVID-19 pandemic.
Clinical Characteristics of Clonorchis sinensis-Associated Cholangiocarcinoma: A Large-Scale, Single-Center Study

Background: Clonorchis sinensis (CS) infection is considered a group 1 carcinogen of cholangiocarcinoma (CCA). There were very few studies regarding clinical characteristics of CS-associated CCA (CACC). This study aimed to investigate clinical characteristics of patients with CCA with or without CS infection. Methods: A total of 367 patients diagnosed with CCA who underwent diagnostic tests for CS infection were enrolled. CS infection was defined as follows: at least one positive serum ELISA test, skin test, stool microscopy, or bile microscopy. Results: There were 95 (26%) patients with CS infections. The median follow-up duration was 14.9 months (range, 6.07–36.17). The following significant differences were noted among patients with CACC compared to non-CACC; diagnosis at younger age (median 62 years vs. 65 years, p = 0.018), higher male to female ratio (83.2 vs. 61.8%, p < 0.001), and residence in CS-endemic area (46.3 vs. 25.4%, p = 0.014). Univariate analysis of prognostic factors indicated that tumor location, curative resection, tumor stage, and laboratory tests including CA 19-9, CEA, and bilirubin were significantly associated with overall survival, but CS infection was not. In multivariate analysis, tumor location, CEA, curative resection and tumor stage were identified as independent prognostic factors. Among patients under age 64, CACC group had lower survival rate than non-CACC group (p = 0.022). Conclusions: CACC had the following significant characteristics compared to non-CACC; diagnosis at younger age, higher male to female ratio, higher prevalence in CS endemic areas and poorer overall survival in patients under age 64.
An Experimentally Validated Finite Element Model of the Lower Limb to Investigate the Efficacy of Blast Mitigation Systems

Improvised explosive devices (IEDs) used in the battlefield cause damage to vehicles and their occupants. The injury burden to the casualties is significant. The biofidelity and practicality of current methods for assessing current protection to reduce the injury severity is limited. In this study, a finite-element (FE) model of the leg was developed and validated in relevant blast-loading conditions, and then used to quantify the level of protection offered by a combat boot. An FE model of the leg of a 35 years old male cadaver was developed. The cadaveric leg was tested physically in a seated posture using a traumatic injury simulator and the results used to calibrate the FE model. The calibrated model predicted hindfoot forces that were in good correlation (using the CORrelation and Analysis or CORA tool) with data from force sensors; the average correlation and analysis rating (according to ISO18571) was 0.842. The boundary conditions of the FE model were then changed to replicate pendulum tests conducted in previous studies which impacted the leg at velocities between 4 and 6.7 m/s. The FE model results of foot compression and peak force at the proximal tibia were within the experimental corridors reported in the studies. A combat boot was then incorporated into the validated computational model. Simulations were run across a range of blast-related loading conditions. The predicted proximal tibia forces and associated risk of injury indicated that the combat boot reduced the injury severity for low severity loading cases with higher times to peak velocity. The reduction in injury risk varied between 6 and 37% for calcaneal minor injuries, and 1 and 54% for calcaneal major injuries. No injury-risk reduction was found for high severity loading cases. The validated FE model of the leg developed here was able to quantify the protection offered by a combat boot to vehicle occupants across a range of blast-related loading conditions. It can now be used as a design and as an assessment tool to quantify the level of blast protection offered by other mitigation technologies.
Amitriptyline Decreases GABAergic Transmission in Basal Forebrain Neurons Using an Optogenetic Model of Aging

The antidepressant drug amitriptyline is used in the treatment of clinical depression and a variety of neurological conditions such as anxiety, neuropathic pain disorders and migraine. Antidepressants are associated with both therapeutic and untoward effects, and their use in the elderly has tripled since the mid-1990s. Because of this widespread use, we are interested in testing the acute effects of amitriptyline on synaptic transmission at therapeutic concentrations well below those that block voltage-gated calcium channels. We found that 3 μM amitriptyline reduced the frequency of spontaneous GABAergic inhibitory postsynaptic currents (IPSCs) and reduced quantal content in mice at ages of 7–10 mo. and 23–25 mo. , suggesting a presynaptic mechanism of action that does not diminish with age. We employed a reduced synaptic preparation of the basal forebrain (BF) and a new optogenetic aging model utilizing a bacterial artificial chromosome (BAC) transgenic mouse line with stable expression of the channelrhodopsin-2 (ChR2) variant H134R specific for GABAergic neurons [VGAT-ChR2(H134R)-EYFP]. This model enables optogenetic light stimulation of specific GABAergic synaptic terminals across aging. Age-related impairment of circadian behavior was used to confirm predictable age-related changes associated with this model. Our results suggest that low concentrations of amitriptyline act presynaptically to reduce neurotransmitter release and that this action is maintained during aging.
Effects of Dietary Energy Level on Performance, Plasma Parameters, and Central AMPK Levels in Stressed Broilers

This study aimed to characterize the effects of diets with different energy levels on the growth performance, plasma parameters, and central AMPK signaling pathway in broilers under dexamethasone (DEX)-induced stress. A total of 216 1-day-old male broiler chickens were allocated to groups fed with high (HED), National Research Council-recommended (control), or low (LED) energy diets. At 10 days old, chickens were treated with or without dexamethasone (DEX, 2 mg/kg body weight) for 3 consecutive days. HED increased broiler average daily gain (ADG) at 10 days old, compared with the LED (P < 0.05), while average daily feed intake (ADFI) and feed conversion rate (FCR) decreased as the dietary energy level increased (P < 0.05). Chickens fed a HED had higher total protein (TP) content, albumin (ALB), glucose (GLU), total cholesterol (TCHO), high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol, compared with the control group (P < 0.05). At 13 days old, DEX decreased ADG and increased FCR in broilers fed with different energy diets (P < 0.05). The DEX-HED group had a higher ADFI than non-DEX treated HED group chickens. In addition, TP, ALB, triglycerides (TG), TCHO, HDL, and LDL content levels in the DEX group were higher than those in the control group (P < 0.05). The uric acid (UA) content of the LED group was higher than that of the HED group (P < 0.05). Further, gene expression levels of liver kinase B1, AMP-activated protein kinase α1, neuropeptide Y, and GC receptor in the hypothalamus were increased in chickens treated with DEX (P < 0.05). There was a trend toward interaction between plasma TCHO and hypothalamic LKB1 expression (0.05 < P < 0.1). In conclusion, this study suggests that HED improves growth performance, plasma glucose and total cholesterol at 10 days old broilers, but had no significant effect on performance, plasma parameters, and central AMPK in stressed broilers.
Naples Prognostic Score: A Novel Prognostic Score in Predicting Cancer-Specific Survival in Patients With Resected Esophageal Squamous Cell Carcinoma

Background Naples prognostic score (NPS) serves as a new prognostic index based on nutritional and inflammatory status in recent years. The aim of the current study was to explore the prognostic effect of NPS and to develop and validate a reliable nomogram based on NPS for individual cancer-specific survival (CSS) prediction in patients with resected ESCC without neoadjuvant therapy. Methods The clinical data for 287 (Jan. 2010 to Jun. 2012, Training sets) and 118 (Jan. 2015 to Dec 2015, Validation sets) consecutive resected ESCC cases were retrospectively analyzed. Two NPS models based on the different cut-off values of parameters were compared. Cut-off values in model 1 were derived from previous published studies, while cut-off values in model 2 were obtained in this study based on receiver operating characteristic (ROC) curves. The relationships between NPS and clinical characteristics and CSS were analyzed. The prediction model of nomogram was developed with independent prognostic factors in the training sets and was validated in the validation sets. Results The 5-year CSS for NPS 0, 1 and 2 were 61.9%, 34.6% and 13.4% in model 1 and 75.0%, 42.4% and 13.0% in model 2, respectively (P<0.001). Subgroup analyses revealed that NPS was also significantly associated with CSS in both model 1 and model 2 in different TNM stages. Multivariate analyses revealed that NPS was an independent prognostic marker regarding CSS in patients with resected ESCC (P<0.001). A predictive nomogram based on NPS was established and validated. The C-indexes of the nomogram in the training sets and validation sets were 0.68 and 0.72 in model 1 and 0.69 and 0.73 in model 2, respectively. These results confirmed that NPS-based nomogram was a more accurate and effective tool for predicting CSS in patients with resected ESCC. Conclusion The current study confirmed that NPS was still a useful independent prognostic score in patients with resected ESCC. The NPS-based nomogram was successfully developed and validated, which may contribute to individual CSS prediction for resected ESCC patients.
Open Access: The Effect of Neurorehabilitation on Multiple Sclerosis—Unlocking the Resting-State fMRI Data

Department of Cybernetics, Faculty of Electrical Engineering, Czech Technical University in Prague, Prague, Czechia, Department of Complex Systems, Institute of Computer Science of the Czech Academy of Sciences, Prague, Czechia, Department of Applied Neuroscience and Neuroimaging, National Institute of Mental Health, Klecany, Czechia, Department of Computing and Control Engineering, University of Chemistry and Technology, Prague, Czechia, 5 Third Faculty of Medicine, Charles University, Prague, Czechia, 6 Radiodiagnostic and Interventional Radiology Department, Institute for Clinical and Experimental Medicine, Prague, Czechia
Effector Avr4 in Phytophthora infestans Escapes Host Immunity Mainly Through Early Termination

Effector genes play critical roles in the antagonistic interactions between plants and pathogens. However, knowledge of mutation mechanisms and evolutionary processes in effector genes and the contribution of climatic factors to the evolution of effector genes are fragmented but important in sustainable management of plant diseases and securing food supply under changing climates. Here, we used a population genetic approach to explore the evolution of the Avr4 gene in Phytophthora infestans, the causal agent of potato blight. We found that the Avr4 gene exhibited a high genetic diversity generated by point mutation and sequence deletion. Frameshifts caused by a single base-pair deletion at the 194th nucleotide position generate two stop codons, truncating almost the entire C-terminal, which is important for effector function and R4 recognition in all sequences. The effector is under natural selection for adaptation supported by comparative analyses of population differentiation (FST ) and isolation-by-distance between Avr4 sequences and simple sequence repeat marker loci. Furthermore, we found that local air temperature was positively associated with pairwise FST in the Avr4 sequences. These results suggest that the evolution of the effector gene is influenced by local air temperature, and the C-terminal truncation is one of the main mutation mechanisms in the P. infestans effector gene to circumvent the immune response of potato plants. The implication of these results to agricultural and natural sustainability in future climate conditions is discussed.
Plasma Microbial Cell-Free DNA Sequencing Technology for the Diagnosis of Sepsis in the ICU

Sepsis is a common life-threatening disease in the intensive care unit (ICU) that is usually treated empirically without pathogen identification. As a non-invasive and high-throughput technology, plasma microbial cell-free DNA (mcfDNA) sequencing can detect unknown pathogens independent of previous clinical or laboratory information. In this study, a total of 199 cases suspected of bloodstream infection (BSI) from January 2020 to June 2020 were collected, and potential pathogens were detected by simultaneous blood culture and plasma mcfDNA sequencing. Other clinical microbiological assays were performed within 7 days of plasma mcfDNA sequencing, including smear, culture of samples taken from relevant infected sites, and β-D-glucan/galactomannan (BDG/GM) tests, among others. The diagnoses were classified as sepsis [94 (47.2%)], non-sepsis [87 (43.7%)], and non-infectious disease [18 (9.0%)]. The sensitivity and specificity of plasma mcfDNA sequencing for diagnosing sepsis were 68.1 and 63.2%, respectively, which were significantly better than those of blood culture, especially for the common bacteria that cause hospital-acquired infection, namely, Acinetobacter baumannii (p < 0.01) and Klebsiella pneumoniae (p < 0.01), and DNA viruses (plasma mcfDNA sequencing only, p < 0.01). However, there was no significant difference in the rate of positivity between plasma mcfDNA sequencing and blood culture for antibiotic-non-exposed cases (43.6 vs. 30.9%, p = 0.17). In the non-sepsis group, 44.8% of cases (13/29) detected only by plasma mcfDNA sequencing showed infections in other parts of the body, such as lower respiratory infection (LRI), intra-abdominal infection (IAI) and central nervous system infection (CNSI). For some common pathogens (not including anaerobes), turnaround time (TAT) 3 (TAT from the initiation of blood sample processing by nucleic acid extraction to the completion of sequencing analysis) was longer than TAT1 (TAT from blood culture bottles in Virtuo to off Virtuo). With disease progression, significant dynamic changes in microbial species were clearly detected by plasma mcfDNA sequencing.
Chemogenetic Activation of Feed-Forward Inhibitory Parvalbumin-Expressing Interneurons in the Cortico-Thalamocortical Network During Absence Seizures

Parvalbumin-expressing (PV+) interneurons are a subset of GABAergic inhibitory interneurons that mediate feed-forward inhibition (FFI) within the cortico-thalamocortical (CTC) network of the brain. The CTC network is a reciprocal loop with connections between cortex and thalamus. FFI PV+ interneurons control the firing of principal excitatory neurons within the CTC network and prevent runaway excitation. Studies have shown that generalized spike-wave discharges (SWDs), the hallmark of absence seizures on electroencephalogram (EEG), originate within the CTC network. In the stargazer mouse model of absence epilepsy, reduced FFI is believed to contribute to absence seizure genesis as there is a specific loss of excitatory α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) at synaptic inputs to PV+ interneurons within the CTC network. However, the degree to which this deficit is directly related to seizure generation has not yet been established. Using chemogenetics and in vivo EEG recording, we recently demonstrated that functional silencing of PV+ interneurons in either the somatosensory cortex (SScortex) or the reticular thalamic nucleus (RTN) is sufficient to generate absence-SWDs. Here, we used the same approach to assess whether activating PV+ FFI interneurons within the CTC network during absence seizures would prevent or reduce seizures. To target these interneurons, mice expressing Cre recombinase in PV+ interneurons (PV-Cre) were bred with mice expressing excitatory Gq-DREADD (hM3Dq-flox) receptors. An intraperitoneal dose of pro-epileptic chemical pentylenetetrazol (PTZ) was used to induce absence seizure. The impact of activation of FFI PV+ interneurons during seizures was tested by focal injection of the “designer drug” clozapine N-oxide (CNO) into either the SScortex or the RTN thalamus. Seizures were assessed in PVCre/Gq-DREADD animals using EEG/video recordings. Overall, DREADD-mediated activation of PV+ interneurons provided anti-epileptic effects against PTZ-induced seizures. CNO activation of FFI either prevented PTZ-induced absence seizures or suppressed their severity. Furthermore, PTZ-induced tonic-clonic seizures were also reduced in severity by activation of FFI PV+ interneurons. In contrast, administration of CNO to non-DREADD wild-type control animals did not afford any protection against PTZ-induced seizures. These data demonstrate that FFI PV+ interneurons within CTC microcircuits could be a potential therapeutic target for anti-absence seizure treatment in some patients.
Bystander Roles in Cyberbullying: A Mini-Review of Who, How Many, and Why

Cyberbullying has progressively increased due to the massive use of the internet and social networks. Bystanders constitute the largest group, occupying a key role in the evolution of the cyberbullying situation and its consequences for the victim. Research shows different ways in which bystanders behave, suggesting different types of sub-roles associated with different study variables. The objective of this literature review is to identify and characterize the roles of bystanders in cyberbullying situations that involve adolescent students. To achieve this objective, a systematic search was carried out in the Web of Science, PubMed, and Scopus databases for articles published between 2015 and 2020, resulting in 233 articles. Articles were then selected by relevant title and summary. Subsequently, the inclusion and exclusion criteria were applied, resulting in a total of nine articles. The findings of this review allowed us to identify two to five types of bystanders, the largest type representing outsiders and the smallest type representing assistants of the aggressor. The identified types of bystanders are characterized for variables such as sex, age, previous experience, and empathy. The results are discussed considering the available theoretical and empirical evidence.