Miracle-dz/UniFAR-FTUs huggingface dataset:
Rare Neurovascular Diseases in Korea: Classification and Related Genetic Variants

Rare neurovascular diseases (RNVDs) have not been well-recognized in Korea. They involve the central nervous system and greatly affect the patients' lives. However, these diseases are difficult to diagnose and treat due to their rarity and incurability. We established a list of RNVDs by referring to the previous literature and databases worldwide to better understand the diseases and their current management status. We categorized 68 RNVDs based on their pathophysiology and clinical manifestations and estimated the prevalence of each disease in Korea. Recent advances in genetic, molecular, and developmental research have enabled further understanding of these RNVDs. Herein, we review each disease, while considering its classification based on updated pathologic mechanisms, and discuss the management status of RNVD in Korea.
Lipoxin A4 protects primary spinal cord neurons from Erastin‐induced ferroptosis by activating the Akt/Nrf2/HO‐1 signaling pathway

Ferroptosis is an iron‐dependent programmed cell death, which participates in the pathogenesis of spinal cord injury (SCI). Our previous study has revealed that Lipoxin A4 (LXA4) exerts a protective role in SCI. Here, we investigated whether LXA4 can protect SCI through inhibiting neuronal ferroptosis. We treated primary spinal cord neurons with Erastin (ferroptosis activator) to induce ferroptosis. Erastin treatment reduced cell viability and enhanced cell death of primary spinal cord neurons, which was rescued by ferrostatin‐1 (ferroptosis inhibitor). Moreover, Erastin repressed glutathione peroxidase 4 (GPX4) expression and the levels of glutathione and cysteine in primary spinal cord neurons. Erastin also enhanced the expression of ferroptosis biomarkers (PTGS2 and ACSL4) and the levels of reactive oxygen species (ROS) in primary spinal cord neurons. The influence conferred by Erastin was effectively abolished by LXA4 treatment. Furthermore, LXA4 enhanced the protein expression of p‐AKT, nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) and haem‐oxygenase‐1 (HO‐1) in primary spinal cord neurons. LXA4‐mediated inhibition of ferroptosis of primary spinal cord neurons was prohibited by LY294002 (AKT inhibitor), brusatol (Nrf2 inhibitor) or zinc protoporphyrin (HO‐1 inhibitor). In conclusion, this work demonstrated that LXA4 exerted a neuroprotective effect in Erastin‐induced ferroptosis of primary spinal cord neurons by activating the Akt/Nrf2/HO‐1 signaling pathway. Thus, this work provides novel insights into the mechanisms of action of LXA4 in ferroptosis of primary spinal cord neurons and indicates that LXA4 may be a potential therapeutic agent for SCI.
Osseodensification effect on implants primary and secondary stability: Multicenter controlled clinical trial

Abstract Background Osseodensification (OD) has shown to improve implant stability; however, the influences of implant design, dimensions, and surgical site characteristics are unknown. Purpose To compare the insertion torque (IT) and temporal implant stability quotients (ISQ) of implants placed via OD or subtractive drilling (SD). Materials and Methods This multicenter controlled clinical trial enrolled 56 patients, whom were in need of at least 2 implants (n = 150 implants). Patients were treated with narrow, regular, or wide implants and short, regular, or long implants in the anterior or posterior region of the maxilla or in the posterior region of the mandible. Osteotomies were performed following manufacturers recommendation. IT was recorded with a torque indicator. ISQ was recorded with resonance frequency analysis immediately after surgery, 3 and 6 weeks. Results Data complied as a function of osteotomy indicated significantly higher IT for OD relative to SD. OD outperformed conventional SD for all pairwise comparisons of arches (maxilla and mandible) and areas operated (anterior and posterior), diameters and lengths of the implants, except for short implants. Overall, ISQ data also demonstrated significantly higher values for OD compared to SD regardless of the healing period. Relative to immediate readings, ISQ values significantly decreased at 3 weeks, returning to immediate levels at 6 weeks; however, ISQ values strictly remained above 68 throughout healing time for OD. Data as a function of arch operated and osteotomy, area operated and osteotomy, implant dimensions and osteotomy, also exhibited higher ISQ values for OD relative to SD on pairwise comparisons, except for short implants. Conclusions OD demonstrated higher IT and temporal ISQ values relative to SD, irrespective of arch and area operated as well as implant design and dimension, with an exception for short implants. Future studies should focus on biomechanical parameters and bone level change evaluation after loading.
Differential regulation of glycinergic and GABAergic nanocolumns at mixed inhibitory synapses

Super‐resolution imaging has revealed that key synaptic proteins are dynamically organized within sub‐synaptic domains (SSDs). To examine how different inhibitory receptors are regulated, we carried out dual‐color direct stochastic optical reconstruction microscopy (dSTORM) of GlyRs and GABAARs at mixed inhibitory synapses in spinal cord neurons. We show that endogenous GlyRs and GABAARs as well as their common scaffold protein gephyrin form SSDs that align with pre‐synaptic RIM1/2, thus creating trans‐synaptic nanocolumns. Strikingly, GlyRs and GABAARs occupy different sub‐synaptic spaces, exhibiting only a partial overlap at mixed inhibitory synapses. When network activity is increased by 4‐aminopyridine treatment, the GABAAR copy numbers and the number of GABAAR SSDs are reduced, while GlyRs remain largely unchanged. This differential regulation is likely the result of changes in gephyrin phosphorylation that preferentially occurs outside of SSDs. The activity‐dependent regulation of GABAARs versus GlyRs suggests that different signaling pathways control the receptors' sub‐synaptic clustering. Taken together, our data reinforce the notion that the precise sub‐synaptic organization of GlyRs, GABAARs, and gephyrin has functional consequences for the plasticity of mixed inhibitory synapses.
Constraints of using historical data for modelling the spatial distribution of helminth parasites in ruminants

Dicrocoelium dendriticum is a trematode that infects ruminant livestock and requires two different intermediate hosts to complete its lifecycle. Modelling the spatial distribution of this parasite can help to improve its management in higher risk regions. The aim of this research was to assess the constraints of using historical data sets when modelling the spatial distribution of helminth parasites in ruminants. A parasitological data set provided by CREMOPAR (Napoli, Italy) and covering most of Italy was used in this paper. A baseline model (Random Forest, VECMAP®) using the entire data set was first used to determine the minimal number of data points needed to build a stable model. Then, annual distribution models were computed and compared with the baseline model. The best prediction rate and statistical output were obtained for 2012 and the worst for 2016, even though the sample size of the former was significantly smaller than the latter. We discuss how this may be explained by the fact that in 2012, the samples were more evenly geographically distributed, whilst in 2016 most of the data were strongly clustered. It is concluded that the spatial distribution of the input data appears to be more important than the actual sample size when computing species distribution models. This is often a major issue when using historical data to develop spatial models. Such data sets often include sampling biases and large geographical gaps. If this bias is not corrected, the spatial distribution model outputs may display the sampling effort rather than the real species distribution.
Role of Solvent in the Shape-Controlled Synthesis of Anisotropic Colloidal Nanostructures

We use molecular dynamics simulations to study the role played by solvent in promoting anisotropic growth of colloidal nanostructures. Considering the growth of Ag nanowires and nanoplates in organic solvent, we study how solvent influences the aggregation of a small and relatively isotropic nanocrystal with a larger nanowire or a square nanoplate. We observe that when the two nanocrystals approach one another they almost always adopt a mesocrystal configuration, a free-energy minimum in which the two particles hover next to each other with their facets parallel and one or two layers of solvent between them—analogous to experimentally observed mesocrystal structures. Nanocrystal aggregation occurs from the mesocrystal state, and the free-energy barrier for aggregation is smallest on the smallest facets, which perpetuates anisotropic growth. By characterizing solvent ordering around the nanocrystal surfaces, as well as aggregation mechanisms, we find that solvent ordering is disrupted at the edges of the c.
Effects of 1800 MHz radiofrequency fields on signal transduction and antioxidant proteins in human A172 glioblastoma cells

Abstract Purpose To assess the effects of 1800 MHz radiofrequency electromagnetic field (RF-EMF) exposure on the expression of signal transduction and antioxidant proteins in a human-derived A172 glioblastoma cell line. Materials and methods Adherent human-derived A172 glioblastoma cells (1.0 × 105 cells per 35 mm culture dish, containing 2 mL DMEM media) were exposed to 1800 MHz continuous-wave (CW) or GSM-modulated RF fields, in the presence or absence of serum for 5, 30 or 240 min at a specific absorption rate (SAR) of 0 (sham) or 2.0 W/kg. Concurrent negative (vehicle) and positive controls (1 µg/mL anisomycin) were included in each experiment. Cell lysates were collected immediately after exposure, stabilized by protease and phosphatase inhibitors in lysis buffer, then frozen and maintained at −80 °C until analysis. The relative expression levels of phosphorylated- and total-signal transduction proteins (CREB, JNK, NF-κB, ERK1/2, Akt, p70S6K, STAT3 and STAT5) and antioxidant proteins (SOD1, SOD2, CAT, TRX1, PRX2) were assessed using Milliplex magnetic bead array panels and a MagPix Multiplex imaging system. Results In cells exposed to 1800 MHz continuous-wave RF-EMF with the presence of serum in the culture medium, CAT expression was statistically significantly decreased after a 30 min exposure, total JNK was decreased at both 30 and 240 min of exposure, STAT3 was decreased after 240 min of exposure and phosphorylated-CREB expression was decreased after 30 min of exposure. In cells exposed to 1800 MHz GSM-modulated RF-EMF in serum-free cultures, the expression level of total STAT5 was decreased after 30 and 240 min of exposure. These observed changes were detected sporadically across time-points, culture conditions and RF-EMF exposure conditions indicating the likelihood of false positive events. When cells were treated with anisomycin for 15 min as a positive control, dramatic increases in the expression of phosphorylated signaling proteins were observed in both serum-starved and serum-fed A172 cells, with larger fold change increases in the serum-free cultures. No statistically significant differences in the expression levels of SOD1, SOD2 or TRX1 were observed under any tested conditions after exposure to RF-EMF. Conclusions The current study found no consistent evidence of changes in the expression of antioxidant proteins (SOD1, SOD2, CAT or TRX2) or a variety of signal transductions proteins (CREB, JNK, NF-κB, ERK1/2, Akt, p70S6K, STAT3, STAT5) in a human-derived glioblastoma A172 cell line in response to exposure to 1800 MHz continuous-wave or GSM-modulated RF-EMF for 5, 30 or 240 min in either serum-free or serum-containing cultures.
The enduring need for prospective cohort studies to more completely characterize the tobacco‐caused burden of cancer

In the mid-20th century before any causal associations between smoking of combustible tobacco cigarettes (henceforth referred to as “cigarettes”) and any disease had been established, case-control studies provided the first evidence from observational studies that cigarette smoking may be linked to cancer (eg, Refs. 1,2). At that time case-control studies were an unorthodox new study design, raising questions about the validity of this approach and hence how to properly interpret the strong statistical associations that had been observed between smoking and lung cancer. The need for data from cohort studies to augment the results of case-control studies was clear. Cohort studies such as the British Doctor's Study, American Cancer Society Cancer Prevention Study and US Veterans Study contributed essential additional evidence that reduced concerns about selection bias and information bias and established the temporal sequence by measuring smoking before cancer occurred, thus making a key contribution to the eventual conclusion that cigarette smoking was a cause of lung cancer (reviewed in Ref. 3). Additional research accumulated in the ensuing decades to document that cigarette smoking is a cause of numerous other malignancies, to the extent that an estimated 48% of all cancer deaths in the United States are attributable to cigarette smoking. With such an enormous body of evidence documenting the health consequences of cigarette smoking, it is possible to get lulled into thinking that investments in prospective cohort studies of cigarette smoking and cancer are no longer necessary. This is certainly not the case. The article authored by Weber and colleagues in this issue entitled “Cancer incidence and cancer death in relation to tobacco smoking in a population-based Australian cohort study” provides an excellent example of why contemporary prospective cohort studies remain vital. This report, based on the 45 and Up Study, addresses the familiar topic of cigarette smoking and cancer, but with features that add important evidence on the topic. The 45 and Up Study is a prospective cohort study of approximately 229 000 people in Australia, a nation-continent that has been underrepresented in largescale cohort studies on this topic. The study's baseline data collection took place in 2006-2009. A cohort assembled this recently has advantages for characterizing the magnitude of the associations between cigarette smoking and cancer in the modern era. Thus, the major novelty of this report does not lie in the study questions addressed, but rather that the study was carried out in a new place and during modern times. There are at least four strong reasons that prospective cohort studies such as the 45 and Up Study that are from new geographic locations and/or carried out in the modern era are particularly valuable:
A new species of Chlamydia isolated from Siamese crocodiles (Crocodylus siamensis)

Chlamydia is a known pathogen in both saltwater and freshwater crocodiles. However, the exact species/strain has not been clearly identified. In this study, we successfully cultivated Siamese crocodile Chlamydia in McCoy cells at a temperature of 30°C. Electron microscopy; phylogeny based on nine conserved taxonomically informative markers, on ompA, or on seven housekeeping genes; and whole-genome sequencing and analysis of the isolate confirmed the identity of the isolate as a new member of the genus Chlamydia, a new species that we name Chlamydia crocodili.
Identification of biological secondary metabolites in three Penicillium species, P. goditanum,

Microorganisms are important components of soil. Some soil filamentous fungi such asPenicilium produce many bioactive small molecules, or secondary metabolites, that range frombeneficial bioactive compounds to harmful toxins. In this study, the metabolites of threepenicillium species (P. goditanum, P. moldavicum and P. corylophilum) were extracted byadding ethyl acetate to liquid cultures. The metabolites were determined using gaschromatography and mass spectrometry. The results obtained from the GC-MS analysis showedthat Penicillium species are sources of bioactive compounds. We have identified differentgroups of compounds, such as alkaloids, alkenes, sesquiterpens, fatty acids, and essential oils.Among them, 1,3,8-p-Menthatriene, 2-methylenecyclohexane, anthracene, neoisolongifolene,[14] annulene and thioxanthene in P. goditanum, isocyclocitral, coumarin-6-ol and 2, 4, 6-Trimethoxystyrene in P. moldavicum as well as asarone in P. corylophilum were majorcompounds. Moreover, several compounds, such as oxalic acid, dibenzothiophene,hexadecanoic acid, and alkane hydrocarbons, were identified in all species.
Cleaved PINK1 induces neuronal plasticity through PKA‐mediated BDNF functional regulation

Mutations in PTEN‐induced kinase 1 (PINK1) lead to early onset autosomal recessive Parkinson's disease in humans. In healthy neurons, full‐length PINK1 (fPINK1) is post‐translationally cleaved into different lower molecular weight forms, and cleaved PINK1 (cPINK1) gets shuttled to the cytosolic compartments to support extra‐mitochondrial functions. While numerous studies have exemplified the role of mitochondrially localized PINK1 in modulating mitophagy in oxidatively stressed neurons, little is known regarding the physiological role of cPINK1 in healthy neurons. We have previously shown that cPINK1, but not fPINK1, modulates the neurite outgrowth and the maintenance of dendritic arbors by activating downstream protein kinase A (PKA) signaling in healthy neurons. However, the molecular mechanisms by which cPINK1 promotes neurite outgrowth remain to be elucidated. In this report, we show that cPINK1 supports neuronal development by modulating the expression and extracellular release of brain‐derived neurotrophic factor (BDNF). Consistent with this role, we observed a progressive increase in the level of endogenous cPINK1 but not fPINK1 during prenatal and postnatal development of mouse brains and during development in primary cortical neurons. In cultured primary neurons, the pharmacological activation of endogenous PINK1 leads to enhanced downstream PKA activity, subsequent activation of the PKA‐modulated transcription factor cAMP response element‐binding protein (CREB), increased intracellular production and extracellular release of BDNF, and enhanced activation of the BDNF receptor‐TRKβ. Mechanistically, cPINK1‐mediated increased dendrite complexity requires the binding of extracellular BDNF to TRKβ. In summary, our data support a physiological role of cPINK1 in stimulating neuronal development by activating the PKA‐CREB‐BDNF signaling axis in a feedforward loop.
Immunotherapy-Related Imaging Findings in Patients with Gynecological Malignancies: What Radiologists Need to Know

Immunotherapy is an effective treatment option for gynecological malignancies. Radiologists dealing with gynecological patients undergoing treatment with immune checkpoint inhibitors should be aware of unconventional immune-related imaging features for the evaluation of tumor response and immune-related adverse events. In this paper, immune checkpoint inhibitors used for gynecological malignancies and their mechanisms of action are briefly presented. In the second part, patterns of pseudoprogression are illustrated, and different forms of immune-related adverse events are discussed.
Impact of a nurse-led brief tobacco cessation training program for healthcare professionals.

OBJECTIVE To assess the impact of a tobacco cessation training program on healthcare professionals' smoking cessation practices, counseling-related opinions, and attitudes about their role in tobacco control. DESIGN A single group pre- and post-design. SAMPLE Eligible participants (n = 133) were health professionals who attended a training program between September 2018 and June 2019 at specific training sites in Malta. MEASUREMENTS An already established questionnaire was used to compare healthcare professionals' practices, opinions, and attitudes before the training program, and at 3-month follow-up. INTERVENTION A public health nurse-led, 3-hr training intervention addressing tobacco use and tobacco cessation with emphasis on the 5As (Ask, Advise, Assess, Assist and Arrange) framework. RESULTS Healthcare professionals were favorably disposed towards counseling patients to stop. While participants still found it difficult to get clients to quit and lacked the time to counsel patients, they were more likely to deliver tobacco cessation interventions frequently at follow-up. CONCLUSION Despite these challenges, this training program was found useful by the participants, who took a more comprehensive approach to address tobacco use. Public health nurses are encouraged to take a leading role in tobacco cessation training initiatives as part of their efforts to improve population health.
Subcutaneous implantable pleural port catheter in the management of malignant pleural effusions in young patients with solid tumors: A new option in the armamentarium of symptomatic treatment

The contribution of subcutaneous implantable pleural port catheter (SIPP) for malignant pleural effusions (MPE) management in young patients with cancer, in a palliative care setting is not well explored. This monocentric series analyzed 38 patients, median age 18 years (range 3–25) with significant pleural effusion. SIPP were considered efficient for eight of 12 evaluable patients (67%) and allowed MPE outpatient management in five cases. SIPPs are safe and efficient device to manage MPE patients with solid tumors, in the palliative care setting. This original tool could help health care providers for thoracic symptom management in alternative to iterative pleural punctures.
Spatial heterogeneity of cutaneous blood flow respiratory-related oscillations quantified via laser speckle contrast imaging

LSCI technique provides experimental data which can be considered in the context of spatial blood flow coherency. Analysis of vascular tone oscillations gives additional information to ensure a better understanding of the mechanisms affecting microvascular physiology. The oscillations with different frequencies are due to different physiological mechanisms. The reasons for the generation of peripheral blood flow oscillations in the 0.14–0.6 Hz frequency band are as follows: cardio-respiratory interactions, pressure variations in the venous part of the circulatory system, and the effect of the sympathetic nervous system on the vascular tone. Earlier, we described the spatial heterogeneity of around 0.3 Hz oscillations and this motivated us to continue the research to find the conditions for the occurrence of spatial phase synchronization. For this purpose, a number of physiological tests (controlled respiration, breath holder, and venous occlusion tests) which influence the blood flow oscillations of 0.14–0.6 Hz were considered, an appropriate measurement system and the required data processing algorithms were developed. At spontaneous respiration, the oscillations with frequencies around 0.3 Hz were stochastic, whereas all the performed tests induced an increase in spatial coherence. The protocols and methods proposed here can help to clarify whether the heterogeneity of respiratory-related blood flow oscillations exists on the skin surface.