Miracle-dz/UniFAR-FTUs huggingface dataset:
Educational assessment of the major lower limb amputations videos on YouTube

Objective Videos of surgical procedures are viewed by some as potential training resources for surgeons and residents. However, there is little evidence on the effectiveness of surgical videos on learning and understanding complex three-dimensional surgical procedures. Lower extremity amputation is a complex surgery, and many residents and surgeons have low exposure to this type of procedures. This paper investigates the educational quality of lower extremity amputation videos posted on YouTube. Methods The search was limited to the first 100 videos. Full-length videos of any major lower limb amputation or disarticulation were included. Key basic video data such as title, YouTube address (http://), country of origin, channel source, uploading date, video duration time, number of views, number of up-voters and number of down-voters were collected. An educational assessment tool has been developed specifically for limb amputations. It consists in 11 items: three general and eight amputation-specific, each having a maximum score of 2. Results In total, 13 videos met the inclusion criteria for final analysis. Four videos reported the surgical technique of above knee amputation, two reported that of knee disarticulation and the remaining seven videos described below knee amputation. The average score (±SD) was 12.77 ± 5.2 yielding an average grade close to “Fair. ” A high level of concordance was found between the two assessors (κ = 0.79). No correlation was found between educational assessment tool score and the pre-set variables (r = 0.6, R2 = 35.4%, F = 1.09, P = 0.4). Conclusions Most videos describing lower extremity amputation techniques were found to be of low-to-moderate quality. Only 4 out of 13 (30.7%) had an excellent educational and technical quality. Surgeons and surgical residents should be aware that not all posted videos on YouTube are beneficial. High educational quality videos are needed since many surgeons and residents have a low exposure to such surgeries.
Diagnostic value of refixation saccades in the Video Head Impulse Test (vHIT) in unilateral definite Meniere’s disease

Abstract Introduction: We currently interpret the video Head Impulse Test (vHIT) results mainly based on the gain value. Aim: The purpose of this study is to evaluate vHIT results for both gain and re-fixation saccades on unilateral definite Meniere's disease (MD) subjects in comparison with normal healthy subjects. Materials and Methods: Forty unilateral definite MD subjects and age-matched healthy subjects were recruited. Pure tone audiometry, the caloric test, and the vHIT test were performed on MD subjects. The vHIT test was performed on healthy subjects. Results: The velocity regression gain (VRG) of the affected ear in patients with MD is significantly lower than of those in healthy subjects. The total percentage of refixation saccades is significantly higher in patients with MD when compared to healthy subjects. VRG values were not well-correlated with the percentage of refixation saccades. VRG asymmetry values are also not well-correlated with the percentage of unilateral canal weakness. A moderately stronger correlation between the percentage of refixation saccades and percentage of unilateral canal weakness, with an r2 of 0.474. Conclusions: The present study suggests that while VRGs are still a diagnostic parameter of detecting MD, the presence of refixation saccades can also have diagnostic value, especially with normal VRGs, in detecting MD.
Integrative Analysis of Methylome and Transcriptome Reveals the Regulatory Mechanisms of Hair Follicle Morphogenesis in Cashmere Goat

Studies in humans and mice have revealed that hair follicle morphogenesis relies on tightly coordinated ectodermal–mesodermal interactions, involving multiple signals and regulatory factors. DNA methylation and long non-coding RNA (lncRNA) play a critical role in early embryonic skin development by controlling gene expression. Acting as an indirect regulator, lncRNA could recruit DNA methyltransferases to specific genomic sites to methylate DNA. However, the molecular regulation mechanisms underlying hair follicle morphogenesis is unclear in cashmere goat. In this study, RNA-seq and whole-genome bisulfite sequencing (WGBS) in embryonic day 65 (E 65) and E 120 skin tissues of cashmere goat were used to reveal this complex regulatory process. The RNA-seq, qRT-PCR, and immunohistochemistry results showed that Wnt signaling played an important role in both hair follicle induction and differentiation stage; transcriptional factors (TFs), including HOXC13, SOX9, SOX21, JUNB, LHX2, VDR, and GATA3, participated in hair follicle differentiation via specific expression at E 120. Subsequently, the combination of WGBS and RNA-seq analysis showed that the expression of some hair follicle differentiation genes and TF genes were negatively correlated with the DNA methylation level generally. A portion of hair follicle differentiation genes were methylated and repressed in the hair follicle induction stage but were subsequently demethylated and expressed during the hair follicle differentiation stage, suggesting that DNA methylation plays an important role in hair morphogenesis by regulating associated gene expression. Furthermore, 45 upregulated and 147 downregulated lncRNAs in E 120 compared with E 65 were identified by lncRNA mapping, and then the potential differentially expressed lncRNAs associated with DNA methylation on the target gene were revealed. In conclusion, critical signals and genes were revealed during hair follicle morphogenesis in the cashmere goat. In this process, DNA methylation was lower in the hair follicle differentiation compared with the hair follicle induction stage and may play an important role in hair morphogenesis by regulating associated gene expression. Furthermore, potential lncRNAs associated with DNA methylation on target genes were delineated. This study enriches the regulatory network and molecular mechanisms on hair morphogenesis.
Synthesis, Antiproliferative Activity and Molecular Docking Studies of Novel Doubly Modified Colchicine Amides and Sulfonamides as Anticancer Agents

Colchicine is a well-known compound with strong antiproliferative activity that has had limited use in chemotherapy because of its toxicity. In order to create more potent anticancer agents, a series of novel colchicine derivatives have been obtained by simultaneous modification at C7 (amides and sulfonamides) and at C10 (methylamino group) positions and characterized by spectroscopic methods. All the synthesized compounds have been tested in vitro to evaluate their cytotoxicity toward A549, MCF-7, LoVo, LoVo/DX and BALB/3T3 cell lines. Additionally, the activity of the studied compounds was investigated using computational methods involving molecular docking of the colchicine derivatives to β-tubulin. The majority of the obtained derivatives exhibited higher cytotoxicity than colchicine, doxorubicin or cisplatin against tested cancer cell lines. Furthermore, molecular modeling studies of the obtained compounds revealed their possible binding modes into the colchicine binding site of tubulin.
Serum Klotho, Cardiovascular Events, and Mortality in Nondiabetic Chronic Kidney Disease

Background: Experimental studies indicate that Klotho deficiency is a pathogenic factor for CKD-related complications, including cardiovascular disease (CVD). However, the association between serum Klotho and clinical outcomes in nondiabetic CKD patients needs to be further clarified. We aimed to determine whether serum Klotho levels are associated with CVD events and mortality in predialysis CKD patients without diabetes. Methods: A total of 336 CKD stage 2–5 predialysis patients without diabetes were recruited and followed from the end of 2014 to January 2019 for CVD events and overall mortality. Serum Klotho was detected by ELISA and divided into quartiles (lowest, middle, second highest, and highest quartiles) according to their serum Klotho category. Results: After a median follow-up of 3.52 years (IQR 3.34–3.76), Kaplan-Meier analysis showed that, compared to participants with a Klotho level in the highest quartile (the reference category), those in the lowest Klotho quartile were associated with a higher all-cause mortality risk (HR = 7.05; 95% CI 1.59–31.25) and a higher CVD event risk (HR = 3.02; 95% CI 1.45–6.30). In addition, the middle Klotho quartile was also associated with CVD event risk (HR = 2.56; 95% CI 1.21–5.41). Moreover, in the multivariate-adjusted model, the lowest Klotho quartile remained significantly associated with all-cause mortality (HR = 5.17; 95% CI 1.07–24.96), and the middle Klotho quartile maintained a significant association with CVD event risk (HR = 2.32; 95% CI 1.03–5.21). Conclusion: These results suggest that lower serum Klotho levels are independently associated with overall mortality and CVD events in nondiabetic predialysis CKD patients.
Pervasive White Matter Fiber Degeneration in Ischemic Stroke

Supplemental Digital Content is available in the text. Background and Purpose— We examined if ischemic stroke is associated with white matter degeneration predominantly confined to the ipsi-lesional tracts or with widespread bilateral axonal loss independent of lesion laterality. Methods— We applied a novel fixel-based analysis, sensitive to fiber tract–specific differences within a voxel, to assess axonal loss in stroke (N=104, 32 women) compared to control participants (N=40, 15 women) across the whole brain. We studied microstructural differences in fiber density and macrostructural (morphological) changes in fiber cross-section. Results— In participants with stroke, we observed significantly lower fiber density and cross-section in areas adjacent, or connected, to the lesions (eg, ipsi-lesional corticospinal tract). In addition, the changes extended beyond directly connected tracts, independent of the lesion laterality (eg, corpus callosum, bilateral inferior fronto-occipital fasciculus, right superior longitudinal fasciculus). Conclusions— We conclude that ischemic stroke is associated with extensive neurodegeneration that significantly affects white matter integrity across the whole brain. These findings expand our understanding of the mechanisms of brain volume loss and delayed cognitive decline in stroke.
Surgical Analgesia, Physiological Responses and Cortisol Levelin Goats Subjected to Exploratory Laparotomy under Distal Paravertebral Nerve Block, Conventional Needle Acupuncture and Aquapuncture

In ruminants, exploratory laparotomy can be used both as a diagnostic tool and a treatment tool in various diseases affecting the abdominal organs Pugh and Baird [1]. It ensures a more precise diagnosis, prognosis and treatment protocol because it allows thorough palpation and examination of the affected organs Radostits [2]. It also complements physical examination, clinical pathologic examination and diagnostic imaging in management of undiagnosed cases Ames [3]. In goats, regional analgesia is the commonly preferred method for administration of anesthesia during surgery. It requires minimal instrumentation, with ease of drug administration and lesser cost. Since the animal is conscious during the procedure, the normal digestive processes of the ruminant are maintained, thereby lessening the complications which might occur during and after the surgery Fubini & Ducharme [4]. Regional anesthesia can be achieved by administering the analgesic agent through local infiltration, inverted L-block, par vertebral block or epidural analgesia. Lidocaine hydrochloride, which is the commonly used analgesic agent, is cheap and locally available but presents some drawbacks. It must be used with caution among patients with severe respiratory depression or bradycardia and most of the time; patients presented for surgery have some of these clinical signs. Goats are sensitive to the effect of lidocaine and some practitioners suggested that the concentration of the drug Abstract
Cutaneous manifestations in COVID‐19: a new contribution

We have read with great interest Dr Recalcati's review about skin manifestations in COVID-19 as it is the first report on this subject1 . In a recent review on clinical characteristics of coronavirus disease 2019 in China, rash was observed in 0,2% of cases2 . However, from the trained eyes of a dermatologist, this percentage may be higher.
Laparoscopic Tubal Re-Anastomosis or IVF in Previously Ligated Patients: A Comparison of Fertility Outcomes and Survey of Patient Attitudes.

STUDY OBJECTIVE To compare live birth rates, cost analysis and a survey of patient attitudes between laparoscopic tubal re-anastomosis and IVF in patients with previous tubal ligation Design: Retrospective cohort review and survey. SETTING Single Reproductive Medicine and IVF unit in Singapore. PATIENTS Retrospective study: Patients who underwent previous tubal ligation and currently seeking fertility. Survey: Patients attending the subfertility clinic. INTERVENTIONS Retrospective study: Laparoscopic tubal re-anastomosis or IVF, from January 2011 to December 2016. Survey: Questionnaire and information sheet on both IVF and tubal re-anastomosis. MEASUREMENTS Retrospective study: First live birth after treatment. Interval to first pregnancy, miscarriages and ectopic pregnancies were also reported. Survey: Choice of treatment before and after reading the information on laparoscopic tubal re-anastomosis and IVF. RESULTS Retrospective study: Twelve patients underwent tubal re-anastomosis while 31 patients underwent IVF treatment. Pregnancy (75.0% vs 35.5%) and live birth (58.3% vs 25.8%) were significantly higher in the tubal surgery group (P<0.05%) after transferring all available embryos in one stimulated IVF cycle. Cost per live birth was also lower in the tubal surgery group ($27,109 vs $52,438). Survey: One hundred patients participated in the survey. A majority of patients preferred tubal surgery to IVF (68.2% vs 31.8%) before given information on the procedures, but indicated a preference for IVF (54.6%) to surgery (45.4%) after receiving information on the procedures. CONCLUSIONS For women less than 40 years of age, desiring fertility after tubal ligation, laparoscopic tubal re-anastomosis offers better live birth rates and cost-effectiveness. Patients in Singapore are equivocal as to their preference after education regarding the choices. Thus laparoscopic tubal re-anastomosis remains a viable alternative to IVF treatment.
Analysis of the Circadian Regulation of Cancer Hallmarks by a Cross-Platform Study of Colorectal Cancer Time-Series Data Reveals an Association with Genes Involved in Huntington’s Disease

Accumulating evidence points to a link between circadian clock dysfunction and the molecular events that drive tumorigenesis. Here, we investigated the connection between the circadian clock and the hallmarks of cancer in an in vitro model of colorectal cancer (CRC). We used a cross-platform data normalization method to concatenate and compare available microarray and RNA-sequencing time series data of CRC cell lines derived from the same patient at different disease stages. Our data analysis suggests differential regulation of molecular pathways between the CRC cells and identifies several of the circadian and likely clock-controlled genes (CCGs) as cancer hallmarks and circadian drug targets. Notably, we found links of the CCGs to Huntington’s disease (HD) in the metastasis-derived cells. We then investigated the impact of perturbations of our candidate genes in a cohort of 439 patients with colon adenocarcinoma retrieved from the Cancer Genome Atlas (TCGA). The analysis revealed a correlation of the differential expression levels of the candidate genes with the survival of patients. Thus, our study provides a bioinformatics workflow that allows for a comprehensive analysis of circadian properties at different stages of colorectal cancer, and identifies a new association between cancer and HD.
NOTCH inhibition promotes bronchial stem cell renewal and epithelial barrier integrity after irradiation

Hyperactivity of the NOTCH pathway is associated with tumor growth and radiotherapy resistance in lung cancer, and NOTCH/γ‐secretase inhibitors (GSIs) are a potential therapeutic target. The therapeutic outcome, however, is often restricted by the dose‐limiting toxicity of combined treatments on the surrounding healthy tissue. The NOTCH signaling pathway is also crucial for homeostasis and repair of the normal airway epithelium. The effects of NOTCH/γ‐secretase inhibition on the irradiation of normal lung epithelium are unknown and may counteract antitumor activity. Here we, therefore, investigated whether normal tissue toxicity to radiation is altered upon NOTCH pathway inhibition. We established air‐liquid interface pseudostratified and polarized cultures from primary human bronchial epithelial cells and blocked NOTCH signaling alone or after irradiation with small‐molecule NOTCH inhibitor/GSI. We found that the reduction in proliferation and viability of bronchial stem cells (TP63+) in response to irradiation is rescued with concomitant NOTCH inhibition. This correlated with reduced activation of the DNA damage response and accelerated repair by 24 hours and 3 days postirradiation. The increase in basal cell proliferation and viability in GSI‐treated and irradiated cultures resulted in an improved epithelial barrier function. Comparable results were obtained after in vivo irradiation, where the combination of NOTCH inhibition and irradiation increased the percentage of stem cells and ciliated cells ex vivo. These encourage further use of normal patient tissue for toxicity screening of combination treatments and disclose novel interactions between NOTCH inhibition and radiotherapy and opportunities for tissue repair after radiotherapy.
High prevalence of SARS-CoV-2 infection in repatriation flights to Greece from three European countries

Highlight Passengers on repatriation flights to Greece from the UK, Spain and Turkey were screened with oropharyngeal swabs on arrival for SARS-CoV-2 infection. Despite almost all passengers being asymptomatic, many tested positive (3.6% from UK, 6.3% from Spain and 6.3% from Turkey), indicating widespread transmission of SARS-CoV-2 in these countries.
Hypoxic-Ischemic Encephalopathy and Mitochondrial Dysfunction: Facts, Unknowns and Challenges.

SIGNIFICANCE Hypoxic ischemic events due to intrapartum complications represent the second cause of neonatal mortality and initiates an acute brain disorder known as hypoxic ischemic encephalopathy (HIE). In HIE, the brain undergoes primary and secondary energy failure phases separated by a latent phase in which partial neuronal recovery is observed. A hypoxic ischemic event leads to oxygen restriction causing ATP depletion, neuronal oxidative stress and cell death. Mitochondrial dysfunction and enhanced oxidant formation in brain cells are characteristic phenomena associated with energy failure. Recent advances: Mitochondrial sources of oxidants in neurons include complex I of the mitochondrial respiratory chain, as a key contributor to O2•- production via succinate by a reverse electron transport mechanism. The reaction of O2•- with nitric oxide (•NO) yields peroxynitrite, a mitochondrial and cellular toxin. Quantitation of the redox state of cytochrome c oxidase, through broadband near infrared spectroscopy, represents a promising monitoring approach to evaluate mitochondrial dysfunction in vivo in humans, in conjunction with the determination of cerebral oxygenation and their correlation with the severity of brain injury. CRITICAL ISSUES Being the energetic failure a key phenomenon in HIE connected with the severity of the encephalopathy, measurement of mitochondrial dysfunction in vivo provides an approach to assess evolution, prognosis and adequate therapies. Restoration of mitochondrial redox homeostasis constitutes a key therapeutic goal. FUTURE DIRECTIONS While hypothermia is the only current accepted therapy in clinical management to preserve mitochondrial function, other mitochondrial-targeted and/or redox-based treatments are likely to synergize to ensure further efficacy.
Built‐in RNA‐mediated chaperone (chaperna) for antigen folding tailored to immunized hosts

High‐quality antibody (Ab) production depends on the availability of immunologically relevant antigens. We present a potentially universal platform for generating soluble antigens from bacterial hosts, tailored to immunized animals for Ab production. A novel RNA‐dependent chaperone, in which the target antigen is genetically fused with an RNA‐interacting domain (RID) docking tag derived from the immunized host, promotes the solubility and robust folding of the target antigen. We selected the N‐terminal tRNA‐binding domain of lysyl‐tRNA synthetase (LysRS) as the RID for fusion with viral proteins and demonstrated the expression of the RID fusion proteins in their soluble and native conformations; immunization predominantly elicited Ab responses to the target antigen, whereas the “self” RID tag remained nonimmunogenic. Differential immunogenicity of the fusion proteins greatly enriched and simplified the screening of hybridoma clones of monoclonal antibodies (mAbs), enabling specific and sensitive serodiagnosis of MERS‐CoV infection. Moreover, mAbs against the consensus influenza hemagglutinin stalk domain enabled a novel assay for trivalent seasonal influenza vaccines. The Fc‐mediated effector function was demonstrated, which could be harnessed for the design of next‐generation “universal” influenza vaccines. The nonimmunogenic built‐in antigen folding module tailored to a repertoire of immunized animal hosts will drive immunochemical diagnostics, therapeutics, and designer vaccines.
Genetic controls of short- and long-term stomatal CO2 responses in Arabidopsis thaliana

Abstract Background and Aims The stomatal conductance (gs) of most plant species decreases in response to elevated atmospheric CO2 concentration. This response could have a significant impact on plant water use in a future climate. However, the regulation of the CO2-induced stomatal closure response is not fully understood. Moreover, the potential genetic links between short-term (within minutes to hours) and long-term (within weeks to months) responses of gs to increased atmospheric CO2 have not been explored. Methods We used Arabidopsis thaliana recombinant inbred lines originating from accessions Col-0 (strong CO2 response) and C24 (weak CO2 response) to study short- and long-term controls of gs. Quantitative trait locus (QTL) mapping was used to identify loci controlling short- and long-term gs responses to elevated CO2, as well as other stomata-related traits. Key Results Short- and long-term stomatal responses to elevated CO2 were significantly correlated. Both short- and long-term responses were associated with a QTL at the end of chromosome 2. The location of this QTL was confirmed using near-isogenic lines and it was fine-mapped to a 410-kb region. The QTL did not correspond to any known gene involved in stomatal closure and had no effect on the responsiveness to abscisic acid. Additionally, we identified numerous other loci associated with stomatal regulation. Conclusions We identified and confirmed the effect of a strong QTL corresponding to a yet unknown regulator of stomatal closure in response to elevated CO2 concentration. The correlation between short- and long-term stomatal CO2 responses and the genetic link between these traits highlight the importance of understanding guard cell CO2 signalling to predict and manipulate plant water use in a world with increasing atmospheric CO2 concentration. This study demonstrates the power of using natural variation to unravel the genetic regulation of complex traits.