Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of a domain critical for Staphylococcus aureus LukED receptor targeting and lysis of erythrocytes

Leukocidin ED (LukED) is a pore-forming toxin produced by Staphylococcus aureus, which lyses host cells and promotes virulence of the bacteria. LukED enables S. aureus to acquire iron by lysing erythrocytes, which depends on targeting the host receptor Duffy antigen receptor for chemokines (DARC). The toxin also targets DARC on the endothelium, contributing to the lethality observed during bloodstream infection in mice. LukED is comprised of two monomers: LukE and LukD. LukE binds to DARC and facilitates hemolysis, but the closely related Panton–Valentine leukocidin S (LukS-PV) does not bind to DARC and is not hemolytic. The interaction of LukE with DARC and the role this plays in hemolysis are incompletely characterized. To determine the domain(s) of LukE that are critical for DARC binding, we studied the hemolytic function of LukE–LukS-PV chimeras, in which areas of sequence divergence (divergence regions, or DRs) were swapped between the toxins. We found that two regions of LukE's rim domain contribute to hemolysis, namely residues 57–75 (DR1) and residues 182–196 (DR4). Interestingly, LukE DR1 is sufficient to render LukS-PV capable of DARC binding and hemolysis. Further, LukE, by binding DARC through DR1, promotes the recruitment of LukD to erythrocytes, likely by facilitating LukED oligomer formation. Finally, we show that LukE targets murine Darc through DR1 in vivo to cause host lethality. These findings expand our biochemical understanding of the LukE–DARC interaction and the role that this toxin-receptor pair plays in S. aureus pathophysiology.
Mental health stigma and professional help-seeking behaviors among Asian American and Asian international students

Abstract Objective: To examine the relationship between stigma and mental health help-seeking among Asian American and Asian international college students. Participants: Asian American college students (401 men, 858 women) and Asian international college students (384 men, 428 women). Methods: Data from the 2018–2019 Healthy Minds Study were used to assess perceived stigma, personal stigma, and help-seeking behaviors of college students. Results: Personal stigma mediated the relationship between perceived stigma and professional help-seeking intentions. The relationship between perceived stigma and personal stigma differed by international status, such that the relationship between perceived stigma and personal stigma was stronger for Asian international students. The indirect effect between perceived stigma and professional help-seeking via personal stigma also differed by international status. Conclusions: These results suggest that, consistent with prior work, stigma impacts help-seeking among Asian college students and international student status affects the strength of the key relationship between perceived stigma and personal stigma.
Mediterranean Diet Adherence among Preschoolers and its Association with Parents’ Beliefs, Attitudes, and Practices

ABSTRACT The effect of parents on nutritional habits in preschool children is undeniable. It is known that parental control in child nutrition can affect the child’s eating habits, and bodyweight. Mediterranean Diet (MD) adherence of children (KIDMED), parents’ beliefs, attitudes and practices (Preschool Feeding Questionnaire-PFQ2) were investigated. The questionnaire prepared was applied by researchers face-to-face to 1413 families who agreed to participate voluntarily in the research with preschool children. Parental beliefs, attitudes, and practices regarding child nutrition status of parents were evaluated using 39-item PFQ2 and their child’s eating habits using the 16-item KIDMED index. Children’s KIDMED scores were found optimal in 34.1%, average in 57.0%, very low in 8.9%. The KIDMED scores of children whose parents are together (6.6 ± 2.1) were found to be significantly higher than children whose parents are separated (4.9 ± 2.2) (p <.001). A correlation was found between the KIDMED scores of the children, the parental control (r = 0.156, p <.001), maternal restriction (r = 0.104, p <.001), and structured feeding (r = 0.162, p <.001). Unfortunately, the adherence of most preschool children with the MD which considered a healthy diet pattern was found below the optimal level.
Transcultural Adaptation and Validation of the Fonseca Anamnestic Index in a Spanish Population with Temporomandibular Disorders

Background: The Fonseca Anamnestic Index (FAI) offers a simple method to screen temporomandibular disorders (TMD). This study aimed to validate the Spanish version of the FAI in patients with TMD. Methods: The sample consisted of 125 subjects (66 TMD and 59 controls) aged over 18 years. Construct validity, internal consistency, test-retest reliability, concurrent validity and capacity to discriminate between TMD and healthy subjects were analyzed. Results: The Spanish version of the FAI showed a structure formed by three factors. Cronbach’s alpha was 0.826. The reliability of the items varied between substantial to almost perfect and was excellent for the total score (intraclass correlation coefficient = 0.937). The standard error of measurement (SEM) was 6.52, with a minimum detectable change (MDC) of 12.78. FAI score showed a significant correlation with headache, neck pain and vertigo measurements. A cut-off point >35 showed a sensitivity = 83.33% and a specificity = 77.97% in differentiating between healthy and TMD patients, with an area under the curve (AUC) = 0.865. Conclusions: The Spanish version of the FAI is a valid and reliable instrument for diagnosing people with TMD, with appropriate general clinimetric properties. Discrimination between patients with and without TMD is excellent.
Comparative clinical outcomes of robot-assisted liver resection versus laparoscopic liver resection: A meta-analysis

Background As an emerging technology, robot-assisted surgical system has some potential merits in many complicated endoscopic procedures compared with laparoscopic surgery. But robot-assisted liver resection is still a controversial problem on its advantages compared with laparoscopic liver resection. We aimed to perform the meta-analysis to assess and compare the clinical outcomes of robot-assisted and laparoscopic liver resection. Methods We searched PubMed, Cochrane Library, Embase databases, Clinicaltrials, and Opengrey through March 24, 2020, including references of qualifying articles. English-language, original investigations in humans about robot-assisted and laparoscopic hepatectomy were included. Titles, abstracts, and articles were reviewed by at least 2 independent readers. Continuous and dichotomous variables were compared by the weighted mean difference (WMD) and odds ratio (OR), respectively. Results Of 936 titles identified in our original search, 28 articles met our criteria, involving 3544 patients. Compared with laparoscopy, the robot-assisted groups had longer operative time (WMD: 36.93; 95% CI, 19.74–54.12; P < 0.001), lower conversion rate (OR: 0.63; 95% CI, 0.46–0.87; P = 0.005), higher transfusion rate (WMD: 2.39; 95% CI, 1.51–3.76; P < 0.001) and higher total cost (WMD:0.49; 95% CI, 0.42–0.55; P < 0.001). In addition, the baseline characteristics of patients about largest tumor size was larger (WMD: 0.36; 95% CI, 0.16–0.56; P < 0.001) and malignant lesions rate was higher (WMD: 1.50; 95% CI, 1.21–1.86; P < 0.001) in the robot-assisted versus laparoscopic hepatectomy. The subgroup analysis of minor hepatectomy showed robot-assisted was associated with longer operative time (WMD: 36.00; 95% CI, 12.59–59.41; P = 0.003), longer length of stay (WMD: 0.51; 95% CI, 0.02–1.01; p = 0.04) and higher total cost (WMD: 0.48; 95% CI, 0.25–0.72; P < 0.001) (Table 3); while the subgroup analysis of major hepatectomy showed robot-assisted was associated with lower estimated blood loss (WMD: -122.43; 95% CI, -151.78–-93.08; P < 0.001). Conclusions Our meta-analysis revealed that robot-assisted was associated with longer operative time, lower conversion rate, higher transfusion rate and total cost, and robot-assisted has certain advantages in major hepatectomy compared with laparoscopic hepatectomy.
Older Aboriginal Australians’ Health Concerns and Preferences for Healthy Ageing Programs

While there is strong evidence of the need for healthy ageing programs for older Aboriginal Australians, few are available. It is important to understand older Aboriginal Australians’ perspectives on healthy ageing in order to co-design culturally-appropriate programs, including views on technology use in this context. Semi-structured interviews were conducted with 34 Aboriginal Australians aged 50 years and older from regional and urban communities to explore participants’ health concerns, preferences for healthy ageing programs, and receptiveness to technology. Qualitative data were analyzed using a grounded theory approach. This study found that older Aboriginal Australians are concerned about chronic health conditions, social and emotional well-being, and difficulties accessing health services. A range of barriers and enablers to participation in current health programs were identified. From the perspective of older Aboriginal people, a successful healthy ageing program model includes physical and cognitive activities, social interaction, and health education. The program model also provides culturally safe care and transport for access as well as family, community, cultural identity, and empowerment regarding ageing well as central tenets. Technology could also be a viable approach for program delivery. These findings can be applied in the implementation and evaluation of culturally-appropriate, healthy ageing programs with older Aboriginal people.
Efficacy of HDAC Inhibitors Belinostat and Panobinostat against Cisplatin-Sensitive and Cisplatin-Resistant Testicular Germ Cell Tumors

Simple Summary There is a need for novel treatment options for patients with testicular germ cell tumors, especially for those that are resistant to standard chemotherapy, who show poor prognosis. In this work, we test two compounds that inhibit epigenetic enzymes called histone deacetylases—belinostat and panobinostat. We show that these enzymes are expressed at different levels in different germ cell tumor subtypes (seminomas and non-seminomas) and that both drugs are effective in reducing tumor cell viability, by decreasing cell proliferation and increasing cell death. These results are promising and should prompt further works with these compounds, envisioning the improvement of care of germ cell tumor patients. Abstract Novel treatment options are needed for testicular germ cell tumor (TGCT) patients, particularly important for those showing or developing cisplatin resistance, the major cause of cancer-related deaths. As TGCTs pathobiology is highly related to epigenetic (de)regulation, epidrugs are potentially effective therapies. Hence, we sought to explore, for the first time, the effect of the two most recently FDA-approved HDAC inhibitors (HDACis), belinostat and panobinostat, in (T)GCT cell lines including those resistant to cisplatin. In silico results were validated in 261 patient samples and differential expression of HDACs was also observed across cell lines. Belinostat and panobinostat reduced cell viability in both cisplatin-sensitive cells (NCCIT-P, 2102Ep-P, and NT2-P) and, importantly, also in matched cisplatin-resistant subclones (NCCIT-R, 2102Ep-R, and NT2-R), with IC50s in the low nanomolar range for all cell lines. Treatment of NCCIT-R with both drugs increased acetylation, induced cell cycle arrest, reduced proliferation, decreased Ki67 index, and increased p21, while increasing cell death by apoptosis, with upregulation of cleaved caspase 3. These findings support the effectiveness of HDACis for treating TGCT patients in general, including those developing cisplatin resistance. Future studies should explore them as single or combination agents.
Donor Hepatectomy and Implantation Time Are Associated With Early Complications After Liver Transplantation: A Single-center Retrospective Study.

BACKGROUND Donor hepatectomy and liver implantation time reduce long-term graft and patient survival after liver transplantation. It is not known whether these surgical times influence early outcomes after liver transplantation. METHODS This single-center study evaluated the effect of donor hepatectomy and implantation time on the risk of nonanastomotic biliary strictures occurring within 1 year and of early allograft dysfunction after deceased-donor solitary liver transplantation, adjusting for other donor, recipient, and surgical factors. RESULTS Of 917 transplants performed between 1/2000 and 12/2016, 106 (11.56%) developed nonanastomotic biliary strictures and 247 (27%) developed early allograft dysfunction. Donor hepatectomy time (median 35 min, IQR: 26-46) was an independent risk factor of nonanastomotic biliary strictures (adjusted hazard ratio (HR): 1.19, 95% CI: 1.04-1.35, p=0.01). Implantation time (median 80 min, IQR: 69-95) was independently associated with early allograft dysfunction (adjusted odds ratio (OR): 1.15, 95% CI:1.07-1.23, p<0.0001). The risk of early allograft dysfunction was increased by anastomosis time of both portal vein (adjusted OR: 1.26, 95% CI: 1.12-14.42, p=0.0001) and hepatic artery (adjusted OR: 1.13, 95%CI: 1.04-1.22, p=0.005). The magnitude of these effects was similar in donation after circulatory death liver grafts. CONCLUSIONS Donor hepatectomy and implantation time negatively affect short-term outcomes.
Mechanisms Underlying the Inhibition of Tyrosine Kinase Inhibitor-Induced Anorexia and Fatigue by Royal Jelly in Renal Cell Carcinoma Patients and the Correlation between Macrophage Colony Stimulating Factor and Inflammatory Mediators

Inflammation is a common adverse event of anti-cancer therapy. Royal jelly (RJ) modulates inflammation by regulating the levels of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, and interleukin (IL)-6 produced by macrophages. Macrophage colony stimulating factor (M-CSF) is a crucial regulator of macrophage activities, and we hypothesized that RJ alters M-CSF levels. In this randomized controlled trial, we investigated the association between M-CSF and adverse events in renal cell carcinoma patients treated with tyrosine kinase inhibitors (TKIs) after an oral intake of RJ (n = 16) or placebo (n = 17). The serum levels of M-CSF, TNF-α, TGF-β, and IL-6 were measured by an enzyme-linked immunosorbent assay, and their temporal changes and correlation between such changes were analyzed. The post-/pretreatment ratio of M-CSF levels was associated with anorexia after 2 weeks and fatigue after 2, 4, and 12 weeks. The M-CSF level in the RJ group was higher than that in the placebo group at the same timepoints. The TNF-α level in the RJ group was lower than that in the placebo group between 6 and 12 weeks, and the TGF-β level in the RJ group was higher than that in the placebo group; however, contrasting findings were detected after 12 weeks. Additionally, the M-CSF level was significantly correlated with the TGF-β level after 4 weeks and IL-6 level after 8 and 10 weeks. Among TNF-α, TGF-β, and IL-6, the post-/pretreatment ratio of TGF-β after 12 weeks was associated with TKI-induced anorexia, and the ratios after 10 and 12 weeks were associated with fatigue. Our results demonstrated that an oral intake of RJ suppressed anorexia and fatigue via complex mechanisms associated with inflammation-related factors, such as M-CSF and TGF-β in renal cell carcinoma patients treated with TKIs. In addition, we newly found that such RJ-related effects were dependent on the treatment duration.
Factors that influence the quality of paid support for adults with acquired neurological disability: scoping review and thematic synthesis

Abstract Purpose Theoretically, individualised funding schemes empower people with disability (PWD) to choose high quality support services in line with their needs and preferences. Given the importance of support, the aim of this scoping review was to understand the factors that influence the quality of paid disability support for adults with acquired neurological disability. Methods A comprehensive scoping review of the published literature from 2009–2019 was conducted on five databases: Medline, CINAHL, Embase, PsycINFO and Scopus. Results Of the 3391 records retrieved, 16 qualitative articles were eligible for review. Thematic synthesis of the findings revealed six key interrelated themes: (1) choice and control, (2) individualised support, (3) disability support worker (DSW) qualities, (4) DSW competence, (5) PWD – DSW relationship, and (6) accessing consistent support. The themes depict factors influencing the quality of paid disability support from the perspective of PWD, close others and DSWs. Conclusions Although the evidence base is sparse, the factors identified were in line with international rights legislation and policy ideals. The findings can provide insights to PWD hiring and managing support, and facilitate the delivery of quality disability support. Further research is required to understand the interactions between the factors and how to optimise support in practice. Implications for rehabilitation The quality of paid disability support is determined by a multitude of interrelated factors influenced by the disability support worker’s qualities and competencies, the interaction between the person with disability and the disability support worker, as well as external contextual factors. Optimising choice and control for adults with acquired neurological disability and providing individualised support should be a significant focus for disability support workers. Training modules for disability support workers can be informed by five of the identified themes: (1) choice and control, (2) individualised support, (3) DSW qualities, (4) DSW competence and (5) the relationship between PWD and DSWs.
May Mangafodipir or Other SOD Mimetics Contribute to Better Care in COVID-19 Patients?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by massive inflammation of the arterial endothelium accompanied by vasoconstriction and widespread pulmonary micro thrombi. As a result, due to the destruction of nitric oxide (•NO) by inflammatory superoxide (O2•−), pulmonary •NO concentration ceases, resulting in uncontrolled platelet aggregation and massive thrombosis, which kills the patients. Introducing •NO by inhalation (INO) may replace the loss of endothelium-derived •NO. The first results from clinical trials with INO in SARS-CoV-2 patients show a rapid and sustained improvement in cardiopulmonary function and decreased inflammation. An ongoing phase III study is expected to confirm the method’s efficacy. INO may hence become a first line treatment in SARS-CoV-2 patients. However, due to the rapid inactivation of •NO by deoxyhemoglobin to nitrate, pulmonary administration of •NO will not protect remote organs. Another INO-related pharmacological approach to protect SARS-CoV-2 patients from developing life-threatening disease is to inhibit the O2•−-driven destruction of •NO by neutralizing inflammatory O2•−. By making use of low molecular weight compounds that mimic the action of the enzyme manganese superoxide dismutase (MnSOD). The MnSOD mimetics of the so-called porphyrin type (e.g., AEOL 10150), salen type (e.g., EUK-8) and cyclic polyamine type (e.g., M40419, today known as GC4419 and avasopasem manganese) have all been shown to positively affect the inflammatory response in lung epithelial cells in preclinical models of chronic obstructive pulmonary disease. The Manganese diPyridoxyL EthylDiamine (MnPLED)-type mangafodipir (manganese dipyridoxyl diphosphate—MnDPDP), a magnetic resonance imaging (MRI) contrast agent that possesses MnSOD mimetic activity, has shown promising results in various forms of inflammation, in preclinical as well as clinical settings. Intravenously administration of mangafodipir will, in contrast to INO, reach remote organs and may hence become an important supplement to INO. From the authors’ viewpoint, it appears logical to test mangafodipr in COVID-19 patients at risk of developing life-threatening SARS-CoV-2. Five days after submission of the current manuscript, Galera Pharmaceuticals Inc. announced the dosing of the first patient in a randomized, double-blind pilot phase II clinical trial with GC4419 for COVID-19. The study was first posted on ClinicalTrials.gov (Identifier: NCT04555096) 18 September 2020.
Role of TSPO/VDAC1 Upregulation and Matrix Metalloproteinase-2 Localization in the Dysfunctional Myocardium of Hyperglycaemic Rats

Clinical management of diabetic cardiomyopathy represents an unmet need owing to insufficient knowledge about the molecular mechanisms underlying the dysfunctional heart. The aim of this work is to better clarify the role of matrix metalloproteinase 2 (MMP-2) isoforms and of translocator protein (TSPO)/voltage-dependent anion-selective channel 1 (VDAC1) modulation in the development of hyperglycaemia-induced myocardial injury. Hyperglycaemia was induced in Sprague-Dawley rats through a streptozocin injection (35 mg/Kg, i.p.). After 60 days, cardiac function was analysed by echocardiography. Nicotinamide Adenine Dinucleotide Phosphate NADPH oxidase and TSPO expression was assessed by immunohistochemistry. MMP-2 activity was detected by zymography. Superoxide anion production was estimated by MitoSOX™ staining. Voltage-dependent anion-selective channel 1 (VDAC-1), B-cell lymphoma 2 (Bcl-2), and cytochrome C expression was assessed by Western blot. Hyperglycaemic rats displayed cardiac dysfunction; this response was characterized by an overexpression of NADPH oxidase, accompanied by an increase of superoxide anion production. Under hyperglycaemia, increased expression of TSPO and VDAC1 was detected. MMP-2 downregulated activity occurred under hyperglycemia and this profile of activation was accompanied by the translocation of intracellular N-terminal truncated isoform of MMP-2 (NT-MMP-2) from mitochondria-associated membrane (MAM) into mitochondria. In the onset of diabetic cardiomyopathy, mitochondrial impairment in cardiomyocytes is characterized by the dysregulation of the different MMP-2 isoforms. This can imply the generation of a “frail” myocardial tissue unable to adapt itself to stress.
An Update on the Incidence and Burden of Diabetic Ketoacidosis in the U.S.

A recent study by Desai et al. (1) showed that the incidence and economic burden of hospitalizations due to diabetic ketoacidosis (DKA) in the U.S. increased between 2003 and 2014 (1). We sought to understand the most recent impact of the disease in the U.S. using the 2017 National Inpatient Sample (NIS) (www.hcup-us.ahrq.gov/nisoverview.jsp). A total of 220,340 patients were identified with a primary diagnosis of DKA (61.6 cases of DKA per 10,000 admissions) (Table 1). The incidence of DKA per 10,000 admissions was higher in males (71.2) than females (54.1), and the majority of DKA patients were covered by Medicaid (79,175 patients [36.0%], P < 0.01). Of all DKA patients, 53.3% were of ages 18–44 years. However, a higher incidence per 10,000 admissions was noted in patients of ages 1–17 years. The mean age of patients with DKA was 38.4 years. The total charges among DKA patients in 2017 were $6,757,748,178, with a mean of $30,836.19. The mean length of stay was 3.22 days. A total of 835 deaths were found among DKA patients, with a mortality rate of 0.38%. The overall …
Absence of SARS-CoV-2 neutralizing activity in pre-pandemic sera from individuals with recent seasonal coronavirus infection

Cross-reactive immune responses elicited by seasonal coronaviruses might impact SARS-CoV-2 susceptibility and disease outcomes. We measured neutralizing activity against SARS-CoV-2 in pre-pandemic sera from patients with prior PCR-confirmed seasonal coronavirus infection. While neutralizing activity against seasonal coronaviruses was detected in nearly all sera, cross-reactive neutralizing activity against SARS-CoV-2 was undetectable.