Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevalence and Outcomes of Multi-Drug Resistant Blood Stream Infections Among Nursing Home Residents Admitted to an Acute Care Hospital

Objective: The prevalence of multi-drug resistant organism (MDRO) colonization in nursing home residents has been well documented, but little is known about the impact of MDRO bloodstream infections (BSIs). The aim of this study was to assess the prevalence, cost, and outcomes of MDRO-BSI vs. non-MDRO-BSI among nursing home residents. Design: Retrospective cohort study Setting: 960 bed tertiary academic medical center Patients: Persons ≥18 years old admitted to an acute care tertiary hospital from Skilled Nursing Facilities with a diagnosis of sepsis between 2015 and 2018. Interventions: Retrospective analysis of prevalence and outcomes. Measurements and Main Results: Among patients admitted to the study hospital with a diagnosis of sepsis during the study period, 7% were from nursing homes. The prevalence of MDRO-BSI was 47%. We identified 54 (50%) gram positive BSIs, 48 (45%) gram negative BSI and 5 (5%) fungal BSI. Thirty-one (57%) of the gram-positive infections and 14 (30%) of the gram-negative infections were with MDROs. The prevalence of BSI organisms were Staphylococcus aureus in 24%, Escherichia coli in 14%, Proteus mirabilis in 13%, Staphylococcus epidermidis in 8%, Enterococcus faecalis in 7%, and Klebsiella pneumoniae in 6%. We found that intensive care unit length of stay (7 days vs 5 days, P = .009), direct cost ($13,639 vs $9,922, P = .027), and total cost ($23,752 vs $17,900 P = .032) were significantly higher in patients with MDRO-BSI vs. non-MDRO-BSI. Patients with MDRO-BSI were twice as likely to receive inappropriate empiric antiinfective therapy (31% vs 16%, P = .006) and were more likely to die (49.1% vs 29.6%, P = .049). Conclusion: Nursing home residents have a high prevalence of MDRO-BSI, which is associated with higher risk of receiving inappropriate initial anti-infective therapy, higher cost, higher ICU LOS, and higher mortality. Our research adds new information about the prevalence of fungemia in this population.
Feasibility of low-dose contrast media in run-off CT angiography on dual-layer spectral detector CT.

Background The aim of the present study was to assess the feasibility of applying low-dose contrast media (CM), and to explore the optimal virtual monoenergetic images (VMIs) in run-off computed tomography (CT) angiography (CTA) on dual-layer spectral detector CT (SDCT). Methods Forty patients were randomly assigned into a control group using routine volume CM (group A) and an experimental group using half-volume CM (group B). In groups A and B, 120 kVp polychromatic conventional images were generated via hybrid iterative reconstruction algorithm defined as A1 and B1, respectively. Additionally, in group B, VMIs (range, 40-120 keV) were reconstructed via a spectral reconstruction algorithm defined as B2-B10. Vascular attenuation, noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and radiation dose were evaluated. Subjective evaluation was performed using a 5-point scale. Results The patient demographics and radiation dose demonstrated no significant difference between groups A and B [dose length product (DLP): 1,823.45±512.68 vs. 2,014.40±453.25 mGy·cm, P=0.229; volume CT dose index: 14.92±3.40 vs. 16.26±2.85 mGy, P=0.208; the effective dose (ED): 10.82±3.02 vs. 11.88±2.67 mSv, P=0.229]. The mean vascular attenuation was higher in group B2 (40 keV) and was lower in group B3 (50 keV) in comparison with that in group A1 (487.07±154.21 vs. 414.35±71.66 HU, 329.90±100.25 vs. 414.35±71.66 HU, P>0.05). Compared with group A1, the mean noise was similar in group B2 (40 keV) and was lower in group B1 and groups B3-B10 (50-120 keV) (14.81±5.67 vs. 17.29±4.70 HU, P>0.05; 6.75±1.23-11.26±3.24 vs. 17.29±4.70 HU, P<0.05). The mean SNR and CNR in group B2 (40 keV), as well as the mean SNR in group B3 (50 keV), were significantly higher than those of group A1 (38.21±7.52 vs. 28.25±7.20, 32.70±7.79 vs. 24.54±6.60, 32.85±7.10 vs. 28.25±7.20, P<0.05), and the mean CNR in group B3 (50 keV) was similar to that in group A1 (26.66±7.32 vs. 24.54±6.60, P>0.05). Scores of subjective image quality (IQ) in group B2 (40 keV) and B3 (50 keV) were similar to those in group A1 {5 [4.25, 5] vs. 5 [4, 5], 5 [5, 5] vs. 5 [4, 5], P>0.05}, and showed a declining trend in group B4 (60 keV) {4 [4, 5] vs. 5 [4, 5], P>0.05}. Conclusions It is feasible to perform run-off CTA using low-dose CM with VMI on SDCT. The VMIs at 40-50 keV were the optimal choice and did not compromise IQ.
Effect of resveratrol on abnormal bone remodeling and angiogenesis of subchondral bone in osteoarthritis.

PURPOSE The effect of resveratrol on subchondral bone in osteoarthritis was explored by constructing a mouse model of osteoarthritis and giving resveratrol as intervention. METHODS The degree of proteoglycan loss in articular cartilage was assessed by safranine fast green staining. The expressions of Lubricin and Aggrecan, COLX, and MMP-13, the co-expression of CD31 and Endomucin, and the expression of angiogenesis-related factors were determined by immunohistochemistry. TRAP stain and immunostaining were used to assess abnormal subchondral bone resorption and bone formation. Angiography was employed to analyze the effect of resveratrol on the proliferation of subchondral bone vessels. RESULTS Resveratrol inhibited cartilage thickening and the increase of COLX and MMP-13 expression, delayed the loss of proteoglycan, Lubricin, and Aggrecan, and inhibited osteoclast differentiation by up-regulating osteoprotegerin (OPG) and down-regulating the expression of RANKL. Angiography showed that resveratrol can reduce the abnormally elevated number and volume of blood vessels in the subchondral bone. Immunostaining showed that resveratrol inhibited CD31hiEmcnhi angiogenesis and high expression of VEGFA and Angiopoietin-1. CONCLUSION Resveratrol inhibits osteoclast differentiation and reduces active bone resorption by regulating the OPG/RANKL/RANK pathway, and inhibits the abnormal proliferation of CD31hiEmcnhi blood vessels by downregulating the expression of VEGFA and Angiopoiein-1, thereby eliminating the pathologic coupling mechanism of osteogenesis and vascularization, and delaying the progression of osteoarthritis.
Myelodysplastic syndrome with genetic predisposition

Myelodysplastic syndrome (MDS) refers to a heterogeneous group of clonal blood disorders characterized by ineffective hematopoiesis, cytopenia, dysplasia, and an increased risk of acute myeloid leukemia (AML). A growing number of inherited genetic loci that contribute to MDS/AML development are rapidly being identified. As genetic sequencing has become increasingly integrated into clinical practice, clearly defined syndromes have emerged, known as the MDS/AML predisposition syndrome. With more patients and families being identified with predisposing conditions, knowledge of the approach of evaluating and managing MDS with genetic predisposition is increasingly essential. This article reviews MDS with genetic predisposition and the practical aspects of management in patients with predisposition syndrome.
Sexual Dimorphism in Hepatocyte Xenograft Models

Humanized liver mouse models are crucial tools in liver research, specifically in the fields of liver cell biology, viral hepatitis and drug metabolism. The livers of these humanized mouse models are repopulated by 3-dimensional islands of fully functional primary human hepatocytes (PHH), which are notoriously difficult to maintain in vitro. As low efficiency and high cost hamper widespread use, optimization is of great importance. In the present study, we analyzed experimental factors associated with Hepatitis E virus (HEV) infection and PHH engraftment in 2 xenograft systems on a Nod-SCID-IL2Ry-/- background: the alb-urokinase plasminogen activator mouse model (uPA-NOG, n=399); and the alb-HSV thymidine kinase model (TK-NOG, n = 198). In a first analysis, HEV fecal shedding in liver humanized uPA-NOG and TK-NOG mice with comparable human albumin levels was found to be similar irrespective of the mouse genetic background. In a second analysis, sex, mouse age at transplantation and hepatocyte donor were the most determinant factors for xenograft success in both models. The sexual imbalance for xenograft success was related to higher baseline ALT levels and lower thresholds for ganciclovir induced liver morbidity and mortality in males. These data call for sexual standardization of human hepatocyte xenograft models, but also provide a platform for further studies on mechanisms behind sexual dimorphism in liver diseases.
Zn‐MOF Encapsulated Antibacterial and Degradable Microneedles Array for Promoting Wound Healing

An infected skin wound caused by external injury remains a serious challenge in clinical practice. Wound dressings with the properties of antibacterial activity and potent regeneration capacity are highly desirable for wound healing. In this paper, a degradable, ductile, and wound‐friendly Zn‐MOF encapsulated methacrylated hyaluronic acid (MeHA) microneedles (MNs) array is fabricated through the molding method for promoting wound healing. Due to the damage capability against the bacteria capsule and oxidative stress of the zinc ion released from the Zn‐MOF, such MNs array presents excellent antibacterial activity, as well as considerable biocompatibility. Besides, the degradable MNs array composed of photo‐crosslinked MeHA possesses the superior capabilities to continuously and steadily release the loaded active ingredients and avoid secondary damage to the wound. Moreover, the low molecular weight hyaluronic acid (HA) generated by hydrolysis of MeHA is also conducive to tissue regeneration. Benefiting from these features, it has been demonstrated that the Zn‐MOF encapsulated degradable MNs array can dramatically accelerate epithelial regeneration and neovascularization. These results indicate that the combination of MOFs and degradable MNs array is of great value for promoting wound healing.
A paclitaxel‐induced variant of hand‐foot syndrome affecting dorsal surfaces

Hand-foot syndrome (HFS), also known as palmar-plantar erythrodysesthesia (PPE), is a localized cutaneous adverse event (CAE) associated with a variety of chemotherapeutic agents, such as doxorubicin, fluorouracil, cytarabine, and docetaxel. HFS is characterized by painful erythema, edema, and desquamation of the skin, most prominently involving the hands and soles of the feet. However, HFS primarily affecting the dorsal hands and feet (also called periarticular thenar erythema and onycholysis or PATEO) is known to occur as a class-based effect with the taxane chemotherapeutic drug class. A 58-year-old African American female with breast cancer began to develop a pruritic bilateral dorsal hand eruption four weeks into a weekly regimen of paclitaxel. On exam, desquamative erythematous and violaceous plaques on the dorsal hands were noted, which were debilitatingly painful and necessitated treatment interruption. Histopathologic sections showed a focal interface dermatitis with keratinocyte apoptosis, dyskeratosis, and atypical mitoses with abnormal maturation. Clinicopathologic correlation strongly supported a diagnosis of taxane-induced HFS. Increased awareness of this HFS variant that preferentially affects dorsal acral sites may improve early identification and/or prevention of this cutaneous adverse reaction. This article is protected by copyright. All rights reserved.
Shelf life of dried products from small indigenous fish species under various packing and storage conditions

The overall quality of five SIS products was found in good condition up to 2 months storage on the basis of organoleptic, biochemical and bacteriological characteristics and all the products was excellent in sealed packed condition up to 45 days of storage. However, quality of the products stored in open air atmospheric temperature was found excellent for first 15 days. In an average the initial moisture content was in the range of 13.5 to 15.0% with highest moisture content in puti and lowest in chapila. At the end of the 60 days the moisture content reached to the range of 18.5 to 19.0% which was more or less near the recommended limit of 16% for dried fishery products. The moisture content beyond the recommended limit as the storage period increased further and at the end of 90 days the moisture content increased to the range of 22.9 to 24% when organoleptically the product quality became very poor. The changes in the value of total volatile base nitrogen (TVB-N), peroxide value (PO), moisture and aerobic plate count (APC) of solar tunnel dried products in sealed polythene packages were investigated during 60 days of storage. There was little or no differences in TVB-N, PO and bacterial load of each species packed under various polythene density. The initial TVB-N values were in the range of 10.30 to 12.40 mg/100g of the samples. TVB-N value increased slowly up to the end of the storage period and was to in the range of 46.20 to 57.00 mg/1 00 g of sample. Initially the peroxide values (P.O.) were in the range of 6.54 to 8.40 m.eq./kg oil of the samples. During 60 days of storage, P.O. values increased slowly and at the end of the storage period these values reached to the range of 22.00 to 25.30meq. /kg of sample. The initial APC was in the range 5.3xl04-7.3x104 CFU/g. The bacterial load increased slowly and at the end of the 60 days storage period reached to the range 6.6x106 - 8.6x107 CFT/g.
Bi‐allelic VPS16 variants limit HOPS/CORVET levels and cause a mucopolysaccharidosis‐like disease

Lysosomal storage diseases, including mucopolysaccharidoses, result from genetic defects that impair lysosomal catabolism. Here, we describe two patients from two independent families presenting with progressive psychomotor regression, delayed myelination, brain atrophy, neutropenia, skeletal abnormalities, and mucopolysaccharidosis‐like dysmorphic features. Both patients were homozygous for the same intronic variant in VPS16, a gene encoding a subunit of the HOPS and CORVET complexes. The variant impaired normal mRNA splicing and led to an ~85% reduction in VPS16 protein levels in patient‐derived fibroblasts. Levels of other HOPS/CORVET subunits, including VPS33A, were similarly reduced, but restored upon re‐expression of VPS16. Patient‐derived fibroblasts showed defects in the uptake and endosomal trafficking of transferrin as well as accumulation of autophagosomes and lysosomal compartments. Re‐expression of VPS16 rescued the cellular phenotypes. Zebrafish with disrupted vps16 expression showed impaired development, reduced myelination, and a similar accumulation of lysosomes and autophagosomes in the brain, particularly in glia cells. This disorder resembles previously reported patients with mutations in VPS33A, thus expanding the family of mucopolysaccharidosis‐like diseases that result from mutations in HOPS/CORVET subunits.
B regulatory cells and monocyte subpopulations in patients with chronic graft-vs-host disease

Aim To assess the correlations of B regulatory cells (Bregs) and monocyte subsets in peripheral blood with the National Institutes of Health (NIH)-consensus-defined clinical manifestations of chronic graft-vs-host disease (cGvHD), in an attempt to establish their role as cellular biomarkers. Methods This multidisciplinary prospective study enrolled adult cGVHD patients treated in the University Hospital Center Zagreb and University of Zagreb School of Medicine. Immunophenotypic subpopulations of CD24highCD38high Bregs (CD27-, CD27+, and total) and monocyte (classical, intermediate, and non-classical) counts were correlated with demographic, transplant, and cGVHD-related data. Bivariate correlation analysis was performed to evaluate the correlations between Bregs and monocytes subsets and cGVHD organ involvement, as well as cGVHD severity and immunosuppression intensity. Results Twenty-two adult patients (54.5% female) with cGVHD were enrolled. The median (range) age was 44.5 years (24-65). All patients were transplanted for hematologic malignancies and 40.9% had severe NIH cGVHD global score. The median time from cGVHD diagnosis to the analysis was 16.6 months (0-176). The organ most frequently affected with cGVHD were the eyes (68.2%), skin (45.5%), lungs (45.5%), and liver (40.9%). Lower total and CD27-Bregs counts were correlated with worse cGVHD severity, higher immunosuppression intensity, and lung cGVHD, in terms of cell count, but also with skin cGVHD, in terms of percentages. Patients with liver and joint/fascia cGVHD had a lower percentage of non-classical monocytes and patients with more severe global NIH score had a higher classical monocytes count. Conclusion Different organs affected by cGVHD are differently associated with different subpopulations of Bregs and monocytes.
Seasonal impact on surgical site infections and wound healing disturbance in carpal tunnel surgery: A retrospective cohort study

Carpal tunnel syndrome is the most common entrapment syndrome of a peripheral nerve. The gold standard treatment is open carpal tunnel release which has a high success rate, a low complication rate, and predictable postoperative results. However, it has not been analysed yet if there is a seasonal influence on complications for carpal tunnel release, a highly elective procedure. In this retrospective study, we determine whether there is a seasonal impact on surgical site infections (SSI) and wound healing disorders (WHD) in primary carpal tunnel syndrome surgery. Between 2014 and 2018, we have assessed 1385 patients (65% female, 35% male) at a mean age of 61.9 (SD 15.3) years, which underwent open carpal tunnel release because of primary carpal tunnel syndrome. The seasonal data such as the warm season (defined as the period from 1st of June until 15th of September), the average daily and monthly temperature, and the average relative humidity were analysed. Patient demographics were examined including body mass index, alcohol and nicotine abuse, the use of anticoagulants and antiplatelet drugs as well as comorbidities. These data were correlated regarding their influence to the rate of surgical site infections and wound healing disorders in our study collective. A postoperative SSI rate of 2.4% and a WHD rate of 7% were detected. Our data confirms the warm season, the average monthly temperature, and male sex as risk factors for increasing rates of WHDs. Serious SSIs with subsequent revision surgery could be correlated with higher age and higher relative humidity. However there is no seasonal impact on SSIs. We therefore advise considering the timing of this elective surgery with scheduling older male patients preferably during the cold season to prevent postoperative WHDs.
Molecular Self-Assembly and Supramolecular Chemistry of Cyclic Peptides

This Review focuses on the establishment and development of self-assemblies governed by the supramolecular interactions between cyclic peptides. The Review first describes the type of cyclic peptides able to assemble into tubular structures to form supramolecular cyclic peptide nanotubes. A range of cyclic peptides have been identified to have such properties, including α-peptides, β-peptides, α,γ-peptides, and peptides based on δ- and ε-amino acids. The Review covers the design and functionalization of these cyclic peptides and expands to a recent advance in the design and application of these materials through their conjugation to polymer chains to generate cyclic peptide–polymer conjugates nanostructures. The Review, then, concentrates on the challenges in characterizing these systems and presents an overview of the various analytical and characterization techniques used to date. This overview concludes with a critical survey of the various applications of the nanomaterials obtained from supramolecular cyclic peptide nanotubes, with a focus on biological and medical applications, ranging from ion channels and membrane insertion to antibacterial materials, anticancer drug delivery, gene delivery, and antiviral applications.
Time‐encoded golden angle radial arterial spin labeling: Simultaneous acquisition of angiography and perfusion data

The objective of the current study was to combine a time‐encoded pseudocontinuous arterial spin labeling (te‐pCASL) scheme with a golden angle radial readout for simultaneous acquisition of angiography and perfusion images from one single dataset, both in a highly flexible single‐slice approach as well as within a multislice setting. A te‐pCASL preparation and the golden angle radial readout were both used as a temporal resolution tool to retrospectively choose the temporal window for the reconstruction of both angiography and perfusion images from a single‐slice dataset. The temporal window could be chosen retrospectively and adjusted to the hemodynamics of the volunteer on the scanner for the single‐slice dataset. Angiographic images were reconstructed at a minimum temporal resolution of 69 ms. For the perfusion phase, only the densely sampled center of k‐space was included in the reconstruction. For a multislice acquisition, the golden angle radial readout allowed reconstruction of images with different spatial resolutions to provide angiographic and perfusion information over 10 slices. The te‐pCASL preparation was used as the only source for dynamic information. The multislice acquisition shows the ability of the golden angle radial readout to display the inflow of the labeled blood into the arteries as well as the perfusion in the tissue with full brain coverage. By combining a te‐pCASL preparation with a golden angle radial readout, single‐slice high temporal resolution angiography and good quality perfusion images were reconstructed in a flexible manner from a single dataset. Optimizing the golden angle radial readout for reconstructions at multiple spatial resolutions allows for multislice acquisition.
Naringin‐generated ROS promotes mitochondria‐mediated apoptosis in Candida albicans

Naringin is a flavonoid which has a therapeutic effect. However, the details of its antifungal mechanism have not yet been fully elucidated. This study focused on clarifying the relationship between naringin and Candida albicans, to understand its mode of antifungal action. In general, naringin is an antioxidant, but our results indicated that 1 mM naringin generates intracellular superoxide (O2−) and hydroxyl radicals (OH−). Reactive oxygen species (ROS) have a serious impact on Ca2+ signaling and the production of mitochondrial ROS. After exposure to enhanced O2− and OH−, mitochondrial Ca2+ overload and mitochondrial O2− generation were confirmed in C. albicans. It was verified that mitochondrial O2− transforms mitochondrial glutathione (GSH) to oxidized GSH (GSSG), leading to extreme oxidative stress in mitochondria. The previously observed Ca2+ accumulation and oxidative stress resulted in mitochondrial membrane potential (MMP) alteration and increased mitochondrial mass. In succession, cytochrome c release from the mitochondria to the cytosol was detected due to MMP loss. Cytochrome c promotes the initiation of apoptosis, and further experiments were performed to assess the apoptotic hallmarks. Metacaspases activation, chromosomal condensation, DNA fragmentation, and phosphatidylserine exposure were observed, indicating that naringin induces apoptosis in C. albicans. In conclusion, our findings manifested that naringin‐generated O2− and OH− damage the mitochondria and that mitochondrial dysfunction‐mediated apoptosis is novel antifungal mechanism of naringin.