Miracle-dz/UniFAR-FTUs huggingface dataset:
Resistance to Echinocandins Complicates a Case of Candida albicans Bloodstream Infection: A Case Report

Invasive candidiasis is known to be one of the most common healthcare-associated complications and is caused by several Candida species. First-line drugs, particularly echinocandins, are effective, but there are increasing reports of resistance to these molecules, though rarely related to C. albicans. Even though the rate of echinocandins resistance remains low (<3%), sporadic cases are emerging. Here, we present a case of bloodstream infection by a pan-echinocandin-resistant Candida albicans affecting a critically ill patient, who died in an intensive care unit following therapeutic failure and multiple organ dysfunction syndrome. This case highlights the need to suspect pan-echinocandin resistance in patients with prolonged echinocandin exposure, particularly in the presence of urinary tract colonization. Our study shows the importance of sequencing to predict therapeutic failure in patients treated with echinocandins and persistent candidemia.
Characterization Of Mixing For A Jet In Cross-o w Using Proper Orthogonal Decomposition

Jet in cross-o w experimental data are analyzed using proper orthogonal decomposition (POD) to gain insight into the most important mixing mechanisms and to demonstrate the usefulness of this statistical approach. The fundamentals of POD and its use of \optimal" basis functions to extract meaningful information is presented. Data obtained from experiments carried out using diering hole patterns and jet mass-ux ratios are used to perform the analysis, and the POD eigenmodes are presented. The physical signicance of these modes is discussed and their importance in determining primary mixing mechanisms is explained.
Heritable Connective Tissue Disorders in Childhood: Increased Fatigue, Pain, Disability and Decreased General Health

Heritable Connective Tissue Disorders (HCTD) show an overlap in the physical features that can evolve in childhood. It is unclear to what extent children with HCTD experience burden of disease. This study aims to quantify fatigue, pain, disability and general health with standardized validated questionnaires. Methods. This observational, multicenter study included 107 children, aged 4–18 years, with Marfan syndrome (MFS), 58%; Loeys-Dietz syndrome (LDS), 7%; Ehlers-Danlos syndromes (EDS), 8%; and hypermobile Ehlers-Danlos syndrome (hEDS), 27%. The assessments included PROMIS Fatigue Parent–Proxy and Pediatric self-report, pain and general health Visual-Analogue-Scales (VAS) and a Childhood Health Assessment Questionnaire (CHAQ). Results. Compared to normative data, the total HCTD-group showed significantly higher parent-rated fatigue T-scores (M = 53 (SD = 12), p = 0.004, d = 0.3), pain VAS scores (M = 2.8 (SD = 3.1), p < 0.001, d = 1.27), general health VAS scores (M = 2.5 (SD = 1.8), p < 0.001, d = 2.04) and CHAQ disability index scores (M = 0.9 (SD = 0.7), p < 0.001, d = 1.23). HCTD-subgroups showed similar results. The most adverse sequels were reported in children with hEDS, whereas the least were reported in those with MFS. Disability showed significant relationships with fatigue (p < 0.001, rs = 0.68), pain (p < 0.001, rs = 0.64) and general health (p < 0.001, rs = 0.59). Conclusions. Compared to normative data, children and adolescents with HCTD reported increased fatigue, pain, disability and decreased general health, with most differences translating into very large-sized effects. This new knowledge calls for systematic monitoring with standardized validated questionnaires, physical assessments and tailored interventions in clinical care.
Successful Treatment of Cryptococcal Meningitis and Cryptococcoma with Isavuconazole in a Patient Living with HIV

We describe the successful use of isavuconazole for treatment of an HIV-positive patient with cryptococcal meningitis following induction therapy with liposomal amphotericin B and flucytosine. Because the Cryptococcus neoformans isolate from cerebrospinal fluid had a borderline minimum inhibitory concentration of 8 mg/L, initial consolidation therapy was given with a daily dose of fluconazole 1200 mg based on area under the curve to minimum inhibitory concentration modelling data. Toxicity, and the radiological emergence of a cryptococcoma in the setting of immune reconstitution inflammatory syndrome, prompted a therapeutic switch to isavuconazole. Subsequent imaging after 19 weeks of isavuconazole shows a significant reduction in cryptococcoma size from 11 mm to complete resolution. The patient remains well after 210 days of therapy with a view to completion of treatment after 1 year.
A Fair Assessment of Evaluation Tools for the Murine Microbead Occlusion Model of Glaucoma

Despite being one of the most studied eye diseases, clinical translation of glaucoma research is hampered, at least in part, by the lack of validated preclinical models and readouts. The most popular experimental glaucoma model is the murine microbead occlusion model, yet the observed mild phenotype, mixed success rate, and weak reproducibility urge for an expansion of available readout tools. For this purpose, we evaluated various measures that reflect early onset glaucomatous changes in the murine microbead occlusion model. Anterior chamber depth measurements and scotopic threshold response recordings were identified as an outstanding set of tools to assess the model’s success rate and to chart glaucomatous damage (or neuroprotection in future studies), respectively. Both are easy-to-measure, in vivo tools with a fast acquisition time and high translatability to the clinic and can be used, whenever judged beneficial, in combination with the more conventional measures in present-day glaucoma research (i.e., intraocular pressure measurements and post-mortem histological analyses). Furthermore, we highlighted the use of dendritic arbor analysis as an alternative histological readout for retinal ganglion cell density counts.
The Emerging Role of HDACs: Pathology and Therapeutic Targets in Diabetes Mellitus

Diabetes mellitus (DM) is one of the principal manifestations of metabolic syndrome and its prevalence with modern lifestyle is increasing incessantly. Chronic hyperglycemia can induce several vascular complications that were referred to be the major cause of morbidity and mortality in DM. Although several therapeutic targets have been identified and accessed clinically, the imminent risk of DM and its prevalence are still ascending. Substantial pieces of evidence revealed that histone deacetylase (HDAC) isoforms can regulate various molecular activities in DM via epigenetic and post-translational regulation of several transcription factors. To date, 18 HDAC isoforms have been identified in mammals that were categorized into four different classes. Classes I, II, and IV are regarded as classical HDACs, which operate through a Zn-based mechanism. In contrast, class III HDACs or Sirtuins depend on nicotinamide adenine dinucleotide (NAD+) for their molecular activity. Functionally, most of the HDAC isoforms can regulate β cell fate, insulin release, insulin expression and signaling, and glucose metabolism. Moreover, the roles of HDAC members have been implicated in the regulation of oxidative stress, inflammation, apoptosis, fibrosis, and other pathological events, which substantially contribute to diabetes-related vascular dysfunctions. Therefore, HDACs could serve as the potential therapeutic target in DM towards developing novel intervention strategies. This review sheds light on the emerging role of HDACs/isoforms in diabetic pathophysiology and emphasized the scope of their targeting in DM for constituting novel interventional strategies for metabolic disorders/complications.
Effects of laparoscopic-assisted gastrectomy on elderly patients with gastric cancer.

PURPOSE Although the acceptance of laparoscopy-assisted gastrectomy (LAG) for the treatment of gastric cancer (GC) has been increasing, it is still controversial that LAG is an applicable treatment method for elderly patients since elderly patients are usually complicated with other diseases. Therefore, this study aimed to investigate the prognostic differences between elderly patients and non-elderly patients after receiving LAG. METHODS Patients (n = 306) who received LAG for the treatment of GC from April 2009 to December 2014 were included in the study. The patients were divided into the elderly group (≥ 65 years old, n = 120) and the non-elderly group (< 65 years old, n=186). The postoperative outcomes as well as the morbidity and the survival rates were compared between the two groups. RESULTS American Society of Anesthesiologists (ASA) score and comprehensive complication index (CCI) score in the elderly group were significantly higher than those in the non-elderly group (p<0.05). In terms of surgical outcomes, there was no significant difference in blood loss or postoperative hospital stay between the elderly group and the non-elderly group. As for postoperative comorbidities, there were significant differences in intraperitoneal hemorrhage and pleural effusion between the elderly group and the non-elderly group. Moreover, the median follow-up time was 38.5 months, and the overall survival of elderly patients with comorbidities was significantly lower than that of the elderly patients without comorbidities (p<0.05). CONCLUSIONS LAG can be performed safely and successfully in the elderly population with acceptable postoperative and long-term results.
Anchored Phylogenomics, Evolution and Systematics of Elateridae: Are All Bioluminescent Elateroidea Derived Click Beetles?

Simple Summary In the era of phylogenomics, new molecular sequencing and computational techniques can aid in resolving phylogenetic relationships that were previously intractable by morphological or limited molecular data. In this study, we used anchored hybrid enrichment—designed to recover DNA sequences from hundreds of single-copy orthologous genes—to resolve the phylogeny of the Elateridae (click-beetles) and establish their placement within superfamily Elateroidea. The resulting data were compatible with published transcriptomes, allowing for integrating our dataset with previously published data. Using a wide range of analyses on these molecular data, we tested hypotheses long-debated in the morphological literature and also the robustness of our phylogenetic inferences. Our results placed the bioluminescent lampyroids (fireflies and relatives) within the click-beetles, challenging the current classification of Elateridae, Lampyridae, Phengodidae, and Rhagophthalmidae. However, despite the large amount of molecular data analyzed, a few nodes with conflicting phylogenetic signals could not be unambiguously resolved. Overall, we recovered well-resolved tree topologies that will serve as a framework for further systematic and evolutionary studies of click-beetles. This work further demonstrates that the click-beetle lineage contains not only pest wireworms, but also many species that benefit agriculture. Abstract Click-beetles (Coleoptera: Elateridae) are an abundant, diverse, and economically important beetle family that includes bioluminescent species. To date, molecular phylogenies have sampled relatively few taxa and genes, incompletely resolving subfamily level relationships. We present a novel probe set for anchored hybrid enrichment of 2260 single-copy orthologous genes in Elateroidea. Using these probes, we undertook the largest phylogenomic study of Elateroidea to date (99 Elateroidea, including 86 Elateridae, plus 5 non-elateroid outgroups). We sequenced specimens from 88 taxa to test the monophyly of families, subfamilies and tribes. Maximum likelihood and coalescent phylogenetic analyses produced well-resolved topologies. Notably, the included non-elaterid bioluminescent families (Lampyridae + Phengodidae + Rhagophthalmidae) form a clade within the otherwise monophyletic Elateridae, and Sinopyrophoridae may not warrant recognition as a family. All analyses recovered the elaterid subfamilies Elaterinae, Agrypninae, Cardiophorinae, Negastriinae, Pityobiinae, and Tetralobinae as monophyletic. Our results were conflicting on whether the hypnoidines are sister to Dendrometrinae or Cardiophorinae + Negastriinae. Moreover, we show that fossils with the eucnemid-type frons and elongate cylindrical shape may belong to Eucnemidae, Elateridae: Thylacosterninae, ancestral hard-bodied cantharoids or related extinct groups. Proposed taxonomic changes include recognition of Plastocerini as a tribe in Dendrometrinae and Hypnoidinae stat. nov. as a subfamily within Elateridae.
Virus-Driven Carcinogenesis

Simple Summary Carcinogens, causes of cancer, are usually invisible and therefore in vivo carcinogenesis is difficult to detect. Tumor viruses, definitive carcinogens, are also usually unremarkable, particularly due to latent infection. However, recent developments in tumor virology are unraveling how a single infected cell becomes a life-threatening cell population from a molecular perspective. The recognition and characterization of virus-driven carcinogenesis is the first step in the eradication of tumor virus-associated cancer. Abstract Cancer arises from the accumulation of genetic and epigenetic alterations. Even in the era of precision oncology, carcinogens contributing to neoplastic process are still an important focus of research. Comprehensive genomic analyses have revealed various combinations of base substitutions, referred to as the mutational signatures, in cancer. Each mutational signature is believed to arise from specific DNA damage and repair processes, including carcinogens. However, as a type of carcinogen, tumor viruses increase the cancer risk by alternative mechanisms, including insertional mutagenesis, viral oncogenes, and immunosuppression. In this review, we summarize virus-driven carcinogenesis to provide a framework for the control of malignant cell proliferation. We first provide a brief overview of oncogenic viruses and describe their implication in virus-related tumors. Next, we describe tumor viruses (HPV, Human papilloma virus; HBV, Hepatitis B virus; HCV, Hepatitis C virus; EBV, Epstein–Barr virus; Kaposi sarcoma herpesvirus; MCV, Merkel cell polyoma virus; HTLV-1, Human T-cell lymphotropic virus, type-1) and tumor virus-related cancers. Lastly, we introduce emerging tumor virus candidates, human cytomegalovirus (CMV), human herpesvirus-6 (HHV-6) and adeno-associated virus-2 (AAV-2). We expect this review to be a hub in a complex network of data for virus-associated carcinogenesis.
Process–Structure–Property Relationships of Copper Parts Manufactured by Laser Powder Bed Fusion

The process–structure–property relationships of copper laser powder bed fusion (L-PBF)-produced parts made of high purity copper powder (99.9 wt %) are examined in this work. A nominal laser beam diameter of 100 μm with a continuous wavelength of 1080 nm was employed. A wide range of process parameters was considered in this study, including five levels of laser power in the range of 200 to 370 W, nine levels of scanning speed from 200 to 700 mm/s, six levels of hatch spacing from 50 to 150 μm, and two layer thickness values of 30 μm and 40 μm. The influence of preheating was also investigated. A maximum relative density of 96% was obtained at a laser power of 370 W, scanning speed of 500 mm/s, and hatch spacing of 100 μm. The results illustrated the significant influence of some parameters such as laser power and hatch spacing on the part quality. In addition, surface integrity was evaluated by surface roughness measurements, where the optimum Ra was measured at 8 μm ± 0.5 μm. X-ray photoelectron spectroscopy (XPS) and energy-dispersive X-ray spectroscopy (EDX) were performed on the as-built samples to assess the impact of impurities on the L-PBF part characteristics. The highest electrical conductivity recorded for the optimum density-low contaminated coils was 81% IACS.
Prospective Study on Factors Associated with Referral of Patients with Opioid Maintenance Therapy from Specialized Addictive Disorders Centers to Primary Care

Background: One of the most important issues for opiate maintenance therapy efficacy is the involvement of primary care physicians (PCPs) in opiate use disorder treatment, especially after referral from specialized units. This study aimed to analyze the progress of subjects in a specialized center and after referral to PCPs. Methods: This study was an observational prospective study. Recruitment took place in a specialized addictive disorder center in western France. All patients were evaluated (sociodemographical data, severity of substance use disorders through the TMSP scale, the quality of life through the TEAQV scale) by physicians during the 5-year-follow up of the study. Analysis focused on four main times during follow-up: entry/last visit into specialized care and into primary care. Results: 113 patients were included in this study; 93% were receiving methadone and 7% buprenorphine. Ninety (90) were referred to primary care. In primary care follow-up, the probability of the lowest severity score for substance use disorders remained stable over time. Conclusions: In daily practice, a center specialized in addictive disorders referred OMT management to PCPs for a majority of patients, and benefits regarding substance use disorders severity and quality of life remained stable after referral. Our results need to be confirmed.
Mobile Oxazolidinone Resistance Genes in Gram-Positive and Gram-Negative Bacteria

Seven mobile oxazolidinone resistance genes, including cfr, cfr(B), cfr(C), cfr(D), cfr(E), optrA, and poxtA, have been identified to date. The cfr genes code for 23S rRNA methylases, which confer a multiresistance phenotype that includes resistance to phenicols, lincosamides, oxazolidinones, pleuromutilins, and streptogramin A compounds. The optrA and poxtA genes code for ABC-F proteins that protect the bacterial ribosomes from the inhibitory effects of oxazolidinones. SUMMARY Seven mobile oxazolidinone resistance genes, including cfr, cfr(B), cfr(C), cfr(D), cfr(E), optrA, and poxtA, have been identified to date. The cfr genes code for 23S rRNA methylases, which confer a multiresistance phenotype that includes resistance to phenicols, lincosamides, oxazolidinones, pleuromutilins, and streptogramin A compounds. The optrA and poxtA genes code for ABC-F proteins that protect the bacterial ribosomes from the inhibitory effects of oxazolidinones. The optrA gene confers resistance to oxazolidinones and phenicols, while the poxtA gene confers elevated MICs or resistance to oxazolidinones, phenicols, and tetracycline. These oxazolidinone resistance genes are most frequently found on plasmids, but they are also located on transposons, integrative and conjugative elements (ICEs), genomic islands, and prophages. In these mobile genetic elements (MGEs), insertion sequences (IS) most often flanked the cfr, optrA, and poxtA genes and were able to generate translocatable units (TUs) that comprise the oxazolidinone resistance genes and occasionally also other genes. MGEs and TUs play an important role in the dissemination of oxazolidinone resistance genes across strain, species, and genus boundaries. Most frequently, these MGEs also harbor genes that mediate resistance not only to antimicrobial agents of other classes, but also to metals and biocides. Direct selection pressure by the use of antimicrobial agents to which the oxazolidinone resistance genes confer resistance, but also indirect selection pressure by the use of antimicrobial agents, metals, or biocides (the respective resistance genes against which are colocated on cfr-, optrA-, or poxtA-carrying MGEs) may play a role in the coselection and persistence of oxazolidinone resistance genes.
Decreased ERβ expression and high cyclin D1 expression may predict early CRC recurrence in high-risk Duke's B and Duke's C stage.

PURPOSE Despite many known risk factors for the colorectal cancer (CRC) recurrence, significant differences in disease-free survival (DFS) impose the need to look for new explanations. This study aimed to determine the degree of expression of ERα, ERβ, PR, Cyclin D1, and Bcl-2 and their association with early CRC relapse. METHODS This retrospective study included 101 radically operated CRC patients in high-risk Duke's B and Duke's C stage. Tissue samples were retrieved from paraffin blocks and clinical and diagnostic data from medical records obtained during further clinical treatment and follow up. Patients were divided into DFS≤24 months group and DFS≥48 months group. Immunostaining of ERα, ERβ, PR, Cyclin D1, and Bcl-2 was performed and analyzed. RESULTS ERα was not expressed in all patients. ERβ moderate expression was present in 25% of all patients, more often in the DFS≥48 group (p=0.001). PR and Bcl-2 showed only moderate expression in 1/5 and 1/3 of the patients, respectively, without significant difference between groups (p=0.145;p=0.566). Cyclin D1 was expressed in the whole sample of patients with strong expression statistically more often in DFS≤24 group (p=0.011) and had 5.2 higher odds of having DFS˂24 months. Moderate expression of ERβ was joined with 79.2% smaller odds for shorter DFS. Advanced T stage had 11.3 times higher odds of having DFS˂24 months. CONCLUSION Early recurrence of CRC in high-risk Duke's B and Duke's C stage relates with reduced ERβ expression and the high cyclin D1 expression, so they could be considered independent prognostic factors, especially in patients in advanced T stage.
Oral Health: Global Research Performance under Changing Regional Health Burdens

Objectives: Inadequate oral hygiene still leads to many serious diseases all over the world. Therefore, this study aimed to analyze scientific research in the field of oral health in order to be able to comprehend their relevant subject areas, research connections, or developments. Methods: This study aimed to assess the global publication output on oral hygiene to create a world map that provides background information on key players, trends, and incentives of research. For this purpose, established bibliometric parameters were combined with state-of-the-art visualization techniques. Results: This study shows the actual key players of research on oral hygiene in high-income economies with only marginal participation from lower economies. This still corresponds to the current burden situations, but they are more and more shifting to the disadvantage of the low-income countries. There is a clear North–South and West–East gradient, with the USA and the Western European nations being the most publishing nations on oral hygiene. As an emerging country, Brazil plays a role in the research. Conclusions: The scientific power players were concentrated in high-income countries. However, the changing epidemiological situation requires a different scientific approach to oral hygiene. This requires an expansion of the international network to meet the demands of future global oral health burdens, which are mainly related to oral hygiene.