Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevalence and prognostic value of MYD88 and CD79B mutations in ocular adnexal large B-cell lymphoma: a reclassification of ocular adnexal large B-cell lymphoma

Aims To (1) reclassify ocular adnexal large B-cell lymphomas (OA-LBCLs) per 2016 WHO lymphoma classification and (2) determine the prevalence of MYD88 and CD79B mutations and their association with clinical parameters among OA-LBCLs. Methods This study is a retrospective analysis of all OA-LBCLs diagnosed in Denmark between 1980 and 2018. Medical records and tissue samples were retrieved. Thirty-four OA-LBCLs were included. Fluorescence in situ hybridisation and Epstein-Barr-encoded RNA in situ hybridisation were used for the reclassification. Mutational status was established by allele-specific PCR and confirmed by Sanger sequencing. Primary endpoints were overall survival, disease-specific survival (DSS) and progression-free survival (PFS). Results Two LBCL subtypes were identified: diffuse large B-cell lymphoma (DLBCL) (27 of 32; 84%) and high-grade B-cell lymphoma (HGBL) with MYC and BCL2 and/or BCL6 rearrangements (5 of 32; 16%). cMYC/BCL2 double-expressor DLBCLs had a poorer DSS than non-double-expressor DLBCLs (5-year DSS, 25% vs 78%) (HR 0.23; 95% CI 0.06 to 0.85; p=0.014). MYD88 mutations were present in 10 (29%) of 34 lymphomas and carried a poorer PFS than wild-type cases (5-year PFS, 0% vs 43%) (HR 0.78; 95% CI 0.61 to 0.98; p=0.039). CD79B mutations were present in 3 (9%) of 34 cases. Conclusion OA-LBCL consists mainly of two subtypes: DLBCL and HGBL with MYC and BCL2 and/or BCL6 rearrangements. MYD88 mutations are important drivers of OA-LBCL. MYD88 mutations, as well as cMYC/BCL2 double-expressor DLBCL, appear to be associated with a poor prognosis. Implementing MYD88 mutational analysis in routine diagnostics may improve OA-LBCL prognostication.
Sophorolipid: a glycolipid biosurfactant as a potential therapeutic agent against COVID-19

ABSTRACT Biosurfactants are natural surfactants produced by a variety of microorganisms. In recent years, biosurfactants have garnered a lot of interest due to their biomedical and pharmaceutical applications. Sophorolipids are glycolipid types of biosurfactants produced by selected nonpathogenic yeasts. In addition to the detergent activity (reduction in surface and interfacial tension), which is commonly utilized by biomedical applications, sophorolipids have shown some unique properties such as, antiviral activity against enveloped viruses, immunomodulation, and anticancer activity. Considering their antiviral activity, the potential of sophorolipids as an antiviral therapy for the treatment of COVID-19 is discussed in this review. Being a surfactant molecule, sophorolipid could solubilize the lipid envelope of SARS-CoV-2 and inactivate it. As an immunomodulator, sophorolipid could attenuate the cytokine storm caused by the SARS-CoV-2 upon infection, and inhibit the progression of COVID-19 in patients. Sophorolipids could also be used as an effective treatment strategy for COVID-19 patients suffering from cancer. However, there is limited research on the use of sophorolipid as a therapeutic agent for the treatment of cancer and viral diseases, and to modulate the immune response. Nevertheless, the multitasking capabilities of sophorolipids make them potential therapeutic candidates for the bench-to-bedside research for the treatment of COVID-19.
Multiprofessional screening protocol for dysphagia in patients with HIV infection: elaboration and content validity

ABSTRACT Purpose To elaborate and validate a multiprofessional protocol to identify the risk of dysphagia in people with HIV at the time of hospitalization. Methods After bibliographic review, the dysphagia screening protocol created was submitted to the analysis of HIV/ Aids expert judges and target audience in the application of this instrument to perform content validity. These evaluators could suggest changes to the protocol, judging clarity, pertinence, and comprehensiveness. The CVI 0.78 was used to confirm the validity of the results. Results The protocol was created including aspects related to oral and pharyngeal swallowing, and the final score was calculated based on the risks for clinical complications. The instrument presented CVI above 0.78 for all items in the two validation phases, as well as total CVI of 0.92. Conclusion Based on the obtained data, it was possible to create and validate the screening protocol from the point of view of appearance and content, once it presented total CVI above the minimum value stipulated in the validation of the expert judges and the target public, obtaining an adequate result for the protocol. Therefore, we can consider the resolution instrument, with the capacity to fulfill what was proposed.
Reply to Grigoriev et al., “Sequences of SARS-CoV-2 ‘Hybrids’ with the Human Genome: Signs of Non-coding RNA?”

High throughput sequencing reads from virally infected cells provide detailed information about both the infected host cells and invading viruses (1). For example, RNA-sequencing techniques from infected cells contains reads that unequivocally align to either the host or the viral transcriptomes, enabling quantification of host and viral gene expressions (2). Occasionally, there are reads with split characteristics, having one part (e.g., the 5' end) unambiguously matching the host and another part (e.g., the 3' end) clearly matching the viral genomes. The split characteristic with unambiguous matching on either part is the key here, typically requiring convincing stretches of sequence matches such as >30bp that we used in our analysis (3). Such reads are termed host-virus chimeric reads (HVCRs). Indeed, HVCRs that surpass statistical reproducibility and signal-to-noise standards might carry novel insights into the biology of host-virus interactions (4, 5). Thus, it is important to unambiguously detect statistically rigorous and biologically relevant HVCRs. We and others have shown that detection of relevant HVCRs is complicated by unfaithful reverse-transcriptase and polymerase enzymes that template-switch during typical high throughput sequencing library preparation protocols (6-9).
Genomic Analysis of a Hospital-Associated Outbreak of Mycobacterium abscessus: Implications on Transmission

Whole-genome sequencing (WGS) has recently been used to investigate acquisition of Mycobacterium abscessus. Investigators have reached conflicting conclusions about the meaning of genetic distances for interpretation of person-to-person transmission. ABSTRACT Whole-genome sequencing (WGS) has recently been used to investigate acquisition of Mycobacterium abscessus. Investigators have reached conflicting conclusions about the meaning of genetic distances for interpretation of person-to-person transmission. Existing genomic studies were limited by a lack of WGS from environmental M. abscessus isolates. In this study, we retrospectively analyzed the core and accessory genomes of 26 M. abscessus subsp. abscessus isolates collected over 7 years. Clinical isolates (n = 22) were obtained from a large hospital-associated outbreak of M. abscessus subsp. abscessus, the outbreak hospital before or after the outbreak, a neighboring hospital, and two outside laboratories. Environmental M. abscessus subsp. abscessus isolates (n = 4) were obtained from outbreak hospital water outlets. Phylogenomic analysis of study isolates revealed three clades with pairwise genetic distances ranging from 0 to 135 single-nucleotide polymorphisms (SNPs). Compared to a reference environmental outbreak isolate, all seven clinical outbreak isolates and the remaining three environmental isolates had highly similar core and accessory genomes, differing by up to 7 SNPs and a median of 1.6% accessory genes, respectively. Although genomic comparisons of 15 nonoutbreak clinical isolates revealed greater heterogeneity, five (33%) isolates had fewer than 20 SNPs compared to the reference environmental isolate, including two unrelated outside laboratory isolates with less than 4% accessory genome variation. Detailed genomic comparisons confirmed environmental acquisition of outbreak isolates of M. abscessus subsp. abscessus. SNP distances alone, however, did not clearly differentiate the mechanism of acquisition of outbreak versus nonoutbreak isolates. We conclude that successful investigation of M. abscessus subsp. abscessus clusters requires molecular and epidemiologic components, ideally complemented by environmental sampling.
Discovery of a Novel Glucuronan Lyase System in Trichoderma parareesei

This paper reports the discovery of a set of six complementary glucuronan lyase enzymes in the mycoparasite Trichoderma parareseei. Apart from the novelty of the discovery of these enzymes in T. parareesei, the key importance of the study is the finding that the majority of these lyases are induced when T. parareesei is inoculated on Basidiomycete cell walls that contain glucuronan. ABSTRACT Glucuronan lyases (EC 4.2.2.14) catalyze depolymerization of linear β-(1,4)-polyglucuronic acid (glucuronan). Only a few glucuronan lyases have been characterized until now, most of them originating from bacteria. Here we report the discovery, recombinant production, and functional characterization of the full complement of six glucuronan specific polysaccharide lyases in the necrotic mycoparasite Trichoderma parareesei. The enzymes belong to four different polysaccharide lyase families and have different reaction optima and glucuronan degradation profiles. Four of them showed endo-lytic action and two, TpPL8A and TpPL38A, displayed exo-lytic action. Nuclear magnetic resonance revealed that the monomeric end product from TpPL8A and TpPL38A underwent spontaneous rearrangements to tautomeric forms. Proteomic analysis of the secretomes from T. parareesei growing on pure glucuronan and lyophilized A. bisporus fruiting bodies, respectively, showed secretion of five of the glucuronan lyases and high-performance anion-exchange chromatography with pulsed amperometric detection analysis confirmed the presence of glucuronic acid in the A. bisporus fruiting bodies. By systematic genome annotation of more than 100 fungal genomes and subsequent phylogenetic analysis of the putative glucuronan lyases, we show that glucuronan lyases occur in several ecological and taxonomic groups in the fungal kingdom. Our findings suggest that a diverse repertoire of glucuronan lyases is a common trait among Hypocreales species with mycoparasitic and entomopathogenic lifestyles. IMPORTANCE This paper reports the discovery of a set of six complementary glucuronan lyase enzymes in the mycoparasite Trichoderma parareseei. Apart from the novelty of the discovery of these enzymes in T. parareesei, the key importance of the study is the finding that the majority of these lyases are induced when T. parareesei is inoculated on Basidiomycete cell walls that contain glucuronan. The study also reveals putative glucuronan lyase encoding genes in a wealth of other fungi that furthermore points at fungal cell wall glucuronan being a target C-source for many types of fungi. In a technical context, the findings may lead to controlled production of glucuronan oligomers for advanced pharmaceutical applications and pave the way for development of new fungal biocontrol agents.
Abiotic Formation of Amide Bond via Surface-Supported Direct Carboxyl-Amine Coupling.

Amide bond formation is one of the most important reactions in biochemistry, notably being of crucial importance for the origin of life. Herein, we combine scanning tunneling microscopy and X-ray photoelectron spectroscopy studies to provide evidence for thermally activated abiotic formation of amide bonds between adsorbed precursors through direct carboxyl-amine coupling under ultrahigh vacuum conditions by means of on-surface synthesis. Complementary insights from temperature-programmed desorption measurements and density functional theory calculations reveal the competition between cross-coupling amide formation and decarboxylation reactions on the Au(111) surface. Furthermore, we demonstrate the critical influence of the employed metal support: whereas on Au(111) the coupling readily occurs, different reaction scenarios prevail on Ag(111) and Cu(111). The systematic experiments signal that archetypical bio-related molecules can be abiotically synthesized in clean environments without water or oxygen.
Chimera and cluster collective states in a dispersal ecological network under state-dependent feedback control and complex habitat structure

Pest control based on an economic threshold (ET) can effectively prevent excessive pest control measures such as pesticide abuse and overharvesting. The instinctive dispersal of pest populations in biological network patches for better survival poses challenges for pest management. As long as the pest density is controlled below the economic threshold and no pest outbreak occurs, the aim of pest management can be achieved and it is not necessary to completely remove the pests. This study focuses on the issues of chimera states and cluster solutions in regular bidirectional biological networks with state-dependent impulsive pest management. We consider the influence of two different control modes on the system states, namely global control and local control. Local control is found to be more likely to induce the chimera state. In addition, in the local coupling mode, a higher coupling strength is more likely to generate a coherent state, whereas a lower coupling strength is more likely to generate chimera and incoherent states. Furthermore, the cluster size is inversely related to the coupling strength under local coupling and global control.
Trainee participation does not adversely affect the safety of thyroid surgery: Systematic review and meta‐analysis

Surgical traineeship is essential but must be safe for patients. In thyroid surgery, surgeon volume correlates with improved clinical/economic outcomes. However, it is presently unclear how far does trainee participation affect post‐thyroidectomy complication rates in real‐world and randomized data. We systematically searched four databases for associations of trainee participation with any post‐thyroidectomy outcome. We conducted univariate meta‐analyses, sensitivity analyses, and assessed publication bias qualitatively and quantitatively. We included 1 randomized and 15 observational studies from 3755 records, comprising 34 774 thyroid surgical patients. Trainee participation was associated with 12 min longer operative time, but not higher complication rates (hypoparathyroidism, recurrent laryngeal nerve palsy, hematoma, blood loss, return to operating room, hospitalization duration, readmission, and mortality). Sensitivity, publication bias, and multivariate analyses did not change our findings. Real‐world and limited randomized data suggest that trainee participation in thyroid surgery is safe, given adequate consultant supervision and appropriate case selection.
Microproteins: a 3D protein structure prediction analysis

Abstract Microproteins are a novel and expanding group of small proteins encoded by less than 100–150 codons that are translated from small open reading frames (smORFs). It has been shown that smORFs and their corresponding microproteins make up a sizable fraction of the genome and proteome, but very little information on microproteins’ structural features exists in the literature. In this paper, we present the results of analyzing the predicted structures of 44 microproteins. The results show that this set of microproteins have a different amino acid composition profiles, similar structural characteristics and fewer small-molecule ligand binding sites than regular proteins. Communicated by Ramaswamy H. Sarma
Comparison of the operative time and presence of voids of incremental and bulk-filling techniques on Class II composite restorations.

OBJECTIVES To compare the operative time and presence of air voids on Class II restorations fabricated by dental practitioners with 1 to 5 years of experience using incremental and bulk-filling techniques. METHOD AND MATERIALS Four techniques were evaluated: incremental, bulk-filling, bulk-filling with heated composite, and snowplow technique. Standardized mandibular first molars with a MOD (mesial, occlusal, and distal) cavity were used. Voluntary operators made two restorations using each technique and the time required for each restoration was recorded. The restorations were scanned by micro-computed tomography to calculate the volume of the restoration occupied by air voids. The "operative time" and "volume of air voids" were analyzed individually by two-way ANOVA and Tukey HSD post hoc (α = .05) for the factors operator and insertion technique. A correlation between "operative time" and "volume of air voids" was evaluated using Pearson coefficient (α = .05). RESULTS The incremental technique required significantly longer time, yet no differences were observed between the bulk-filling techniques. There were no significant differences between techniques regarding the volume of air voids. A significant, but weak, and inverse linear correlation (P = .0059; r = -.29; r2 = 8.41%) was found between the operative time and volume of air voids. CONCLUSION There were no significant differences in the volume of air voids among the evaluated techniques, although bulk-filling techniques required a shorter operative time. Hence, implementing bulk-filling techniques by dental schools and restorative dental practitioners with different levels of expertise may reduce chair time and produce a volume of air voids similar to the incremental technique.
Cannabis-based medicine in treatment of patients with Gilles de la Tourette syndrome.

INTRODUCTION Gilles de la Tourette syndrome (GTS) is a childhood onset disorder characterised by the presence of motor and vocal tics. The guidelines of both the American Academy of Neurology (AAN) as well as the European Society for the Study of Tourette Syndrome (ESSTS) recommend behavioural therapy and pharmacotherapy, mainly with antipsychotics, as first line treatments for tics. In spite of these well-established therapeutic approaches, a significant number of patients are dissatisfied because of insufficient tic reduction or intolerable side effects. Previous studies have suggested that cannabis-based medicine (CBM) might be an alternative treatment in these patients. MATERIAL AND METHODS Two reviewers (KS, NS) searched the electronic database of PubMed on 1 July, 2021 for relevant studies using the search terms: ('Tourette syndrome' [MeSH Terms] OR 'Gilles de la Tourette syndrome' [MeSH Terms] OR 'tic disorders' [MeSH Terms] OR 'tics' [MeSH Terms] OR 'tic disorders'[Title/Abstract]) AND ('cannabis-based medicine' [Title/Abstract] OR 'cannabis' [Title/Abstract] OR 'dronabinol' [Title/Abstract] OR 'nabiximols' [Title/Abstract] OR 'tetrahydrocannabinol' [Title/Abstract] OR 'THC' [Title/Abstract] OR 'cannabidiol' [Title/Abstract], limit: 'humans'. These studies were further reviewed for additional relevant citations. The titles and abstracts of the studies obtained through this search were examined by two reviewers (KS, NS) in order to determine article inclusion. Discrepancies were addressed by the reviewers through discussion and eventually conversation with the senior reviewer (KMV). RESULTS Although the amount of evidence supporting the use of CBM in GTS is growing, the majority of studies are still limited to case reports, case series, and open uncontrolled studies. To date, only two small randomised controlled trials (RCTs) using tetrahydrocannabinol (THC, dronabinol) have been published demonstrating the safety and efficacy of this intervention in the treatment of tics in patients with GTS. On the other hand, another RCT with Lu AG06466 (formerly known as ABX-1431), a modulator of endocannabinoid neurotransmission, has failed to prove effective in the therapy of GTS. Accordingly, under the guidelines of both the ESSTS and the AAN, treatment with CBM is categorised as an experimental intervention that should be applied to patients who are otherwise treatment-resistant. CONCLUSIONS Increasing evidence suggests that CBM is efficacious in the treatment of tics and psychiatric comorbidities in patients with GTS. The results of ongoing larger RCTs, such as CANNA-TICS (ClinicalTrials.gov Identifier: NCT03087201), will further clarify the role of CBM in the treatment of patients with GTS.
Distribution and risk factors of postoperative endophthalmitis in people with diabetes

Purpose: To evaluate (i) the distribution of postoperative endophthalmitis (POE) in patients who underwent cataract surgery, (ii) risk factors in diabetic versus nondiabetic patients, and (iii) distribution of POE in those who had undergone rapid reduction of preoperative blood sugar levels versus those with normal blood sugar levels. Methods: Medical records were reviewed from January 1995 to July 2021. In total, 391 eyes of 391 patients who developed POE after cataract surgery were studied. Patients with POE were divided into Group A, patients with diabetes (n = 128), and Group B, patients without diabetes (n = 263), and the associations of various clinical factors in the two groups were studied. Patients with diabetes with raised random blood sugars (RBS) preoperatively were subjected to a rapid reduction of blood sugar (RBS <200 mg%) to be considered eligible for surgery. Microbiological profile of patients was examined. Results: The cumulative incidence of POE over 26 years was 0.09%. Those who underwent a rapid reduction in preoperative blood sugar levels had higher rates of POE (53.1%) compared with (46.9%) those with blood sugar levels under control (P = 0.486). Men with diabetes had 1.634 times higher odds of POE (P = 0.048), and those with diabetes and hypertension had 3.961 times greater odds of having POE (P < 0.001) when adjusted for age, alcohol, smoking, and socioeconomic strata and presence of posterior capsule rupture. Positive culture results were observed in 45/128 (35%) patients with diabetes and 71/263 (27%) patients without diabetes. Staphylococcus epidermidis was the most commonly identified organism and was detected in 10/45 (22%) in those with diabetes and 21/71 (29%) in those without diabetes of all the culture-positive cases. Conclusion: In patients with POE, the odds are greater for men with diabetes, those with a history of hypertension, as well as those who undergo a rapid reduction of preoperative blood sugar.