Improving lab-of-origin prediction of genetically engineered plasmids via deep metric learning.

Genome engineering is undergoing unprecedented development and is now becoming widely available. Genetic engineering attribution can make sequence-lab associations and assist forensic experts in ensuring responsible biotechnology innovation and reducing misuse of engineered DNA sequences. Here we propose a method based on metric learning to rank the most likely labs of origin while simultaneously generating embeddings for plasmid sequences and labs. These embeddings can be used to perform various downstream tasks, such as clustering DNA sequences and labs, as well as using them as features in machine learning models. Our approach employs a circular shift augmentation method and can correctly rank the lab of origin 90% of the time within its top-10 predictions. We also demonstrate that we can perform few-shot learning and obtain 76% top-10 accuracy using only 10% of the sequences. Finally, our approach can also extract key signatures in plasmid sequences for particular labs, allowing for an interpretable examination of the model's outputs.

Measurement of isoagglutinins in immunoglobulins for intravenous application by flow cytometry.

Isoagglutinins present in intravenous immunoglobulin (IVIG) products have been linked to haemolysis. Therefore, accurately assessing isoagglutinin content in IVIG products is important. The standard European Pharmacopoeia (Ph.Eur.) direct assay is limited by low precision. Here, we describe the development of a fluorescence-activated cell sorting (FACS) method for assessing isoagglutinin levels. Serially diluted IVIG samples were incubated with red blood cells (RBCs), RBC-bound anti-A and anti-B antibodies were detected using a fluorescently-labelled antibody and the median fluorescence intensity of samples was assessed by FACS. Results were compared with the Ph.Eur. direct assay. The method was used to determine isoagglutinins in commercial products produced with and without isoagglutinin reduction steps. Assay precision, reported as the coefficient of variation, for the FACS method was 14% and 8% for anti-A and anti-B, respectively versus 33% and 20% with the Ph.Eur. direct assay. Application of the method on commercially available IVIGs revealed differences in isoagglutinin content between products produced with and without isoagglutinin reduction steps. This FACS assay allows for quantification of isoagglutinin concentrations in IVIGs with higher precision than the Ph.Eur. direct assay. Also the FACS assay confirms differences in isoagglutinin levels between IVIG products and the efficacy of isoagglutinin reduction measures.

Laparoscopic approach for a spontaneous posterior rectus sheath hernia.

Spontaneous posterior rectus sheath hernia is perhaps one of the rarest hernias described only in a few published cases. We present the case of a small bowel herniation through the posterior rectus sheath in a woman without previous abdominal surgical history, resulting in acute small bowel obstruction who was successfully treated by laparoscopy. This is the first case report of this kind of hernia managed with laparoscopic technique. Although the laparoscopic approach is not considered standard treatment for strangulated hernias, in selected cases, it allows the identification and repair of the defect.

Laparoscopic deroofing of a ruptured hepatic cyst presenting as an acute abdomen.

The rupture of a nonparasitic hepatic cyst is a rare complication for which there is no optimal treatment strategy yet. Laparoscopic deroofing is the standard approach for the elective treatment of symptomatic NHCs but it has seldom been described as an option for a ruptured hepatic cyst. The authors report a case of a male patient presenting to the emergency room with an acute abdomen caused by the rupture of a hepatic cyst. The patient was successfully treated by urgent laparoscopic deroofing of the cyst. Laparoscopic surgery can be a valid option for treating urgent cases presenting the same efficacy and less morbidity than open surgery.

Isoagglutinin Reduction in Human Immunoglobulin Products by Donor Screening.

INTRODUCTION: Hemolysis is considered a class effect and a rare adverse event that can occur following therapy with human normal immunoglobulin for intravenous administration [i.e., intravenous immunoglobulin (IVIG)]. Anti-A/B isoagglutinins (also referred to as isohemagglutinins) originating from donor plasma are present in polyvalent immunoglobulin G (IgG) products and are considered a probable risk factor for hemolysis. We hypothesized that, by excluding plasma from donors with high isoagglutinin titers, the final IVIG product would have a meaningful reduction in anti-A/B isoagglutinin titers. METHODS: A method for screening donor plasma for anti-A isoagglutinins using an automated indirect agglutination test (IAT) was developed. A cut-off for donor plasma exclusion was defined. Industry-scale donor plasma pools and final IVIG product were prepared according to the manufacturing process of Privigen(®) (CSL Behring, Berne, Switzerland; human 10% liquid IVIG). Anti-A/B isoagglutinin content in pooled plasma and final IVIG product was measured by IAT, direct agglutination test, and a flow cytometry-based assay [fluorescence-activated cell sorting (FACS) anti-A]. RESULTS: Screening of plasma from 705 donors identified 48 (6.8%) donors with high anti-A isoagglutinin titers in plasma (IAT agglutination score ≥2+ in a 1:200 pre-dilution). Exclusion of plasma from these donors resulted in a one-titer-step reduction of anti-A isoagglutinin in pooled plasma, confirmed by a twofold anti-A isoagglutinin concentration reduction measured by FACS anti-A (1,352 vs. 2,467 µg/g IgG). When the same screening and exclusion were applied to industrial-scale plasma pools (resulting in the exclusion of plasma from 5% of donors), anti-A isoagglutinins were reduced by one titer step in the final IVIG product. Anti-B isoagglutinins were also reduced by one titer step, as many donors with high anti-A isoagglutinins also have high anti-B. CONCLUSION: Reduction of anti-A/B isoagglutinin titers in IVIG products on an industrial scale is feasible through implementation of anti-A donor screening, which may reduce the risk of hemolysis following IVIG therapy.

Injúria Renal Aguda (IRA): evolução de um conceito / Acute renal injury (ARI): evolution of a concept

O termo injúria (dano ou lesão) renal aguda é, atualmente, o recomendado para definir alterações agudas na função renal. O último consenso publicado pelo KDIGO utiliza a creatinina sérica e o débito urinário na classificação da síndrome. O artigo é uma revisão sobre aspectos desta síndrome que está relacionada a significativa mortalidade.

Acute kidney injury is the recommended term to define acute changes in renal function. The last KDIGO consensus recommend the use of serum creatinine and the urinary output in its classification. The present paper review some aspects of this syndrome that is associated with significant mortality.

Vitiligo / Vitilig

O vitiligo é uma leucodermia adquirida relativamente comum, afetando cerca de 1% da população. É caracterizada por máculas acrômicas distribuídas pela superfície cutânea. Essa dermatose pode estar associada a diversas doenças ou apresentar-se isoladamente. Sua prevalência e impacto na qualidade de vida dos pacientes torna extremamente importante, para o dermatologista e para o clinico, o conhecimento sobre suas manifestações e opções disponíveis de tratamento.

Dermatozoonoses por artrópodes / Dermatozoonoses by arthropods

Ectoparasitoses são doenças causadas por certas espécies do filo Artropoda. Têm sua importância clinica devido à distribuição global dos artrópodes, fazendo parte da rotina de muitos serviços médicos ao redor do globo.Podem ser classificados como exclusivas do homem (parasitárias) e não exclusivas do homem (não-parasitárias) e têm como seu local de infecção a pele do indivíduo, de maneira a produzir doença direta ou indiretamente (ex: peste, infecção bacteriana secundária, etc). Dentre as principais ectoparasitoses, destacamos a Escabiose, Pediculose, Tungíase, Fitiríase e Miíase-as quais trataremos de abordar no presente estudo, descrevendo suas apresentações clinicas, seus diagnósticos e tratamentos.