Generalized Property-Based Encoders and Digital Signal Processing Facilitate Predictive Tasks in Protein Engineering.

Computational methods in protein engineering often require encoding amino acid sequences, i.e., converting them into numeric arrays. Physicochemical properties are a typical choice to define encoders, where we replace each amino acid by its value for a given property. However, what property (or group thereof) is best for a given predictive task remains an open problem. In this work, we generalize property-based encoding strategies to maximize the performance of predictive models in protein engineering. First, combining text mining and unsupervised learning, we partitioned the AAIndex database into eight semantically-consistent groups of properties. We then applied a non-linear PCA within each group to define a single encoder to represent it. Then, in several case studies, we assess the performance of predictive models for protein and peptide function, folding, and biological activity, trained using the proposed encoders and classical methods (One Hot Encoder and TAPE embeddings). Models trained on datasets encoded with our encoders and converted to signals through the Fast Fourier Transform (FFT) increased their precision and reduced their overfitting substantially, outperforming classical approaches in most cases. Finally, we propose a preliminary methodology to create de novo sequences with desired properties. All these results offer simple ways to increase the performance of general and complex predictive tasks in protein engineering without increasing their complexity.

Coristoma pancreático en la vesícula biliar: Reporte de dos casos / Pancreatic choristoma in the gallbladder: Report of two cases

Pancreatic choristoma is the ocurrence of normal pancreatic tissue in an abnormal location without any anatomic continuity with the main body of the gland. Although heterotopia is uncommon in the gallbladder and biliary tract, anecdotic cases of gastric mucosa, liver, adrenal gland and pancreas among other tissues have been described. We report an eight year-old male and a 22 year-old female, electively operated for symptomatic cholelithiasis. On pathology, a nodule identified as a pancreatic endocrine and exocrine choristoma, was found in the gallbladder wall of both patients. We employed immunohistochemistry to characterize this choristoma. Tubular and epithelial structures were immunoreactive to cytokeratins 7, 8, 18, 19 and 20 and to CA19-9. Exocrine activity was documented by immunoreactivity to al-antitrypsin and al-chemotrypsin. Other immunohistochemical markers such as insulin and somatostatin were positive identifying endocrine activity.

Predictive value of white blood cell count and C-reactive protein in children with appendicitis.

BACKGROUND/PURPOSE: Few studies have addressed the predictive value of white blood cells (WBCs) and C-reactive protein (CRP) at different cutoff values in appendicitis. Our purpose was to determine the cutoff values for WBC and CRP at different periods during clinical evolution of appendicitis and to establish their use for the diagnosis of appendicitis and differentiation of simple from perforated appendicitis. METHODS: We studied 198 patients operated on for appendicitis, which were further divided into 4 subgroups according to the time from the onset of symptoms to diagnosis. Receiver operating characteristic curves were constructed for CRP and WBC; the best cutoff points were used to calculate the sensitivity and specificity to discriminate patients with and without appendicitis and patients with simple and perforated appendicitis. RESULTS: White blood cell and CRP individually and together had a high sensitivity to differentiate patients with and without appendicitis. The specificity of WBC and CRP taken individually and together to differentiate patients with simple and perforated appendicitis was high, but the sensitivity was low. CONCLUSIONS: White blood cell and CRP could be used to support the clinical diagnosis of appendicitis, and, depending on the time from the onset of symptoms to diagnosis, to differentiate patients with and without appendicitis and discriminate simple from perforated appendicitis.

Coristoma hepático en la pared de la vesícula biliar: report of one case / Hepatic choristoma in the gallbladder wall

El tejido hepático heterotópico es una condición poco común que se identifica con mayor frecuencia durante la exploración quirúrgica del abdomen por otras indicaciones. Describimos un caso de tejido hepático heterotópico localizado en la pared externa de la vesícula biliar de un paciente masculino de 47 años de edad, en el cual se realizó una colecistectomía laparoscópica porcolelitiasis sintomática. El reporte histopatológico informa de cambios crónicos en la pared vesicular y leve infiltrado linfocitario difuso en el corion de la mucosa y muscularis mucosae sin compromiso inflamatorio o infiltración por otros tejidos. El nodulo hepático compromete solo la serosa y mide 12x8x6 mm, la arquitectura es típica del parénquima hepático con su arquitectura lobulillar conservada y leve hiperemia centrolobulillar difusa. Aún cuando el coristoma hepático de nuestro paciente constituye un hallazgo inesperado, es importante destacar las implicaciones patológicas de este tejido y el potencial de malignidad asociado al mismo.

Occult pancreaticobiliary reflux in gallbladder cancer and benign gallbladder diseases.

BACKGROUND AND OBJECTIVES: It was proposed that occult pancreaticobiliary reflux (OPBR) was associated with precancerous mucosal changes in the gallbladder, hence the importance of this disorder. There are no published reports investigating the incidence of OPBR in patients operated on for the entire spectrum of benign gallbladder diseases and gallbladder cancer. Our aim was to determine the incidence of OPBR and measure the levels of active pancreatic enzymes (amylase and lipase) in gallbladder bile of patients undergoing cholecystectomy for benign and malignant gallbladder diseases. METHODS: One hundred eight patients with normal pancreaticobiliary junction evidenced by operative cholangiography were included in the study. RESULTS: According to gallbladder bile amylase and lipase levels, 84.2% and 89% patients respectively had OPBR. OPBR was present in all gallbladder cancer patients; in these patients the biliary levels of amylase and lipase were significantly higher than the levels found in patients with benign gallbladder pathology (P < 0.0001). CONCLUSIONS: OPBR could lead to inflammatory changes of the biliary epithelium and progress towards the development of precancerous mucosal changes and gallbladder cancer. The reason why such high levels of pancreatic enzymes are regurgitated into the biliary tree of patients with gallbladder cancer should be clarified.

[Pancreatic choristoma in the gallbladder: report of two cases]. / Coristoma pancreático en la vesícula biliar: reporte de dos casos.

Pancreatic choristoma is the occurrence of normal pancreatic tissue in an abnormal location without any anatomic continuity with the main body of the gland. Although heterotopia is uncommon in the gallbladder and biliary tract, anecdotic cases of gastric mucosa, liver, adrenal gland and pancreas among other tissues have been described. We report an eight year-old male and a 22 year-old female, electively operated for symptomatic cholelithiasis. On pathology, a nodule identified as a pancreatic endocrine and exocrine choristoma, was found in the gallbladder wall of both patients. We employed immunohistochemistry to characterize this choristoma. Tubular and epithelial structures were immunoreactive to cytokeratins 7, 8, 18, 19 and 20 and to CA19-9. Exocrine activity was documented by immunoreactivity to al-antitrypsin and al-chemotrypsin. Other immunohistochemical markers such as insulin and somatostatin were positive identifying endocrine activity.