A bacterial sensor taxonomy across earth ecosystems for machine learning applications.

Microbial communities have evolved to colonize all ecosystems of the planet, from the deep sea to the human gut. Microbes survive by sensing, responding, and adapting to immediate environmental cues. This process is driven by signal transduction proteins such as histidine kinases, which use their sensing domains to bind or otherwise detect environmental cues and "transduce" signals to adjust internal processes. We hypothesized that an ecosystem's unique stimuli leave a sensor "fingerprint," able to identify and shed insight on ecosystem conditions. To test this, we collected 20,712 publicly available metagenomes from Host-associated, Environmental, and Engineered ecosystems across the globe. We extracted and clustered the collection's nearly 18M unique sensory domains into 113,712 similar groupings with MMseqs2. We built gradient-boosted decision tree machine learning models and found we could classify the ecosystem type (accuracy: 87%) and predict the levels of different physical parameters (R2 score: 83%) using the sensor cluster abundance as features. Feature importance enables identification of the most predictive sensors to differentiate between ecosystems which can lead to mechanistic interpretations if the sensor domains are well annotated. To demonstrate this, a machine learning model was trained to predict patient's disease state and used to identify domains related to oxygen sensing present in a healthy gut but missing in patients with abnormal conditions. Moreover, since 98.7% of identified sensor domains are uncharacterized, importance ranking can be used to prioritize sensors to determine what ecosystem function they may be sensing. Furthermore, these new predictive sensors can function as targets for novel sensor engineering with applications in biotechnology, ecosystem maintenance, and medicine.IMPORTANCEMicrobes infect, colonize, and proliferate due to their ability to sense and respond quickly to their surroundings. In this research, we extract the sensory proteins from a diverse range of environmental, engineered, and host-associated metagenomes. We trained machine learning classifiers using sensors as features such that it is possible to predict the ecosystem for a metagenome from its sensor profile. We use the optimized model's feature importance to identify the most impactful and predictive sensors in different environments. We next use the sensor profile from human gut metagenomes to classify their disease states and explore which sensors can explain differences between diseases. The sensors most predictive of environmental labels here, most of which correspond to uncharacterized proteins, are a useful starting point for the discovery of important environment signals and the development of possible diagnostic interventions.

The divided zygoma: a meta-analysis of its prevalence with a review of the literature.

BACKGROUND: Divided zygoma (DZ) is an important structure in the midfacial region. The anatomy of DZ is poorly researched, but knowledge about this entity could be useful during posttraumatic facial reconstructions. The aim of this study was to estimate the prevalence and anatomy of DZ in different regions around the world. Therefore, the authors performed a meta-analysis, including all studies that report extractable data on the DZ. MATERIALS AND METHODS: The main online medical databases such as PubMed, EBSCO, ScienceDirect, Web of Science, SciELO, BIOSIS, Current Content Connect, Korean Journal Database and Russian Citation Index, were utilised to gather all studies on anatomical characteristics, prevalence, symmetry, and a number of divisions of zygomatic bone. RESULTS: A total of 20 studies were included in this meta-analysis. Data were grouped and analysed in five categories: (1) prevalence of DZ bone, (2) prevalence of DZ skulls, (3) gender prevalence of DZ with sides, (4) divisions of zygomatic bone, (5) symmetry of DZ. CONCLUSIONS: In conclusion, the authors of the present study believe that this study can be considered an up-to-date meta-analysis regarding the prevalence, divisions, and symmetricity of the DZ. The data provided by the present study may be useful information for physicians in recognizing the DZ of the fracture and may be important information during zygomatic bone osteotomy. Detailed anatomical knowledge of the midfacial region can prevent surgical complications when operating in this area.

The cranio-orbital foramen: a meta-analysis with a review of the literature.

BACKGROUND: The goal of the present study was to provide accurate data on the prevalence and morphometrical aspects of the cranio-orbital foramen (COF), which can surely be of use by surgeons performing procedures on the lateral orbit. Furthermore, the embryology and the clinical significance of this osseous structure were thoroughly discussed. MATERIALS AND METHODS: Major online medical databases such as PubMed, Scopus, Embase, Web of Science, and Google Scholar were searched to find all relevant studies regarding COF. RESULTS: Eventually, a total of 25 studies that matched the required criteria and contained complete and relevant data were included in this meta-analysis. The pooled prevalence of COF was found to be 48.37% (95% confidence interval [CI]: 41.67-55.10%). The occurrence of the COF unilaterally was set to be 71.92% (95% CI: 41.87-96.97%). The occurrence of the COF bilaterally was set at 26.08% (95% CI: 3.03-58.13%). CONCLUSIONS: In conclusion, we believe that this is the most accurate and up-to- -date study regarding the anatomy of the COF. The COF is prevalent in 48.37% of the cases, and it is most frequently unilateral (73.92%). Furthermore, the prevalence of accessory COFs was found to be 16.72%. The presence of these foramina may represent a source of haemorrhage that ophthalmic surgeons should be aware of when performing procedures in the lateral part of the orbit.

Estudio epidemiológico observacional prospectivo del manejo del dolor en pacientes oncológicos en tratamiento radioterápico: estudio GORVAMUR / Pain management in cancer patients receiving radiotherapy: GORVAMUR study, a prospective, observational, epidemiological study

Objetivos: Estudiar el manejo del dolor irruptivo en pacientes de oncología radioterápica que lo experimentan, y su impacto en el control analgésico del mismo, la tolerabilidad de los tratamientos analgésicos utilizados, así como la satisfacción y el impacto en la calidad de vida del paciente. Material y métodos: Estudio epidemiológico, observacional, prospectivo, multicéntrico, en pacientes con diagnóstico de cáncer y dolor de origen oncológico tratado con una pauta analgésica de 3er escalón, que iniciaron un tratamiento con radioterapia (RT) susceptible de que el oncólogo modificara su control analgésico. Los pacientes se reclutaron de 15 servicios de Oncología Radioterápica procedentes de centros de las regiones de Valencia y Murcia entre mayo de 2013 y diciembre de 2014. Basalmente se recogieron: datos sociodemográficos, caracterización del proceso oncológico y del dolor, tratamiento analgésico y tipo, y dosis/intensidad de la RT empleada. Al mes y a los tres meses se caracterizó el dolor mediante la valoración del cambio en la dimensión del dolor del cuestionario breve de dolor (CBD) y de la cantidad de dolor producido por episodios de dolor irruptivo, el nivel de satisfacción, la calidad de vida (EuroQol-5D) y la tolerabilidad al tratamiento analgésico. Resultados: Los pacientes incluidos en el análisis (n = 49) fueron mayoritariamente hombres (72,3 %) y la edad media (± desviación estándar) 63,7 ± 11,5 años. En el 26,5 % de los pacientes el tumor se encontraba en pulmón y en el 28,6 % en cabeza y cuello. Todos, excepto uno, refirieron dolor en el momento de la visita basal (20,8 % debido al tumor primario, 54,2 % metástasis y en 22,9 % tratamiento con RT). La mediana (Q1-Q3) del número de crisis al día fue 3,0 (2-4,5). El 60,4 % estaban recibiendo tratamiento para el dolor irruptivo, siendo fentanilo el principio activo más frecuentemente utilizado (70,4 %). Las estrategias para manejar el dolor fueron: refuerzo/modificación de analgésicos de larga duración (30,4 %), corta duración (21,7 %), ambos (21,7 %) o disminución/supresión en analgésicos de acción rápida o de larga (26,1 %). Independientemente de la estrategia, se observa una disminución en cuanto al "máximo dolor", y la cantidad total de dolor entre las 3 visitas, y una mejoría en cuanto a la "calidad de vida", "ganancia de salud" y la "satisfacción global del tratamiento". Solo se reportaron dos reacciones adversas. Conclusiones: El dolor irruptivo en los pacientes oncológicos en tratamiento de radioterapia, constituye un síntoma de elevada prevalencia. No hay una estrategia analgésica predominante para el manejo de estos pacientes, pero el fentanilo es el fármaco más frecuentemente utilizado. Los pacientes están satisfechos con el tratamiento y la reducción del dolor irruptivo repercute favorablemente en el estado general y calidad de vida de los pacientes (AU)

Objectives: To assess breakthrough pain management in patients at radiation oncology and its impact on pain control in these patients, as well as the tolerability of the analgesic treatments used and the satisfaction and impact on the quality of life of patients. Material and methods: An epidemiological, observational, prospective, multicentre study carried out in patients diagnosed with cancer and with cancer pain treated with a 3rd step analgesic therapy who had begun radiotherapy treatment (RT) susceptible to modification by an oncologist, for pain control. Patients were recruited from 15 Radiation Oncology Services centres from the regions of Valencia and Murcia between May 2013 and December 2014. Patient data collected included: demographic data, basal cancer process characterization and baseline pain, and information on basal analgesic treatment and RT employed. Pain level was recorded at 1 and 3 months by assessing: the change in the dimension of Brief Pain Inventory (BPI) pain and the amount of pain caused by episodes of breakthrough pain, the level of satisfaction, the quality of life (EQ-5D), and the tolerability to analgesic treatment. Results: Patients included in the analysis (n = 49) were mainly males (72.3 %) and the mean age (± Standard Deviation) was 63.7 ± 11.5 years. In 26.5 % of patients the tumours were located in lungs and 28.6 % in head and neck. All but one of the patients reported pain during the baseline visit (20.8 % due to the primary tumour, 54.2 % to metastases, and 22.9 % to RT treatment). The median (Q1-Q3) number of breakthrough crises/day was 3.0 (2-4.5). Overall, 60.4 % were receiving treatment for breakthrough pain and Fentanyl was the most commonly used drug (70.4 %). Pain management strategies were: reinforcement/modification of long-term analgesics (30.4%), reinforcement/modification of short-term analgesics (21.7%), reinforcement/modification of long-term and short-term analgesics (21.7 %), and decrease/suppression of any fast- or long-term analgesics (26.1 %). Independently from the strategy, a decrease in the maximum pain and the total amount of pain were observed over time, and an improvement during the follow-up visits was observed in the quality of life, health gain, and overall treatment satisfaction. Only two adverse reactions were reported. Conclusions: Breakthrough pain in cancer patients, who underwent radiotherapy treatment, is a symptom of high prevalence. There is no predominant analgesic strategy in the management of these patients, but Fentanyl is the drug most frequently used. Patients are very satisfied with the pharmacologic treatment and the reduction in the breakthrough pain obtained has a favourable effect on the global health status and quality of life of patients (AU)

Analysis of fiducial markers used for on-line verification in the external-beam radiotherapy of patients with cranial tumours.

PURPOSE: Evaluate the fiducial marker-based position verification in the external-beam radiotherapy of patients with cranial tumour. METHODS: Thirteen patients with intracranial tumours were treated with external- beam radiotherapy using 3 gold markers implanted in the skull. Before each fraction the patient was positioned on the treatment table and 2 orthogonal portal images were performed to localise the 3 gold seeds and the target position was calculated using a commercialised computer program (ISOLOC software, MEDTEC). This program provides the couch movements required to move the target to the isocentre. RESULTS: When the set-up error was corrected using the coordinates of the 3 markers, the final movements were less than 2 mm in all cases: lateral, mean v., 1.21 mm; longitudinal, 1.23 mm; and anteroposterior, 1.18 mm. No serious complications related to the gold marker insertion were noted. CONCLUSION: The use of 3 implanted fiducial seeds is an optimal technique for precise set-up in patients with brain tumours treated with external radiotherapy. This commercial system is highly suitable for fractionated stereotactic irradiation.

Analysis of fiducial markers used for on-line verification in the external-beam radiotherapy of patients with cranial tumours

PURPOSE: Evaluate the fiducial marker-based position verification in the external-beam radiotherapy of patients with cranial tumour. METHODS: Thirteen patients with intracranial tumours were treated with external- beam radiotherapy using 3 gold markers implanted in the skull. Before each fraction the patient was positioned on the treatment table and 2 orthogonal portal images were performed to localise the 3 gold seeds and the target position was calculated using a commercialised computer program (ISOLOC software, MEDTEC). This program provides the couch movements required to move the target to the isocentre. RESULTS: When the set-up error was corrected using the coordinates of the 3 markers, the final movements were less than 2 mm in all cases: lateral, mean v., 1.21 mm; longitudinal, 1.23 mm; and anteroposterior, 1.18 mm. No serious complications related to the gold marker insertion were noted. CONCLUSION: The use of 3 implanted fiducial seeds is an optimal technique for precise set-up in patients with brain tumours treated with external radiotherapy. This commercial system is highly suitable for fractionated stereotactic irradiation (AU)

[Effect of PSA nadir and the time to nadir in the disease-free period in localized prostatic carcinoma treated with radical radiation]. / Influencia del nadir de PSA y el tiempo a nadir en el periodo libre de enfermedad (PLE) del carcinoma prostático localizado tratado con irradiación radical.

OBJECTIVE: To evaluate the prognostic significance of PSA nadir (nPSA) and the time to nadir in disease free of recurrence (DFR) in localized carcinoma of prostate treated with radical radiotherapy (RTR). MATERIAL AND METHODS: From October 1984 to December 1998, 86 patients have been treated with prostate carcinoma. It was considered of Low risk those patients with PSA < or = 10 ng/ml, Gleason = 6 or stage T1-T2. Moderate risk: those with one elevated of the three parameters. High risk: two or more parameters. The treatment was carried out in a lineal accelerator using photons of 15 MV, with standard technique and frationation, administering a median dose of 66 Gy (58-75 Gy). It was defined disease free of recurrence (DFR), the time to clinical PSA or biochemical failure. This one was defined as the time starting from the date of nadir PSA to the second consecutive increase of PSA value after three separate serial measurements separated for at least one month. RESULTS: The median of initial PSA value was of 16 ng/ml (1-270), initial clinical stage T1-T2 (70p), stages T3-T4 (14p), and unknown in 2p. The median of Gleason score was 6 (2-10). According to the group of risk they were classified as: low risk in 16 patients (19%), moderated risk in 22 patients (26%), high risk in 21 patients (24%), and unknown in 27 patients (31%). Median nPSA value was 0.8 ng/ml (limits: 0-139) and the median time elapsed between the initial PSA and nPSA has been of 11 months (limits: 0-72 months). The actuarial DFR projected to five years in those patients with nPSA = 1 ng/ml was of 67% vs. 47% in patient with nPSA figures > 1 ng/ml (p = 0.0018). The PFD in patients with time to nadir (t nadir) < 12 months it was of 20% vs. 80% in patients with t nadir > 12 months (p < 0.0001). Multivariate analysis demonstrated that time to nadir (H.R: 0.11 p = 0.001), group of risk (H.R: 28.72 p = 0.020), and grade of differentiation (HR: 28.72 p = 0.010), were determinant to DFR. CONCLUSIONS: nPSA is an important factor to determine the objective response to radiotherapy. nPSA and time to nadir are prognostic factors that influences significantly on the DFR. The indication of adjuvant treatment in those patients with unfavorable prognostic factors such us those who do not reach nadir PSA < or = 1 ng/ml and time to nadir < or = 12 months, deserves the realization of a prospective study.

Successful use of intraoperative radiotherapy for local control of an Askin's tumor recurrence.

Askin s tumor is an infrequent disease, with a high tendency to local recurrence. We present the case of a 16-year-old female diagnosed with a new recurrence of this tumor affecting the thoracic wall. There had been a previous 5-year history of 3 local recurrences treated each time by apparently complete surgery. A multidisciplinary approach consisting of chemotherapy, complete chest tumor resection and intraoperative radiotherapy was undertaken. After 2-year follow-up, the patient is alive and free of disease. The role of surgery is still the key to obtaining good survival, but in this case intraoperative radiotherapy proved to be a good adjuvant treatment.

Influencia del nadir de PSA y el tiempo a nadir en el periodo libre de enfermedad (pie) del carcinoma prostatico localizado tratado con irradiación radical / Prognostic significance of PSA nadir and the time to nadir in disease free of recurrence in localized carcinoma of prostate treated with radical radiotherapy

Objetivo: Valorar el significado pronóstico del nadir de PSA (nPSA) y del tiempo a nadir en el periodo libre de enfermedad (PLE) del carcinoma de próstata localizado tratado con radioterapia radical (RTR). Material y métodos: Desde Octubre 1984 hasta Diciembre 1998 se han tratado 86 (p) con el diagnóstico de carcinoma de próstata. Se consideró de Bajo riesgo aquellos pacientes con PSA 1 ng/ml (p= 0,0018). El PLE a 5 años en pacientes con tiempo a nadir (t nadir) 12 meses (p<0,0001). El estudio multivariado demostró diferencias estadísticamente significativas para factores como tiempo t nadir (H.R: 0,11 p=0,001), grupos de riesgo (H.R: 28,72 p=0,020), y grado de diferenciación (HR: 28,72 p=0,010).Conclusiones: El nPSA es un factor importante para determinar la respuesta objetiva a la RT. El nPSA y t nadir son factores pronósticos que influyen significativamente sobre el PLE. La indicación de un tratamiento complementario en aquellos pacientes con factores pronósticos desfavorables como en el grupo que no llega a un nadir<= 1 ng/ml y en aquellos con tnadir menor de doce meses, merece la realización de un estudio prospectivo (AU)