Takshan/R1 huggingface dataset:
Differential Sampling of Visual Space in Ventral and Dorsal Early Visual Cortex.

A fundamental feature of cortical visual processing is the separation of visual processing for the upper and lower visual fields. In early visual cortex (EVC), the upper visual field is processed ventrally, with the lower visual field processed dorsally. This distinction persists into several category-selective regions of occipitotemporal cortex, with ventral and lateral scene-, face-, and object-selective regions biased for the upper and lower visual fields, respectively. Here, using an elliptical population receptive field (pRF) model, we systematically tested the sampling of visual space within ventral and dorsal divisions of human EVC in both male and female participants. We found that (1) pRFs tend to be elliptical and oriented toward the fovea with distinct angular distributions for ventral and dorsal divisions of EVC, potentially reflecting a radial bias; and (2) pRFs in ventral areas were larger (∼1.5×) and more elliptical (∼1.2×) than those in dorsal areas. These differences potentially reflect a tendency for receptive fields in ventral temporal cortex to overlap the fovea with less emphasis on precise localization and isotropic representation of space compared with dorsal areas. Collectively, these findings suggest that ventral and dorsal divisions of EVC sample visual space differently, likely contributing to and/or stemming from the functional differentiation of visual processing observed in higher-level regions of the ventral and dorsal cortical visual pathways. SIGNIFICANCE STATEMENT The processing of visual information from the upper and lower visual fields is separated in visual cortex. Although ventral and dorsal divisions of early visual cortex (EVC) are commonly assumed to sample visual space equivalently, we demonstrate systematic differences using an elliptical population receptive field (pRF) model. Specifically, we demonstrate that (1) ventral and dorsal divisions of EVC exhibit diverging distributions of pRF angle, which are biased toward the fovea; and (2) ventral pRFs exhibit higher aspect ratios and cover larger areas than dorsal pRFs. These results suggest that ventral and dorsal divisions of EVC sample visual space differently and that such differential sampling likely contributes to different functional roles attributed to the ventral and dorsal pathways, such as object recognition and visually guided attention, respectively.
Cumulative Doses to Brain and Other Critical Structures After Multisession Gamma Knife Stereotactic Radiosurgery for Treatment of Multiple Metastatic Tumors.

Purpose: Repeat stereotactic radiosurgery (SRS) is an attractive alternative to whole brain radiation therapy (WBRT) for treatment of recurrent brain metastases (BM). The purpose of this study is to determine the cumulative doses to the brain and critical normal structures in patients who underwent repeat courses of Gamma Knife (GK) SRS. Materials and methods: We retrospectively identified ten patients who received at least three GK-SRS sessions for multiply recurrent BM at our institution from 2013 to 2016. We used Velocity™ 3.1.0 software to co-register the magnetic resonance imaging images and the dose data of all treatment sessions for each patient. The cumulative doses to brain, lenses, eyes, brainstem, optic nerves, chiasm, and hippocampi were calculated. Dose-volume histograms, as well as the mean, median and maximum doses of these structures, were analyzed. Results: The median number of SRS was five sessions (range = 3-7 sessions) per patient over a median treatment span of 510 days (112-1,197 days), whereas the median number of metastatic tumors treated per patient was 25.0 (10-63). The median of the total tumor volume was 9.5 cc (2.3-75.9 cc). The median of the mean cumulative dose to the whole brain was 4.1 Gy (1.7-16.4 Gy). The medians of the maximum doses to the critical structures were as follows: brainstem, 6.1 Gy (2.2-28.9 Gy), chiasm, 3.9 Gy (1.8-10.8 Gy), right optic nerve, 2.9 Gy (1.2-9.0 Gy), and left optic nerve, 2.6 Gy (1.0-6.5 Gy). The medians of the mean and maximum cumulative doses to the hippocampi were 3.4 Gy (1.0-14.4 Gy) and 13.8 Gy (1.5-39.3 Gy), respectively. The median survival for the entire cohort was 26.7 months, and no patients developed radiation necrosis. Conclusion: Our study demonstrated that multisession GKSRS could be delivered with low cumulative doses to critical normal structures. Further studies are required to fully establish its role as an alternative treatment strategy to WBRT for the treatment of multiply recurrent BM.
Confident predictability: identifying reliable gene expression patterns for individualized tumor classification using a local minimax kernel algorithm.

BACKGROUND: Molecular classification of tumors can be achieved by global gene expression profiling. Most machine learning classification algorithms furnish global error rates for the entire population. A few algorithms provide an estimate of probability of malignancy for each queried patient but the degree of accuracy of these estimates is unknown. On the other hand local minimax learning provides such probability estimates with best finite sample bounds on expected mean squared error on an individual basis for each queried patient. This allows a significant percentage of the patients to be identified as confidently predictable, a condition that ensures that the machine learning algorithm possesses an error rate below the tolerable level when applied to the confidently predictable patients. RESULTS: We devise a new learning method that implements: (i) feature selection using the k-TSP algorithm and (ii) classifier construction by local minimax kernel learning. We test our method on three publicly available gene expression datasets and achieve significantly lower error rate for a substantial identifiable subset of patients. Our final classifiers are simple to interpret and they can make prediction on an individual basis with an individualized confidence level. CONCLUSIONS: Patients that were predicted confidently by the classifiers as cancer can receive immediate and appropriate treatment whilst patients that were predicted confidently as healthy will be spared from unnecessary treatment. We believe that our method can be a useful tool to translate the gene expression signatures into clinical practice for personalized medicine.
7 versus 14 days of antibiotic treatment for critically ill patients with bloodstream infection: a pilot randomized clinical trial.

BACKGROUND: Shorter-duration antibiotic treatment is sufficient for a range of bacterial infections, but has not been adequately studied for bloodstream infections. Our systematic review, survey, and observational study indicated equipoise for a trial of 7 versus 14 days of antibiotic treatment for bloodstream infections; a pilot randomized clinical trial (RCT) was a necessary next step to assess feasibility of a larger trial. METHODS: We conducted an open, pilot RCT of antibiotic treatment duration among critically ill patients with bloodstream infection across 11 intensive care units (ICUs). Antibiotic selection, dosing and route were at the discretion of the treating team; patients were randomized 1:1 to intervention arms consisting of two fixed durations of treatment - 7 versus 14 days. We recruited adults with a positive blood culture yielding pathogenic bacteria identified while in ICU. We excluded patients with severe immunosuppression, foci of infection with an established requirement for prolonged treatment, single cultures with potential contaminants, or cultures yielding Staphylococcus aureus or fungi. The primary feasibility outcomes were recruitment rate and adherence to treatment duration protocol. Secondary outcomes included 90-day, ICU and hospital mortality, relapse of bacteremia, lengths of stay, mechanical ventilation and vasopressor duration, antibiotic-free days, Clostridium difficile, antibiotic adverse events, and secondary infection with antimicrobial-resistant organisms. RESULTS: We successfully achieved our target sample size (n = 115) and average recruitment rate of 1 (interquartile range (IQR) 0.3-1.5) patient/ICU/month. Adherence to treatment duration was achieved in 89/115 (77%) patients. Adherence differed by underlying source of infection: 26/31 (84%) lung; 18/29 (62%) intra-abdominal; 20/26 (77%) urinary tract; 8/9 (89%) vascular-catheter; 4/4 (100%) skin/soft tissue; 2/4 (50%) other; and 11/12 (92%) unknown sources. Patients experienced a median (IQR) 14 (8-17) antibiotic-free days (of the 28 days after blood culture collection). Antimicrobial-related adverse events included hepatitis in 1 (1%) patient, Clostridium difficile infection in 4 (4%), and secondary infection with highly resistant microorganisms in 10 (9%). Ascertainment was complete for all study outcomes in ICU, in hospital and at 90 days. CONCLUSION: It is feasible to conduct a RCT to determine whether 7 versus 14 days of antibiotic treatment is associated with comparable 90-day survival. TRIAL REGISTRATION: ClinicalTrials.gov , identifier: NCT02261506 . Registered on 26 September 2014.
Environmental and economic benefits of variable rate nitrogen fertilization in a nitrate vulnerable zone.

Agronomic input and management practices have traditionally been applied uniformly on agricultural fields despite the presence of spatial variability of soil properties and landscape position. When spatial variability is ignored, uniform agronomic management can be both economically and environmentally inefficient. The objectives of this study were to: i) identify optimal N fertilizer rates using an integrated spatio-temporal analysis of yield and site-specific N rate response; ii) test the sensitivity of site specific N management to nitrate leaching in response to different N rates; and iii) demonstrate the environmental benefits of variable rate N fertilizer in a Nitrate Vulnerable Zone. This study was carried out on a 13.6ha field near the Venice Lagoon, northeast Italy over four years (2005-2008). We utilized a validated crop simulation model to evaluate crop response to different N rates at specific zones in the field based on localized soil and landscape properties under rainfed conditions. The simulated rates were: 50kgNha(-1) applied at sowing for the entire study area and increasing fractions, ranging from 150 to 350kgNha(-1) applied at V6 stage. Based on the analysis of yield maps from previous harvests and soil electrical resistivity data, three management zones were defined. Two N rates were applied in each of these zones, one suggested by our simulation analysis and the other with uniform N fertilization as normally applied by the producer. N leaching was lower and net revenue was higher in the zones where variable rates of N were applied when compared to uniform N fertilization. This demonstrates the efficacy of using crop models to determine variable rates of N fertilization within a field and the application of variable rate N fertilizer to achieve higher profit and reduce nitrate leaching.
Tumor engraftment in nude mice and enrichment in stroma- related gene pathways predict poor survival and resistance to gemcitabine in patients with pancreatic cancer.

PURPOSE: The goal of this study was to evaluate prospectively the engraftment rate, factors influencing engraftment, and predictability of clinical outcome of low-passage xenografts from patients with resectable pancreatic ductal adenocarcinoma (PDA) and to establish a bank of PDA xenografts. EXPERIMENTAL DESIGN: Patients with resectable PDA scheduled for resection at the Johns Hopkins Hospital were eligible. Representative pieces of tumor were implanted in nude mice. The status of the SMAD4 gene and content of tumor-generating cells were determined by immunohistochemistry. Gene expression was carried out by using a U133 Plus 2.0 array. Patients were followed for progression and survival. RESULTS: A total of 94 patients with PDA were resected, 69 tumors implanted in nude mice, and 42 (61%) engrafted. Engrafted carcinomas were more often SMAD4 mutant, and had a metastatic gene expression signature and worse prognosis. Tumors from patients resistant to gemcitabine were enriched in stroma-related gene pathways. Tumors sensitive to gemcitabine were enriched in cell cycle and pyrimidine gene pathways. The time to progression for patients who received treatment with gemcitabine for metastatic disease (n = 7) was double in patients with xenografts sensitive to gemcitabine. CONCLUSION: A successful xenograft was generated in 61% of patients attempted, generating a pool of 42 PDA xenografts with significant biological information and annotated clinical data. Patients with PDA and SMAD4 inactivation have a better engraftment rate. Engraftment is a poor prognosis factor, and engrafted tumors have a metastatic gene expression signature. Tumors from gemcitabine-resistant patients were enriched in stromal pathways.
Host response transcriptional profiling reveals extracellular components and ABC (ATP-binding cassette) transporters gene enrichment in typhoid fever-infected Nigerian children.

BACKGROUND: Salmonella enterica serovar Typhi (S. Typhi) is a human-specific pathogen that causes typhoid fever, and remains a global health problem especially in developing countries. Its pathogenesis is complex and host response is poorly understood. In Africa, typhoid fever can be a major cause of morbidity in young infected children. The onset of the illness is insidious and clinical diagnosis is often unreliable. Gold standard blood culture diagnostic services are limited, thus rapid, sensitive, and affordable diagnostic test is essential in poor-resourced clinical settings. Routine typhoid fever vaccination is highly recommended but currently licensed vaccines provide only 55-75% protection. Recent epidemiological studies also show the rapid emergence of multi-drug resistant S. Typhi strains. High-throughput molecular technologies, such as microarrays, can dissect the molecular mechanisms of host responses which are S. Typhi-specific to provide a comprehensive genomic component of immunological responses and suggest new insights for diagnosis and treatment. METHODS: Global transcriptional profiles of S. Typhi-infected young Nigerian children were obtained from their peripheral blood and compared with that of other bacteremic infections using Agilent gene expression microarrays. The host-response profiles of the same patients in acute vs. convalescent phases were also determined. The top 96-100 differentially-expressed genes were identified and four genes were validated by quantitative real-time PCR. Gene clusters were obtained and functional pathways were predicted by DAVID (Database for Annotation, Visualization and Integrated Discovery). RESULTS: Transcriptional profiles from S. Typhi-infected children could be distinguished from those of other bacteremic infections. Enriched gene clusters included genes associated with extracellular peptides/components such as lipocalin (LCN2) and systemic immune response which is atypical in bacterial invasion. Distinct gene expression profiles can also be obtained from acute vs. convalescent phase during typhoid fever infection. We found novel down-regulation of ABC (ATP-binding cassette) transporters genes such as ABCA7, ABCC5, and ABCD4 and ATPase activity as the highest enriched pathway. CONCLUSIONS: We identified unique extracellular components and ABC transporters gene enrichments in typhoid fever-infected Nigerian children, which have never been reported. These enriched gene clusters may represent novel targeted pathways to improve diagnostic, prognostic, therapeutic and next-generation vaccine strategies for typhoid fever in Africa.
Chronic Chagas Cardiomyopathy Patients and Resynchronization Therapy: a Survival Analysis.

INTRODUCTION: Chagas disease represents an important health problem with socioeconomic impacts in many Latin-American countries. It is estimated that 20% to 30% of the people infected by Trypanosoma cruzi will develop chronic Chagas cardiomyopathy (CCC), which is generally accompanied by heart failure (HF). Cardiac resynchronization therapy (CRT) may be indicated for patients with HF and electromechanical dysfunctions. OBJECTIVE: The primary endpoint of this study was to analyze the response to CRT in patients with CCC, while the secondary endpoint was to estimate the survival rates of CRT responder patients. METHODS: This is an observational, cross-sectional and retrospective study. The records of 50 patients with CRT pacing devices implanted between June 2009 and March 2017 were analyzed. For statistical analyses, Pearson's correlation was used along with Student's t-test, and survival was analyzed using the Kaplan-Meier method. A P value of <0.05 was considered significant. RESULTS: Out of 50 patients, 56% were male, with a mean age of 63.4±13.3 years and an average CRT duration of 61.2±21.7 months. The mean QRS duration was 150.12±12.4 ms before and 116.04±2.2 ms after the therapy (P<0.001). The mean left ventricular ejection fractions (LVEF) were 29±7% and 39.1±12.2% before and after CRT, respectively (P<0.001). A total of 35 (70%) patients had a reduction of at least one New York Heart Association (NYHA) functional class after six months of therapy (P=0.014). The survival rate after 72 months was 45%. CONCLUSION: This study showed clinical improvement and a nonsignificant survival rate in patients with CCC after the use of CRT.
Efficacy of T-DM1 for leptomeningeal and brain metastases in a HER2 positive metastatic breast cancer patient: new directions for systemic therapy - a case report and literature review.

BACKGROUND: Herein, we report a complete response after whole brain radiotherapy (WBRT) and concomitant T-DM1 in a patient with HER2-positive metastatic breast cancer (MBC) and extensive brain and leptomeningeal involvement. CASE PRESENTATION: A 46 years old Caucasian woman with HER2-positive MBC and no baseline CNS involvement, started in August 2015 1st line therapy with Pertuzumab-Trastuzumab-Docetaxel, with partial response. However, in April 2016 the patient eventually progressed with emergence of brain and leptomeningeal metastases. Hence, she started in May 2016 2nd line therapy with T-DM1 and concomitant WBRT, with complete response (CR) after 3 courses of therapy, with complete resolution of neurological symptoms and no relevant toxicities. The CR is lasting over 13 months and the patient is out of corticosteroid use. CONCLUSIONS: To the best of our knowledge, this is the first case reporting interesting antitumor activity of T-DM1 and concomitant WBRT in both brain and leptomeningeal metastases, with a favorable safety profile and prolonged extracranial disease control. Further prospective studies should confirm these findings.
Predicting the Risk of New Cerebral Lesions After Stereotactic Radiosurgery (SRS) for Brain Metastases from Breast Cancer.

AIM: To generate a tool that estimates the probability of developing new cerebral metastases after stereotactic radiosurgery (SRS) in breast cancer patients. PATIENTS AND METHODS: SRS dose plus seven characteristics (age, performance score, number of cerebral metastases, maximum diameter of all metastases, location of metastases, extra-cerebral spread and time from breast cancer diagnosis until SRS) were analyzed regarding their ability to predict the probability of new cerebral metastases development following SRS. For those characteristics deemed significant, points of 0 (higher risk of new lesions) or 1 (lower risk) were given. Scores were generated by adding the points of significant characteristics. RESULTS: Performance score (p=0.013) and maximum diameter of all metastases (p=0.022) were associated with development of subsequent brain metastases. Two groups were created, 0-1 and 2 points. Freedom from new cerebral metastases rates were 27% and 92%, respectively, at 15 months (p=0.003). CONCLUSION: This tool helps select breast cancer with few cerebral metastases receiving SRS who may benefit from additional whole-brain irradiation.
Lipiodol versus diaphragm in 4D-CBCT-guided stereotactic radiotherapy of hepatocellular carcinomas.

Lipiodol versus Zwerchfell in 4D-CBCT-geführter stereotaktischer Strahlentherapie bei hepatozellulären Karzinomen. PURPOSE: The purpose of this work was to investigate the potential of lipiodol as a direct tumor surrogate alternative to the diaphragm surrogate on four-dimensional cone-beam computed tomography (4D-CBCT) image guidance for stereotactic radiotherapy of hepatocellular carcinomas. METHODS: A total of 29 hepatocellular carcinomas (HCC) patients treated by stereotactic radiotherapy following transarterial chemoembolization (TACE) with homogeneous or partial defective lipiodol retention were included. In all, 4-7 pretreatment 4D-CBCT scans were selected for each patient. For each scan, either lipiodol or the diaphragm was used for 4D registration. Resulting lipiodol/diaphragm motion ranges and position errors relative to the reconstructed midventilation images were analyzed to obtain the motion variations, and group mean (ΔM), systematic (Σ), and random (σ) errors of the treatment setup. RESULTS: Of the lipiodolized tumors, 55 % qualified for direct localization on the 4D-CBCT. Significant correlations of lipiodol and diaphragm positions were found in the left-right (LR), craniocaudal (CC), and anteroposterior (AP) directions. ΔM and σ obtained with lipiodol and diaphragm were similar, agreed to within 0.5 mm in the LR and AP, and 0.3 mm in the CC directions, and Σ differed by 1.4 (LR), 1.1 (CC), and 0.6 (AP) mm. Variations of diaphragm motion range > 5 mm were not observed with lipiodol and in one patient with diaphragm. The margin required for the tumor prediction error using the diaphragm surrogate was 6.7 (LR), 11.7 (CC), and 4.1 (AP) mm. CONCLUSION: Image-guidance combining lipiodol with 4D-CBCT enabled accurate localization of HCC and thus margin reduction. A major limitation was the degraded lipiodol contrast on 4D-CBCT.
Local tumor control probability modeling of primary and secondary lung tumors in stereotactic body radiotherapy.

BACKGROUND AND PURPOSE: To evaluate whether local tumor control probability (TCP) in stereotactic body radiotherapy (SBRT) varies between lung metastases of different primary cancer sites and between primary non-small cell lung cancer (NSCLC) and secondary lung tumors. MATERIALS AND METHODS: A retrospective multi-institutional (n=22) database of 399 patients with stage I NSCLC and 397 patients with 525 lung metastases was analyzed. Irradiation doses were converted to biologically effective doses (BED). Logistic regression was used for local tumor control probability (TCP) modeling and the second-order bias corrected Akaike Information Criterion was used for model comparison. RESULTS: After median follow-up of 19months and 16months (n.s.), local tumor control was observed in 87.7% and 86.7% of the primary and secondary lung tumors (n.s.), respectively. A strong dose-response relationship was observed in the primary NSCLC and metastatic cohort but dose-response relationships were not significantly different: the TCD90 (dose to achieve 90% TCP; BED of maximum planning target volume dose) estimates were 176Gy (151-223) and 160Gy (123-237) (n.s.), respectively. The dose-response relationship was not influenced by the primary cancer site within the metastatic cohort. CONCLUSIONS: Dose-response relationships for local tumor control in SBRT were not different between lung metastases of various primary cancer sites and between primary NSCLC and lung metastases.