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Although patient-derived xenografts (PDX) are commonly used for preclinical modeling in cancer research, a standard approach to in vivo tumor growth analysis and assessment of antitumor activity is lacking, complicating the comparison of different studies and determination of whether a PDX experiment has produced evidence needed to consider a new therapy promising. We present consensus recommendations for assessment of PDX growth and antitumor activity, providing public access to a suite of tools for in vivo growth analyses. We expect that harmonizing PDX study design and analysis and assessing a suite of analytical tools will enhance information exchange and facilitate identification of promising novel therapies and biomarkers for guiding cancer therapy.

Development of multicellular organisms is orchestrated by persistent cell–cell communication between neighboring partners. Direct interaction between different cell types can induce molecular signals that dictate lineage specification and cell fate decisions. Current single-cell RNA-seq technology cannot adequately analyze cell–cell contact-dependent gene expression, mainly due to the loss of spatial information. To overcome this obstacle and resolve cell–cell contact-specific gene expression during embryogenesis, we performed RNA sequencing of physically interacting cells (PIC-seq) and assessed them alongside similar single-cell transcriptomes derived from developing mouse embryos between embryonic day (E) 7.5 and E9.5. Analysis of the PIC-seq data identified gene expression signatures that were dependent on the presence of specific neighboring cell types. Our computational predictions, validated experimentally, demonstrated that neural progenitor (NP) cells upregulate Lhx5 and Nkx2-1 genes, when exclusively interacting with definitive endoderm (DE) cells. Moreover, there was a reciprocal impact on the transcriptome of DE cells, as they tend to upregulate Rax and Gsc when in contact with NP cells. Using individual cell transcriptome data, we formulated a means of computationally predicting the impact of one cell type on the transcriptome of its neighboring cell types. We have further developed a distinctive spatial-t-distributed stochastic neighboring embedding to display the pseudospatial distribution of cells in a 2-dimensional space. In summary, we describe an innovative approach to study contact-specific gene regulation during embryogenesis., Development of multicellular organisms is orchestrated by persistent cell–cell communication between neighboring partners. Direct interaction between different cell types can induce molecular signals that dictate lineage specification and cell fate decisions. Current single-cell RNA-seq technology cannot adequately analyze cell–cell contact-dependent gene expression, mainly due to the loss of spatial information. To overcome this obstacle and resolve cell–cell contact-specific gene expression during embryogenesis, we performed RNA sequencing of physically interacting cells (PIC-seq) and assessed them alongside similar single-cell transcriptomes derived from developing mouse embryos between embryonic day (E) 7.5 and E9.5. Analysis of the PIC-seq data identified gene expression signatures that were dependent on the presence of specific neighboring cell types. Our computational predictions, validated experimentally, demonstrated that neural progenitor (NP) cells upregulate Lhx5 and Nkx2-1 genes, when exclusively interacting with definitive endoderm (DE) cells. Moreover, there was a reciprocal impact on the transcriptome of DE cells, as they tend to upregulate Rax and Gsc when in contact with NP cells. Using individual cell transcriptome data, we formulated a means of computationally predicting the impact of one cell type on the transcriptome of its neighboring cell types. We have further developed a distinctive spatial-t-distributed stochastic neighboring embedding to display the pseudospatial distribution of cells in a 2-dimensional space. In summary, we describe an innovative approach to study contact-specific gene regulation during embryogenesis.

Development of multicellular organisms is orchestrated by persistent cell–cell communication between neighboring partners. Direct interaction between different cell types can induce molecular signals that dictate lineage specification and cell fate decisions. Current single-cell RNA-seq technology cannot adequately analyze cell–cell contact-dependent gene expression, mainly due to the loss of spatial information. To overcome this obstacle and resolve cell–cell contact-specific gene expression during embryogenesis, we performed RNA sequencing of physically interacting cells (PIC-seq) and assessed them alongside similar single-cell transcriptomes derived from developing mouse embryos between embryonic day (E) 7.5 and E9.5. Analysis of the PIC-seq data identified gene expression signatures that were dependent on the presence of specific neighboring cell types. Our computational predictions, validated experimentally, demonstrated that neural progenitor (NP) cells upregulate Lhx5 and Nkx2-1 genes, when exclusively interacting with definitive endoderm (DE) cells. Moreover, there was a reciprocal impact on the transcriptome of DE cells, as they tend to upregulate Rax and Gsc when in contact with NP cells. Using individual cell transcriptome data, we formulated a means of computationally predicting the impact of one cell type on the transcriptome of its neighboring cell types. We have further developed a distinctive spatial-t-distributed stochastic neighboring embedding to display the pseudospatial distribution of cells in a 2-dimensional space. In summary, we describe an innovative approach to study contact-specific gene regulation during embryogenesis., Development of multicellular organisms is orchestrated by persistent cell–cell communication between neighboring partners. Direct interaction between different cell types can induce molecular signals that dictate lineage specification and cell fate decisions. Current single-cell RNA-seq technology cannot adequately analyze cell–cell contact-dependent gene expression, mainly due to the loss of spatial information. To overcome this obstacle and resolve cell–cell contact-specific gene expression during embryogenesis, we performed RNA sequencing of physically interacting cells (PIC-seq) and assessed them alongside similar single-cell transcriptomes derived from developing mouse embryos between embryonic day (E) 7.5 and E9.5. Analysis of the PIC-seq data identified gene expression signatures that were dependent on the presence of specific neighboring cell types. Our computational predictions, validated experimentally, demonstrated that neural progenitor (NP) cells upregulate Lhx5 and Nkx2-1 genes, when exclusively interacting with definitive endoderm (DE) cells. Moreover, there was a reciprocal impact on the transcriptome of DE cells, as they tend to upregulate Rax and Gsc when in contact with NP cells. Using individual cell transcriptome data, we formulated a means of computationally predicting the impact of one cell type on the transcriptome of its neighboring cell types. We have further developed a distinctive spatial-t-distributed stochastic neighboring embedding to display the pseudospatial distribution of cells in a 2-dimensional space. In summary, we describe an innovative approach to study contact-specific gene regulation during embryogenesis.

Cells have evolved their communication methods to sense their microenvironments and send biological signals. In addition to communication using ligands and receptors, cells use diverse channels including gap junctions to communicate with their immediate neighbors. Current approaches, however, cannot effectively capture the influence of various microenvironments. Here, we propose a novel approach to investigate cell neighbor-dependent gene expression (CellNeighborEX) in spatial transcriptomics (ST) data. To categorize cells based on their microenvironment, CellNeighborEX uses direct cell location or the mixture of transcriptome from multiple cells depending on ST technologies. For each cell type, CellNeighborEX identifies diverse gene sets associated with partnering cell types, providing further insight. We found that cells express different genes depending on their neighboring cell types in various tissues including mouse embryos, brain, and liver cancer. Those genes are associated with critical biological processes such as development or metastases. We further validated that gene expression is induced by neighboring partners via spatial visualization. The neighbor-dependent gene expression suggests new potential genes involved in cell–cell interactions beyond what ligand-receptor co-expression can discover.

Cells have evolved their communication methods to sense their microenvironments and send biological signals. In addition to communication using ligands and receptors, cells use diverse channels including gap junctions to communicate with their immediate neighbors. Current approaches, however, cannot effectively capture the influence of various microenvironments. Here, we propose a novel approach to investigate cell neighbor-dependent gene expression (CellNeighborEX) in spatial transcriptomics (ST) data. To categorize cells based on their microenvironment, CellNeighborEX uses direct cell location or the mixture of transcriptome from multiple cells depending on ST technologies. For each cell type, CellNeighborEX identifies diverse gene sets associated with partnering cell types, providing further insight. We found that cells express different genes depending on their neighboring cell types in various tissues including mouse embryos, brain, and liver cancer. Those genes are associated with critical biological processes such as development or metastases. We further validated that gene expression is induced by neighboring partners via spatial visualization. The neighbor-dependent gene expression suggests new potential genes involved in cell–cell interactions beyond what ligand-receptor co-expression can discover.

Through a multicenter study, we collected seven cases of gastric plexiform fibromyxoma including four females and three males, 21 to 79 y old (46.1 ± 10.1). All cases showed a unilocular lesion measuring 0.3 to 17 cm (5.3 ± 2.4), arising from antrum (5/7) or body (2/7). Six of the seven cases had intraoperative frozen sections and/or endoscopic ultrasound fine needle aspiration (EUS-FNA), and all of them were preoperatively or intraoperatively diagnosed as gastrointestinal stromal tumor (GIST). EUS-FNA material showed markedly elongated spindle cells with streaming oval to elongated nuclei with rounded ends. Histologically, the tumors exhibited a plexiform growth pattern and were composed of a rich myxoid stroma and cytologically bland uniform spindle cells without mitotic figures, with the exception of one case which displayed nuclear pleomorphism and increased mitosis. Immunostains showed the tumor cells to be focally positive for SMA (6/6), focally and weakly positive for desmin (3/6) and caldesmon (2/3), negative for CD117 (0/7), CD34 (0/7), DOG1 (0/4), and S100 (0/5). No mutations were identified on Next-Generation Sequencing test, and no loss of SDHB immunoreactivity was identified in the tumor with nuclear pleomorphism. One case was treated with Gleevec because of the initial diagnosis of GIST. All patients had a follow-up for up to 11 y, with no tumor recurrence or metastasis reported. Our results suggest that gastric plexiform fibromyxoma is rare and may be underrecognized and misinterpreted as GIST during intraoperative frozen section or preoperative EUS-FNA diagnosis without immunostains leading to inappropriate treatment.

Through a multicenter study, we collected seven cases of gastric plexiform fibromyxoma including four females and three males, 21 to 79 y old (46.1 ± 10.1). All cases showed a unilocular lesion measuring 0.3 to 17 cm (5.3 ± 2.4), arising from antrum (5/7) or body (2/7). Six of the seven cases had intraoperative frozen sections and/or endoscopic ultrasound fine needle aspiration (EUS-FNA), and all of them were preoperatively or intraoperatively diagnosed as gastrointestinal stromal tumor (GIST). EUS-FNA material showed markedly elongated spindle cells with streaming oval to elongated nuclei with rounded ends. Histologically, the tumors exhibited a plexiform growth pattern and were composed of a rich myxoid stroma and cytologically bland uniform spindle cells without mitotic figures, with the exception of one case which displayed nuclear pleomorphism and increased mitosis. Immunostains showed the tumor cells to be focally positive for SMA (6/6), focally and weakly positive for desmin (3/6) and caldesmon (2/3), negative for CD117 (0/7), CD34 (0/7), DOG1 (0/4), and S100 (0/5). No mutations were identified on Next-Generation Sequencing test, and no loss of SDHB immunoreactivity was identified in the tumor with nuclear pleomorphism. One case was treated with Gleevec because of the initial diagnosis of GIST. All patients had a follow-up for up to 11 y, with no tumor recurrence or metastasis reported. Our results suggest that gastric plexiform fibromyxoma is rare and may be underrecognized and misinterpreted as GIST during intraoperative frozen section or preoperative EUS-FNA diagnosis without immunostains leading to inappropriate treatment.

Obesity is a known risk factor for PDA and recent reports suggest obesity has a negative impact on clinical outcomes in patients with PDA. Pretreatment body mass index (BMI) and serum albumin (SA) have been shown to be associated with worse overall survival in patients with advanced and metastatic PDA. However, minimal data exists on the impact of BMI and SA on perioperative and long-term clinical outcomes in patients with early-stage resected PDA. Herein, we report on the impact of these variables on perioperative clinical outcomes, overall survival (OS) and disease free survival (DFS) in patients with resected PDA. With IRB approval, we evaluated 1,545 patients with PDA treated at a single institution from 2007-2013 and identified 106 patients who underwent upfront resection with curative intent. BMI and SA were calculated preoperatively and at the time of last clinical evaluation. Influence of preoperative BMI, SA, change in either variable, and influence of other clinical and pathologic variables on perioperative morbidity and mortality was assessed. The impact of these variables on DFS and OS was assessed with cox regression modeling and ANOVA. Actuarial estimates for DFS and OS were calculated using Kaplan-Meier methods. Median follow up time was 16 months (3-89). Mean age was 68 years. Median survival was 14 months (3-65) and median time to recurrence was 11 months (1-79). Length of hospital stay was associated with BMI (p = .023), change in BMI (p = .003) and SA (p = .004). Post-operative transfusion rate was associated with SA (p = .021). There was a strong correlation between BMI change and positive margin (p = .04) and lymph node status (p = .01). On multivariate analysis, change in SA (p = .03) and node positivity (p = .008) were associated with decreased DFS. Additionally, preoperative SA (p = .023), node positivity (p = .026) and poor differentiation (p = .045) were associated with worse OS on multivariate analysis. Low preoperative SA was associated w

Sale of property of Jose Trevino to Henry Raguet. Signed by Henry Raguet, fiscal agent for the Republic; and Charles S. Taylor, signor of Texas Declaration of Independence.

Purpose. The purpose of the study was to determine whether the Individualized Criterion Referenced Test (ICRT) yields valid and reliable results of student reading achievement when its results are expressed in terms of Normal Curve Equivalents (NCEs). Delimitations. Pre and post NCEs from the ICRT and California Achievement Test (CAT) for the 1978-79 school year were examined. NCEs belonging to twenty students from each of the second, fourth, and sixth grade levels at the Santo Nino Elementary School were randomly selected. Santo Nino Elementary School was located in a low socio-economic neighborhood in Laredo, Texas. Null Hypotheses. The null hypotheses for the study were: (1) There is no statistically significant difference between pre-CAT and pre-ICRT reading achievement as measured by NCEs among second, fourth, and sixth grade students. (2) There is no statistically significant difference between post-CAT and post-ICRT reading achievement as measured by NCEs among second, fourth, and sixth grade students. (3) There is no statistically significant difference between pre- to post-CAT and ICRT reading gains as measured by NCEs among second grade students. (4) There is no statistically significant difference between pre- to post-CAT and ICRT reading gains as measured by NCEs among fourth grade students. (5) There is no statistically significant difference between pre- to post-CAT and ICRT reading gains as measured by NCEs among sixth grade students. (6) There is no statistically significant difference in pre- to post-CAT reading gains as measured by NCEs among second, fourth, and sixth grade students. (7) There is no statistically significant difference in pre- to post-ICRT reading gains as measured by NCEs among second, fourth, and sixth grade students. (8) There is no statistically significant test-retest reliability between pre-test and post-test administrations of the CAT and ICRT. (9) There is no statistically significant coefficient of correlation between the

This is the completed Mexican Wolf Recovery Plan. It has been approved by the U.S. Fish and Wildlife Service and Dirección General de la Fauna Silvestre. It does not necessarily represent official positions or approvals of cooperating agencies nor does it necessarily represent the views of all recovery team members who played the key role in preparing this plan. This plan is subject to modification as dictated by new findings and changes in species status and completion of tasks described in the plan. Goals and objectives will be attained and funds expended contingent upon appropriations, priorities, and other budgetary constraints. The Mexican gray wolf (Canis lupus baileyi) has been described as smallest in size of the American subspecies of Canis lupis. Fewer than 50 specimens may remain in the wild plus a handful in captivity. These southern subspecies are of special scientific interest because of possible adaptations, however subtle, to the environmenta1 and ecological conditions at the extreme southern limits of the species' range. Now, only baileyi remains as a living specimen. Many persons today feel that there are many other reasons, besides scientific knowledge, to prevent extinction of life forms, even large predators, including continuation of maximum genetic diversity and the intrinsic right of all forms to exist.

This is the completed Mexican Wolf Recovery Plan. It has been approved by the U.S. Fish and Wildlife Service and Dirección General de la Fauna Silvestre. It does not necessarily represent official positions or approvals of cooperating agencies nor does it necessarily represent the views of all recovery team members who played the key role in preparing this plan. This plan is subject to modification as dictated by new findings and changes in species status and completion of tasks described in the plan. Goals and objectives will be attained and funds expended contingent upon appropriations, priorities, and other budgetary constraints. The Mexican gray wolf (Canis lupus baileyi) has been described as smallest in size of the American subspecies of Canis lupis. Fewer than 50 specimens may remain in the wild plus a handful in captivity. These southern subspecies are of special scientific interest because of possible adaptations, however subtle, to the environmenta1 and ecological conditions at the extreme southern limits of the species' range. Now, only baileyi remains as a living specimen. Many persons today feel that there are many other reasons, besides scientific knowledge, to prevent extinction of life forms, even large predators, including continuation of maximum genetic diversity and the intrinsic right of all forms to exist.

A class of situations is considered where the usual techniques of operations research do not indicate the possibility of reducing to a common unit all the operating characteristics of a system caused by some decision and thus defining a criterion function. A special example of this class is furnished by the management of raw materials inventory in the face of fluctuation prices in the raw material market. Statistically reliable explanatory models of the random behavior of price are constructed, and decision rules are defined as transformation of appropriately chosen state variables. Some functionals of the random outcomes of decisions are computed as functions of the undetermined parameters open in the decision rule. Trade-offs between such functionals or system characteristics are analyzed with a view to obtain a basis for the selection of 'good' values of the parameters. Theoretical results are compared against simulated systems using actual series as inputs. (Author)

A special instance of the general problem of decision-making under uncertainty is condidered. In the absence of a well-defined utility function, the following method is adopted: First, a reasonable or acceptable policy is chosen with unspecified parameters. Then, the associated decision rule is formulated; typically, these are functional transforms of appropiate state variables. Analysis is made of the outcomes produced by the rule in conjunction with the stochastic price process. Finally, some functionals of the (random) outcomes are computed with a view to obtain measures of performance of the decision rule. In each case, the derivations indicate the dependence of the measures (of performance) on the unspecified parameters. (Author)

Sale of property of Jose Trevino to Henry Raguet. Signed by Henry Raguet, fiscal agent for the Republic; and Charles S. Taylor, signor of Texas Declaration of Independence.

Stamped paper document promissory note given by Jose Trevino to William Logan, signed by Henry Raguet.