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Complexity of the thoracic spine pedicle anatomy.

Transpedicular screw fixation provides rigid stabilization of the thoracolumbar spine. For accurate insertion of screws into the pedicles and to avoid pedicle cortex perforations, more precise knowledge of the anatomy of the pedicles is necessary. This study was designed to visualize graphically the surface anatomy and internal architecture of the pedicles of the thoracic spine. Fifteen vertebrae distributed equally among the upper, middle, and lower thoracic regions were used. For the purpose of mapping surface anatomy, each pedicle was cleaned, spray-painted white, and marked with more than 100 fine points. Using an optoelectronic digitizer, three-dimensional coordinates of the marked points and three additional points, representing a coordinate system, were digitized. A solid modeling computer program was used to create three-dimensional surface images of the pedicle. To obtain cross-sectional information, each pedicle was sectioned with a thin diamond-blade saw to obtain four slices, 1 mm in thickness and 0.5 mm apart. The pedicle slices were X-rayed and projected onto a digitizer. The internal and external contours were digitized and converted into graphs by a computer. The pedicles exhibited significant variability in their shape and orientation, not only from region to region within the thoracic spine, but also within the same region and even within the same pedicle. These variations are extremely significant in light of current techniques utilized in transpedicular screw fixation in the thoracic spine. Information documenting the three-dimensional complexity of pedicle anatomy should be valuable for surgeons and investigators interested in spinal instrumentation.

Adult↗

Differences in factors of health orientation of older women.

The purpose of this exploratory study was to examine the factor structure of health orientation. A secondary purpose was to determine differences in the stability and lability of health orientation. The sample consisted of four women in their sixties and four women in their eighties. A replicated, single-subject design was used to assess short-term intraindividual change in health orientation. Participants completed the Health Orientation Scale questionnaire for 100 days, and P-technique factor analysis was used to determine the factor structure of health orientation. These health orientation factors were graphed over time to assess stability and change. Results indicate that health orientation is more complex for participants in their eighties than for those in their sixties; this may represent age-appropriate development. Health orientation factors were found to be more labile or statelike for women in their eighties. These findings may help health care providers understand differences in interest or adherence to health-seeking behavior in the elderly and improve age-appropriate health care for this population.

Age Factors↗

Cyclosporine challenge in the decision of combined kidney-pancreas versus solitary pancreas transplantation.

Combined kidney-pancreas transplantation has become the treatment of choice for many patients with end-stage diabetic nephropathy. Pancreas transplantation (PTx) alone is an option for type I diabetic patients without end-stage diabetic nephropathy. Knowledge of factors contributing to or predicting the rate of renal deterioration (including the effect of CsA on the patient's renal function before transplantation) is necessary to determine candidacy for either kidney-pancreas transplantation or PTx alone. To address this issue, we selected 12 pre-uremic patients with creatinine clearances (CrCl) above 40 ml/min and less than 100 ml/min to participate in a 6-week oral CsA challenge test. Serum chemistries, including serum creatinine (SCr) and CsA level, were measured weekly. Urinary protein and CrCl were measured at 0, 2, 4, and 6 weeks. Glomerular filtration rate (GFR) (by 125I-sodium iothalamate clearance) was measured at 0, 3, and 6 weeks. All patients initially received oral CsA at 10 mg/kg/day in 2 divided doses. Doses were adjusted to maintain a 12-hr trough level of 500-1000 ng/ml using a whole blood polyclonal TDX assay. Data are presented as mean +/- SEM and as box-plot graphs. One patient was a CsA challenge test failure because SCr exceeded 3.0 mg/dl despite a reduction in CsA dose and level. Therefore, this patient was not a candidate for PTx alone and was excluded from further analysis. Among the 11 nonfailures, the mean CsA level at 6 weeks was 640 +/- 76 ng/ml. SCr increased from 1.2 +/- 0.1 mg/dl to 1.6 +/- 0.1 mg/dl (33% increase) (P = 0.0001). CrCl decreased from 82 +/- 9 ml/min to 63 +/- 8 ml/min (24% decrease) (P = 0.03). GFR decreased from 95 +/- 15 ml/min to 70 +/- 10 ml/min (26% decrease) (P = 0.009). CrCl and GFR did not differ from one another at 0 and 6 weeks (r = 0.77 and 0.98; P = 0.3 and 0.7, respectively). Urinary protein decreased from 1.0 +/- 0.3 g/day to 0.7 +/- 0.3 g/day at both 4 and 6 weeks (P = 0.03 and 0.06, respectively). Three of the 11 patients have not yet received transplants. Eight patients subsequently received PTx alone and were followed prospectively. Two allografts were lost early to rejection. Six were followed from 5 to 19 months after PTx alone. Serum creatinine and CrCL measurements during the CsA challenge test predicted post-PTx levels: SCr 1.6 +/- 0.1 vs. 1.7 +/- 0.3 mg/dl, P = 0.48, and CrCl 68 +/- 10 vs. 53 +/- 3 ml/min, P = 0.17, respectively.

Adult↗

KEGG: kyoto encyclopedia of genes and genomes.

KEGG (Kyoto Encyclopedia of Genes and Genomes) is a knowledge base for systematic analysis of gene functions, linking genomic information with higher order functional information. The genomic information is stored in the GENES database, which is a collection of gene catalogs for all the completely sequenced genomes and some partial genomes with up-to-date annotation of gene functions. The higher order functional information is stored in the PATHWAY database, which contains graphical representations of cellular processes, such as metabolism, membrane transport, signal transduction and cell cycle. The PATHWAY database is supplemented by a set of ortholog group tables for the information about conserved subpathways (pathway motifs), which are often encoded by positionally coupled genes on the chromosome and which are especially useful in predicting gene functions. A third database in KEGG is LIGAND for the information about chemical compounds, enzyme molecules and enzymatic reactions. KEGG provides Java graphics tools for browsing genome maps, comparing two genome maps and manipulating expression maps, as well as computational tools for sequence comparison, graph comparison and path computation. The KEGG databases are daily updated and made freely available (http://www. genome.ad.jp/kegg/).

Animals↗

Enhancing text categorization with semantic-enriched representation and training data augmentation.

OBJECTIVE: Acquiring and representing biomedical knowledge is an increasingly important component of contemporary bioinformatics. A critical step of the process is to identify and retrieve relevant documents among the vast volume of modern biomedical literature efficiently. In the real world, many information retrieval tasks are difficult because of high data dimensionality and the lack of annotated examples to train a retrieval algorithm. Under such a scenario, the performance of information retrieval algorithms is often unsatisfactory, therefore improvements are needed. DESIGN: We studied two approaches that enhance the text categorization performance on sparse and high data dimensionality: (1) semantic-preserving dimension reduction by representing text with semantic-enriched features; and (2) augmenting training data with semi-supervised learning. A probabilistic topic model was applied to extract major semantic topics from a corpus of text of interest. The representation of documents was projected from the high-dimensional vocabulary space onto a semantic topic space with reduced dimensionality. A semi-supervised learning algorithm based on graph theory was applied to identify potential positive training cases, which were further used to augment training data. The effects of data transformation and augmentation on text categorization by support vector machine (SVM) were evaluated. RESULTS AND CONCLUSION: Semantic-enriched data transformation and the pseudo-positive-cases augmented training data enhance the efficiency and performance of text categorization by SVM.

Algorithms↗

Expert system support using Bayesian belief networks in the diagnosis of fine needle aspiration biopsy specimens of the breast.

AIM: To develop an expert system model for the diagnosis of fine needle aspiration cytology (FNAC) of the breast. METHODS: Knowledge and uncertainty were represented in the form of a Bayesian belief network which permitted the combination of diagnostic evidence in a cumulative manner and provided a final probability for the possible diagnostic outcomes. The network comprised 10 cytological features (evidence nodes), each independently linked to the diagnosis (decision node) by a conditional probability matrix. The system was designed to be interactive in that the cytopathologist entered evidence into the network in the form of likelihood ratios for the outcomes at each evidence node. RESULTS: The efficiency of the network was tested on a series of 40 breast FNAC specimens. The highest diagnostic probability provided by the network agreed with the cytopathologists' diagnosis in 100% of cases for the assessment of discrete, benign, and malignant aspirates. Atypical probably benign cases were given probabilities in favour of a benign diagnosis. Suspicious cases tended to have similar probabilities for both diagnostic outcomes and so, correctly, could not be assigned as benign or malignant. A closer examination of cumulative belief graphs for the diagnostic sequence of each case provided insight into the diagnostic process, and quantitative data which improved the identification of suspicious cases. CONCLUSION: The further development of such a system will have three important roles in breast cytodiagnosis: (1) to aid the cytologist in making a more consistent and objective diagnosis; (2) to provide a teaching tool on breast cytological diagnosis for the non-expert; and (3) it is the first stage in the development of a system capable of automated diagnosis through the use of expert system machine vision.

Bayes Theorem↗

GECKO: a complete large-scale gene expression analysis platform.

BACKGROUND: Gecko (Gene Expression: Computation and Knowledge Organization) is a complete, high-capacity centralized gene expression analysis system, developed in response to the needs of a distributed user community. RESULTS: Based on a client-server architecture, with a centralized repository of typically many tens of thousands of Affymetrix scans, Gecko includes automatic processing pipelines for uploading data from remote sites, a data base, a computational engine implementing approximately 50 different analysis tools, and a client application. Among available analysis tools are clustering methods, principal component analysis, supervised classification including feature selection and cross-validation, multi-factorial ANOVA, statistical contrast calculations, and various post-processing tools for extracting data at given error rates or significance levels. On account of its open architecture, Gecko also allows for the integration of new algorithms. The Gecko framework is very general: non-Affymetrix and non-gene expression data can be analyzed as well. A unique feature of the Gecko architecture is the concept of the Analysis Tree (actually, a directed acyclic graph), in which all successive results in ongoing analyses are saved. This approach has proven invaluable in allowing a large (approximately 100 users) and distributed community to share results, and to repeatedly return over a span of years to older and potentially very complex analyses of gene expression data. CONCLUSIONS: The Gecko system is being made publicly available as free software http://sourceforge.net/projects/geckoe. In totality or in parts, the Gecko framework should prove useful to users and system developers with a broad range of analysis needs.

Carcinoma↗

The prenatal development of the normal human skeleton: a combined ultrasonographic and post-mortem radiographic study.

Post-mortem radiography of fetuses with skeletal dysplasia is essential for diagnostic classification. Interpretation of the radiographs should be based on the knowledge of morphology and dimensions of the normal skeleton in all stages of development. A retrospective post-mortem radiographic study is presented with measurements of the lengths of the long bones and thoracic and lumbar spine. The study included 69 fetuses and neonates with a normal skeleton, whose gestational age ranged from 13-42 weeks and who died perinatally or lived for less than one week. The measurements of the long bones were plotted on growth curves obtained from a prospective longitudinal ultrasonographic investigation of another group of 63 normal fetuses from 12-40 weeks of gestation. Thoracic and lumbar spine measurements by ultrasonography were not available. The radiographic data of thoracic and lumbar spine were, therefore, compared to radiographic studies from the literature. No disagreement with these studies was found. It can be concluded that measurements of bones from standardized post-mortem radiographs in cases of questionable gestational age or defects of bone development can be compared with ultrasonographic measurements. To illustrate the usefulness of the graphs, 13 fetuses with various types of skeletal dysplasia were evaluated retrospectively.

Bone Diseases, Developmental↗

[Factors determining patients' choice of hospital].

OBJECTIVE: To identify the best way to inform patients about centers and services so that they can make a responsible choice, and to identify which factors determine patients' decisions. SUBJECTS AND METHODS: Data on three illnesses (breast cancer, benign prostatic hypertrophy, and cataracts) in three fictitious hospitals were shown to patients. The data were presented to 1,259 subjects through four different means: a brochure including a table, a brochure with a bar graph, three brochures with tables, and three brochures with bar graphs. Data on each of the hospitals included: professional profiles, medical and surgical outcomes, side effects, patients' and relatives' satisfaction, and hospital complaints. The subjects completed a questionnaire evaluating the information received. RESULTS: Most patients (88%) preferred to receive full information and to share decision-making with their physician. Sixty-four percent of the patients chose the hospital with the best medical or surgical outcomes. Patients preferred the data presented through a brochure with a table (p < 0.001). Three factors were identified with severe illness (satisfaction, outcomes and complaints) and two factors with non-severe illness (satisfaction and outcomes). Men paid more attention to medical and surgical outcomes (p < 0.001), relapses (p < 0.001), and side effects (p < 0.001). When performing comparisons, health professionals paid greater attention to medical and surgical outcomes than to patients' and relatives' satisfaction (t range between 0.40 and 0.90, p < 0.01). CONCLUSIONS: Differences were found in the need for information and in comprehension depending on the way information was presented and on the type of disease. Gender and health knowledge seem to be predictors of patients' information needs when choosing a hospital.

Access to Information↗

Isolation and identification of tetracycline resistant lactic acid bacteria from pre-packed sliced meat products.

In recent years, the food chain has been recognised as one of the main routes for transmission of antibiotic resistant bacteria between the animal and human population. In this regard, the current study aimed to investigate if tetracycline resistant (tetR) lactic acid bacteria (LAB) are present in ready-to-eat modified atmosphere packed (MAP) sliced meat products including fermented dry sausage, cooked chicken breast meat and cooked ham. From population graphs based on doubling tetracycline concentrations between 0 and 256 microg ml(-1), only fermented dry sausage was shown to contain a high-level retR LAB population (5.10(1) - 2,23.10(4) CFU/g), and this in four out of ten examined sausages. From these four positive sausages, a total of 100 strains were isolated on de Man, Rogosa and Sharpe-sorbic acid (MRS-S) agar without tetracycline (n = 45) and on MRS-S agar supplemented with a tetracycline breakpoint concentration of 64 microg ml(-1) (n = 55). Using resistance histograms derived from the disc diffusion method, all these strains were grouped as sensitive to rifampicin, erythromycin and ampicillin. All strains from the tetracycline-containing MRS-S plates were resistant to tetracycline. Identification with whole-cell protein profiling revealed that the total strain set represented four different species: Pediococcus pentosaceus, Lactobacillus plantarum, Lactobacillus sakei subsp. carnosus and Lactobacillus curvatus. All species are commonly associated with fermented dry sausage, either as starter culture or as natural contaminants. The latter three species were found to comprise all tetracycline resistant strains. To our knowledge, this is the first report providing evidence for the presence of tetR LAB in final ready-to-eat pre-packed fermented dry sausages.

Food Microbiology↗

Spontaneous changes of unilateral nasal airflow in man. A re-examination of the 'nasal cycle'.

It is now over 100 years since Kayser (Archiv für Laryngol Rhinol 1895; 3: 101-120) first reported in the scientific literature that the human nasal passages exhibit spontaneous changes in unilateral nasal airway resistance, yet our understanding of this unusual phenomenon is still very confused. Spontaneous, reciprocal changes in unilateral nasal resistance are often referred to as a "nasal cycle" and although this term is now commonly used to describe spontaneous changes in nasal resistance in man and animals, there is little evidence for any true periodicity. A major problem in increasing our knowledge and understanding of the so-called "nasal cycle" is that most studies have relied on simple descriptions of the changes in nasal resistance and have not developed any numerical parameters to quantify the changes in resistance over time. This lack of definition of what actually constitutes a nasal cycle has meant that the literature of the present day generally accepts the views put forward by Heetderks (Am J Med Sci 1927; 174; 231-244) and Stoksted (Acta Otolaryngol (Stockh) 1953; Suppl 109: 159-175) that around 80% of the healthy population exhibit a regular cycle. In order to define the characteristics of the spontaneous changes in nasal airway resistance we have used numerical measures of reciprocity and also developed a measurement of the division of airflow between the nasal passages over time. With these two parameters it is possible to describe the nature of the spontaneous changes in airflow in numerical terms and to define what exactly constitutes a nasal cycle. Fifty-two volunteers underwent hourly measurement of unilateral nasal airflow for 8 h. For each volunteer, two values were derived from the graph of unilateral nasal airflows against time; the correlation coefficient between unilateral airflows (r) and the airflow distribution ratio between the two nasal airways (ADR). The spread of different types of airflow pattern (nasal cycle) throughout the population was illustrated by plotting r against ADR for each subject. A nasal cycle was defined as having an r value between -0.6 and -1.0, and an ADR value between 0.7 and 1.0. Only 21% (11 of the 52 volunteers) exhibited airflow patterns that could be defined as a nasal cycle in these terms. This finding contradicts the generally accepted, but undefined, view that around 80% of the population exhibit a regular nasal cycle. The numerical definition of a nasal cycle in terms of both reciprocity and airflow distribution, as described in this paper may help to clarify our understanding of this interesting phenomenon and allow rhinologists to describe the spontaneous changes in nasal airflow in more exact terms than have been used previously in the literature.

Adult↗

Symbolic dynamics and computation in model gene networks.

We analyze a class of ordinary differential equations representing a simplified model of a genetic network. In this network, the model genes control the production rates of other genes by a logical function. The dynamics in these equations are represented by a directed graph on an n-dimensional hypercube (n-cube) in which each edge is directed in a unique orientation. The vertices of the n-cube correspond to orthants of state space, and the edges correspond to boundaries between adjacent orthants. The dynamics in these equations can be represented symbolically. Starting from a point on the boundary between neighboring orthants, the equation is integrated until the boundary is crossed for a second time. Each different cycle, corresponding to a different sequence of orthants that are traversed during the integration of the equation always starting on a boundary and ending the first time that same boundary is reached, generates a different letter of the alphabet. A word consists of a sequence of letters corresponding to a possible sequence of orthants that arise from integration of the equation starting and ending on the same boundary. The union of the words defines the language. Letters and words correspond to analytically computable Poincare maps of the equation. This formalism allows us to define bifurcations of chaotic dynamics of the differential equation that correspond to changes in the associated language. Qualitative knowledge about the dynamics found by integrating the equation can be used to help solve the inverse problem of determining the underlying network generating the dynamics. This work places the study of dynamics in genetic networks in a context comprising both nonlinear dynamics and the theory of computation. (c) 2001 American Institute of Physics.

Journal Article↗

Fitness Landscapes and the Precautionary Principle: The Geometry of Environmental Risk.

/ A generalized mathematical model for exploring the implications of the Precautionary Principle is developed. This model draws on recent developments in the field of complex adaptive systems theory. The existence and importance of the Precautionary Principle in the field of environmental law is taken as given and used as justification for the development of models for exploring the principle's implications.The Precautionary Principle is a legal mechanism for managing the environmental risk arising from incomplete scientific knowledge of a proposal's impacts. The Precautionary Principle is applied to actions that carry with them the potential for serious or irreversible environmental change. The model proposed in this paper draws on methods used in a range of disciplines for modeling (potentially highly nonlinear) interactions between multiple parts of a complex system. These methods have been drawn together under the common mathematical umbrella of Fitness Landscape Theory. It is argued that the model, called "Environmental Impact Fitness Landscapes," allows statements about the sensitivity of the gross effect from a set of impacts to be made when the number of impacts in the set, and/or their degree of interaction, is varied. It is argued that this can be achieved through identification of "meta" or "emergent" properties of the set itself, without reference to the specific causal chains determining behavior in specific instances. While such properties are very general, they may at least allow for the parameterization of the effects of sets of impacts where interactions are highly uncertain and empirical data severely limited, i.e., situations that would typically invoke the Precautionary Principle.KEY WORDS: Fitness landscapes; Precautionary Principle; Nonlinear interactions; Graph theoryhttp://link.springer-ny.com/link/service/journals/00267/bibs/24n1p121.html

Journal Article↗

[Evaluation of the effect of the health education intervention project "Healthy School"].

UNLABELLED: Contemporary health-education intervention programs are increasingly used as a tool for improving health of school children [1-4]. Since 1992 a Network of 13 elementary Health Promoting Schools established in Yugoslavia (though not yet admitted to the European Network) has been operational. The Project was approved by the Ministries of Health, Education and Ecology from the very beginning, and financially supported by the Government of Serbia since 1995. The team of up to 40 health professionals, school principals and school project managers worked together for four years to change the working conditions in schools knowledge, attitudes and behaviour of school children and staff in order to improve their health [5]. The goal of this paper is to present results of health education intervention in changing of hygienic conditions in schools, as well as some of the attitudes, behaviour and knowledge of pupils and their parents. METHOD: The study took place before and after the intervention--at two points in time--during 1993 and 1996. The tri-angular approach including (1) pupils, (2) schools (teachers, school environment), and (3) parents, was used. A random pretest and post-test study design with control group (12 experimental and two control schools) has been implemented. The multiphase cluster sample was employed in order to represent all of the country typical regions. Six types of especially designed questionnaires were used to provide comparable variables in the sample of pupils, their parents and teachers. Exception were 1st-graders and 4th-graders for whom information were gathered by means of a "draw-and-write" investigation technique [6]. The response rate was 88.70% before and 98.28% after intervention. Data were analyzed by descriptive and inferential statistics using SPSS/PC software. RESULTS: Schools are somewhat less overcrowded, much cleaner and better maintained after the four-year intervention. Toilets are in a better condition, but there is still much more to be done. The 1st- and 4th-graders, surveyed by the draw-and-write method, mentioned numerous ways of keeping and improving health, which were summarized as fifteen health-improvement measures (Graph 1). The most frequently mentioned measures were nutrition, physical activity, general hygiene, oral and dental hygiene, sleeping and fresh air. Each of these measures was mentioned by over 20% of the surveyed pupils. Eleven of 15 variables showed significant increase in frequencies (at the level of at least p < 0.01) after the intervention. As an indicator of a nutrition behaviour, the regularity of main meals is analyzed (Graph 2). The majority of children eat regularly and the difference before and after intervention is significant only for the school meal (c2 = 30.715, p < 0.001). Although over 70% of children learn that general hygiene is good for health in junior graders, only about little more than 30% of senior graders have a bath or shower every day, while others only once or twice a week. The differences are significant before and after the intervention (c2 = 10.648, p < 0.05) only for everyday practice. More than 90% of senior-grade pupils brush their teeth at least once or several times a day. Over 60% of children in our survey go in for sport, whereas about 20% never do so. It seems that the intervention contributed symbolically to this practice important for health, though before-after difference is significant (c2 = 6.673, p < 0.05). However, in the control group schools children have much less physical activity in 1996, and this difference is significant (c2 = 14.070, p < 0.010). The psycho-emotional status of Yugoslav young people is strongly influenced by the situation in the country the war, the economic disaster and the impact of international sanctions. Consequently, more than one-fourth of the children complained of frequent exhaustion and concentration problems, which their parents also noticed. (ABSTRACT TRUNCATED)

Child↗

An enriched unified medical language system semantic network with a multiple subsumption hierarchy.

OBJECTIVE: The Unified Medical Language System's (UMLS's) Semantic Network's (SN's) two-tree structure is restrictive because it does not allow a semantic type to be a specialization of several other semantic types. In this article, the SN is expanded into a multiple subsumption structure with a directed acyclic graph (DAG) IS-A hierarchy, allowing a semantic type to have multiple parents. New viable IS-A links are added as warranted. DESIGN: Two methodologies are presented to identify and add new viable IS-A links. The first methodology is based on imposing the characteristic of connectivity on a previously presented partition of the SN. Four transformations are provided to find viable IS-A links in the process of converting the partition's disconnected groups into connected ones. The second methodology identifies new IS-A links through a string matching process involving names and definitions of various semantic types in the SN. A domain expert is needed to review all the results to determine the validity of the new IS-A links. RESULTS: Nineteen new IS-A links are added to the SN, and four new semantic types are also created to support the multiple subsumption framework. The resulting network, called the Enriched Semantic Network (ESN), exhibits a DAG-structured hierarchy. A partition of the ESN containing 19 connected groups is also derived. CONCLUSION: The ESN is an expanded abstraction of the UMLS compared with the original SN. Its multiple subsumption hierarchy can accommodate semantic types with multiple parents. Its representation thus provides direct access to a broader range of subsumption knowledge.

Algorithms↗

Healthy imaginations: a social history of the epidemiology of Aboriginal and Torres Strait Islander health.

It is difficult to imagine Aboriginal and Torres Strait Islander health without the powerful descriptors of epidemiology. The statistical imagery of numerical tables, pie charts, and bar graphs have become a key element in the public presentation of Indigenous public health issues. Such quantitative measurements of health draw on the authority of neutral, objective science and are thus rarely questioned in terms of their social meaning. This paper traces the history of this imagery through the 20th century, providing a social account of epidemiological description. Historical notions such as social Darwinism, assimilation, and dangerous other are all seen to be woven into the epidemiological text. The enormous rise in the epidemiological description of Indigenous health problems in recent years needs to be analyzed as a social phenomenon and, in particular, as an aspect of emerging forms of governmentality. Finally, it is argued that such analyses are needed in order to promote an anthropology of epidemiology and to avoid limiting medical anthropology to applications within epidemiology.

Adult↗

Learning directed acyclic graphs for ligands and receptors based on spatially resolved transcriptomic data of ovarian cancer.

To unravel the mechanism of immune activation and suppression within tumors, a critical step is to identify transcriptional signals governing cell-cell communication between tumor and immune/stromal cells in the tumor microenvironment. Central to this communication are interactions between secreted ligands and cell-surface receptors, creating a highly connected signaling network among cells. Recent advancements in in situ-omics profiling, particularly spatial transcriptomic (ST) technology, provide unique opportunities to directly characterize ligand-receptor signaling networks that power cell-cell communication. In this paper, we propose a novel statistical method, LRnetST, to characterize the ligand-receptor interaction networks between adjacent tumor and immune/stroma cells based on ST data. LRnetST utilizes a directed acyclic graph model with a novel approach to handle the zero-inflated distributions of ST data. It also leverages existing ligand-receptor regulation databases as prior information, and employs a bootstrap aggregation strategy to achieve robust network estimation. Application of LRnetST to ST data of high-grade serous ovarian tumor samples revealed both common and distinct ligand-receptor regulations across different tumors. Some of these interactions were validated through both a MERFISH dataset and a CosMx SMI dataset of independent ovarian tumor samples. These results cast light on biological processes relating to the communication between tumor and immune/stromal cells in ovarian tumors. An open-source R package of LRnetST is available on GitHub at https://github.com/jie108/LRnetST.

Humans↗

[The effect of synchronization on estrus and pregnancy in sheep and on levels of thyroxine, triiodothyronine, 17 beta-estradiol, progesterone and cholesterol].

Knowledge of pathogenesis of sexual dysfunctions at altered thyroid activity is limited by the knowledge of multiple and ubiquitous action of its hormones throughout the organism. One of the possibilities of modulatory influence of thyroid hormones on sexual functions can be realized through the participation of thyroxine and triiodothyronine in the synthesis and metabolism of primary substrate of steroid synthesis--cholesterol. The presented work is aimed at the study of simultaneous dynamic changes of concentrations of thyroxine (T4), triiodothyronine (T3), 17 beta-estradiol (E2), progesterone (P4) and cholesterol (Chol) during synchronization of the rutting period and gravidity at parallel correlative evaluation of mutual relations of the followed parameters in ten Merino sheep in the seasonal period. Synchronization was achieved by chlorsuperlutin (Agelin--vaginal swabs, Spofa; 20 mg of chlorsuperlutin/swab) and PMSG (500 I. U./animal). Blood was sampled by means of a jugular vein puncture at the time of swab insertion (-13th day) and after three (-10th day) and seven (-7th day) following days, at the removal of swabs and application of PMSG (-3rd day), on the day of insemination (zero day), on the 7th, 14th and 17th day and in the middle of the 2nd, 3rd, 4th and 5th month of gravidity. In the phase of oestrus synchronization a significant increase of E2 concentrations on days -7 and -3 of the experiment (0.47 +/- 0.079 and 0.542 +/- 0.177 nmol.l-1 of serum, P less than 0.001; P less than 0.001) was observed compared to the E2 values on day -13 (0.084 +/- 0.036 nmol.l-1 of serum). Parallel to these observations, marked intermittent changes of T4 (Tab. I, Graph 1) were recorded with the lowest values of this parameter observed on days -10 (41.75 +/- 20.23, P less than 0.05) and -3 (50.22 +/- 18.77, P less than 0.05) and the highest on day -7 (96.77 +/- 17.51 nmol.l-1, P less than 0.01) and day zero (85.40 +/- 19.59 nmol.l-1 of serum, P less than 0.05) in comparison with the -13th day (67.22 +/- 18.29 nmol.l-1 of serum). Concentrations of P4 (Tab. I, Graph 4) declined to the lowest values on day zero observation (0.09 +/- 0.08 nmol.l-1 of serum, P less than 0.05 vs 3.40 +/- 3.61 nmol.l-1 on day -13). No significant changes of concentrations of T3 (Tab. I, Graph 2) and Chol (Tab. I, Graph 5) were observed during oestrus synchronization. During gravidity, concentrations of E2 (Tab. I Graph 3) showed an increasing trend compared to the -13th day.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗