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The letter to the editor discusses a recent article on the role of post-operative interleukin-6 (IL-6) in pediatric appendicitis. The authors of the letter provide additional commentary on the study's conclusions and highlight several limitations that were not addressed. They note the absence of important clinical variables, such as leukocytosis and fever, which could have provided valuable insights. The small sample size and wide confidence intervals raise concerns about the reliability of the observed associations. Additionally, the authors suggest that a more dynamic approach to IL-6 assessment could provide a better understanding of its predictive value. Overall, while the study offers valuable insights, addressing these limitations in future research is necessary for a more robust understanding of IL-6's clinical utility. [Extracted from the article]

Unlike the traditional view of suffering in philosophy and theology as a deviation from the ideal, John Keats's vale of soul-making attends to the potentiality of the suffering body in the world for fashioning the identities of the modern subject. Keats thereby exhibits a notion of the body that shows more affinity with Maurice Merleau-Ponty's emphasis on the primary role of perception in knowledge than with John Locke's empiricist account of sensation. Turning to the prereflective experience, Merleau-Ponty concedes the limits of reasoning in the face of an opaque world and hints at a quality similar to Keats's negative capability. [ABSTRACT FROM AUTHOR]

Deep learning (DL) techniques have grown in leaps and bounds in both academia and industry over the past few years. Despite the growth of DL projects, there has been little study on how DL projects evolve, whether maintainers in this domain encounter a dramatic increase in workload and whether or not existing maintainers can guarantee the sustained development of projects. To address this gap, we perform an empirical study to investigate the sustainability of DL projects, understand maintainers' workloads and workloads growth in DL projects, and compare them with traditional open‐source software (OSS) projects. In this regard, we first investigate how DL projects grow, then, understand maintainers' workload in DL projects, and explore the workload growth of maintainers as DL projects evolve. After that, we mine the relationships between maintainers' activities and the sustainability of DL projects. Eventually, we compare it with traditional OSS projects. Our study unveils that although DL projects show increasing trends in most activities, maintainers' workloads present a decreasing trend. Meanwhile, the proportion of workload maintainers conducted in DL projects is significantly lower than in traditional OSS projects. Moreover, there are positive and moderate correlations between the sustainability of DL projects and the number of maintainers' releases, pushes, and merged pull requests. Our findings shed lights that help understand maintainers' workload and growth trends in DL and traditional OSS projects and also highlight actionable directions for organizations, maintainers, and researchers. [ABSTRACT FROM AUTHOR]

This article commends the authors of a study on the impact of the COVID-19 pandemic on acute appendicitis in a local cluster of hospitals. The study found no significant delay in patient presentation or differences in outcomes during the fifth wave of the pandemic compared to the pre-COVID-19 era. However, the study's findings may not be generalizable to other regions with different healthcare systems and patient populations. The exclusion of non-surgical management cases raises questions about the overall trends in acute appendicitis cases during the pandemic. Additionally, the study does not account for potential changes in patient management, hospital protocols, or public perceptions of COVID-19 that occurred during later stages of the pandemic. These limitations highlight the importance of considering regional differences, non-operative management, and evolving pandemic dynamics when interpreting the findings. [Extracted from the article]

Microfold (M) cells are epithelial cells present in mucosal tissues and specialized for the capture of luminal microparticles and their delivery to underlying immune cells; thus, they are crucial participants in mucosal immune surveillance. Multiple phenotypic subsets of M cells have now been described, all sharing a unique apical morphology that provides clues to their ability to capture microbial particles. The existence of diverse M cell phenotypes, especially inflammation-inducible M cells, provides an intriguing puzzle: some variants may augment luminal surveillance to boost mucosal immunity, while others may promote microbial access to tissues. Here, I consider the unique induction requirements of each M cell subset and functional differences, highlighting the potentially distinct consequences in mucosal immunity. [ABSTRACT FROM AUTHOR]

Testing is a pivotal activity in ensuring the quality of software. Code coverage is a common metric used as a yardstick to measure the efficacy and adequacy of testing. However, does higher coverage actually lead to a decline in postrelease bugs? Do files that have higher test coverage actually have fewer bug reports? The direct relationship between code coverage and actual bug reports has not yet been analyzed via a comprehensive empirical study on real bugs. Past studies only involve a few software systems or artificially injected bugs (mutants). In this empirical study, we examine these questions in the context of open-source software projects based on their actual reported bugs. We analyze 100 large open-source Java projects and measure the code coverage of the test cases that come along with these projects. We collect real bugs logged in the issue tracking system after the release of the software and analyze the correlations between code coverage and these bugs. We also collect other metrics such as cyclomatic complexity and lines of code, which are used to normalize the number of bugs and coverage to correlate with other metrics as well as use these metrics in regression analysis. Our results show that coverage has an insignificant correlation with the number of bugs that are found after the release of the software at the project level, and no such correlation at the file level. [ABSTRACT FROM PUBLISHER]

Many change classification techniques have been proposed to identify defect-prone changes. These techniques consider all developers’ historical change data to build a global prediction model. In practice, since developers have their own coding preferences and behavioral patterns, which causes different defect patterns, a separate change classification model for each developer can help to improve performance. Jiang, Tan, and Kim refer to this problem as personalized change classification, and they propose PCC+ to solve this problem. A software project has a number of developers; for a developer, building a prediction model not only based on his/her change data, but also on other relevant developers’ change data can further improve the performance of change classification. In this paper, we propose a more accurate technique named collective personalized change classification (CPCC), which leverages a multiobjective genetic algorithm. For a project, CPCC first builds a personalized prediction model for each developer based on his/her historical data. Next, for each developer, CPCC combines these models by assigning different weights to these models with the purpose of maximizing two objective functions (i.e., F1-scores and cost effectiveness). To further improve the prediction accuracy, we propose CPCC+ by combining CPCC with PCC proposed by Jiang, Tan, and Kim To evaluate the benefits of CPCC+ and CPCC, we perform experiments on six large software projects from different communities: Eclipse JDT, Jackrabbit, Linux kernel, Lucene, PostgreSQL, and Xorg. The experiment results show that CPCC+ can discover up to 245 more bugs than PCC+ (468 versus 223 for PostgreSQL) if developers inspect the top 20% lines of code that are predicted buggy. In addition, CPCC+ can achieve F1-scores of 0.60–0.75, which are statistically significantly higher than those of PCC+ on all of the six projects. [ABSTRACT FROM PUBLISHER]

During the evolution of a software system, a large number of bug reports are submitted. Locating the source code files that need to be fixed to resolve the bugs is a challenging problem. Thus, there is a need for a technique that can automatically figure out these buggy files. A number of bug localization solutions that take in a bug report and output a ranked list of files sorted based on their likelihood to be buggy have been proposed in the literature. However, the accuracy of these tools still needs to be improved. In this paper, to address this need, we propose AmaLgam+, which is a method for locating relevant buggy files that puts together fives sources of information, namely, version history, similar reports, structure, stack traces, and reporter information. We perform a large-scale experiment on four open source projects, namely, AspectJ, Eclipse, SWT, and ZXing to localize more than 3000 bugs. We compare AmaLgam + with several state-of-the-art approaches including AmaLgam, BLUiR+, BRtracer+, BugLocator, and TFIDF-DHbPd. These approaches leverage one or several of the sources of information analyzed by AmaLgam+, but not all of them. On average, AmaLgam + achieves a 6.0% improvement over AmaLgam, which merges three sources of information, in terms of Mean Average Precision (MAP). For AspectJ and Eclipse datasets, in which there are many bug reports with stack traces and many reporters submit multiple bug reports, AmaLgam + achieves a 12.0% improvement over AmaLgam in terms of MAP. Compared with the other state-of-the-art approaches, AmaLgam + achieves an improvement of 20.3%, 22.5%, 33.1%, and 73.9% over BLUiR+, BRtracer+, BugLocator, and TFIDF-DHbPd in terms of MAP, respectively. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Chemoradiation (CRT) may modulate the intratumoral and peripheral immune milieu by serving as an in situ vaccine. The impact of the rapid dose delivery of brachytherapy (BT) on the T-cell repertoire has not been examined. HPV-related cancers express viral oncoproteins E6/E7, which could function as tumor antigens (Ag) and are thus ideal for investigating the impact of CRT in generating tumor-specific immunity. 11 pts with cervical cancer were enrolled on a multi-institutional prospective tissue banking protocol from 1/2020—2022. Pts underwent standard external beam RT (EBRT) spanning 5-7 wks with concurrent weekly 40mg/m2 cisplatin, then BT boost with either high dose rate (HDR) in 5 fx or pulse dose rate (PDR) in 2 fx. Cervical tumor swabs were taken at 5 timepoints: baseline (T1), wk 1 (T2 , after 5 fx), wk 3 (T3 , after 10-15 fx), wk 5 (T4 , at conclusion of EBRT and prior to 1st BT), prior to 2nd BT (T4B), and at 1st follow-up (T5 , 12 wks post-treatment). Samples underwent functional expansion of HPV Ag-specific T cells before DNA extraction and multiplex deep sequencing of the CDR3 region of TCR-β using immunoSEQ PCR (Adaptive Biotech). TCR productive frequency (freq), templates, clonality, and rearrangements were compared across timepoints. Separately, HPV-responsive T-cell clones underwent ex vivo expansion by incubation with HPV long peptide sequences of E6/E7 overnight (ON). TCR sequences were compared between HPV-stimulated T cells and evaluated against incubations with CEF (positive control peptides) or media (negative control). Statistical analysis was via Mann-Whitney U. Median age was 47 yrs (range 27-57). 6 pts (54.5%) had SCC; 5 (45.5%) had adenocarcinoma. 4 pts (36.4%) had FIGO 2018 ≤Stage IIB disease, 45.5% were Stage III, and 18.2% were Stage IVA/B. 7 pts (63.6%) received PDR BT and 4 pts (36.4%) underwent HDR BT. At median follow-up of 7.5 mo, all pts are alive and with NED. In serially sampled peritumoral microenvironment (TME) isolates, TCR productive clonality increased after first BT, culminating in a significant increase at T5 during the first post-treatment follow-up (Fig 1A). There was a trend (ns) toward increased productive templates throughout CRT and BT (Fig 1B), but this decreased by T5. Productive freq was significantly higher at T5 compared to prior to BT (T1—T4), Fig 1C. Productive rearrangements trended toward abundance throughout CRT and BT (ns), but decreased at T5 (Fig 1D). Functional HPV Ag stimulation assays of peritumoral T-cells in the full cohort did not show significant changes in the TCR repertoire after ON incubation with HPV E6/7 peptides. However, 4 pts had notable E6/E7-responsive increases in these metrics at either T4 or T4B—namely, abundance of productive templates (ranges: 1.9—30.3 fold-increase from baseline), freq (1.25—5.5), rearrangements (1.5—13.8), and clonality (1.31—3.8). We characterized TCR remodeling during BT in this first translational analysis, demonstrating (i) increased peritumoral TCR productive freq and clonality post-BT at T5, and (ii) transient rise in productive templates and rearrangements through CRT and BT, with a numeric return to baseline post-BT at T5. Some pts had functional Ag-specific activation upon HPV stimulation during and after BT. These findings suggest that despite the cytotoxic effects of radiation, BT alters the TME to facilitate expansion of specific T-cell populations, which may contribute to treatment efficacy. [ABSTRACT FROM AUTHOR]

Bug fixing is one of the most important activities in software development and maintenance. Bugs are reported, recorded, and managed in bug tracking systems such as Bugzilla. In general, a bug report contains many fields, such as product, component, severity, priority, fixer, operating system (OS), and platform, which provide important information for the bug triaging and fixing process. Our previous study finds that approximately 80% of bug reports have their fields reassigned and refined at least once, and bugs with reassigned and refined fields take more time to fix than bugs with no reassigned and refined fields. Thus, automatically predicting which bug report fields get reassigned and refined could help developers to save bug fixing time. Considering that a bug report could have multiple field reassignments and refinements (e.g., the product, component, fixer, and other fields of a bug report can get reassigned and refined), in this paper, we propose a multi-label learning algorithm to predict which bug report fields might be reassigned and refined. We note that the number of bug reports with some types of reassignment and refinement (e.g., bugs whose severity fields gets reassigned and refined) is a small proportion of the whole bug report collection, indicating the class imbalance problem. Thus, we propose imbalanced ML.KNN (Im-ML.KNN), which extends ML.KNN, one of the state-of-the-art multi-label learning algorithms, to achieve better performance. Im-ML.KNN is a composite model that combines 3 multi-label classifiers built using different types of features (i.e., meta, textual, and mixed features). We evaluate our solution on 4 large bug report datasets including OpenOffice, Netbeans, Eclipse, and Mozilla containing a total of 190,558 bug reports. We show that Im-ML.KNN can achieve an average F-measure score of 0.56–0.62. We also compare Im-ML.KNN with other state-of-art methods, such as the method proposed by Lamkanfi , ML.KNN, and HOMER-NB. The results show that Im-ML.KNN, on average, improves the average F-measure scores of Lamkanfi 's method, ML.KNN, and HOMER-NB by 119.69%, 9.11%, and 161.08%, respectively. [ABSTRACT FROM AUTHOR]

Bug resolution refers to the activity that developers perform to diagnose, fix, test, and document bugs during software development and maintenance. Given a bug report, we would like to recommend the set of bug resolvers that could potentially contribute their knowledge to fix it. We refer to this problem as developer recommendation for bug resolution. In this paper, we propose a new and accurate method named DevRec for the developer recommendation problem. DevRec is a composite method that performs two kinds of analysis: bug reports based analysis (BR-Based analysis) and developer based analysis (D-Based analysis). We evaluate our solution on five large bug report datasets including GNU Compiler Collection, OpenOffice, Mozilla, Netbeans, and Eclipse containing a total of 107,875 bug reports. We show that DevRec could achieve recall@5 and recall@10 scores of 0.4826-0.7989, and 0.6063-0.8924, respectively. The results show that DevRec on average improves recall@5 and recall@10 scores of Bugzie by 57.55% and 39.39%, outperforms DREX by 165.38% and 89.36%, and outperforms NonTraining by 212.39% and 168.01%, respectively. Moreover, we evaluate the stableness of DevRec with different parameters, and the results show that the performance of DevRec is stable for a wide range of parameters. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT Spectrum-based fault localization is a promising approach to automatically locate root causes of failures quickly. Two well-known spectrum-based fault localization techniques, Tarantula and Ochiai, measure how likely a program element is a root cause of failures based on profiles of correct and failed program executions. These techniques are conceptually similar to association measures that have been proposed in statistics, data mining, and have been utilized to quantify the relationship strength between two variables of interest (e.g., the use of a medicine and the cure rate of a disease). In this paper, we view fault localization as a measurement of the relationship strength between the execution of program elements and program failures. We investigate the effectiveness of 40 association measures from the literature on locating bugs. Our empirical evaluations involve single-bug and multiple-bug programs. We find there is no best single measure for all cases. Klosgen and Ochiai outperform other measures for localizing single-bug programs. Although localizing multiple-bug programs, Added Value could localize the bugs with on average smallest percentage of inspected code, whereas a number of other measures have similar performance. The accuracies of the measures in localizing multi-bug programs are lower than single-bug programs, which provokes future research. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Previous studies have demonstrated that ciliary neurotrophic factor (CNTF) enhances survival and process outgrowth from magnocellular neurons in the paraventricular (PVN) and the supraoptic (SON) nuclei. However, the mechanisms by which CNTF facilitates these processes remain to be determined. Therefore, the aim of this study was to identify the immediate signal transduction events that occur within the rat SON following administration of exogenous rat recombinant CNTF (rrCNTF) and to determine the contribution of those intracellular signaling pathway(s) to neuronal survival and process outgrowth, respectively. Immunohistochemical and Western blot analyses demonstrated that axonal injury and acute unilateral pressure injection of 100ng/μl of rrCNTF directly over the rat SON resulted in a rapid and transient increase in phosphorylated-STAT3 (pSTAT3) in astrocytes but not neurons in the SON in vivo. Utilizing rat hypothalamic organotypic explant cultures, we then demonstrated that administration of 25ng/ml rrCNTF for 14days significantly increased the survival and process outgrowth of OT magnocellular neurons. In addition, pharmacological inhibition of the Jak-STAT pathway via AG490 and cucurbitacin I significantly reduced the survival of OT magnocellular neurons in the SON and PVN; however, the contribution of the Jak-STAT pathway to CNTF-mediated process outgrowth remains to be determined. Together, these data indicate that CNTF-induced survival of OT magnocellular neurons is mediated indirectly through astrocytes via the Jak-STAT signaling pathway. [Copyright &y& Elsevier]

Abstract: Mucosal epithelium M cells are dispersed across Peyer’s patch follicle associated epithelium (PPFAE) with minimal clustering. Since Notch signaling can influence patterning in epithelia, we examined its influence on PPFAE M cell distribution. Conditional deletion of Notch1 in intestinal epithelium increased PPFAE M cells and also increased M cell clustering, implying a role for Notch in both M cell numbers and lateral inhibition. By contrast, conditional deletion of the ligand Jagged1 also increased M cell clustering, but with a paradoxical decrease in M cell density. In vitro, inhibition of Notch signaling reduced expression of an M cell associated gene CD137, consistent with cis-promoting effects on M cell development. Thus, Jagged1 may have a cis-promoting role in committed M cells, but a trans-inhibitory effect on neighboring cells. In sum, Jagged1–Notch signaling may edit the pattern of M cells across the PPFAE, which may help optimize mucosal immune surveillance. [Copyright &y& Elsevier]

Abstract: Libraries usually impose constraints on how clients should use them. Often these constraints are not well-documented. In this paper, we address the problem of recovering such constraints automatically, a problem referred to as specification mining. Given some client programs that use a given library, we identify constraints on the library usage that are (almost) satisfied by the given set of clients. The class of rules we target for mining combines simple binary temporal operators with state predicates (composed of equality constraints) and quantification. This is a simple yet expressive subclass of temporal properties (LTL formulae) that allows us to capture many common API usage rules. We focus on recovering rules from execution traces and apply classical data mining concepts to be robust against bugs (API usage rule violations) in clients. We present new algorithms for mining rules from execution traces. We show how a propositional rule mining algorithm can be generalized to treat quantification and state predicates in a unified way. Our approach enables the miner to be complete (i.e. , mine all rules within the targeted class that are satisfied by the given traces) while avoiding an exponential blowup. We have implemented these algorithms and used them to mine API usage rules for several Windows APIs. Our experiments show the efficiency and effectiveness of our approach. [Copyright &y& Elsevier]

Introduction The Organ Injury Scale for chest wall trauma, last updated in 1992, governs the diagnosis and management of nearly half of all trauma patients. When this scale is used in association with the abbreviated injury score (AIS) and the trauma injury severity score (TRISS), overall survival following trauma can be estimated. There is presently no standardized scoring system for blunt chest wall trauma in the setting of lung herniation. Methods A systematic review of the literature on blunt chest wall trauma was completed and all reports of lung hernias since 1500 compiled. Four hundred cases of blunt trauma to the chest leading to lung herniation were identified and used to develop a classification scheme for extrathoracic lung herniation, adapt the organ injury scale for chest wall trauma to include extrathoracic lung hernias, and elucidate a treatment algorithm based on the type of lung hernia. Results Lung hernias can be divided into anterior and posterior; anterior hernias can be further divided into intercostal and parasternal. Intercostal hernias should be managed acutely by way of anterior chest wall exposure and potential thoracotomy due to the significantly higher risk of incarceration and/or strangulation. Discussion Anterior lung hernias should be grade III (AIS 3), parasternal lung hernias as grade IV (AIS 4), posterior lung hernias or the presence of any incarcerated lung as grade V (AIS 4), and strangulated lung hernias as grade VI (AIS 5). Incarcerated or strangulated lung has a high reported morbidity and mortality. [ABSTRACT FROM AUTHOR]

Abstract: A sequential rule expresses a relationship between two series of events happening one after another. Sequential rules are potentially useful for analyzing data in sequential format, ranging from purchase histories, network logs and program execution traces. In this work, we investigate and propose a syntactic characterization of a non-redundant set of sequential rules built upon past work on compact set of representative patterns. A rule is redundant if it can be inferred from another rule having the same support and confidence. When using the set of mined rules as a composite filter, replacing a full set of rules with a non-redundant subset of the rules does not impact the accuracy of the filter. We consider several rule sets based on composition of various types of pattern sets—generators, projected-database generators, closed patterns and projected-database closed patterns. We investigate the completeness and tightness of these rule sets. We characterize a tight and complete set of non-redundant rules by defining it based on the composition of two pattern sets. Furthermore, we propose a compressed set of non-redundant rules in a spirit similar to how closed patterns serve as a compressed representation of a full set of patterns. Lastly, we propose an algorithm to mine this compressed set of non-redundant rules. A performance study shows that the proposed algorithm significantly improves both the runtime and compactness of mined rules over mining a full set of sequential rules. [Copyright &y& Elsevier]

Abstract: Ciliary neurotrophic factor (CNTF) is expressed by glial cells at multiple levels of the magnocellular neurosecretory system (MNS). CNTF is present in astrocytes in the hypothalamic supraoptic nucleus (SON) as well as in perivascular cells in the neurohypophysis, and a several fold increase in CNTF immunoreactivity occurs in the SON following either axotomy of magnocellular neurons or during axonal sprouting by intact magnocellular neurons. CNTF also promotes survival and stimulates process outgrowth from magnocellular neurons in vitro. While these findings suggest that CNTF may act as a growth factor in support of neuronal plasticity in the MNS, little is known regarding possible expression of receptors for CNTF in the MNS. We have therefore used immunocytochemistry and in situ hybridization to examine the expression of CNTF receptor alpha (CNTFRα) in the rat MNS. Robust immunoreactivity for CNTFRα was observed associated with oxytocinergic and vasopressinergic neurons distributed throughout the SON. Astrocytes located within the ventral glial lamina (VGL) of the SON were also immunoreactive for CNTFRα. Robust hybridization of an anti-sense [35S]-cRNA probe to CNTFRα mRNA was observed throughout the SON, while binding of a control sense probe was much lower. Grains were found clustered predominantly over neuronal somata, indicative of expression by magnocellular neurons within the SON. We next examined changes in expression of CNTFRα mRNA by magnocellular neurons 7 days following unilateral transection of the hypothalamo-neurohypophysial tract. The level of CNTFRα mRNA was increased 32% (compared to age-matched intact controls; p <0.05) in magnocellular neurons in the SON contralateral to the lesion, which are undergoing extensive collateral axonal sprouting, but was unchanged in axotomized magnocellular neurons in the SON ipsilateral to the lesion. These findings suggest that CNTF produced by MNS glia and acting via CNTFRα may exert neurotrophic effects on magnocellular neurons. [Copyright &y& Elsevier]

Duplication of the gallbladder is a rare congenital anomaly of the biliary system. We herein present a case of a 9-month-old full-term female with a prenatally identified gallbladder duplication cyst managed via laparoscopic excision. [ABSTRACT FROM AUTHOR]

Code search is a core software engineering task. Effective code search tools can help developers substantially improve their software development eiciency and efectiveness. In recent years, many code search studies have leveraged diferent techniques, such as deep learning and information retrieval approaches, to retrieve expected code from a large-scale codebase. However, there is a lack of a comprehensive comparative summary of existing code search approaches. To understand the research trends in existing code search studies, we systematically reviewed 81 relevant studies. We investigated the publication trends of code search studies, analyzed key components, such as codebase, query, and modeling technique used to build code search tools, and classified existing tools into focusing on supporting seven diferent search tasks. Based on our findings, we identified a set of outstanding challenges in existing studies and a research roadmap for future code search research. [ABSTRACT FROM AUTHOR]

Abstract: The expression of ciliary neurotrophic factor (CNTF) was investigated immunocytochemically during the axonal degeneration and collateral axonal sprouting response that follows partial denervation of the rat neurohypophysis. A significant increase in the number of CNTF-immunoreactive (CNTF-ir) cells was observed in the neurohypophysis of partially denervated animals compared to age-matched sham-operated controls by 5 days post-denervation, remaining elevated throughout the 30 day post-denervation period. Stereometric assessment of the numbers of CNTF-ir cells within the partially denervated neurohypophysis demonstrated a 36% increase by 3 days following denervation reaching 130% of control values by 10 days post-lesion. The cell numbers remained elevated throughout the 30 day post-lesion period suggesting that CNTF may play a role in the neurosecretory axonal sprouting process known to occur between 10 and 30 days post-denervation. Subsequent preparations pairing anti-CNTF with antibodies against ED1, CR3, p75 low affinity neurotrophin receptor (p75LNGFR), and S100β, demonstrated that CNTF was exclusively localized in a phenotypically-distinct population of perivascular cells. The association of perivascular cells with phagocytic activity was confirmed by dual-label fluorescence microscopy showing the colocalization of P75LNGFR-ir and OX-42-ir in cells expressing the ED-1 antigen. No increase in CNTF-ir was observed in non-injured animals in which heightened levels of neurosecretory activity were induced physiologically. These results suggest that increased CNTF-ir occurs in response to conditions which induce high levels of phagocytic activity by perivascular cells in the axotomized neurohypophysis which is sustained throughout a period in which axonal sprouting is known to occur in the partially denervated neurohypophysis. [Copyright &y& Elsevier]

Software evolution incurs difficulties in program comprehension and software verification, and hence it increases the cost of software maintenance. In this study, we propose a novel technique to mine from program execution traces a sound and complete set of statistically significant temporal rules of arbitrary lengths. The extracted temporal rules reveal invariants that the program observes, and will consequently guide developers to understand the program behaviors, and facilitate all downstream applications such as verification and debugging. Different from previous studies that were restricted to mining two-event rules (e.g., →), our algorithm discovers rules of arbitrary lengths. In order to facilitate downstream applications, we represent the mined rules as temporal logic expressions, so that existing model checkers or other formal analysis toolkit can readily consume our mining results. Performance studies on benchmark data sets and a case study on an industrial system have been performed to show the scalability and utility of our approach. We performed case studies on JBoss application server and a buggy concurrent versions system application, and the result clearly demonstrates the usefulness of our technique in recovering underlying program designs and detecting bugs. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: The immune system is a host defense system comprised of both innate mechanisms able to rapidly recognize and respond to conserved pathogen associated molecular patterns (PAMPs) as well as adaptive mechanisms able to respond to a wide variety of non-conserved and conserved pathogen associated molecules. In vitro and in vivo studies have demonstrated that the kinetics and type of immune response triggered by pathogenic insults is a function of both the nature of the insult and the subsequent cross-regulatory interactions between the responding immune cells. In this context, the potential immunomodulatory influences of the nervous system have been often viewed as exerting minimal modulatory effects and thus of being largely irrelevant in the development of immune responses. Here, using a Saturday Night Live (SNL)-styled point:counterpoint format, we discuss whether and to what extent the nervous system can shape the responses of the immune system. Finally, we examine whether primary degenerative disorders of the CNS are likely to lead to alterations in immune function. [Copyright &y& Elsevier]

This paper builds on our August 2004 paper where data fusion is used to combine results from multiple audio and video localizers in order to locate a talker in video conferencing applications. The two studies differ in the type of data fusion engine used. The former study explored using a summing voter for data fusion, whereas this study employs a Bayesian network. The novelty of both papers is the use of reliability estimates to improve the overall localization performance and robustness. Reliability estimates, which are derived based on known physical properties of each individual localizer, were used to gauge the trustworthiness of the current localization results. These reliability estimates were introduced into the fusion engines to achieve better performance. Although the summing voter fusion engine used in [1] improves the overall localization performance, it does not take into account the unique characteristics of each localizer. The Bayesian network allows the inclusion of these unique characteristics as part of the fusion process and therefore further improves the overall localization performance. When one or more localizers fails, the persistent erroneous data streams from the failed localizers can negatively affect a statistically based data fusion method, like the Bayesian network, resulting in poor localization accuracy [2]. The study described in this paper explores the use of the reliability estimates to automatically stop the failed devices from contributing in the data fusion process, hence improving the overall robustness of the system. In this paper, we investigate the impact of 1) using a Bayesian network as the data fusion engine, 2) adding reliability estimates into the fusion engine, and 3) using reliability estimates to stop the failed localizers from contributing in the fusion process. [ABSTRACT FROM AUTHOR]

This paper proposes a new method for performing joint audio-video talker localization that explores the reliability of the individual localization estimates such as audio, motion detection, and skin-color detection. The reliability information is estimated from the audio and video data separately. The proposed method then uses this reliability information in conjunction with a simple summing voter to dynamically discriminate erroneous outputs from the localizers while performing fusion on the localization results. Based on the voter output, a majority rule is then used to make the final decision of the active talker's current location. The results show that adding the reliability information during fusion improves localization performance when compared to audio only, motion detection only, skin-color detection only, and joint audio-video using straight summing fusion localization methods. The computational complexity of the proposed method is comparable to the existing ones. [ABSTRACT FROM AUTHOR]

Mammalian Peyer’s Patches possess specialized epithelium, the follicle associated epithelium (FAE), and specialized cells called M cells which mediate transcytosis of antigens to underlying lymphoid tissue. To identify FAE specific genes, we used TOGA gene expression profiling of microdissected mouse Peyer’s Patch tissue. We found expression of laminin β3 across the FAE, and scattered expression of peptidoglycan recognition protein (PGRP)-S. Using the M cell specific lectin Ulex europaeus agglutinin 1 (UEA-1), PGRP-S expression was nearly exclusively co-localized with UEA-1+ M cells. By contrast, the related gene PGRP-L was expressed among a subset of UEA-1 negative FAE cells. Expression of these proteins in transfected cells demonstrated distinct subcellular localization. PGRP-S showed a vesicular pattern and extracellular secretion, while PGRP-L showed localization to both the cytoplasm and the cell surface. The potential function of these PGRP proteins as pattern recognition receptors and their distinctive cellular distribution suggests a complex coordination among specialized cells of the FAE in triggering mucosal immunity and innate immune responses. [Copyright &y& Elsevier]

Drug delivery technologies are commonly directed towards formulations to control the delivery of therapeutic compounds. However, many processes in the human body have evolved to regulate the transport of various molecules, cells, or particles across epithelial barriers. To take advantage of this biology, we used TOGA® gene expression profiling to identify receptor or transporter molecules to target delivery vehicles for transport across an epithelial barrier. In the case of intestinal epithelium, we sought molecules associated with the transport of particles by Peyer’s patch M cells. We have identified genes specific to Peyer’s patch epithelium, some of which appear to be M cell specific. Discoveries made by this process will provide targets for development of new vaccines, but also provide new insights into the biology of transepithelial transport. The power of this gene profiling approach also suggests application to other systems, such as the response to metabolic changes or drug treatments. [Copyright &y& Elsevier]

The mammalian defense system can respond to a variety of threats, but this capability is not just a simple alarm system for triggering antigen-presenting cells and initiating cellular immunity. Instead, the body is an integrated system in which nearly every cell type can relay the alarm through the production of chemokines, which recruit specific inflammatory cells to the target tissues. This chemokine production is carefully regulated at several levels so that the kinetics and character of local tissue inflammation is tailored to the specific threat. First, the production of nuclear factor-κB-regulated chemokines can be modulated in non-bone marrow-derived cells through transcriptional repression mediated by RelB. RelB is also implicated in the differentiation of lymphoid dendritic cells, suggesting that this gene regulates the transition from acute inflammation to adaptive immunity. Second, tissue parenchymal cells, in their capacity as sentinel cells, are able to produce different patterns of chemokines in response to different alarm stimuli. Third, cells from different tissues also show distinct potentials for chemokine responses so that the non-specific damage from inflammation might be avoided in some cases. FInally, the differentiation of T-cell effectors allows for further regulation of local inflammation as their cytokines can also affect chemokine production. This integration of innate and adaptive immunity allows for both rapid responses and dynamic regulation of inflammation in vivo. [ABSTRACT FROM AUTHOR]

Over the past decade, there have been many studies determining the effect of dietary ω-3 and ω-6 fatty acids intake on cognitive performance; however, they have largely been inconsistent in their conclusions. In this letter, we provide context to the article by Dong et al., titled "Association of dietary ω-3 and ω-6 fatty acids intake with cognitive performance in older adults: National Health and nutrition examination Survey (NHANES) 2011-2014" and provide methodological considerations with regards to covariate measurement and inclusion that can be generalized to future cross-sectional studies. In particular, delineating 1) the type and source of fatty acid, in context of an individual's overall dietary patterns, 2) sociobehavioral risk factors and physical & mental comorbidities, 3) and daily cognitive activity are important to adequately control for covariates. [ABSTRACT FROM AUTHOR]

We are happy to introduce you to this special issue that presents selected papers from the 15th IEEE International Working Conference on Source Code Analysis and Manipulation (SCAM 2015). SCAM is a leading conference that brings together researchers and practitioners working on theory, techniques, and applications that concern analysis and/or manipulation of the source code of computer systems. While much attention in the wider software engineering community is properly directed towards other aspects of systems development and evolution, such as specification, design, and requirements engineering, it is the source code that contains the only precise description of the behavior of the system. The analysis and manipulation of source code thus remains a pressing concern. SCAM 2015 was held on September 27 to 28, 2015, in Bremen, Germany, together with 31st International Conference on Software Maintenance and Evolution (ICSME). [ABSTRACT FROM AUTHOR]

Chemoradiation (CRT) may modulate the immune milieu as an in-situ vaccine. Rapid dose delivery of brachytherapy has unclear impact on T-cell repertoires. HPV-associated cancers express viral oncoproteins E6/E7, which enable tracking antigen/tumor-specific immunity during CRT. Thirteen cervical cancer patients on a multi-institutional prospective protocol from 1/2020–1/2023 underwent standard-of-care CRT with pulsed-dose-rate brachytherapy boost (2 fractions). Cervix swabs at various timepoints underwent multiplex DNA deep sequencing of the TCR-β/CDR3 region with immunoSEQ. Separately, HPV-responsive T-cell clones were also expanded ex vivo. Statistical analysis was via Mann-Whitney-U. TCR productive clonality, templates, frequency, or rearrangements increased post-brachytherapy in 8 patients. Seven patients had E6/E7-responsive evolution over CRT with increased productive templates (ranges: 1.2–50.2 fold-increase from baseline), frequency (1.2–1.7), rearrangements (1.2–40.2), and clonality (1.2–15.4). Five patients had HPV-responsive clonal expansion post-brachytherapy, without changes in HPV non-responsive clones. Epitope mapping revealed VDJ rearrangements targeting cervical cancer-associated antigens in 5 patients. The only two patients with disease recurrence lacked response in all metrics. A lack of global TCR remodeling correlated with worse recurrence-free survival, p = 0.04. CRT and brachytherapy alters the cervical cancer microenvironment to facilitate the expansion of specific T-cell populations, which may contribute to treatment efficacy. [ABSTRACT FROM AUTHOR]

This article discusses a study conducted by Ono et al. on the potential role of anti-inflammatory cytokines in postpartum depression (PPD) in perinatal women. The study suggests that low levels of anti-inflammatory cytokines, specifically IL-10, may have a protective effect against the development of PPD. However, the article highlights the need for future research to control for confounding variables such as socioeconomic status and medications, which can also contribute to PPD and cytokine levels. Additionally, the study had a limited number of subjects and lacked diversity, which may limit the generalizability of the findings. The article concludes by emphasizing the importance of further research and improvement in understanding the association between cytokine levels and PPD. [Extracted from the article]

Therefore, we propose conducting a subgroup analysis of study participants based on their age at diabetes diagnosis to determine whether this variable influences the risk of dementia. Overall, this subgroup analysis would help determine whether or not mental illness may be a confounding variable in the onset of dementia. We read with pleasure the article by Zhao et al[1] titled "Thiazolidinedione use is associated with reduced risk of dementia in patients with type 2 diabetes mellitus: A retrospective cohort study" and would like to provide critical commentary on the inclusion of modifiable and nonmodifiable risk factors for dementia in subgroup analyses for patients taking thiazolidinediones (TZDs). [Extracted from the article]

Importance: Diabulimia is a disordered eating behavior in which a person with type 1 diabetes withholds insulin injections to lose weight. It is thought that the psychosocial stress of managing this chronic disease, which is termed diabetes distress, may contribute to developing diabulimia. Objective: This paper explores links between diabetes distress and diabulimia and their relevance to the diagnosis and treatment of diabulimia by assessing whether people with diabulimia report measurable evidence of diabetes distress. Evidence Review: We evaluated studies examining the qualitative experiences of people with disordered eating behaviors in the setting of type 1 diabetes for themes of diabetes distress by identifying aspects of the patients' stories that matched the criteria in the Diabetes Distress Scale. Selected studies recorded primary data, analyzed qualitative data, examined lived experiences of individuals with diabulimia, and were made available in English-language peer-reviewed journals between January 1, 2000 and August 31, 2022. Exclusion criteria included partial articles, editorials, reviews, and abstracts along with studies of patients with type 2 diabetes. Findings. Over forty individual participants across twelve studies were found to have aspects of their experiences that met one or more criteria from the Diabetes Distress Scale. Participants reported experiences that matched criteria items from each of the seven subscales of the Diabetes Distress Scale. Participants in the twelve studies included 185 individuals with type 1 diabetes experiencing diabulimia, including 164 females (88.6%), 20 males (10.8%), and 1 non-reported gender (0.54%). Conclusion: We believe this discovery warrants further research probing the prevalence of diabetes distress among people with diabulimia as well as other links between the two conditions. We advocate for a diabetes distress-informed approach to diabulimia treatment and for diabetes distress screening in every patient with type 1 diabetes. Highlights: It is thought that the psychosocial stress of managing diabetes, termed diabetes distress, may contribute to developing diabulimia, which is a disordered eating behavior in which a person withholds insulin injections to lose weight. We explore links between diabetes distress and diabulimia and their relevance to the diagnosis and treatment of diabulimia. Studies were evaluated by examining the qualitative experiences of people with disordered eating behaviors in the setting of type 1 diabetes for themes of diabetes distress by identifying aspects of the patients' stories that matched the criteria in the Diabetes Distress Scale. Over forty individual participants across twelve studies were found to have aspects of their experiences that met one or more criteria from the Diabetes Distress Scale. We believe this discovery warrants further research probing the prevalence of diabetes distress among people with diabulimia as well as other links between the two conditions. Plain English summary: Diabulimia is a disordered eating behavior in people with type 1 diabetes who intentionally withhold insulin injections to lose weight. This study investigates the connection between diabulimia and diabetes distress, the daily psychosocial stress of managing diabetes. We examined the qualitative narratives of 40 participants with diabulimia as recorded in 12 studies and found that they reported experiences matching criteria from the Diabetes Distress Scale, a tool to measure diabetes-related stress. We suggest further research to understand the prevalence of diabetes distress in people with diabulimia. Also, we advocate for using a diabetes distress-informed approach in diabulimia treatment, including screening for diabetes distress in all individuals with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Lung exposures to dusts, pollutants, and other aerosol particulates are known to be associated with pulmonary diseases such as asthma and Chronic Obstructive Pulmonary Disease. These health impacts are attributed to the ability of aerosol components to induce pulmonary inflammation, which promotes tissue remodeling, including fibrosis, tissue degradation, and smooth muscle proliferation. Consequently, the distribution of these effects can have a significant impact on the physiologic function of the lung. In order to study the impact of distribution of inhaled particulates on lung pathogenesis, we compared the effect of different methods of particle delivery. By comparing intranasal versus aerosol delivery of fluorescent microspheres, we observed strikingly distinct patterns of particle deposition; intranasal delivery provided focused deposition concentrated on larger airways, while aerosol delivery showed unform deposition throughout the lung parenchyma. Recognizing that the impacts of inflammatory cells are contingent upon their recruitment and behavior, we postulate that these variations in distribution patterns can result in significant alterations in biological responses. To elucidate the relevance of these findings in terms of biological representation, we subsequently conducted an investigation into the responses elicited by the administration of endotoxin (bacterial Lipopolysaccharide, or LPS) in a transgenic neutrophil reporter mouse model. As with the microsphere results, patterns of recruited neutrophil inflammatory responses matched the delivery method; that is, despite the active migratory behavior of neutrophils, inflammatory histopathology patterns were either focused on large airways (intranasal administration) or diffusely throughout the parenchyma (aerosol). These results demonstrate the importance of modes of aerosol delivery as different patterns of inflammation and tissue remodeling will have distinct impacts on lung physiology. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) is the primary driver of cervical cancer. Although studies in other malignancies correlated peripheral blood DNA clearance with favorable outcomes, research on the prognostic value of HPV clearance in gynecologic cancers using intratumoral HPV is scarce. We aimed to quantify the intratumoral HPV virome in patients undergoing chemoradiation therapy (CRT) and associate this with clinical characteristics and outcomes. This prospective study enrolled 79 patients with stage IB-IVB cervical cancer undergoing definitive CRT. Cervical tumor swabs collected at baseline and week 5 (end of intensity modulated radiation therapy) were sent for shotgun metagenome sequencing and processed via VirMAP, a viral genome sequencing and identification tool for all known HPV types. The data were categorized into HPV groups (16, 18, high risk [HR], and low risk [LR]). We used independent t tests and Wilcoxon signed-rank to compare continuous variables and χ2 and Fisher exact tests to compare categorical variables. Kaplan-Meier survival modeling was performed with log-rank testing. HPV genotyping was verified using quantitative polymerase chain reaction to validate VirMAP results using receiver operating characteristic curve and Cohen's kappa. At baseline, 42%, 12%, 25%, and 16% of patients were positive for HPV 16, HPV 18, HPV HR, and HPV LR, respectively, and 8% were HPV negative. HPV type was associated with insurance status and CRT response. Patients with HPV 16+ and other HPV HR+ tumors were significantly more likely to have a complete response to CRT versus patients with HPV 18 and HPV LR/HPV-negative tumors. Overall HPV viral loads predominantly decreased throughout CRT, except for HPV LR viral load. Rarer, less well-studied HPV types in cervical tumors are clinically significant. HPV 18 and HPV LR/negative tumors are associated with poor CRT response. This feasibility study provides a framework for a larger study of intratumoral HPV profiling to predict outcomes in patients with cervical cancer. [ABSTRACT FROM AUTHOR]

The article titled "Serving size estimates using digital food photographs among Japanese adults: a critical analysis" discusses the accuracy of estimating serving sizes using digital food photographs among Japanese adults. The study found that there are significant differences between estimated and true serving sizes for most food items, but on average, the relative difference was small. Factors such as the type, shape, texture, and size of the food, as well as the conditions of the study and the characteristics of the participants, can impact the accuracy of estimates. The article suggests considering food consumption rather than just portion sizes served and using multiple methods, such as visual aids and standardized measurement tools, to improve accuracy. It also recommends making the web-based questionnaire anonymous and including questions related to eating disorders and hunger levels in future iterations of the survey. Overall, the authors commend the study and look forward to future research in this area. [Extracted from the article]

This article is a letter to the editor in response to a study on the seasonal association between vitamin D concentration, muscle mass, and strength in postmenopausal women. The authors offer additional commentary on the study's conclusions regarding the influence of diet, sun exposure, skin pigmentation, and genetics on vitamin D levels and their impact on muscle mass and strength. They suggest that future research should consider the effect of diet, quantify sun exposure levels, and study participants with varying levels of melanin to ensure validity of results in all populations. Additionally, they highlight the importance of genetic variants in influencing vitamin D storage and metabolism. The authors commend the study and look forward to future research on these factors. [Extracted from the article]

The article titled "Comparison and convergent validity of five Mediterranean dietary indexes applied to Brazilian adults and older adults: data from a population-based study (2015 ISA-Nutrition): a critical analysis" discusses the limitations and implications of a study on the adherence to the Mediterranean diet in Brazilian adults. The authors highlight the need for further research to generalize the findings to global populations and consider the impact of pre-existing disorders, socioeconomic status, and the COVID-19 pandemic on access to food and adherence to the diet. They also emphasize the importance of excluding individuals with substance abuse disorders, eating disorders, and mental health conditions from the study. Additionally, the authors discuss the influence of socioeconomic status and barriers to food access on dietary choices and adherence to the Mediterranean diet. They suggest that future research should include post-pandemic data to gain a better understanding of eating habits and adherence to specific diets. [Extracted from the article]

This article is a letter to the editor of the Journal of Nutritional Science, providing additional commentary on a previous article about the association between selenium intake and cognitive function among older adults in the US. The authors suggest that further research should explore the impact of medications, diet, and viral infections on selenium's bioavailability and cognitive function. They also highlight the importance of factors such as oxidative stress, diet high in antioxidants, and viral infections in understanding cognitive decline. The authors acknowledge the limitations of the previous study and emphasize the need for future research to strengthen the validity of the findings. [Extracted from the article]

Common diagnoses associated with right upper quadrant and epigastric pain include cholecystitis, peptic ulcer disease (PUD), biliary colic, gastroesophageal reflux disease (GERD) and irritable bowel syndrome (IBS). Multiseptate gallbladder is a rare congenital anomaly that can cause symptoms of biliary colic, however it may present with atypical symptoms, which can prolong definitive diagnosis and treatment. We present a case of multiseptate gallbladder in a 21-year-old female who initially presented with GERD and IBS. After multiple failed treatment regimens for IBS, she ultimately was found to have multiseptate gallbladder and was successfully treated with cholecystectomy. [ABSTRACT FROM AUTHOR]

Billions of dollars are spent annually on software-related cost. It is estimated that up to 45 percent of software cost is due to the difficulty in understanding existing systems when performing maintenance tasks (i.e., adding features, removing bugs, etc.). One of the root causes is that software products often come with poor, incomplete, or even without any documented specifications. In an effort to improve program understanding, Lo et al. have proposed iterative pattern mining which outputs patterns that are repeated frequently within a program trace, or across multiple traces, or both. Frequent iterative patterns reflect frequent program behaviors that likely correspond to software specifications. To reduce the number of patterns and improve the efficiency of the algorithm, Lo et al. have also introduced mining closed iterative patterns, i.e., maximal patterns without any superpattern having the same support. In this paper, to technically deepen research on iterative pattern mining, we introduce mining iterative generators, i.e., minimal patterns without any subpattern having the same support. Iterative generators can be paired with closed patterns to produce a set of rules expressing forward, backward, and in-between temporal constraints among events in one general representation. We refer to these rules as representative rules. A comprehensive performance study shows the efficiency of our approach. A case study on traces of an industrial system shows how iterative generators and closed iterative patterns can be merged to form useful rules shedding light on software design. [ABSTRACT FROM AUTHOR]

T cells undergo homeostatic proliferation under states of lymphopenia in the body. Detailed molecular mechanisms regulating this phenomenon have not been completely elucidated. Our previous studies suggested that the homeostatic chemokine receptor, CCR7, may play a role in T cell homeostatic proliferation and autoimmunity induction. In this study, we tested if CCR7 signal itself stimulates T cell proliferation and/or if it promotes T cell survival in in vitro culture experiments with CCR7 ligands. The results show that, when purified T cells were cultured in the absence of TCR stimulation, more cells survived in the present of CCR7 ligands treatment, in a dose response manner, indicating that CCR7 signal can promote T cell survival. Interestingly, CD4+ T cells seemed to be more responsive to CCR7 ligand treatment than CD8+ T cells. Although signaling through CCR7 alone does not induce proliferation of ligand-treated T cells, this treatment can increase anti-CD3 induced T cell proliferation. However, CCR7 ligand treatment did not increase anit-CD3 stimulated cytokine expression and CD44 upregulation, suggesting that CCR7 does not provide a bona fide co-stimulation for T cell. These data suggest that signaling through CCR7 may positively modulate T cell homeostatic proliferation by enhancing signals from MHC/peptide and by promoting T cell survival. [ABSTRACT FROM AUTHOR]

Cloud applications are increasingly shifting from large monolithic services to complex graphs of loosely coupled microservices. Despite their benefits, microservices are prone to cascading performance issues, and can lead to prolonged periods of degraded performance. We present Sage, a machine-learning-driven root cause analysis system for interactive cloud microservices that is both accurate and practical. We show that Sage correctly identifies the root causes of performance issues across a diverse set of microservices and takes action to address them, leading to more predictable, performant, and efficient cloud systems. [ABSTRACT FROM AUTHOR]