bluuebunny/crossref_metadata_2025_split huggingface dataset:
Commensal-bacteria-derived butyrate promotes the T-cell-independent IgA response in the colon
Authors: Isobe Junya , Maeda Shintarou , Obata Yuuki , Iizuka Keito , Nakamura Yutaka , Fujimura Yumiko , Kimizuka Tatsuki , Hattori Kouya , Kim Yun-Gi , Morita Tatsuya , Kimura Ikuo , Offermanns Stefan , Adachi Takahiro , Nakao Atsuhito , Kiyono Hiroshi , Takahashi Daisuke , Hase Koji 
Published: December 2019

AbstractSecretory immunoglobulin A (SIgA), the most abundant antibody isotype in the body, maintains a mutual relationship with commensal bacteria and acts as a primary barrier at the mucosal surface. Colonization by commensal bacteria induces an IgA response, at least partly through a T-cell-independent process. However, the mechanism underlying the commensal-bacteria-induced T-cell-independent IgA response has yet to be fully clarified. Here, we show that commensal-bacteria-derived butyrate promotes T-cell-independent IgA class switching recombination (CSR) in the mouse colon. Notably, the butyrate concentration in human stools correlated positively with the amount of IgA. Butyrate up-regulated the production of transforming growth factor β1 and all-trans retinoic acid by CD103+CD11b+ dendritic cells, both of which are critical for T-cell-independent IgA CSR. This effect was mediated by G-protein-coupled receptor 41 (GPR41/FFA3) and GPR109a/HCA2, and the inhibition of histone deacetylase. The butyrate-induced IgA response reinforced the colonic barrier function, preventing systemic bacterial dissemination under inflammatory conditions. These observations demonstrate that commensal-bacteria-derived butyrate contributes to the maintenance of the gut immune homeostasis by facilitating the T-cell-independent IgA response in the colon.
The potential application of PD-1 blockade therapy for early-stage biliary tract cancer
Authors: Umemoto Kumiko , Togashi Yosuke , Arai Yasuhito , Nakamura Hiromi , Takahashi Shinichiro , Tanegashima Tokiyoshi , Kato Mikiya , Nishikawa Tsubasa , Sugiyama Daisuke , Kojima Motohiro , Gotohda Naoto , Kuwata Takeshi , Ikeda Masafumi , Shibata Tatsuhiro , Nishikawa Hiroyoshi 
Published: December 2019

AbstractBiliary tract cancer (BTC) is an aggressive cancer with a poor prognosis partially due to the limited success in developing novel therapies, including molecularly targeted therapies and immunotherapies. Programmed cell death-1 (PD-1) blockade therapy is less effective against BTCs, necessitating further studies to understand the detailed immunological status of the tumor microenvironment (TME) in BTC. Here, we examined the immunological status of the TME in 37 BTCs with early- to late-stage disease, especially focusing on PD-1+CD8+ T cells. PD-1+CD8+ T cells, which are reportedly associated with the clinical response to PD-1 blockade therapy, were frequently observed in early-stage BTC and decreased with disease progression. Imaging mass cytometry for representative PD-1+CD8+TIL-high and -low patients demonstrated that tumor-infiltrating PD-1+CD8+ T cells were localized adjacent to tumor cells, whereas PD-1−CD8+ T cells were detected mainly in the stroma of the TME. In a mouse model, PD-1 expression by tumor-infiltrating CD8+ T cells was higher in smaller tumors and decreased with tumor growth. Consequently, large tumors became resistant to PD-1 blockade, while small tumors containing higher numbers of PD-1+CD8+ T cells were sensitive. We propose the important role of tumor-infiltrating PD-1+CD8+ T cells in anti-tumor immunity and the potential application of PD-1 blockade therapy for early-stage BTC.
Moving Molecular Profiling to Routine Clinical Practice: A Way Forward?
Authors: Freidlin Boris , Allegra Carmen J , Korn Edward L 
Published: December 2019

Abstract
Molecular profiling of a patient’s tumor to guide targeted treatment selection offers the potential to advance patient care by improving outcomes and minimizing toxicity (by avoiding ineffective treatments). However, current development of molecular profile (MP) panels is often based on applying institution-specific or subjective algorithms to nonrandomized patient cohorts. Consequently, obtaining reliable evidence that molecular profiling is offering clinical benefit and is ready for routine clinical practice is challenging. In particular, we discuss here the problems with interpreting for clinical utility nonrandomized studies that compare outcomes in patients treated based on their MP vs those treated with standard of care, studies that compare the progression-free survival (PFS) seen on a MP-directed treatment to the PFS seen for the same patient on a previous standard treatment (PFS ratio), and multibasket trials that evaluate the response rates of targeted therapies in specific molecularly defined subpopulations (regardless of histology). We also consider some limitations of randomized trial designs. A two-step strategy is proposed in which multiple mutation-agent pairs are tested for activity in one or more multibasket trials in the first step. The results of the first step are then used to identify promising mutation-agent pairs that are combined in a molecular panel that is then tested in the step-two strategy-design randomized clinical trial (the molecular panel–guided treatment for the selected mutations vs standard of care). This two-step strategy should allow rigorous evidence-driven identification of mutation-agent pairs that can be moved into routine clinical practice.
Making Sense of “Somatization”: A Systematic Review of its Relationship to Pediatric Pain
Authors: Boerner Katelynn E , Green Katherine , Chapman Andrea , Stanford Elizabeth , Newlove Theresa , Edwards Katherine , Dhariwal Amrit 
Published: December 2019

AbstractObjectivesPain and other physical symptoms commonly co-occur in childhood. There is debate about the relevance of somatization in understanding pain. The present review critically appraised and synthesized the extant literature on the relationship between pediatric pain and somatization.MethodsA systematic review (PROSPERO registration #95956) was conducted in Medline, PsycINFO, EMBASE, and CINAHL using search terms related to pain and somatization in children and adolescents. A total of 156 articles were eligible for inclusion in the review. For studies that measured somatization using a symptom questionnaire, descriptions of “somatization” were extracted. Data regarding the relationship between pain and somatization were extracted for studies measuring somatization using a diagnostic category (e.g., Somatic Symptom and Related Disorders [SSRDs]).ResultsWhile many studies using somatic symptom questionnaires described somatization as having a psychological component, this was not always captured in measurement tools. Pain was reported as a common symptom in patients with an SSRD diagnosis, though rates varied depending on the specific diagnosis and pain location. Rates of SSRD diagnoses among pain patients were less frequent than rates of pain amongst SSRD patients.ConclusionsSSRDs and pain commonly co-occur, though rates differ depending on diagnosis and pain location. Understanding the relationship between pain and somatization is complicated by the discrepancy between how somatization is defined and measured in questionnaire studies. A comprehensive and measurable definition of somatization is needed so researchers can better identify the shared and unique contributions of pain and somatization in pediatric populations.
Role of blue and red light in stomatal dynamic behaviour
Authors: Matthews Jack S A , Vialet-Chabrand Silvere , Lawson Tracy 
Published: December 2019

AbstractPlants experience changes in light intensity and quality due to variations in solar angle and shading from clouds and overlapping leaves. Stomatal opening to increasing irradiance is often an order of magnitude slower than photosynthetic responses, which can result in CO2 diffusional limitations on leaf photosynthesis, as well as unnecessary water loss when stomata continue to open after photosynthesis has reached saturation. Stomatal opening to light is driven by two distinct pathways; the ‘red’ or photosynthetic response that occurs at high fluence rates and saturates with photosynthesis, and is thought to be the main mechanism that coordinates stomatal behaviour with photosynthesis; and the guard cell-specific ‘blue’ light response that saturates at low fluence rates, and is often considered independent of photosynthesis, and important for early morning stomatal opening. Here we review the literature on these complicated signal transduction pathways and osmoregulatory processes in guard cells that are influenced by the light environment. We discuss the possibility of tuning the sensitivity and magnitude of stomatal response to blue light which potentially represents a novel target to develop ideotypes with the ‘ideal’ balance between carbon gain, evaporative cooling, and maintenance of hydraulic status that is crucial for maximizing crop performance and productivity.
Ethylene regulates post-germination seedling growth in wheat through spatial and temporal modulation of ABA/GA balance
Authors: Sun Menghan , Tuan Pham Anh , Izydorczyk Marta S , Ayele Belay T 
Published: December 2019

Abstract
This study aimed to gain insights into the molecular mechanisms underlying the role of ethylene in regulating germination and seedling growth in wheat by combining pharmacological, molecular, and metabolomics approaches. Our study showed that ethylene does not affect radicle protrusion but controls post-germination endospermic starch degradation through transcriptional regulation of specific α-amylase and α-glucosidase genes, and this effect is mediated by alteration of endospermic bioactive gibberellin (GA) levels, and GA sensitivity via expression of the GA signaling gene, TaGAMYB. Our data implicated ethylene as a positive regulator of embryo axis and coleoptile growth through transcriptional regulation of specific TaEXPA genes. These effects were associated with modulation of GA levels and sensitivity, through expression of GA metabolism (TaGA20ox1, TaGA3ox2, and TaGA2ox6) and signaling (TaGAMYB) genes, respectively, and/or the abscisic acid (ABA) level and sensitivity, via expression of specific ABA metabolism (TaNCED2 or TaCYP707A1) and signaling (TaABI3) genes, respectively. Ethylene appeared to regulate the expression of TaEXPA3 and thereby root growth through its control of coleoptile ABA metabolism, and root ABA signaling via expression of TaABI3 and TaABI5. These results show that spatiotemporal modulation of ABA/GA balance mediates the role of ethylene in regulating post-germination storage starch degradation and seedling growth in wheat.
Between Exclusion and Intersection: Heidegger’s Philosophy and Jewish Volkism1
Authors: Herskowitz Daniel M 
Published: December 2019

Abstract
This article deals with some unexplored Jewish resp.onses to the volkish elements in Martin Heidegger’s philosophy. Heidegger’s idiosyncratic and deeply philosophical account of volkism stood at the heart of his political support of National Socialism and of his exclusion of the Jews from the ontological task of thinking. This article demonstrates, however, that some of Heidegger’s Jewish readers identified with volkish moments in his philosophy and found these to be pertinent to their own condition as Jews in the modern world. This was made possible by the fact that, within the intellectual climate in which Heidegger’s thinking took shape, the volkish lexicon (Volk, Gemeinschaft, ‘fate’, ‘destiny’, and even ‘struggle’) was commonplace, indicated no clear association with any certain political view, and, indeed, was a central organ through which Jews made sense of their own existence and historical and political situation. Thus, while Heidegger’s volkism led to a philosophical marginalization of Jews, the multifariousness and widespread currency of volkish thinking brought some Jewish readers to recognize their shared conceptual horizon with Heidegger and to differentiate between Heidegger’s practical politics, which were anti-Jewish and loathsome, and his volkism, which was seen as fitting and useful for the Jewish case.
Deskilling unpacked: Comparing Filipino and Polish migrant nurses’ professional experiences in Norway
Authors: Korzeniewska Lubomiła , Erdal Marta Bivand 
Published: December 2019

Abstract
This article offers empirically based analytical scrutiny of what deskilling looks like and means for migrant nurses. We draw on 30 interviews with Filipino and Polish nurse migrants in Oslo, Norway, which we analyze comparatively. Through empirical attention to nurse migrants’ professional experiences, we address the analytically oriented question of what constitutes deskilling in their experience. Concerns over deskilling, in relation to nurse migration and beyond, prompt attention to instances of human capital not being employed in meaningful and productive ways. We argue that attention to migrants’ professional identities provides analytical opportunity to better unpack what deskilling entails. Borrowing from theorization of identities, deskilling as linked to migrants’ professional identities is understood as dynamic, processual, and situated. We propose that deskilling should be understood as part of the multi-dimensional and interacting processes of de-, re-, and upskilling. We find cases of obvious and wasteful deskilling related to authorization procedures for non-EU-trained nurses, but also instances where it may be disputable whether human resources are used well, or not, and cases of upskilling and reskilling over time. Our findings uncover three core insights. First, our approach to deskilling reveals both the scope for and the salience of migrants’ agency, despite structural constraints. Second, the importance of time and of capturing change over time in migration research becomes apparent. Third, we argue that improved conceptualizations of deskilling, linked to migrants’ professional identities, could inform policies that make better use of migrants’ human capital, and through this also contribute to migrants’ well-being.
Detection of invasive pulmonary aspergillosis in mice using lung perfusion single-photon emission computed tomography with [99mTc]MAA
Authors: Yoshida Masataka , Tashiro Masato , Nishi Kodai , Mishima Maki , Kawano Kei , Takazono Takahiro , Saijo Tomomi , Yamamoto Kazuko , Imamura Yoshifumi , Miyazaki Taiga , Kudo Takashi , Yanagihara Katsunori , Mukae Hiroshi , Izumikawa Koichi 
Published: December 2019

Abstract
There is an urgent need for development of better diagnostic strategies to improve outcomes in patients with invasive pulmonary aspergillosis (IPA). We hypothesized that lung perfusion single-photon emission computed tomography (SPECT) may be more sensitive and specific than computed tomography (CT) of the chest for detection of IPA because it is an angioinvasive pulmonary infection with characteristics that are different from those of bacterial pneumonia. We used SPECT with injection of technetium-99m-labeled macroaggregated albumin ([99mTc]MAA) to measure pulmonary perfusion in noninfected mice, mice with IPA, and mice with bacterial pneumonia. Histopathologic analysis was performed to evaluate the correlation between the perfusion defect and mould invasion. We also attempted to quantitatively evaluate the SPECT images to identify differences in decreased perfusion levels in affected areas in the mouse lung. Histopathologic analysis in the IPA mouse model showed a clear match between areas with a perfusion defect and the presence of mold, indicating that the location of the perfusion defect on a SPECT image reflects angioinvasion of the mould in the lungs. Some of these perfusion defects could be seen before appearance of the infiltrate of CT images. Quantitative analysis confirmed that perfusion in the affected areas was significantly decreased in the IPA model but not in the bacterial pneumonia model (P &lt; .0001). This imaging method may be preferable to the alternative methods presently used to identify the presence of mold in a patient's lungs.
Structural basis for osmotic regulation of the DNA binding properties of H-NS proteins
Authors: Qin Liang , Bdira Fredj Ben , Sterckx Yann G J , Volkov Alexander N , Vreede Jocelyne , Giachin Gabriele , van Schaik Peter , Ubbink Marcellus , Dame Remus T 
Published: December 2019

Abstract
H-NS proteins act as osmotic sensors translating changes in osmolarity into altered DNA binding properties, thus, regulating enterobacterial genome organization and genes transcription. The molecular mechanism underlying the switching process and its conservation among H-NS family members remains elusive. Here, we focus on the H-NS family protein MvaT from Pseudomonas aeruginosa and demonstrate experimentally that its protomer exists in two different conformations, corresponding to two different functional states. In the half-opened state (dominant at low salt) the protein forms filaments along DNA, in the fully opened state (dominant at high salt) the protein bridges DNA. This switching is a direct effect of ionic strength on electrostatic interactions between the oppositely charged DNA binding and N-terminal domains of MvaT. The asymmetric charge distribution and intramolecular interactions are conserved among the H-NS family of proteins. Therefore, our study establishes a general paradigm for the molecular mechanistic basis of the osmosensitivity of H-NS proteins.
Can the Public Be Educated About Constituents in Smokeless Tobacco? A Three-Wave Randomized Controlled Trial
Authors: Loken Barbara , Borgida Eugene , Wang Tzushuo , Madzelan Molly K , Williams Allison L , Hatsukami Dorothy , Stepanov Irina 
Published: December 2019

AbstractIntroductionThe U.S. Food and Drug Administration (FDA) is required by law to inform the public about levels of harmful and potentially harmful tobacco constituents in a format that is “understandable and not misleading to a lay person.” Our study addresses a critical gap in research on communicating such information for smokeless tobacco (SLT) products.MethodsThe design included random assignment to one of the experimental (online interactive) conditions differing in presentation format or a control condition (receiving no information). Experimental respondents viewed information on levels and health risks of 5 harmful constituents in up to 79 products. Outcome measures included knowledge of health risks of constituents, perception of constituent variability in SLT products, disease risk ratings, self-reported SLT use, and side-by-side product comparisons. The sample of 333 SLT users, 535 cigarette smokers, and 663 nontobacco users participated at baseline, time of intervention, and 6 weeks postintervention.ResultsPresentation formats showed few systematic differences so were combined in analyses. Experimental condition respondents increased their knowledge about constituent health effects and their perceptions of constituent variability in SLT products, from baseline to postintervention, and relative to the control condition. Changes in respondents’ ratings of disease risk and their estimates of constituent exposure from specific products were observed, but not in self-reported SLT use.ConclusionsInteractive online graphic and numeric presentation formats can be efficient in increasing people’s knowledge of health effects and perceived variation of constituents in SLT products. Further research on longer-term behavioral assessment, and usefulness of this approach for regulatory agencies, is needed.ImplicationsResearch on communicating the information about harmful constituents in SLT products to lay persons is critically lacking. This study proposes novel formats for effective communication about the levels and the health effects of SLT constituents to multiple user groups. The lack of misperceptions among study participants that some tobacco products are safe suggests that such formats can potentially be used for public display of SLT constituent data by the FDA and regulatory agencies in other countries.
Chemotherapy-associated neutropenic enterocolitis of the transverse colon post right hemicolectomy
Authors: Principe Daniel R , Koch Regina M , Bergsten Tova M , Rubin Jonathan 
Published: December 2019

Abstract
Neutropenic enterocolitis (NE) is a life-threatening infection of the immunocompromised. NE ubiquitously affects the cecum, often with involvement of the ascending colon and ileum. Classically, NE is associated with high mortality leading to the frequent use of aggressive treatment strategies including surgery. Although conservative approaches are often successful, there are currently no standardized treatment guidelines for NE and it is unclear when such strategies should be implemented. Here, we describe a patient with suspected chemotherapy-associated NE despite having previously undergone a right hemicolectomy. As computed tomography imaging failed to provide a conclusive diagnosis, we performed a gentle endoscopic evaluation that affirmed a diagnosis of NE of the transverse colon, and suggested the patient would benefit from conservative treatment. This case demonstrates that endoscopy can be a safe and useful tool in the diagnosis of NE, and is an important reminder that NE can affect any part of the gastrointestinal tract.
Natural History of Untreated Transverse/Sigmoid Sinus Thrombosis Following Posterior Fossa Surgery: Case Series and Literature Review
Authors: Orlev Alon , Jackson Christopher M , Luksik Andrew , Garzon-Muvdi Tomas , Yang Wuyang , Chien Wade , Harnof Sagi , Tamargo Rafael J 
Published: December 2019

Abstract

BACKGROUND
Transverse or sigmoid sinus thrombosis occurs in 4% to 11% of patients following posterior fossa surgery. Anticoagulation has been the mainstay treatment, mostly based on extrapolation from the literature on spontaneous sinus thrombosis.

OBJECTIVE
To analyze the rate and associated complications of postoperative transverse/sigmoid sinus thrombosis for patients undergoing posterior fossa tumor resection. In this series, no antithrombotic therapy was initiated, and no postoperative treatment alterations were made following thrombosis diagnosis.

METHODS
Prospectively accrued cases from a single surgeon operating at a single academic center were retrospectively reviewed to determine the natural history of untreated transverse/sigmoid sinus thrombosis following posterior fossa surgery. Inclusion criteria were patients 18 yr or older undergoing resection of a posterior fossa tumor. A total of 538 patients were analyzed.

RESULTS
In all 26 out of 538 (4.8%) patients were diagnosed with transverse/sigmoid sinus thrombosis on routine postoperative imaging. Early postoperative complication rate was 38% in the sinus thrombosis group, as compared to 15% in the no-thrombosis group (P = .02). A significantly higher rate of pseudomeningocele, dysphagia requiring gastrostomy, and cerebellar stroke signs were noted in patients with postoperative sinus thrombosis. However, only 3 of the 26 patients (12%) with postoperative sinus occlusion suffered prolonged central nervous system complications.

CONCLUSION
Transverse/sigmoid sinus thrombosis following suboccipital craniectomy results in a higher rate of early complications; however, most of these complications resolve without anticoagulation. It may be reasonable, therefore, to manage these patients conservatively in order to avoid the risks associated with anticoagulation in the perioperative period.