bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor Cell–Derived MMP3 Orchestrates Rac1b and Tissue Alterations That Promote Pancreatic Adenocarcinoma
Authors: Mehner Christine , Miller Erin , Khauv Davitte , Nassar Aziza , Oberg Ann L. , Bamlet William R. , Zhang Lizhi , Waldmann Jens , Radisky Evette S. , Crawford Howard C. , Radisky Derek C. 
Published: May 2014

Abstract
Pancreatic ductal adenocarcinoma (PDA) arises at the convergence of genetic alterations in KRAS with a fostering microenvironment shaped by immune cell influx and fibrotic changes; identification of the earliest tumorigenic molecular mediators evokes the proverbial chicken and egg problem. Matrix metalloproteinases (MMP) are key drivers of tumor progression that originate primarily from stromal cells activated by the developing tumor. Here, MMP3, known to be expressed in PDA, was found to be associated with expression of Rac1b, a tumorigenic splice isoform of Rac1, in all stages of pancreatic cancer. Using a large cohort of human PDA tissue biopsies specimens, both MMP3 and Rac1b are expressed in PDA cells, that the expression levels of the two markers are highly correlated, and that the subcellular distribution of Rac1b in PDA is significantly associated with patient outcome. Using transgenic mouse models, coexpression of MMP3 with activated KRAS in pancreatic acinar cells stimulates metaplasia and immune cell infiltration, priming the stromal microenvironment for early tumor development. Finally, exposure of cultured pancreatic cancer cells to recombinant MMP3 stimulates expression of Rac1b, increases cellular invasiveness, and activation of tumorigenic transcriptional profiles.
Implications: MMP3 acts as a coconspirator of oncogenic KRAS in pancreatic cancer tumorigenesis and progression, both through Rac1b-mediated phenotypic control of pancreatic cancer cells themselves, and by giving rise to the tumorigenic microenvironment; these findings also point to inhibition of this pathway as a potential therapeutic strategy for pancreatic cancer. Mol Cancer Res; 12(10); 1430–9. ©2014 AACR.
Co-opting the Secondary Matriarchs
Authors: Reiss Moshe , Zucker David J. 
Published: May 2014

Sarah, Rebekah, Leah, and Rachel are termed the “Matriarchs.” In contrast to these women, Bilhah, Zilpah, Tamar, and Aseneth/Asenath are the “Secondary Matriarchs.” They are “foreign wives.” Bilhah and Zilpah are Arameans and the mothers of the eponymous ancestors of the tribes of Dan, Naphtali, Gad, and Asher. Canaanite Tamar bears Judah’s son Perez, who becomes the link to the Judah tribal line. The Egyptian Aseneth, Joseph’s wife, bears the eponymous ancestors of the tribes of Manasseh and Ephraim. The “foreignness” of these Secondary Matriarchs is not noteworthy in Genesis. Years later, however, Ezra/Nehemiah promote endogamy and reject foreign wives/exogamy. A similar pro-endogamy/anti-exogamy view is found in the Maccabean and Herodian times, although sometimes conversion – voluntary or forced – is another strategy. It is difficult to understand the growth of the Jewish people however defined or calculated – from the period of Ezra/Nehemiah to the destruction of the Second Temple – without these conversions. In the pseudepigraphic writings of the late and then postbiblical Second Temple period, as well as in rabbinic literature, the ethnic origins of the Secondary Matriarchs becomes an issue; consequently they become co-opted into the “Abrahamic” family – they are shown to be Jews. This article begins with a wide variety of examples in the Pseudepigrapha and rabbinic writings (Talmud, midrash) to address how the Secondary Matriarchs are understood to be ethnically “family” and not “foreigners.” It then analyzes the issue of endogamy/exogamy in Ezra/Nehemiah, as well as in the Maccabean-Herodian and rabbinic periods, as an explanation for the creation of the “additional biographies” of Bilhah, Zilpah, Tamar, and Aseneth.
On the Energy Exchange between Tropical Ocean Basins Related to ENSO*
Authors: Mayer Michael , Haimberger Leopold , Balmaseda Magdalena A. 
Published: May 2014

Abstract
Vast amounts of energy are exchanged between the ocean, atmosphere, and space in association with El Niño–Southern Oscillation (ENSO). This study examines energy budgets of all tropical (30°S–30°N) ocean basins and the atmosphere separately using different, largely independent oceanic and atmospheric reanalyses to depict anomalous energy flows associated with ENSO in a consistent framework. It is found that variability of area-averaged ocean heat content (OHC) in the tropical Pacific to a large extent is modulated by energy flow through the ocean surface. While redistribution of OHC within the tropical Pacific is an integral part of ENSO dynamics, variability of ocean heat transport out of the tropical Pacific region is found to be mostly small. Noteworthy contributions arise from the Indonesian Throughflow (ITF), which is anticorrelated with ENSO at a few months lag, and from anomalous oceanic poleward heat export during the La Niña events in 1999 and 2008. Regression analysis reveals that atmospheric energy transport and radiation at the top of the atmosphere (RadTOA) almost perfectly balance the OHC changes and ITF variability associated with ENSO. Only a small fraction of El Niño–related heat lost by the Pacific Ocean through anomalous air–sea fluxes is radiated to space immediately, whereas the major part of the energy is transported away by the atmosphere. Ample changes in tropical atmospheric circulation lead to enhanced surface fluxes and, consequently, to an increase of OHC in the tropical Atlantic and Indian Ocean that almost fully compensates for tropical Pacific OHC loss. This signature of energy redistribution is robust across the employed datasets for all three tropical ocean basins and explains the small ENSO signal in global mean RadTOA.
Voice Outcome of Modified Frontolateral Partial Laryngectomy in Excised Canine Larynges and Finite Element Model
Authors: Xu Hongming , Kvit Anton A. , Devine Erin E. , Ying Xinjiang , Dong Pin 
Published: May 2014

ObjectiveTo evaluate vocal parameters after modified frontolateral partial laryngectomy (MFLPL) and frontolateral partial laryngectomy (FLPL) in both excised canine and finite element models.Study DesignFLPL and MFLPL were compared, using a prospective paired case control laboratory study with excised canine larynx and computational modeling.SettingBasic science study conducted in university laboratory.MethodsFLPL and MFLPL were performed serially on 9 excised canine larynges. The excised larynx bench apparatus was used to collect phonation threshold pressure (PTP) and high‐speed video data. A finite element model was built to compare a normal vocal fold with applied tension, a cut fold with no applied tension (simulating FLPL), and a cut fold with applied tension (simulating MFLPL). Stress values and distributions across the 3 conditions were computed.ResultsThe mean PTP increase after MFLPL (15.45‐17.46 cmH2O) was not statistically significant. In the excised canine model, fundamental frequency (F0) showed a significant increase for the MFLPL (P =. 039). Differences in vibration amplitudes were not statistically significant. Von Mises stress distribution was most similar between the MFLPL model and the normal fold. Maximum von Mises stresses at the midline were 17.56, 21.63, and 5.10 kPa for the normal, MFLPL, and FLPL, respectively, and 47.57, 63.98, and 101.97 kPa at the peripheries.ConclusionsFrom these results, we conclude that MFLPL has the potential to give a better voice outcome while avoiding tracheotomy in partial laryngectomy patients. In vivo study in canines to examine the healing process would lend further evidence‐based support for this surgical method.
What does confidence mean to people who have had a stroke? – A qualitative interview study
Authors: Horne Jane , Lincoln Nadina Berrice , Preston Jenny , Logan Pip 
Published: May 2014

Objective: To explore the meaning of confidence to stroke patients after stroke in order to inform the development of a measurement tool. Design: Qualitative interview study using interpretative phenomenological analysis (IPA). Methods: Ten stroke survivors were purposively selected from those participating in a multi-centre randomised trial of outdoor mobility rehabilitation. Interviews about confidence were conducted in participants’ homes, audio recorded and transcribed verbatim. Results: Six themes emerged from the analysis. These were loss of identity, fear, social confidence, role confidence, mastering skill and attitudes and beliefs. Loss of identity was particularly evident in the early stages of stroke recovery. Fear was a barrier to regaining confidence and was associated with avoidance behaviours. Lack of social confidence was a common problem which appeared difficult to resolve. Life roles motivated participants to re-engage in daily life activities. Personal attitudes and beliefs, combined with the attitudes of significant others, contributed to personal feelings of competence. Conclusion: This study provides a coherent definition of the meaning of confidence through the experiences of stroke survivors. Being successful in gradually re-engaging in activities, including social activities and life roles helped to establish a positive self-belief. The influence of others, such as family and friends reinforce self-beliefs. Confidence and self-efficacy appear to be a similar construct. However, participants in this study also identified a relationship between confidence and self-esteem. The findings indicate that all six themes need to be included in a confidence measure to encompass the meaning of confidence as described by participants with stroke.
The Stroke Assessment of Fall Risk (SAFR): predictive validity in inpatient stroke rehabilitation
Authors: Breisinger Terry P , Skidmore Elizabeth R , Niyonkuru Christian , Terhorst Lauren , Campbell Grace B 
Published: May 2014

Objective: To evaluate relative accuracy of a newly developed Stroke Assessment of Fall Risk (SAFR) for classifying fallers and non-fallers, compared with a health system fall risk screening tool, the Fall Harm Risk Screen. Design and setting: Prospective quality improvement study conducted at an inpatient stroke rehabilitation unit at a large urban university hospital. Participants: Patients admitted for inpatient stroke rehabilitation ( N = 419) with imaging or clinical evidence of ischemic or hemorrhagic stroke, between 1 August 2009 and 31 July 2010. Interventions: Not applicable. Main outcome measure(s): Sensitivity, specificity, and area under the curve for Receiver Operating Characteristic Curves of both scales’ classifications, based on fall risk score completed upon admission to inpatient stroke rehabilitation. Results: A total of 68 (16%) participants fell at least once. The SAFR was significantly more accurate than the Fall Harm Risk Screen ( p < 0.001), with area under the curve of 0.73, positive predictive value of 0.29, and negative predictive value of 0.94. For the Fall Harm Risk Screen, area under the curve was 0.56, positive predictive value was 0.19, and negative predictive value was 0.86. Sensitivity and specificity of the SAFR (0.78 and 0.63, respectively) was higher than the Fall Harm Risk Screen (0.57 and 0.48, respectively). Conclusions: An evidence-derived, population-specific fall risk assessment may more accurately predict fallers than a general fall risk screen for stroke rehabilitation patients. While the SAFR improves upon the accuracy of a general assessment tool, additional refinement may be warranted.
MBL2 gene variants coding for mannose-binding lectin deficiency are associated with increased risk of nephritis in Danish patients with systemic lupus erythematosus
Authors: Tanha N , Troelsen L , From Hermansen M-L , Kjær L , Faurschou M , Garred P , Jacobsen S 
Published: May 2014

Objectives Autoimmunity may in part result from deficiencies in the processing of apoptotic debris. As mannose-binding lectin (MBL) is involved in such processes, we hypothesized that the variants in the MBL2 gene resulting in MBL deficiency confer an increased risk of nephritis in systemic lupus erythematosus (SLE). Methods A total of 171 SLE patients attending a Danish tertiary rheumatology referral center were included. Common variant alleles in exon 1 of the MBL2 gene (R52C, rs5030737; G54D, rs1800450; G57E, rs1800451) were genotyped. The normal allele and variant alleles are termed A and O, respectively. The follow-up period was defined as the time from fulfillment of the ACR 1987 classification criteria for SLE until the occurrence of an event (nephritis, end-stage renal disease (ESRD), or death) or end of follow-up. Cox regression analyses were controlled for gender, age and race. Results During a median follow-up of 5.7 years, nephritis developed in 94 patients, and ESRD developed in 16 of these patients. Twenty-seven patients died. The distribution of the MBL2 genotypes A/A, A/O and O/O was 58%, 35% and 7.0%, respectively. Compared to the rest, O/O patients had 2.6 times (95% CI: 1.2–5.5) higher risk of developing nephritis, and their risk of death after 10 years was 6.0 times increased (95% CI: 1.0–36). MBL serum levels below 100 ng/ml were associated with a 2.0 (95% CI: 1.2–3.4; p = 0.007) increased risk of developing nephritis. ESRD and histological class of nephritis were not associated with MBL deficiency. Conclusions Genetically determined MBL deficiency was associated with development of nephritis in SLE patients, but not with histological class of nephritis or ESRD.
Time to Death and Reenrollment After Live Discharge From Hospice
Authors: LeSage Kirstin , Borgert Andrew J. , Rhee Laura S. 
Published: May 2014

Background: The purpose of our study was to identify time to death and/or reenrolled patients alive at the time of hospice discharge. Methods: Medical records of all adults alive at hospice discharge during a 5-year period were retrospectively reviewed. Results: In all, 83 patients were alive at discharge, with 3 lost to follow-up. Average time from discharge to death was 199.9 days for all patients and 50 days for the 17 patients who reenrolled. Average time from discharge to reenrollment was 245 days. Conclusion: Our research supports past findings that over a third of patients disenrolled from hospice die within 6 months, indicating ongoing hospice eligibility up to the time of death. Interestingly, if enrollment was revoked by patient or family, as often was done to allow the patient to pursue more aggressive treatments, the mortality risk was higher in the 6 months after discharge. This should prompt careful reevaluation of disenrolled hospice patients in the months after disenrollment, and hospice reenrollment should be continually available and offered during this time.
Anatomic Study of the Deltoid Ligament of the Ankle
Authors: Panchani Prakash N. , Chappell Todd M. , Moore Garrett D. , Tubbs R. Shane , Shoja Mohammadali M. , Loukas Marios , Kozlowski Piotr B. , Khan Khurram H. , DiLandro Anthony C. , D’Antoni Anthony V. 
Published: May 2014

Background: There is heterogeneity in the literature regarding the anatomy and number of ligamentous bands that form the deltoid ligament (DL). Anatomic knowledge of the DL and its variations are important for surgeons who repair ankle fractures. Methods: The DL was dissected in 33 ankles from 17 formalin-fixed cadavers (mean age at death, 76.6 years) to examine its morphology. The length, width, and thickness of its constituent bands were recorded with a digital caliper. Descriptive and correlational statistics were used to investigate the relationships between band size, age at death, and sex. A literature review was conducted to compare our data to those of previous studies. Results: The DL has superficial and deep layers with up to 8 different bands. Conclusion: The DL stabilizes the medial ankle and should be evaluated in flatfoot deformities and severe ankle fractures. Clinical Relevance: Anatomic knowledge of DL variations should aid the surgeon in repairing torn DLs.
Acute limb ischemia in cancer patients: Aggressive treatment is justified
Authors: Silverberg Daniel , Yalon Tal , Reinitz Emanuel R , Yakubovitch Dmitry , Segev Tal , Halak Moshe 
Published: May 2014

Background The outcome of cancer patients with acute limb ischemia (ALI) is not well defined. The purpose of this study is to report our experience treating patients with active malignancy who developed ALI and compare their outcome with non-cancer patients. Methods A retrospective review of patients treated for ALI between 2009 and 2012 with ALI. We identified those patients who suffered from ALI and compared the outcome of those with active malignancy to those without malignancy. Results Of 147 patients treated for ALI (122 lower extremity, 25 upper extremity), 24 (16%) were cancer patients. Mean follow-up was 9.8 months for the malignancy group and 13.4 months for the control. Perioperative mortality rates were similar among cancer and non-cancer patients (20% vs. 16%, respectively, NS). Freedom from major amputation at 30 months was similar (95% vs. 89%, NS). Long-term survival rates of cancer patients were significantly lower compared to non-cancer patients (45% vs. 77% respectively, P < 0.05). Conclusions Treatment of ALI among cancer patients can be achieved with perioperative mortality and limb salvage rates comparable to non-cancer patients. Aggressive treatment is justified when treating cancer patients with ALI.
CLL-cells induce IDOhi CD14+HLA-DRlo myeloid-derived suppressor cells that inhibit T-cell responses and promote TRegs
Authors: Jitschin Regina , Braun Martina , Büttner Maike , Dettmer-Wilde Katja , Bricks Juliane , Berger Jana , Eckart Michael J. , Krause Stefan W. , Oefner Peter J. , Le Blanc Katarina , Mackensen Andreas , Mougiakakos Dimitrios 
Published: May 2014

Key Points
Monocytic IDOhi MDSCs are increased in CLL patients, suppress T cells, and promote TReg induction. CLL cells induce conversion of monocytes into MDSCs suggesting bidirectional crosstalk between CLL cells, MDSCs, and TRegs.
Erythropoietin therapy after allogeneic hematopoietic cell transplantation: a prospective, randomized trial
Authors: Jaspers Aurélie , Baron Frédéric , Willems Évelyne , Seidel Laurence , Hafraoui Kaoutar , Vanstraelen Gaetan , Bonnet Christophe , Beguin Yves 
Published: May 2014

Key Points
Erythropoietin therapy can be effective to hasten erythroid recovery and reduce transfusion requirements after allogeneic HCT.
The HMI™ module: a new tool to study the Host-Microbiota Interaction in the human gastrointestinal tract in vitro
Authors: Marzorati Massimo , Vanhoecke Barbara , De Ryck Tine , Sadaghian Sadabad Mehdi , Pinheiro Iris , Possemiers Sam , Van den Abbeele Pieter , Derycke Lara , Bracke Marc , Pieters Jan , Hennebel Tom , Harmsen Hermie J , Verstraete Willy , Van de Wiele Tom 
Published: May 2014

Abstract

Background
Recent scientific developments have shed more light on the importance of the host-microbe interaction, particularly in the gut. However, the mechanistic study of the host-microbe interplay is complicated by the intrinsic limitations in reaching the different areas of the gastrointestinal tract (GIT) in vivo. In this paper, we present the technical validation of a new device - the Host-Microbiota Interaction (HMI) module - and the evidence that it can be used in combination with a gut dynamic simulator to evaluate the effect of a specific treatment at the level of the luminal microbial community and of the host surface colonization and signaling.

Results
The HMI module recreates conditions that are physiologically relevant for the GIT: i) a mucosal area to which bacteria can adhere under relevant shear stress (3 dynes cm−2); ii) the bilateral transport of low molecular weight metabolites (4 to 150 kDa) with permeation coefficients ranging from 2.4 × 10−6 to 7.1 × 10−9 cm sec−1; and iii) microaerophilic conditions at the bottom of the growing biofilm (PmO2 = 2.5 × 10−4 cm sec−1). In a long-term study, the host’s cells in the HMI module were still viable after a 48-hour exposure to a complex microbial community. The dominant mucus-associated microbiota differed from the luminal one and its composition was influenced by the treatment with a dried product derived from yeast fermentation. The latter - with known anti-inflammatory properties - induced a decrease of pro-inflammatory IL-8 production between 24 and 48 h.

Conclusions
The study of the in vivo functionality of adhering bacterial communities in the human GIT and of the localized effect on the host is frequently hindered by the complexity of reaching particular areas of the GIT. The HMI module offers the possibility of co-culturing a gut representative microbial community with enterocyte-like cells up to 48 h and may therefore contribute to the mechanistic understanding of host-microbiome interactions.
Artemin Growth Factor Increases Nicotinic Cholinergic Receptor Subunit Expression and Activity in Nociceptive Sensory Neurons
Authors: Albers Kathryn M , Zhang Xiu Lin , Diges Charlotte M , Schwartz Erica S , Yang Charles I , Davis Brian M , Gold Michael S 
Published: May 2014

Background: Artemin (Artn), a member of the glial cell line-derived growth factor (GDNF) family, supports the development and function of a subpopulation of peptidergic, TRPV1-positive sensory neurons. Artn (enovin, neublastin) is elevated in inflamed tissue and its injection in skin causes transient thermal hyperalgesia. A genome wide expression analysis of trigeminal ganglia of mice that overexpress Artn in the skin (ART-OE mice) showed elevation in nicotinic acetylcholine receptor (nAChR) subunits, suggesting these ion channels contribute to Artn-induced sensitivity. Here we have used gene expression, immunolabeling, patch clamp electrophysiology and behavioral testing assays to investigate the link between Artn, nicotinic subunit expression and thermal hypersensitivity. Results: Reverse transcriptase-PCR validation showed increased levels of mRNAs encoding the nAChR subunits α3 (13.3-fold), β3 (4-fold) and β4 (7.7-fold) in trigeminal ganglia and α3 (4-fold) and β4 (2.8-fold) in dorsal root ganglia (DRG) of ART-OE mice. Sensory ganglia of ART-OE mice had increased immunoreactivity for nAChRα3 and exhibited increased overlap in labeling with GFRα3-positive neurons. Patch clamp analysis of back-labeled cutaneous afferents showed that while the majority of nicotine-evoked currents in DRG neurons had biophysical and pharmacological properties of α7-subunit containing nAChRs, the Artn-induced increase in α3 and β4 subunits resulted in functional channels. Behavioral analysis of ART-OE and wildtype mice showed that Artn-induced thermal hyperalgesia can be blocked by mecamylamine or hexamethonium. Complete Freund's adjuvant (CFA) inflammation of paw skin, which causes an increase in Artn in the skin, also increased the level of nAChR mRNAs in DRG. Finally, the increase in nAChRs transcription was not dependent on the Artn-induced increase in TRPV1 or TRPA1 in ART-OE mice since nAChRs were elevated in ganglia of TRPV1/TRPA1 double knockout mice. Conclusions: These findings suggest that Artn regulates the expression and composition of nAChRs in GFRα3 nociceptors and that these changes contribute to the thermal hypersensitivity that develops in response to Artn injection and perhaps to inflammation.