bluuebunny/crossref_metadata_2025_split huggingface dataset:
Moxifloxacin Improves Treatment Outcomes in Patients with Ofloxacin-Resistant Multidrug-Resistant Tuberculosis
Authors: Chien Jung-Yien , Chien Shun-Tien , Chiu Wei-Yih , Yu Chong-Jen , Hsueh Po-Ren 
Published: May 2016

ABSTRACT

It is unclear whether the use of moxifloxacin (MFX), a newer synthetic fluoroquinolone, results in better outcomes in patients with ofloxacin (OFX)-resistant multidrug-resistant tuberculosis (MDR-TB). During the period from April 2006 to December 2013, a total of 2,511 patients with culture-confirmed tuberculosis (TB) were treated at a TB referral hospital in southern Taiwan. Of the 2,511 patients, 325 (12.9%) had MDR-TB, and of those 325 patients, 81 (24.9%) had OFX-resistant MDR-TB and were included in the study. Among the 81 patients with OFX-resistant MDR-TB, 50 (61.7%) were successfully treated and 31 (38.3%) had unfavorable outcomes, including treatment failure (
n
= 25; 30.9%), loss to follow-up (
n
= 2; 2.5%), and death (
n
= 4; 4.9%). Patients treated with MFX had a significantly higher rate of treatment success (77.3% versus 43.2%; odds ratio [OR] = 4.46, 95% confidence interval [CI] = 1.710 to 11.646,
P
= 0.002) than patients not treated with MFX, especially among those infected with MFX-susceptible isolates (40.7%) or isolates with low-level resistance to MFX (28.4%). Multivariate logistic regression analysis showed that treatment with MFX (adjusted odds ratio = 6.54, 95% CI = 1.44 to 29.59,
P
= 0.015) was the only independent factor associated with treatment success. Mutation at codon 94 in the
gyrA
gene was the most frequent mutation (68.0%) associated with high-level MFX resistance. Multivariate Cox proportional hazards regression analysis showed that treatment with MFX was also an independent factor associated with early culture conversion (hazard ratio = 3.12, 95% CI = 1.48 to 6.54,
P
= 0.003). Our results show that a significant proportion of OFX-resistant MDR-TB isolates were susceptible or had low-level resistance to MFX, indicating that patients with OFX-resistant MDR-TB benefit from treatment with MFX.
The MisR Response Regulator Is Necessary for Intrinsic Cationic Antimicrobial Peptide and Aminoglycoside Resistance in Neisseria gonorrhoeae
Authors: Kandler Justin L. , Holley Concerta L. , Reimche Jennifer L. , Dhulipala Vijaya , Balthazar Jacqueline T. , Muszyński Artur , Carlson Russell W. , Shafer William M. 
Published: May 2016

ABSTRACT

During infection, the sexually transmitted pathogen
Neisseria gonorrhoeae
(the gonococcus) encounters numerous host-derived antimicrobials, including cationic antimicrobial peptides (CAMPs) produced by epithelial and phagocytic cells. CAMPs have both direct and indirect killing mechanisms and help link the innate and adaptive immune responses during infection. Gonococcal CAMP resistance is likely important for avoidance of host nonoxidative killing systems expressed by polymorphonuclear granulocytes (e.g., neutrophils) and intracellular survival. Previously studied gonococcal CAMP resistance mechanisms include modification of lipid A with phosphoethanolamine by LptA and export of CAMPs by the MtrCDE efflux pump. In the related pathogen
Neisseria meningitidis
, a two-component regulatory system (2CRS) termed MisR-MisS has been shown to contribute to the capacity of the meningococcus to resist CAMP killing. We report that the gonococcal MisR response regulator but not the MisS sensor kinase is involved in constitutive and inducible CAMP resistance and is also required for intrinsic low-level resistance to aminoglycosides. The 4- to 8-fold increased susceptibility of
misR
-deficient gonococci to CAMPs and aminoglycosides was independent of phosphoethanolamine decoration of lipid A and the levels of the MtrCDE efflux pump and seemed to correlate with a general increase in membrane permeability. Transcriptional profiling and biochemical studies confirmed that expression of
lptA
and
mtrCDE
was not impacted by the loss of MisR. However, several genes encoding proteins involved in membrane integrity and redox control gave evidence of being MisR regulated. We propose that MisR modulates the levels of gonococcal susceptibility to antimicrobials by influencing the expression of genes involved in determining membrane integrity.
Integrated environmental modelling: achieving the vision
Authors: Moore R. V. , Hughes A. G. 
Published: May 2016

Abstract
Integrated environmental modelling (IEM) is a recent phenomenon that offers the opportunity to solve complex environmental problems. Whilst it has made great strides in recent years, there are still challenges to be met before IEM is universally accepted and used. This paper describes the current state of IEM and sets out a roadmap for achieving its full potential. A multidisciplinary, multi-agency approach will be required, the main goals of which are to: (1) raise awareness and build confidence in IEM; (2) ensure availability and accessibility of IEM techniques, tools and standards; (3) establish a minimum set of standards; (4) build the IEM skills base; (5) establish an underpinning research and development (R&D) programme; (6) co-ordinate and promote collaboration; and (7) foster IEM use by government, industry and the public. Once these goals have been achieved, then IEM can be deployed to help resolve currently intractable environmental issues, and the IEM methodology can be transferred to other fields.
Vertebrate palaeontology in Central America: a narrative and analytical history
Authors: Lucas Spencer G. , Alvarado Guillermo E. 
Published: May 2016

Abstract
Central American vertebrate fossils are primarily of late Cenozoic age and represent all of the major taxonomic groups of vertebrates. The vertebrate fossils of Central America play an important part in understanding the great American biotic interchange after the closure of the Panamanian isthmus. We divide the narrative history of vertebrate palaeontology in Central America into three periods: earliest discoveries (1858–1936); a developing record (1937–80); and a vertebrate palaeontological renaissance (1980–present). An analytical history, applying the ‘model’ proposed by Basalla of how science diffuses into any non-European nation, indicates a poor fit of Central American vertebrate palaeontology to this ‘model’. Central American vertebrate palaeontology mostly remains in the first phase of Basalla's ‘model’, primarily providing vertebrate fossils for study by palaeontologists in the USA; phase 2 (colonial science) was essentially skipped and phase 3 (establishment of an independent scientific programme) is in an early stage. The development of vertebrate palaeontology in Central America better fits the idea that all three phases of Basalla's ‘model’ are ongoing and intermingled. Vertebrate palaeontology is a science of little economic significance and this largely explains its slow development in Central America, where political instabilities and economic disadvantages have long affected the development of science.
A Novel EGFR Extracellular Domain Mutant, EGFRΔ768, Possesses Distinct Biological and Biochemical Properties in Neuroblastoma
Authors: Keller James , Nimnual Anjaruwee S. , Varghese Mathew S. , VanHeyst Kristen A. , Hayman Michael J. , Chan Edward L. 
Published: May 2016

Abstract
EGFR is a popular therapeutic target for many cancers. EGFR inhibitors have been tested in children with refractory neuroblastoma. Interestingly, partial response or stable disease was observed in a few neuroblastoma patients. As EGFR mutations are biomarkers for response to anti-EGFR drugs, primary neuroblastoma tumors and cell lines were screened for mutations. A novel EGFR extracellular domain deletion mutant, EGFRΔ768, was discovered and the biologic and biochemical properties of this mutant were characterized and compared with wild-type and EGFRvIII receptors. EGFRΔ768 was found to be constitutively active and localized to the cell surface. Its expression conferred resistance to etoposide and drove proliferation as well as invasion of cancer cells. While EGFRΔ768 had similarity to EGFRvIII, its biologic and biochemical properties were distinctly different from both the EGFRvIII and wild-type receptors. Even though erlotinib inhibited EGFRΔ768, its effect on the mutant was not as strong as that on wild-type EGFR and EGFRvIII. In addition, downstream signaling of EGFRΔ768 was different from that of the wild-type receptor. In conclusion, this is the first study to demonstrate that neuroblastoma express not only EGFRvIII, but also a novel EGFR extracellular domain deletion mutant, EGFRΔ768. The EGFRΔ768 also possesses distinct biologic and biochemical properties which might have therapeutic implications for neuroblastoma as well as other tumors expressing this novel mutant.
Implications: Neuroblastoma expressed a novel EGFR mutant which possesses distinct biologic and biochemical properties that might have therapeutic implications. Mol Cancer Res; 14(8); 740–52. ©2016 AACR.
Effects of Walnut Consumption on Colon Carcinogenesis and Microbial Community Structure
Authors: Nakanishi Masako , Chen Yanfei , Qendro Veneta , Miyamoto Shingo , Weinstock Erica , Weinstock George M. , Rosenberg Daniel W. 
Published: May 2016

Abstract
Walnuts are composed of a complex array of biologically active constituents with individual cancer-protective properties. Here, we assessed the potential benefit of whole walnut consumption in a mouse tumor bioassay using azoxymethane. In study 1, a modest reduction (1.3-fold) in tumor numbers was observed in mice fed a standard diet (AIN-76A) containing 9.4% walnuts (15% of total fat). In study 2, the effects of walnut supplementation was tested in the Total Western Diet (TWD). There was a significant reduction (2.3-fold; P &lt; 0.02) in tumor numbers in male mice fed TWD containing 7% walnuts (10.5% of total fat). Higher concentrations of walnuts lacked inhibitory effects, particularly in female mice, indicating there may be optimal levels of dietary walnut intake for cancer prevention. Since components of the Mediterranean diet have been shown to affect the gut microbiome, the effects of walnuts were therefore tested in fecal samples using 16S rRNA gene sequencing. Carcinogen treatment reduced the diversity and richness of the gut microbiome, especially in male mice, which exhibited lower variability and greater sensitivity to environmental changes. Analysis of individual operational taxonomic units (OTU) identified specific groups of bacteria associated with carcinogen exposure, walnut consumption, and/or both variables. Correlation analysis also identified specific OTU clades that were strongly associated with the presence and number of tumors. Taken together, our results indicate that walnuts afford partial protection to the colon against a potent carcinogenic insult, and this may be due, in part, to walnut-induced changes to the gut microbiome. Cancer Prev Res; 9(8); 692–703. ©2016 AACR.
Effector Regulatory T Cells Reflect the Equilibrium between Antitumor Immunity and Autoimmunity in Adult T-cell Leukemia
Authors: Ureshino Hiroshi , Shindo Takero , Nishikawa Hiroyoshi , Watanabe Nobukazu , Watanabe Eri , Satoh Natsuko , Kitaura Kazutaka , Kitamura Hiroaki , Doi Kazuko , Nagase Kotaro , Kimura Hiromi , Samukawa Makoto , Kusunoki Susumu , Miyahara Masaharu , Shin-I Tadasu , Suzuki Ryuji , Sakaguchi Shimon , Kimura Shinya 
Published: May 2016

AbstractThe regulatory T cells (Treg) with the most potent immunosuppressive activity are the effector Tregs (eTreg) with a CD45RA–Foxp3++CCR4+ phenotype. Adult T-cell leukemia (ATL) cells often share the Treg phenotype and also express CCR4. Although mogamulizumab, a monoclonal antibody to CCR4, shows marked antitumor effects against ATL and peripheral T-cell lymphoma, concerns have been raised that it may induce severe autoimmune immunopathology by depleting eTregs. Here, we present case reports for two patients with ATL who responded to mogamulizumab but developed a severe skin rash and autoimmune brainstem encephalitis. Deep sequencing of the T-cell receptor revealed that ATL cells and naturally occurring Tregs within the cell population with a Treg phenotype can be clearly distinguished according to CADM1 expression. The onset of skin rash and brainstem encephalitis was coincident with eTreg depletion from the peripheral blood, whereas ATL relapses were coincident with eTreg recovery. These results imply that eTreg numbers in the peripheral blood sensitively reflect the equilibrium between antitumor immunity and autoimmunity, and that mogamulizumab might suppress ATL until the eTreg population recovers. Close monitoring of eTreg numbers is crucial if we are to provide immunomodulatory treatments that target malignancy without severe adverse events. Cancer Immunol Res; 4(8); 644–9. ©2016 AACR.
Observed Concentration Budgets of Arctic and Antarctic Sea Ice
Authors: Holland Paul R. , Kimura Noriaki 
Published: May 2016

Abstract
In recent decades, Antarctic sea ice has expanded slightly while Arctic sea ice has contracted dramatically. The anthropogenic contribution to these changes cannot be fully assessed unless climate models are able to reproduce them. Process-based evaluation is needed to provide a clear view of the capabilities and limitations of such models. In this study, ice concentration and drift derived from AMSR-E data during 2003–10 are combined to derive a climatology of the ice concentration budget at both poles. This enables an observational decomposition of the seasonal dynamic and thermodynamic changes in ice cover. In both hemispheres, the results show spring ice loss dominated by ice melting. In other seasons ice divergence maintains freezing in the inner pack while advection causes melting at the ice edge, as ice is transported beyond the region where it is thermodynamically sustainable. Mechanical redistribution provides an important sink of ice concentration in the central Arctic and around the Antarctic coastline. This insight builds upon existing understanding of the sea ice cycle gained from ice and climate models, and the datasets may provide a valuable tool in validating such models in the future.
Nissen Fundoplication for Laryngopharyngeal Reflux After Patient Selection Using Dual pH, Full Column Impedance Testing
Authors: Carroll Thomas L. , Nahikian Kael , Asban Ammar , Wiener Daniel 
Published: May 2016

Objectives: Prior studies demonstrate inconsistent diagnostic strategies for laryngopharyngeal reflux disease (LPR) patients who are offered laparoscopic Nissen fundoplication (Nissen). Superior symptom resolution outcomes are demonstrated in patients with accompanying typical gastroesophageal reflux (GERD) symptoms. This study aims to evaluate the efficacy of selecting patients with LPR complaints for Nissen using full column, dual pH impedance catheters (multichannel intraluminal impedance catheters [MII]). Methods: All patients who underwent Nissen for management of LPR symptoms refractory to at least 3 months of twice daily (BID) proton pump inhibitor (PPI) therapy with reflux symptom index (RSI) of 13 or higher and who had demonstrable reflux on MII were included. Pre- and (minimum) 16 week post-Nissen RSI scores as well as LPR-specific complaints were collected. Results: Eleven patients met criteria. Nine subjects (5 female, 4 male) had complete data. All 9 (100%) achieved improvement in RSI. The average pre-Nissen RSI was 31.7, and average post-Nissen RSI was 10 ( P < .001). Six (67%) subjects dropped below an RSI of 13. Seven subjects (78%) had resolution of their primary LPR symptom, and 6 (67%) subjects had resolution of all LPR symptoms. Conclusions: Patients with LPR who are selected using dual pH and full column impedance are likely to demonstrate improvement in RSI following Nissen.
Symptoms, Quality of Life, and Daily Activities in People With Newly Diagnosed Solid Tumors Presenting to a Medical Oncologist
Authors: Thomas Shirley , Walsh Declan , Shrotriya Shiva , Aktas Aynur , Hullihen Barbara , Estfan Bassam , Budd G.Thomas , Hjermstad Marianne Jensen , O’Connor Brenda 
Published: May 2016

Introduction: Symptom and Quality of Life (QOL) data are important patient reported outcomes. Early identification of these is critical for appropriate interventions. Data collection may be helped by modern information technology. Aim: This study examined symptoms and QOL in people with solid tumors at their first visit to a medical oncologist. We also evaluated the clinical utility of tablet computers (TC) to collect this data. Methods: This was a prospective study of 105 consecutive patients in the cancer outpatient clinic of a tertiary level academic medical center. Symptom and QOL data was collected by TC with wireless database upload. Results: One-third participants had moderate to severe pain; almost half clinically significant pain that interfered with daily activities. Tiredness, anxiety, and drowsiness were common (prevalence - 79%, 63% and 50% respectively). One-third of those who had items identified from the Edmonton System Assessment System also volunteered other symptoms, mostly gastrointestinal problems. Many of those affected also reported impaired Global Wellbeing and low Overall QOL. There was a 98% completion rate, which took on average ten minutes. Direct observation and informal feedback from patients and physicians regarding the acceptability of TC in this setting was uniformly positive. Conclusions: Amongst people with newly diagnosed solid tumors clinically important psychological and physical symptoms, QOL problems and difficulties with daily activities were commonly present in the 24-hour period and in the week before a first Medical Oncology visit. Symptom and QOL data collection by TC in busy outpatient clinics showed good clinical utility.
Coming of age in L3 initial stages transfer models: Deriving developmental predictions and looking towards the future
Authors: Alonso Jorge González , Rothman Jason 
Published: May 2016

Aims: Over the past decade in particular, formal linguistic work within L3 acquisition has concentrated on hypothesizing and empirically determining the source of transfer from previous languages—L1, L2 or both—in L3 grammatical representations. In view of the progressive concern with more advanced stages, we aim to show that focusing on L3 initial stages should be one continued priority of the field, even—or especially—if the field is ready to shift towards modeling L3 development and ultimate attainment. Approach: We argue that L3 learnability is significantly impacted by initial stages transfer, as such forms the basis of the initial L3 interlanguage. To illustrate our point, the insights from studies using initial and intermediary stages L3 data are discussed in light of developmental predictions that derive from the initial stages models. Conclusions: Despite a shared desire to understand the process of L3 acquisition in whole, inclusive of offering developmental L3 theories, we argue that the field does not yet have—although is ever closer to—the data basis needed to effectively do so. Originality: This article seeks to convince the readership of the need for conservatism in L3 acquisition theory building, whereby offering a framework on how and why we can most effectively build on the accumulated knowledge of the L3 initial stages in order to make significant, steady progress. Significance: The arguments exposed here are meant to provide an epistemological base for a tenable framework of formal approaches to L3 interlanguage development and, eventually, ultimate attainment.
Vascular Structures of the Right Colon: Incidence and Variations with Their Clinical Implications
Authors: Alsabilah J. , Kim W. R. , Kim N. K. 
Published: May 2016

Background and Aims: There is a demand for a better understanding of the vascular structures around the right colonic area. Although right hemicolectomy with the recent concept of meticulous lymph node dissection is a standardized procedure for malignant diseases among most surgeons, variations in the actual anatomical vascular are not well understood. The aim of the present review was to present a detailed overview of the vascular variation pertinent to the surgery for right colon cancer. Materials and Methods: Medical literature was searched for the articles highlighting the vascular variation relevant to the right colon cancer surgery. Results: Recently, there have been many detailed studies on applied surgical vascular anatomy based on cadaveric dissections, as well as radiological and intraoperative examinations to overcome misconceptions concerning the arterial supply and venous drainage to the right colon. Ileocolic artery and middle colic artery are consistently present in all patients arising from the superior mesenteric artery. Even though the ileocolic artery passes posterior to the superior mesenteric vein in most of the cases, in some cases courses anterior to the superior mesenteric artery. The right colic artery is inconsistently present ranging from 63% to 10% across different studies. Ileocolic vein and middle colic vein is always present, while the right colic vein is absent in 50% of patients. The gastrocolic trunk of Henle is present in 46%–100% patients across many studies with variation in the tributaries ranging from bipodal to tetrapodal. Commonly, it is found that the right colonic veins, including the right colic vein, middle colic vein, and superior right colic vein, share the confluence forming the gastrocolic trunk of Henle in a highly variable frequency and different forms. Conclusion: Understanding the incidence and variations of the vascular anatomy of right side colon is of crucial importance. Failure to recognize the variation during surgery can result in troublesome bleeding especially during minimal invasive surgery.