bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms of Antibiotic Resistance
Authors: Munita Jose M. , Arias Cesar A. 
Published: April 2016

ABSTRACT
Emergence of resistance among the most important bacterial pathogens is recognized as a major public health threat affecting humans worldwide. Multidrug-resistant organisms have not only emerged in the hospital environment but are now often identified in community settings, suggesting that reservoirs of antibiotic-resistant bacteria are present outside the hospital. The bacterial response to the antibiotic “attack” is the prime example of bacterial adaptation and the pinnacle of evolution. “Survival of the fittest” is a consequence of an immense genetic plasticity of bacterial pathogens that trigger specific responses that result in mutational adaptations, acquisition of genetic material, or alteration of gene expression producing resistance to virtually all antibiotics currently available in clinical practice. Therefore, understanding the biochemical and genetic basis of resistance is of paramount importance to design strategies to curtail the emergence and spread of resistance and to devise innovative therapeutic approaches against multidrug-resistant organisms. In this chapter, we will describe in detail the major mechanisms of antibiotic resistance encountered in clinical practice, providing specific examples in relevant bacterial pathogens.
Recent Advances and Understanding of Using Probiotic-Based Interventions to Restore Homeostasis of the Microbiome for the Prevention/Therapy of Bacterial Diseases
Authors: Suchodolski Jan S. , Jergens Albert E. 
Published: April 2016

ABSTRACT
The importance of the microbiome in health and disease has galvanized interest in using manipulations of the gastrointestinal ecosystem to prevent and/or combat gut bacterial infections and to restore mucosal homeostasis in patients with generalized microbial imbalances (i.e., dysbiosis), including the human inflammatory bowel diseases, Crohn’s disease, and ulcerative colitis. Probiotics, prebiotics, or their combination use (i.e., synbiotics) are one mechanism for modifying the microbiota and exerting direct and indirect effects on the host immune responses and metabolomics profiles. These beneficial effects are transferred through various pathways, including the production of antimicrobial peptides, promoting the growth of beneficial microbes and enhancing immunomodulatory functions via various metabolites. While probiotic therapy has been used empirically for decades with mixed success, the recent advances in molecular and mass spectrophotometric techniques for the characterization of the complexity and diversity of the intestinal microbiome has aided in better understanding of host-microbe interactions. It is important to better understand the functional properties of the microbiome, because it is now clear that the microbiota secretes many metabolites that have a direct impact on host immune responses. This information will improve selection of the most appropriate probiotic strains that selectively target intestinal disease processes.
Exploring the experience of sleep and fatigue in male and female adults over the 2 years following traumatic brain injury: a qualitative descriptive study
Authors: Theadom Alice , Rowland Vickie , Levack William , Starkey Nicola , Wilkinson-Meyers Laura , McPherson Kathryn 
Published: April 2016

ObjectivesTo explore the experience of fatigue and sleep difficulties over the first 2 years after traumatic brain injury (TBI).DesignLongitudinal qualitative descriptive analysis of interviews completed as part of a larger longitudinal study of recovery following TBI. Data relating to the experience of fatigue and/or sleep were extracted and coded by two independent researchers.SettingCommunity-based study in the Hamilton and Auckland regions of New Zealand.Participants30 adult participants who had experienced mild, moderate or severe brain injury within the past 6 months (>16 years of age). 15 participants also nominated significant others to take part. Interviews were completed at 6, 12 and 24 months postinjury.ResultsParticipants described feeling unprepared for the intensity, impact and persistent nature of fatigue and sleep difficulties after injury. They struggled to learn how to manage their difficulties by themselves and to adapt strategies in response to changing circumstances over time. Four themes were identified: (1) Making sense of fatigue and sleep after TBI; (2) accepting the need for rest; (3) learning how to rest and; (4) need for rest impacts on ability to engage in life.ConclusionsTargeted support to understand, accept and manage the sleep and fatigue difficulties experienced may be crucial to improve recovery and facilitate engagement in everyday life. Advice needs to be timely and revised for relevance over the course of recovery.
CYCLE pilot: a protocol for a pilot randomised study of early cycle ergometry versus routine physiotherapy in mechanically ventilated patients
Authors: Kho Michelle E , Molloy Alexander J , Clarke France , Herridge Margaret S , Koo Karen K Y , Rudkowski Jill , Seely Andrew J E , Pellizzari Joseph R , Tarride Jean-Eric , Mourtzakis Marina , Karachi Timothy , Cook Deborah J ,   the Canadian Critical Care Trials Group
Published: April 2016

IntroductionEarly exercise with in-bed cycling as part of an intensive care unit (ICU) rehabilitation programme has the potential to improve physical and functional outcomes following critical illness. The objective of this study is to determine the feasibility of enrolling adults in a multicentre pilot randomised clinical trial (RCT) of early in-bed cycling versus routine physiotherapy to inform a larger RCT.Methods and analysis60-patient parallel group pilot RCT in 7 Canadian medical-surgical ICUs. We will include all previously ambulatory adult patients within the first 0–4 days of mechanical ventilation, without exclusion criteria. After informed consent, patients will be randomised using a web-based, centralised electronic system, to 30 min of in-bed leg cycling in addition to routine physiotherapy, 5 days per week, for the duration of their ICU stay (28 days maximum) or routine physiotherapy alone. We will measure patients' muscle strength (Medical Research Council Sum Score, quadriceps force) and function (Physical Function in ICU Test (scored), 30 s sit-to-stand, 2 min walk test) at ICU awakening, ICU discharge and hospital discharge. Our 4 feasibility outcomes are: (1) patient accrual of 1–2 patients per month per centre, (2) protocol violation rate <20%, (3) outcome measure ascertainment >80% at the 3 time points and (4) blinded outcomes ascertainment >80% at hospital discharge. Hospital outcome assessors are blinded to group assignment, whereas participants, ICU physiotherapists, ICU caregivers, research coordinators and ICU outcome assessors are not blinded to group assignment. We will analyse feasibility outcomes with descriptive statistics.Ethics and disseminationEach participating centre will obtain local ethics approval, and results of the study will be published to inform the design and conduct of a future multicentre RCT of in-bed cycling to improve physical outcomes in ICU survivors.Trial registration numberNCT02377830; Pre-results.
Dysregulation of the intrinsic apoptotic pathway mediates megakaryocytic hyperplasia in myeloproliferative neoplasms
Authors: Malherbe Jacques A J , Fuller Kathryn A , Mirzai Bob , Kavanagh Simon , So Chi-Chiu , Ip Ho-Wan , Guo Belinda B , Forsyth Cecily , Howman Rebecca , Erber Wendy N 
Published: April 2016

AimsMegakaryocyte expansion in myeloproliferative neoplasms (MPNs) is due to uncontrolled proliferation accompanied by dysregulation of proapoptotic and antiapoptotic mechanisms. Here we have investigated the intrinsic and extrinsic apoptotic pathways of megakaryocytes in human MPNs to further define the mechanisms involved.MethodsThe megakaryocytic expression of proapoptotic caspase-8, caspase-9, Diablo, p53 and antiapoptotic survivin proteins was investigated in bone marrow specimens of the MPNs (n=145) and controls (n=15) using immunohistochemistry. The megakaryocyte percentage positivity was assessed by light microscopy and correlated with the MPN entity,JAK2V617F/CALRmutation status and platelet count.ResultsThe proportion of megakaryocytes in the MPNs expressing caspase-8, caspase-9, Diablo, survivin and p53 was significantly greater than controls. A greater proportion of myeloproliferative megakaryocytes expressed survivin relative to its reciprocal inhibitor, Diablo. Differences were seen between myelofibrosis, polycythaemia vera and essential thrombocythaemia for caspase-9 and p53.CALR-mutated cases had greater megakaryocyte p53 positivity compared to those with theJAK2V617Fmutation. Proapoptotic caspase-9 expression showed a positive correlation with platelet count, which was most marked in myelofibrosis andCALR-mutated cases.ConclusionsDisruptions targeting the intrinsic apoptotic cascade promote megakaryocyte hyperplasia and thrombocytosis in the MPNs. There is progressive dysfunction of apoptosis as evidenced by the marked reduction in proapoptotic caspase-9 and accumulation of p53 in myelofibrosis. The dysfunction of caspase-9, which is necessary for proplatelet formation, may be the mechanism for the excess thrombocytosis associated withCALRmutations. Survivin seems to be the key protein mediating the megakaryocyte survival signature in the MPNs and is a potential therapeutic target.
Defining a Population of Stem-like Human Prostate Cancer Cells That Can Generate and Propagate Castration-Resistant Prostate Cancer
Authors: Chen Xin , Li Qiuhui , Liu Xin , Liu Can , Liu Ruifang , Rycaj Kiera , Zhang Dingxiao , Liu Bigang , Jeter Collene , Calhoun-Davis Tammy , Lin Kevin , Lu Yue , Chao Hsueh-Ping , Shen Jianjun , Tang Dean G. 
Published: April 2016

Abstract
Purpose: We have shown that the phenotypically undifferentiated (PSA−/lo) prostate cancer cell population harbors long-term self-renewing cancer stem cells (CSC) that resist castration, and a subset of the cells within the PSA−/lo population bearing the ALDHhiCD44+α2β1+ phenotype (Triple Marker+/TM+) is capable of robustly initiating xenograft tumors in castrated mice. The goal of the current project is to further characterize the biologic properties of TM+ prostate cancer cell population, particularly in the context of initiating and propagating castration-resistant prostate cancer (CRPC).
Experimental Design: The in vivo CSC activities were measured by limiting-dilution serial tumor transplantation assays in both androgen-dependent and androgen-independent prostate cancer xenograft models. In vitro clonal, clonogenic, and sphere-formation assays were conducted in cells purified from xenograft and patient tumors. qPCR, Western blot, lentiviral-mediated gene knockdown, and human microRNA arrays were performed for mechanistic studies.
Results: By focusing on the LAPC9 model, we show that the TM+ cells are CSCs with both tumor-initiating and tumor-propagating abilities for CRPC. Moreover, primary patient samples have TM+ cells, which possess CSC activities in “castrated” culture conditions. Mechanistically, we find that (i) the phenotypic markers are causally involved in CRPC development; (ii) the TM+ cells preferentially express castration resistance and stem cell–associated molecules that regulate their CSC characteristics; and (iii) the TM+ cells possess distinct microRNA expression profiles and miR-499-5p functions as an oncomir.
Conclusions: Our results define the TM+ prostate cancer cells as a population of preexistent stem-like cancer cells that can both mediate and propagate CRPC and highlight the TM+ cell population as a therapeutic target. Clin Cancer Res; 22(17); 4505–16. ©2016 AACR.
A Genome-Wide Association Study Identifies a Novel Locus for Bortezomib-Induced Peripheral Neuropathy in European Patients with Multiple Myeloma
Authors: Magrangeas Florence , Kuiper Rowan , Avet-Loiseau Hervé , Gouraud Wilfried , Guérin-Charbonnel Catherine , Ferrer Ludovic , Aussem Alexandre , Elghazel Haytham , Suhard Jérôme , Der Sakissian Henri , Attal Michel , Munshi Nikhil C. , Sonneveld Pieter , Dumontet Charles , Moreau Philippe , van Duin Mark , Campion Loïc , Minvielle Stéphane 
Published: April 2016

Abstract
Purpose: Painful peripheral neuropathy is a frequent toxicity associated with bortezomib therapy. This study aimed to identify loci that affect susceptibility to this toxicity.
Experimental Design: A genome-wide association study (GWAS) of 370,605 SNPs was performed to identify risk variants for developing severe bortezomib-induced peripheral neuropathy (BiPN) in 469 patients with multiple myeloma who received bortezomib–dexamethasone therapy prior to autologous stem cell in randomized clinical trials of the Intergroupe Francophone du Myelome (IFM) and findings were replicated in 114 patients with multiple myeloma of the HOVON-65/GMMG-HD4 clinical trial.
Results: An SNP in the PKNOX1 gene was associated with BiPN in the exploratory cohort [rs2839629; OR, 1.89, 95% confidence interval (CI), 1.45–2.44; P = 7.6 × 10−6] and in the replication cohort (OR, 2.04; 95% CI, = 1.11–3.33; P = 8.3 × 10−3). In addition, rs2839629 is in strong linkage disequilibrium (r2 = 0.87) with rs915854, located in the intergenic region between PKNOX1 and cystathionine-ß-synthetase (CBS). Expression quantitative trait loci mapping showed that both rs2839629 and rs915854 genotypes have an impact on PKNOX1 expression in nerve tissue, whereas rs2839629 affects CBS expression in skin and blood.
Conclusions: The use of GWAS in multiple myeloma pharmacogenomics has identified a novel candidate genetic locus mapping to PKNOX1 and in the immediate vicinity of CBS at 21q22.3 associated with the severe bortezomib-induced toxicity. The proximity of these two genes involved in neurologic pain whose tissue-specific expression is modified by the two variants provides new targets for neuroprotective strategies. Clin Cancer Res; 22(17); 4350–5. ©2016 AACR.
Toward a Modern Science of Obesity at Washington University: How We Do It and What is the Payoff?
Authors: Colditz Graham A. , Gehlert Sarah , Bowen Deborah J. , Carson Kenneth , Hovmand Peter S. , Lee Jung Ae , Moley Kelle H. 
Published: April 2016

Abstract
In our Cancer Prevention Program at Washington University in Saint Louis (WUSTL), we have made extraordinary efforts to create the kind of cancer prevention and control program that is both translational and transdisciplinary in nature, to accelerate the march from basic discoveries to population change. Here we present an overview of our obesity-related research currently ongoing in our Center, paying particular attention to both the translational– transdisciplinary process and to community-based participatory research. We end with our future directions for improving obesity-related cancer outcomes research. Cancer Prev Res; 9(7); 503–8. ©2016 AACR.
Myth and mythologization in ideology and politcs. The mythologization of Japanese identity in the Meiji period
Authors: Lisiecki Marcin 
Published: April 2016

Myth and mythologization in ideology and politcs. The mythologization of Japanese identity in the Meiji periodIs myth a word or a thought? Searching for the etymological roots proves to show that it is both. However, does it really exhaust all the possible understandings of the myth and does it enable the grasp of its multiple usages? Answering those questions seems very important not only because we do not have the precise definition of a myth but mainly for that reason that we often fail to notice that it functions in all the societies and political regimes playing quite a vital role at the same time. The purpose of this paper is not only sketching the possible answers but also their exemplification through the example of Japan in the period of Meiji. The choice of that example results from that fact it is a conspicuous example of the way in which political elites are engaged in creating symbols and rituals and in shaping national awareness. The examples of the process of shaping national identity presented in this paper are focused on demonstrating two fundamental myths related to the Emperor, the aim of which was to consolidate the national identity. Mitologizacja japońskiej narodowości. Mit a mitologizowanie narodu. W stronę mitu politycznego w nowożytnej JaponiiCzy mit to słowo, czy myśl? Etymologicznie okazuje się jednym i drugim. Jednakże czy wyczerpuje to możliwe rozumienia mitu oraz umożliwia uchwycenie jego rozlicznych zastosowań? Odpowiedzi na te pytania wydają się niezwykle ważne nie tylko dlatego, że nie posiadamy precyzyjnej definicji mitu, lecz przede wszystkim z tego względu, że często nie dostrzegamy, że funkcjonuje on we wszystkich społeczeństwach i systemach politycznych, pełniąc w nich niezwykle ważne role. Celem niniejszego artykułu jest nie tylko zarysowanie możliwych odpowiedzi, lecz także ich egzemplifikacja na przykładzie Japonii w okresie Meiji. Wybór tego przypadku wynika z tego, że stanowi on czytelny przykład tego, w jaki sposób elity polityczne angażują się w kreowanie symboli i rytuałów oraz kształtowanie świadomości narodowej. Przedstawione w artykule przykłady procesu kształtowania tożsamości narodowej skupione są na ukazaniu dwóch podstawowych mitów związanych z cesarzem, których zadaniem było konsolidowanie tożsamości narodowej.
Štefan Polakovič - słowacki ideolog i teoretyk narodu
Authors: Chrobak Tadeusz 
Published: April 2016

Štefan Polakovič - slovak ideologue and theoretician of the nationŠtefan Polakowice is a leading representative of the philosophy of the people inSlovakia. The opinions of Š. Polakovič about the nation changed. In the early period of creativeness he characterized the nation in terms of the organism. In his late works he was examining the substance of the nation in terms of atomism and moderate individualism. The fundamental metaphysical thesis about the existence of the nation is the one that the nation, just like a man, is a creation of God. Hence, the nation has the tasks to be accomplished designated by God. It is the duty of creative members of the nation to recognize the will of God in relation to the nation. Š. Polakovič in connection with the diversity concept of the nation recognized the need for existence of philosophical science of the nation - nationology. Nationology is to examine fundamental issues metaphysical, epistemological and axiological of the nation as being incomparable with any other object. Štefan Polakovič - słowacki ideolog i teoretyk naroduŠtefan Polakovič jest czołowym przedstawicielem filozofii narodu na Słowacji. Poglądy Š. Polakovicia na naród zmieniały się. We wczesnym okresie twórczości naród charakteryzował on w kategoriach organizmu. W późnej twórczości analizował istotę narodu w kategoriach atomizmu i umiarkowanego indywidualizmu. Zasadniczą tezą metafizyczną dotyczącą istnienia narodu jest twierdzenie, że naród, tak jak człowiek, jest tworem Boga. Stąd też naród ma zadania do zrealizowania, wyznaczone mu przez Boga. Obowiązkiem twórczych członków narodu jest rozpoznanie woli Boga w stosunku do narodu. Š. Polakovič w związku z różnorodnością koncepcji narodu uznał, że konieczna jest filozoficzna nauka o narodzie – nacjologia. Nacjologia ma badać fundamentalne zagadnienia metafizyczne, epistemologiczne i aksjologiczne narodu, jako bytu nieporównywalnego z żadnym innym obiektem.
Ochrona kultury narodowej w koncepcjach współczesnej prawicy narodowej w Polsce
Authors: Radomski Grzegorz 
Published: April 2016

Protection of natural culture in concepts of the contemporary National Right Wing in PolandIn the centre of the system of values of the National Right Wing which revived after 1989 there are still nation, family and religion. The nation as community of culture is in opinion of the said parties exposed to dangers. The main risks are in their opinion as follows: cosmopolitism, Communist ideology, individualism, liberalism; secularization.In Poland, such ideas are, in the opinion of the National Right Wing, propagated by the liberal and post-communist circles. In the beginning they demanded that the communist activists are brought to justice. Some columnists refer to antisemitism. They perceive also the fall of the literary output. They assess critically the novels of Czesław Miłosz, Stanisław Barańczak or Olga Tokarczuk. Similar assessments regard the works of Polish historians. As preventive measures the following is mentioned: appropriate educational activity, statutory protection of national heritage, broadening of Catholicism, promotion of national culture. They attach great importance to the national branding. Its components are history, language, political regime, architecture, literature, art, religion, icons landscape, music. They would probably accept the opinion of Michael Porter: “Many contemporary discussions of international competition stress global homogenization and a diminished role for nations. But, in truth, national differences are at the heart of competitive success.” Ochrona kultury narodowej w koncepcjach współczesnej prawicy narodowej w PolsceW centrum systemu wartości odrodzonego po 1989 roku ruchu narodowego pozostają naród, rodzina i religia. Naród, traktowany jako wspólnota kultury, narażony jest w ocenie wspominanych wyżej środowisk na liczne zagrożenia. Za najgroźniejsze uznają one: kosmopolityzm, ideologię komunistyczną, indywidualizm, liberalizm, sekularyzację. W Polsce wspomniane idee mają być propagowane przez środowiska liberalne i postkomunistyczne. W wypowiedziach publicystów narodowych pojawiają się także akcenty antysemickie. Krytyczna ocena dotyczy też współczesnej polskiej literatury, a zwłaszcza twórczości Czesława Miłosza, Stanisława Barańczaka czy Olgi Tokarczuk. Podobne oceny odnoszone są do prac polskich historyków. Za istotną uznano więc puryfikację kultury narodowej. Wśród środków zaradczych środowiska narodowe proponują: rozwój edukacji historycznej, ochronę dziedzictwa narodowego, rozwój katolicyzmu i promocję kultury narodowej. W tym ostatnim wypadku za niezwykle ważny uznają one branding narodowy. Jego podstawowe składniki to historia, język, architektura, krajobraz, reżim polityczny itp. Polscy narodowcy zapewne zaakceptowaliby opinię sformułowaną przez Michaela Portera. Twierdzi on, iż co prawda nastąpiła globalna homogenizacja, ale podkreślanie odrębności narodowej jest źródłem sukcesu.
Tracheoinnominate Artery Fistula as a Complication of Radiation Therapy
Authors: Reiter David , Piccone Bruce R. , Littman Philip , Lisker Sheldon A. 
Published: April 2016

Tracheoinnominate artery fistulization is a well‐known complication of tracheostomy and of tracheal resection. The first known occurrence of this problem in a patient in whom no transtracheal procedure had ever been performed is reported, and high‐dose radiation therapy delivered three years before for a mediastinal malignancy is suggested as the cause. No evidence of tumor was found in or adjacent to the tracheovascular communication.The tracheoinnominate artery fistula must be considered a potential complication of radiation therapy as well as of surgery.
Anterior Cervical Pain Syndromes
Authors: Karlan Marc S. , Beroza Lawrence , Cassisi Nicholas J. 
Published: April 2016

The paucity of clinical findings in patients with glossopharyngeal neuralgia, superior laryngeal neuralgia, styloid process syndrome, hyoid syndrome, or carotidynia presents an enigma to the patient and the physician. Manifest symptoms appear extraneous or incongruous unless the essential element is identified. Common to all these syndromes is the radiation of pain over the neck and face, starting from the anterior cervical area of the neck.Case histories of seven patients are presented. The rationale of underlying pathophysiologic mechanisms is discussed and supported by relevant recent basic pain research, and conceptual speculations are presented.