bluuebunny/crossref_metadata_2025 huggingface dataset:
From nationalist communitarianism to fragmentary neoliberalism: Japan’s crisis of social reproduction
Authors: Carroll Myles
Published: October 2019

This article explores elements of contemporary Japan’s long-term and deep-rooted organic crisis. It is a crisis with various inter-related components, including a long-term economic crisis that has now spanned nearly three decades, a political crisis that brought about significant upheaval and discord, particularly in the 1990s and 2000s, and a cultural crisis characterized by widespread popular anxiety over the future, all without any clear alternative in sight, echoing Gramsci’s understanding of organic crisis as conditions under which ‘the old is dying and the new cannot be born’. This article considers how conditions of social reproduction have been affected by the crisis. It argues that efforts to restore conditions for profitable accumulation pursued in the wake of economic stagnation in the 1990s and 2000s, including labor market reform, led to the decline of what Mari Miura has called Japan’s ‘welfare-through-work’ model of welfare, and the emergence of a new employment and welfare regime that provides little job security for a growing number of workers has led to a disconnect between conditions deemed necessary for capital accumulation and those necessary for stable and progressive social reproduction, prompting a crisis of social reproduction.
The Effect of Career Counselor Behavior on Reemployment
Authors: Behrendt Peter , Heuer Katharina , Göritz Anja S.
Published: October 2019

When looking at career interventions, one-on-one career counseling is one of the most effective and firmly established types of intervention. Furthermore, career counseling process quality has been validated as a predictor of job seekers’ reemployment. To elucidate the underlying components of a high-quality counseling process, the effects of counselor behavior in mandatory counseling sessions at three Swiss job centers are investigated. Based on a transfer of psychotherapeutic effectiveness research into the domain of career counseling, three behavior categories are proposed as components of a high-quality counseling process: providing structured guidance during the counseling process, providing personalized support, and activating job seekers’ resources. Scientific observers rated these counselor behavior categories in 32 counseling sessions. The ratings of “providing structured guidance” predicted job seekers’ reemployment speed at a correlation of .58. The measured effect equals yearly savings of 831 million Swiss Francs CHF (US$839) in Swiss unemployment benefits. The correlations with the other two behavior category ratings were in the same direction but nonsignificant.
Transnational sustainability laws and the regulation of global value chains: comparison and a framework for analysis
Authors: Salminen Jaakko , Rajavuori Mikko
Published: October 2019

Several corporate disclosure and due diligence laws related to the social and environmental impacts of globalized production have been enacted across the world over the last decade. While the emergence, operation and impact of such ‘transnational sustainability laws’ have already been extensively analysed, their legal operability remains poorly understood. This a significant omission because transnational sustainability laws form a novel and increasingly important attempt to conceptualize and govern the new logic of global production networks—global value chains—and their regulatory infrastructure. Against this backdrop, this article deploys a comparison of eleven recent transnational sustainability laws and develops an analytical framework to probe legally-operative conceptualizations of global value chains. By analysing how transnational sustainability laws conceptualize the value chain, the lead firm and adequate value chain governance, we argue, these instruments emerge as proxies for a legally-operative framework that better delineates the emerging law of global value chains. Thus, our analysis contributes to growing literature on the potential and limits of transnational sustainability laws as well as to the development of nascent ‘global value chain law’.
Safe rates and unpaid labour: Non-driving pay and truck driver work hours
Authors: Kudo Takahiko , Belzer Michael H
Published: October 2019

In the trucking industry, truck drivers’ duties include not only driving trucks but also non-driving labor. However, non-driving work is not necessarily paid. This article analyses how the payment for non-driving duties (non-driving pay) affects truck drivers’ work hours. Using the National Institute for Occupational Safety and Health Long-Haul Truck Driver survey, the study finds that remunerating drivers for non-driving duties decreases drivers’ work hours. Drivers who are paid for their non-driving labor may reach their target earnings in fewer work hours, leading them to refrain from working extremely long hours and more willingly comply with working time regulations. The policy implication is that paying for non-driving labor can prevent drivers from working excessively long hours, mitigating fatigue, and consequent accidents. Thus, pay for non-driving labor may enhance their safety and health.
2019 AAFP Feline Zoonoses Guidelines
Authors: Lappin Michael R , Elston Tom , Evans Lisanne , Glaser Carol , Jarboe Lorraine , Karczmar Peter , Lund Cathy , Ray Michael
Published: October 2019

Aim:

The overarching purpose of the 2019 AAFP Feline Zoonoses Guidelines (hereafter referred to as the ‘Guidelines’) is to provide accurate information about feline zoonotic diseases to owners, physicians and veterinarians to allow logical decisions to be made concerning cat ownership.

Scope and accessibility:

The Panelists are physicians and veterinarians who worked closely together in an attempt to make these Guidelines a document that can be used to support the International One Health movement. This version of the Guidelines builds upon the first feline zoonosis panel report, published in 2003 ( catvets.com/guidelines ), and provides an updated reference list and recommendations. Each of the recommendations received full support from every Panelist. Primary recommendations are highlighted in a series of ‘Panelists’ advice’ boxes.
“Falling into the Sky”: Gravity and Levity in Pynchon’s Mason & Dixon
Authors: Haynes Doug
Published: October 2019

My argument follows geographer Gunnar Olsson when he asks, “What is geography if it is not the drawing and interpreting of a line? And what is the drawing of a line if it is not also the creation of new objects?” Using Thomas Pynchon’s 1997 novel Mason & Dixon ( MD), about the drawing of the Mason-Dixon line, I explore how the mapmaker’s productive power is never merely reflective, but generative too, constructing a world as much as representing one. I question the consequent relation between “above and below,” drawing on Farinelli’s insight that critique of such constructions must recognize an antagonistic humor in the production of maps and territories. Pynchon’s novel, I argue, is exemplary in the wit with which it pits the anomalous, strange, and contingent phenomena of the below against the homogenizing, categorizing power of above. His approach helps us understand the dark heart of Enlightenment cartography and society.
Difficulties and associated coping methods regarding visual hallucinations caused by dementia with Lewy bodies
Authors: Yumoto Akiyo , Suwa Sayuri
Published: October 2019

Individuals who have dementia with Lewy bodies present various symptoms that differ from those associated with Alzheimer’s disease. Of the several characteristic symptoms of dementia with Lewy bodies, visual hallucinations often appear in the early stages of the disease, and some hallucinations cause people with dementia with Lewy bodies to experience unique difficulties in their daily lives. The aim of this paper is to clarify the visual hallucination-related difficulties experienced by people with dementia with Lewy bodies as well as their coping methods. Participants were 10 people with dementia with Lewy bodies who were living at home, with input also obtained from their family members. Data were collected through semi-structured interviews, and a qualitative content analysis was consequently performed. The qualitative analysis showed four primary difficulties in the period before a patient realizes that their visual hallucinations are a symptom of an underlying disease; these included “feeling something strange is happening” and “restrictions on activities.” Realizing that what they were experiencing was not real was a significant turning point for the participants, with some discovering this by discussing their apparitions with their families. It was consequently determined that, after an individual realizes that their hallucinations are indicative of a more serious condition, two further difficulties arise, including the “inability to discuss the visual hallucinations with friends and family.” With regard to coping methods, some participants reported rearranging their living environments to hide areas where hallucinations commonly appeared. This paper suggests that care is needed to help people with dementia with Lewy bodies recognize that their visual hallucinations are a manifestation of their illness. In particular, psychological support should be made available to address the anxiety caused by the appearance of visual hallucinations and to help patients adjust their environments to reduce or prevent the appearance of such hallucinations.
Introduction: The Reactionary in the Fan and the Fan in the Reactionary
Authors: Stanfill Mel
Published: October 2019

This special issue explores the intersection of reactionary politics and fandom. Fandom has traditionally been thought of as progressive, but this has been limited and limiting. Moreover, considerations of the relationship between politics and fandom have especially focused on democratization and new media–enabled participation. However, it is important to expand our understanding to other aspects of politicization. This introduction situates the issue in relation to foundations of fan studies, examinations of political fandom and fannish politics, and growing recognition of inequality and conflict in fandom. These considerations are important in an era in which fandoms have increasingly overtly embraced reactionary politics and reactionary politics has increasingly taken fannish forms. It is this intersection of the reactionary and the fannish that this special issue seeks to unravel.
Effects of Intraperitoneal and Intrathecal Morphine Analgesia on the Expression of μ-Opioid Receptors in Bone Cancer Pain Rats
Authors: Liu Wei , Liu Heqi , Zhang Zongde , Huang Jiapeng
Published: October 2019

Backgrounds:

This study compared analgesic effects and μ-opioid receptor expression levels during long-term intraperitoneal and intrathecal treatment in a bone cancer pain rat.

Methods:

Twenty-four female Sprague-Dawley rats were injected Walker 256 tumor cells into the femur to create a bone cancer pain model. The control group was injected with saline intraperitoneally and intrathecally. The intraperitoneal group was injected with morphine intraperitoneally and saline intrathecally. The intrathecal group was injected saline intraperitoneally and morphine intrathecally. Changes in pain threshold, μ-opioid receptor expression levels in spinal cord, and tumor tissue were compared between 3 groups.

Results:

The intrathecal morphine group and the intraperitoneal group showed no difference in analgesia effects ( P > .05). Western blot and immunohistochemical staining of μ-opioid receptors demonstrated that its level in the intrathecal group was significantly lower than the intraperitoneal group ( P < .05) and without significant difference with the control group ( P > .05). The expression levels of μ-opioid receptor in the spinal cord tissue did not reveal a difference among these 3 groups ( P > .05).

Conclusion:

Intrathecal group and intraperitoneal group showed significant difference in μ-opioid receptor expressions although with no difference in analgesia effects. Long-term intrathecal morphine administration provided similar analgesia compared to systemic morphine.
Anatomical Variants of the Infraorbital Canal: Implications for the Prelacrimal Approach to the Orbital Floor
Authors: Li Lifeng , London Nyall R. , Prevedello Daniel M. , Carrau Ricardo L.
Published: October 2019

Background

The infraorbital nerve (ION) and its canal are important landmarks during surgical approaches to the orbital floor and pterygopalatine fossa. However, variations in the anatomy of the infraorbital canal and its corresponding neurovascular bundle may impact the access.

Objective

To investigate anatomic variants of the infraorbital canal from a prelacrimal endoscopic perspective and to explore the impact of these variants on exposing the lateral orbital floor.

Methods

Ten cadaveric specimens (20 sides) were dissected through an endonasal prelacrimal approach. Anatomic variants of the ION including location, branching pattern, and relationship to the infraorbital artery were assessed. The need for ION transposition to increase exposure of the lateral orbital floor was also investigated.

Results

Incidence of previously described Types 1, 2, and 3 ION variants were 30.0%, 60.0%, and 10.0%, respectively. Although the orbital floor could be directly accessed in Type 1 and Type 3 IONs, transposition of the ION was necessary to expose the lateral orbital floor in 5 of 12 sides (42%) for Type 2 ION. Bony dehiscence of the orbital floor was identified in 8 of 20 sides (40%) and branching of the ION in 2 of 20 sides (10%).

Conclusion

Anatomic variations of the infraorbital canal impact surgical exposure of the orbital floor via a prelacrimal approach. Type 1 and Type 3 ION variants allow a direct exposure of the entire orbital floor. A Type 2 ION may require transposition of the nerve to adequately expose the lateral orbital floor.
Anakinra for corticosteroid-dependent and colchicine-resistant pericarditis: The IRAP (International Registry of Anakinra for Pericarditis) study
Authors: Imazio Massimo , Andreis Alessandro , De Ferrari Gaetano Maria , Cremer Paul C , Mardigyan Vartan , Maestroni Silvia , Luis Sushil Allen , Lopalco Giuseppe , Emmi Giacomo , Lotan Dor , Marcolongo Renzo , Lazaros George , De Biasio Marzia , Cantarini Luca , Dagna Lorenzo , Cercek Andreja Cerne , Pivetta Emanuele , Varma Beni , Berkson Laeora , Tombetti Enrico , Iannone Florenzo , Prisco Domenico , Caforio Alida Linda P , Vassilopoulos Dimitrios , Tousoulis Dimitrios , De Luca Giacomo , Giustetto Carla , Rinaldi Mauro , Oh Jae K , Klein Allan L , Brucato Antonio , Adler Yehuda
Published: October 2019

Aims

Novel therapies are needed for recurrent pericarditis, particularly when corticosteroid dependent and colchicine resistant. Based on limited data, interleukin-1 blockade with anakinra may be beneficial. The aim of this multicentre registry was to evaluate the broader effectiveness and safety of anakinra in a ‘real world’ population.

Methods and results

This registry enrolled consecutive patients with recurrent pericarditis who were corticosteroid dependent and colchicine resistant and treated with anakinra. The primary outcome was the pericarditis recurrence rate after treatment. Secondary outcomes included emergency department visits, hospitalisations, corticosteroid use and adverse events. Among 224 patients (46 ± 14 years old, 63% women, 75% idiopathic), the median duration of disease was 17 months (interquartile range 9–33). Most patients had elevated C-reactive protein (91%) and pericardial effusion (88%). After a median treatment of 6 months (3–12), pericarditis recurrences were reduced six-fold (2.33–0.39 per patient per year), emergency department admissions were reduced 11-fold (1.08–0.10 per patient per year), hospitalisations were reduced seven-fold (0.99–0.13 per patient per year). Corticosteroid use was decreased by anakinra (respectively from 80% to 27%; P < 0.001). No serious adverse events occurred; adverse events consisted mostly of transient skin reactions (38%) at the injection site. Adverse events led to discontinuation in 3%. A full-dose treatment duration of over 3 months followed by a tapering period of over 3 months were the therapeutic schemes associated with a lower risk of recurrence.

Conclusion

In patients with recurrent pericarditis, anakinra appears efficacious and safe in reducing recurrences, emergency department admissions and hospitalisations.
Platelet Biogenesis in the Lung Circulation
Authors: Looney Mark
Published: October 2019

Platelets are indispensable in hemostasis, thrombosis, and immune responses. In humans, billions of platelets are produced each day from megakaryocytes, however the mechanisms of mature platelet production are incompletely understood. Megakaryocytes are produced in the bone marrow and have been visualized to communicate with the bone marrow sinusoids to release proplatelet fragments. Megakaryocytes have also been found in other tissues, including the lung, but the function of megakaryocytes in these locations is unclear. Historical data indicate that the lung may be a site of platelet biogenesis. The concentration of megakaryocytes in the blood exiting the lung is much lower than the blood entering the lung (implying filtering) and conversely, platelet counts are higher in blood draining from the lungs. Additionally, when the lung circulation in entirely bypassed, megakaryocytes accumulate in the blood and there is a high incidence of thrombocytopenia. However, direct proof of platelet biogenesis in the lung is lacking. We used lung intravital microscopy combined with fluorescently labeled mouse strains and directly visualized intravascular megakaryocytes releasing platelets in the lung circulation. We also visualized megakaryocytes in the bone marrow and spleen releasing proplatelet fragments, and megakaryocyte migration in toto from the bone marrow, which are presumably the source material for lung platelet production. The megakaryocyte-releasing events in the lung were quantified and represent at least half of the total platelet production in mice, which can be increased by the application of thrombopoietin. We also observed a much larger extravascular pool of megakaryocytes in the lung that were not platelet generating as observed by lung intravital imaging. The function of these lung-resident megakaryocytes is unknown, but RNA-Seq data points to a potential role in lung immunity. Orthotopic, single-lung transplantation experiments into thrombocytopenic and hematopoietic progenitor-deficient animals (c-mpl-/-) revealed that peripheral blood platelet counts and bone marrow hematopoietic progenitors could be fully reconstituted by the lung transplant procedure implying the presence of hematopoietic progenitors in the mouse lung. Indeed, these progenitors were directly detected in the extravascular lung and purified populations of hematopoietic progenitors in the lung could correct thrombocytopenia in c-mpl-/-animals. Finally, the lung transplant procedure produced donor-derived chimerism of other hematopoietic lineages such as neutrophils and lymphocytes. We conclude that the lung has significant hematopoietic potential including being a major site of platelet biogenesis.

Disclosures

No relevant conflicts of interest to declare.
SLAMF7 in Primary Effusion Lymphoma, Target for Individualized Therapy?
Authors: Quentmeier Hilmar , Pommerenke Claudia , Dirks Wilhelm G , Hauer Vivien , Koeppel Max , Nagel Stefan , Scherr Michaela , Zaborski Margarete , Drexler Hans G.
Published: October 2019

Primary effusion lymphoma (PEL) is a rare, aggressive form of B-cell lymphoma. With a median survival time of around six months the prognosis for PEL patients is poor. Therefore, there is a medical need for novel therapeutic strategies.

We performed expression array analysis to find potential targets for antibody-based therapy. Unsupervised clustering analysis revealed that PEL cell lines grouped separate from cell lines derived from other B-non Hodgkin lymphoma (B-NHL) entities. Notably, PEL and Hodgkin Lymphoma (HL) cell lines clustered on one arm, separate from all cell lines representing less-differentiated B-NHL variants.

PEL and HL cell lines were characterized by a set of common up- and downregulated genes. Typical for PEL and HL was the expression of CCND2 and the absence of Brutons tyrosine kinase and of B-cell markers including CD19, CD20, CD79A and CD79B.

Highly expressed in PEL - but not in HL - were CD138, IL-10, SLAMF7 and PRDM1. PRDM1/BLIMP1 is a master regulator of terminal B-cell differentiation. Originally described as repressor, BLIMP1 can also enhance transcription of SLAMF7 in multiple myeloma (MM) and of IL-10 in type 1 regulatory T-cells. Thus, coexpression of the three genes suggests a causal relationship between transcriptionally active PRDM1/BLIMP1 and its targets SLAMF7 and IL-10 also in PEL.

Expression of SLAMF7 in PEL is especially noteworthy because a monoclonal antibody targeting SLAMF7 (elotuzumab) has been approved for treatment of patients with MM. We observed that SLAMF7 is comparably expressed in PEL and in MM cell lines. If the results on cell lines can be translated to primary PEL, i.e. if PEL tumor cells express SLAMF7, the patients might benefit from an antibody-based targeted therapy against this antigen.

Disclosures

No relevant conflicts of interest to declare.
AC0010, a Novel BTK Inhibitor, Exerts Anti-Leukemia Effects and Synergizes the Efficiency of Homoharringtonine in AML
Authors: Jin Jie , Huang Shujuan
Published: October 2019

Ibrutinib, an inhibitor of Bruton's tyrosine kinase(BTK), has shown promising pharmacologic effects in acute myeloid leukemia (AML). In this study, we report that AC0010 as a novel BTK inhibitor inhibits the cell proliferation, reduces colony-forming capacity, induces cell apoptosis and arrests cell cycle in AML cells, especially in those carrying FLT3 mutations. Surprisingly, AC0010 is found more sensitive than ibrutinib in treating AML. Mechanically, we showed that AC0010 not only targeting the phosphorylation of BTK, but also the crucial PI3K survival pathway. Furthermore, we observed that AC0010 could also suppress the expression of p-FLT3 and downstream target p-STAT5 in AML cells with FLT3 mutations. Moreover, our in vitro and in vivo data clarify that AC0010 can synergize with Homoharringtonine (HHT), a natural plant alkaloid, in treating AML with or without FLT3-ITD mutations. Collectively, our results suggest that AC0010 might be a promising drug in treating AML patients, and synergizes the efficiency of Homoharringtonine in AML.

Disclosures

Jin: College of Medicine, Zhejiang University: Employment; The National Natural Science Foundation of China: Research Funding.
Long Term Results for Childhood Acute Lymphoblastic Leukemia: An Institutional Review
Authors: Mai Huirong , Fang Ximin , Yuan Xiuli , Wang Xiaodong , Liu Sixi , Wang Ying , Li Changgang , Li Chi Kong , Wen Feiqiu
Published: October 2019

Objective s: To exam the outcomes of children with acute lymphoblastic leukemia (ALL) treated on Berlin-Frankfürt-Münster (BFM) International ALL- based protocol, GD 2008ALL protocol.

Method s : In total, 274 patients with newly diagnosed ALL age 1 to 16 years were enrolled onto GD2008ALL protocol from July 1, 2008 to June 30, 2016. Five-year overall survival (OS) rates and even-free survival (EFS) rates were examined with additional analyses of causes of relapse and death.

Results:The 5-year probabilities of OS and EFS were 90.8% and 86.9%. The 5-year EFS were 91.7% in SR group, 86.5% in IR group and 82.6% in HR group, respectively. Twenty-five patients were died. Reasons for mortality included 8 cases due to relapse of leukemia, seven cases due to severe infection, one case due to hepatic failure, one case due to intracranial hemorrhage from accident, eight cases abandoned after relapse. There were 29 cases relapsed, including 22 cases (75%) relapsed of the bone marrow alone, 1 case (3.6%) CNS relapsed alone, 2 cases (7.1%) testicular relapsed and 4 cases (14.3%) relapsed of bone marrow and extramedullary. Eleven patients survived after therapy for relapse, of which 7 had received HSCT, two out of the 7 had relapsed after HSCT, and continued on CART therapy. Four out of the 11 relapsed patients received relapsed ALLR3 protocol for treatment. All 11 patients remained in remission status.

Conclusion:Our single institutional review of pediatric ALL treated on GD 2008ALL Protocol was tolerated and has good long term outcomes. Although relapse is a major factor affecting long term survival, there are still have options such as HSCT or immunotherapy available for these patients.

Disclosures

No relevant conflicts of interest to declare.
Electric Field Controlled Indirect-Direct-Indirect Band Gap Transition in Monolayer InSe
Authors: Xiao Xian-Bo , Ye Qian , Liu Zheng-Fang , Wu Qing-Ping , Li Yuan , Ai Guo-Ping
Published: October 2019

Electronic structures of monolayer InSe with a perpendicular electric field are investigated. Indirect-direct-indirect band gap transition is found in monolayer InSe as the electric field strength is increased continuously. Meanwhile, the global band gap is suppressed gradually to zero, indicating that semiconductor-metal transformation happens. The underlying mechanisms are revealed by analyzing both the orbital contributions to energy band and evolution of band edges. These findings may not only facilitate our further understanding of electronic characteristics of layered group III-VI semiconductors, but also provide useful guidance for designing optoelectronic devices.
DIRECT: RNA contact predictions by integrating structural patterns
Authors: Jian Yiren , Wang Xiaonan , Qiu Jaidi , Wang Huiwen , Liu Zhichao , Zhao Yunjie , Zeng Chen
Published: October 2019

Background

It is widely believed that tertiary nucleotide-nucleotide interactions are essential in determining RNA structure and function. Currently, direct coupling analysis (DCA) infers nucleotide contacts in a sequence from its homologous sequence alignment across different species. DCA and similar approaches that use sequence information alone typically yield a low accuracy, especially when the available homologous sequences are limited. Therefore, new methods for RNA structural contact inference are desirable because even a single correctly predicted tertiary contact can potentially make the difference between a correct and incorrectly predicted structure. Here we present a new method DIRECT (Direct Information REweighted by Contact Templates) that incorporates a Restricted Boltzmann Machine (RBM) to augment the information on sequence co-variations with structural features in contact inference.

Results

Benchmark tests demonstrate that DIRECT achieves better overall performance than DCA approaches. Compared to mfDCA and plmDCA, DIRECT produces a substantial increase of 41 and 18%, respectively, in accuracy on average for contact prediction. DIRECT improves predictions for long-range contacts and captures more tertiary structural features.

Conclusions

We developed a hybrid approach that incorporates a Restricted Boltzmann Machine (RBM) to augment the information on sequence co-variations with structural templates in contact inference. Our results demonstrate that DIRECT is able to improve the RNA contact prediction.
Comparison of GeneXpert and line probe assay for detection of Mycobacterium tuberculosis and rifampicin-mono resistance at the National Tuberculosis Reference Laboratory, Kenya
Authors: Aricha S. A. , Kingwara L. , Mwirigi N. W. , Chaba L. , Kiptai T. , Wahogo J. , Otwabe J. S. , Onyango P. O. , Karanja M. , Ayieko C. , Matu S. W.
Published: October 2019

Background

The dual challenge of low diagnostic sensitivity of microscopy test and technical challenge of performing a TB culture test poses a problem for case detection and initiation of Tuberculosis (TB) second-line treatment. There is thus need for a rapid, reliable and easily accessible assay. This comparative analysis was performed to assess diagnostic performance characteristics of GeneXpert MTB/RIF and Line Probe Assay (LPA).

Methods

Three hundred twenty nine sputum samples of patients across the 47 counties in Kenya suspected to have drug resistant TB were picked and subjected to GeneXpert, LPA and Culture MGIT at the National TB Reference Laboratory. Sensitivity, specificity and predictive values were then determined to assess the performance characteristics of the various assays.

Results

Against culture MGIT as the gold standard for TB diagnosis, GeneXpert had a sensitivity, specificity, positive predictive value, and negative predictive value of 78.5, 64.9, 59.4 and 82.2% respectively while LPA had 98.4, 66.0, 65.4 and 98.4%. For diagnosis of rifampicin mono-resistance GeneXpert had a moderate agreement (Kappa 0.59, P < 0.01) (sensitivity 62.50%, specificity 96.50%) while LPA that had almost perfect agreement (Kappa = 0.89, p < 0.01) with a (sensitivity 90.0% and specificity 99.1%).

Conclusion

LPA has a better performance characteristic to GeneXpert and an alternative to culture with regards to detection of RIF’s mono-resistance.
Microorganisms involved in deep neck infection (DNIs) in Greece: detection, identification and susceptibility to antimicrobials
Authors: Beka Despoina , Lachanas Vasileios A. , Doumas Stergios , Xytsas Stelios , Kanatas Anastasios , Petinaki Efi , Skoulakis Charalampos
Published: October 2019

Background

To determine, from October 2010 to October 2018, the epidemiology of Deep Neck Infections (DNIs), regarding the detection, the identification and the susceptibility to antimicrobials of causative microorganisms, in Thessaly-Central Greece.

Methods

An analysis of data from a prospective database was conducted on 610 consecutive patients with DNIs treated in the Otolaryngology / Head & Neck Surgery Department of University Hospital of Larissa. Demographics, clinical features and microbiological data were analyzed.

Results

Among the 610 patients (1,9/1 male to female ratio, mean age: 39,24 ± 17,25) with DNIs, 579 had a single space (94,9%), while the remaining 31 had a multi-space (5,1%) DNI. The most common areas affected were the peritonsillar space (84,6%) followed by the submandibular space (6,5%). Clinical samples were obtained from 462 patients, and were tested by culture and by the application of 16S rRNA PCR. Two hundred fifty-five samples (55,2%) gave positive cultures, in which Streptococcus pyogenes and Staphylococcus aureus were predominant. The application of the 16S rRNA PCR revealed that 183 samples (39,6%) were positive for bacterial DNA; 22 of them, culture negative, were found to be positive for anaerobic (Fusobacterium necrophorum, Actinomyces israellii etc) and for fastidious microorganisms (Brucella mellitensis, Mycobacterium avium).

Conclusion

DNIs represent a medical and surgical emergency and evidence-guided empirical treatment with intravenous infusion of antibiotics at the time of diagnosis is mandatory, highlighting the importance of epidemiological studies regarding the causative microorganisms. Although, in our study, the predominant pathogens were S. pyogenes and S. aureus, the combination of culture and molecular assay revealed that anaerobic bacteria play also a significant role in the pathogenesis of DNIs. Based on the local epidemiology, we propose as empirical therapy the intravenous use of a beta-lactam /beta-lactamase inhibitor; metronidazole or clindamycin can be added only in specific cases such as in immunocompromised patients.
Histological evidence for the cardiac safety of high-dose pegylated liposomal doxorubicin in a patient with HIV-associated Kaposi sarcoma: a case report and literature review
Authors: Ishihara Ayaka , Hatakeyama Shuji , Suzuki Jun , Amano Yusuke , Sasahara Teppei , Toshima Masaki , Morisawa Yuji
Published: October 2019

Background

Pegylated liposomal doxorubicin plays an important role in the treatment of patients with severe refractory human immunodeficiency virus (HIV)-associated Kaposi sarcoma (KS). High cumulative doses of conventional doxorubicin exceeding 500 mg/m2 are known to cause cardiac toxicity. However, the safe cumulative dose of pegylated liposomal doxorubicin is unclear.

Case presentation

A 40-year-old Japanese man with HIV infection presented with pain, edema, and multiple skin nodules on both legs which worsened over several months. He was diagnosed with HIV-associated KS. He received long-term pegylated liposomal doxorubicin combined with antiretroviral therapy for advanced, progressive KS. The cumulative dose of pegylated liposomal doxorubicin reached 980 mg/m2. The patient’s left ventricular ejection fraction remained unchanged from baseline during treatment. After he died as a result of cachexia and wasting, caused by recurrent sepsis and advanced KS, an autopsy specimen of his heart revealed little or no evidence of histological cardiac damage. We also conducted a literature review focusing on histological changes of the myocardium in patients treated with a cumulative dose of pegylated liposomal doxorubicin exceeding 500 mg/m2.

Conclusions

This case report and literature review suggest that high (> 500 mg/m2) cumulative doses of pegylated liposomal doxorubicin may be used without significant histological/clinical cardiac toxicity in patients with HIV-associated KS.
History and epidemiology of foot-and-mouth disease in Afghanistan: a retrospective study
Authors: Osmani Arash , Robertson Ian Duncan , Habib Ihab , Aslami Ahmad Arash
Published: October 2019

Background

Foot and mouth disease (FMD) is endemic in Afghanistan with serotypes O, A and Asia 1 being prevalent. A retrospective study of data collected through passive surveillance of outbreaks of FMD in Afghanistan from 1995 to 2016 was undertaken to determine the temporal and spatial distribution of FMD in the country.

Results

A total of 4171 outbreaks were reported between 1995 and 2008 with a strong correlation between the number of outbreaks and the number of provinces (r = 0.85, s = 68.2, p < 0.001); and between the number of outbreaks and the number of districts containing infected animals (r = 0.68, s = 147.8, p = 0.008). Of 7558 samples collected from livestock originating from 34 provinces in 2009, 2011 and 2013–2015, 54.1% were test positive (FMDV 3ABC-trapping ELISA) and the prevalence varied significantly between years (χ2 = 263.98, df = 4, P < 0.001). Clinically suspected cases were reported in 2016 with a substantial positive correlation (r = 0.70, P < 0.001) between the number of districts with cases and the number of reported cases. Serotype O was the predominant serotype detected during the study period, although serotypes A and Asia1 were also detected. Cattle were involved in all outbreaks in the study period and infections were detected in all years of the study in Hirat province in the north-west (bordering Iran), Nangarhar province in the east (bordering Pakistan) and Kabul province in the centre of the country.

Conclusions

The current paper was the first analysis of existing data focusing on the spatiotemporal distribution of FMD in Afghanistan. The findings from this study provide valuable direction for further research to understand the epidemiology of FMD and its control in Afghanistan.
Distribution, dynamics and functional roles of phosphatidylserine within the cell
Authors: Kay Jason G. , Fairn Gregory D.
Published: October 2019

Phosphatidylserine (PtdSer), an essential constituent of eukaryotic membranes, is the most abundant anionic phospholipid in the eukaryotic cell accounting for up to 10% of the total cellular lipid. Much of what is known about PtdSer is the role exofacial PtdSer plays in apoptosis and blood clotting. However, PtdSer is generally not externally exposed in healthy cells and plays a vital role in several intracellular signaling pathways, though relatively little is known about the precise subcellular localization, transmembrane topology and intracellular dynamics of PtdSer within the cell. The recent development of new, genetically-encoded probes able to detect phosphatidylserine is leading to a more in-depth understanding of the biology of this phospholipid. This review aims to give an overview of recent developments in our understanding of the role of PtdSer in intracellular signaling events derived from the use of these recently developed methods of phosphatidylserine detection.
JAZF1–SUZ12 endometrial stromal sarcoma forming subserosal masses with extraordinary uptake of fluorodeoxyglucose on positron emission tomography: a case report
Authors: Fujiishi Koto , Nagata Shigenori , Kano Rieko , Kubo Chiaki , Shirayanagi Maasa , Ozaki Megumi , Yamamoto Takashi , Nakanishi Katsuyuki , Kamiura Shoji , Nakatsuka Shin-ichi
Published: October 2019

Background

Low-grade endometrial stromal sarcoma (ESS) is rare mesenchymal neoplasm, recently specified as harboringJAZF1–SUZ12rearrangement. TypicalJAZF1–SUZ12ESS is slow growing, in which high uptake of fluorodeoxyglucose (FDG) on positron emission tomography (PET) and subserosal masses are quite unusual.

Case presentation

A 69-year-old Japanese woman complained of urinary incontinence. Pelvic magnetic resonance imaging showed uterine lesions composed of (1) a 9 × 8 × 7-cm mass protruding from the right-anterior wall, (2) a 4.5-cm mass attached to the right-posterior wall, and (3) a 6.5-cm intramural mass in the fundus. FDG-PET demonstrated maximum standardized uptake value of 13.28 confined to the two subserosal masses (1 & 2) in contrast to no uptake of the intramural mass (3). She was diagnosed with a high-grade uterine sarcoma concomitant with leiomyomas and underwent total hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy. The removed uterus had three tumors—two in the right-anterior and right-posterior subserosa, respectively, and the remaining in the fundal myometrium. Microscopically, the three tumors shared morphologic features characterized by neoplastic cells similar to proliferative-phase endometrial stromal cells, in which neither round-cell component, pleomorphism, nor high mitotic activity was recognized. Nuclear cyclin D1 immunostaining was identified 50% of neoplastic cells in the two subserosal tumors (1 &2) whereas < 1% positive cells in the intramural component (3). Reverse transcriptase-polymerase chain reaction showed the same-sized electrophoretic bands indicatingJAZF1–SUZ12gene fusion shared by the three uterine tumors and a focal tumor extension into the extrauterine vein. The patient is alive without evidence of recurrence at 14 months after surgery.

Conclusions

Pathologists and clinicians should not exclude the possibility ofJAZF1–SUZ12ESS even when uterine subserosal masses demonstrate extraordinary FDG uptake on PET. Molecular analysis is helpful for diagnostic confirmation ofJAZF1–SUZ12ESS with a complex growth pattern.
The use or generation of biomedical data and existing medicines to discover and establish new treatments for patients with rare diseases – recommendations of the IRDiRC Data Mining and Repurposing Task Force
Authors:   on behalf of the IRDiRC Data Mining and Repurposing Task Force, Southall Noel T , Natarajan Madhusudan , Lau Lilian Pek Lian , Jonker Anneliene Hechtelt , Deprez Benoît , Guilliams Tim , Hunter Lawrence , Rademaker Carin MA , Hivert Virginie , Ardigò Diego
Published: October 2019

The number of available therapies for rare diseases remains low, as fewer than 6% of rare diseases have an approved treatment option. The International Rare Diseases Research Consortium (IRDiRC) set up the multi-stakeholder Data Mining and Repurposing (DMR) Task Force to examine the potential of applying biomedical data mining strategies to identify new opportunities to use existing pharmaceutical compounds in new ways and to accelerate the pace of drug development for rare disease patients. In reviewing past successes of data mining for drug repurposing, and planning for future biomedical research capacity, the DMR Task Force identified four strategic infrastructure investment areas to focus on in order to accelerate rare disease research productivity and drug development: (1) improving the capture and sharing of self-reported patient data, (2) better integration of existing research data, (3) increasing experimental testing capacity, and (4) sharing of rare disease research and development expertise. Additionally, the DMR Task Force also recommended a number of strategies to increase data mining and repurposing opportunities for rare diseases research as well as the development of individualized and precision medicine strategies.
LncRNA H19 over-expression inhibited Th17 cell differentiation to relieve endometriosis through miR-342-3p/IER3 pathway
Authors: Liu Zheying , Liu Liya , Zhong Yun , Cai Mingbo , Gao Junbi , Tan Chaoyue , Han Xiaoxiao , Guo Ruixia , Han Liping
Published: October 2019

Objective

To investigate the mechanism of LncRNA H19 in Th17 cell differentiation and endometrial stromal cells (ESCs) proliferation in endometriosis (EMS).

Methods

LncRNA H19, miR-342-3p and IER3 expressions were detected by qRT-PCR and western blot. The percentage of Th17 cells/CD4+ T cells was detected by flow cytometry. IL-17 level was measured by ELISA. The interaction of miR-342-3p and IER3 was confirmed by Luciferase reporter assay.

Results

LncRNA H19 and IER3 expressions were down-regulated in mononuclear cells from peritoneal fluid (PFMCs) of patients with EMS or under Th17 differentiation conditions, whereas miR-342-3p expression was up-regulated and the percentage of Th17 cells was increased in PFMCs of patients with EMS or under Th17 differentiation conditions. Over-expression of LncRNA H19 decreased IL-17 level and the percentage of Th17 cells/CD4+ T cells. Besides, we confirmed that miR-342-3p could target to IER3 and negatively regulate IER3 expression. LncRNA H19 over-expression suppressed Th17 differentiation and ESC proliferation through regulating miR-342-3p/IER3. In vivo experiments showed LncRNA H19 over-expression suppressed the growth of Th17 cell differentiation-induced endometriosis-like lesions.

Conclusion

LncRNA H19 was down-regulated in PFMC of patients with EMS or under Th17 polarizing conditions, and LncRNA H19 over-expression suppressed Th17 cell differentiation and ESCs proliferation through miR-342-3p/IER3 pathway.
Neurosurgical applications of MRI guided laser interstitial thermal therapy (LITT)
Authors: Salem Usama , Kumar Vinodh A. , Madewell John E. , Schomer Donald F. , de Almeida Bastos Dhiego Chaves , Zinn Pascal O. , Weinberg Jeffrey S. , Rao Ganesh , Prabhu Sujit S. , Colen Rivka R.
Published: October 2019

MRI-guided laser interstitial thermal therapy (LITT) is the selective ablation of a lesion or a tissue using heat emitted from a laser device. LITT is considered a less invasive technique compared to open surgery that provides a nonsurgical solution for patients who cannot tolerate surgery. Although laser ablation has been used to treat brain lesions for decades, recent advances in MRI have improved lesion targeting and enabled real-time accurate monitoring of the thermal ablation process. These advances have led to a plethora of research involving the technique, safety, and potential applications of LITT.

LITT is a minimally invasive treatment modality that shows promising results and is associated with decreased morbidity. It has various applications, such as treatment of glioma, brain metastases, radiation necrosis, and epilepsy. It can provide a safer alternative treatment option for patients in whom the lesion is not accessible by surgery, who are not surgical candidates, or in whom other standard treatment options have failed. Our aim is to review the current literature on LITT and provide a descriptive review of the technique, imaging findings, and clinical applications for neurosurgery.
Resveratrol modulates the Akt/GSK-3β signaling pathway in a middle cerebral artery occlusion animal model
Authors: Park Dong-Ju , Kang Ju-Bin , Shah Fawad-Ali , Koh Phil-Ok
Published: October 2019

Cerebral ischemia is a major cause of neurodegenerative disease. It induces neuronal vulnerability and susceptibility, and leads to neuronal cell death. Resveratrol is a polyphenolic compound that acts as an anti-oxidant. It exerts a neuroprotective effect against focal cerebral ischemic injury. Akt signaling pathway is accepted as a representative cell survival pathway, including proliferation, growth, and glycogen synthesis. This study investigated whether resveratrol regulates Akt/glycogen synthase kinase-3β (GSK-3β) pathway in a middle cerebral artery occlusion (MCAO)-induced ischemic brain injury. Adult male rats were intraperitoneally injected with vehicle or resveratrol (30 mg/kg) and cerebral cortices were isolated 24 h after MCAO. Neurological behavior test, corner test, brain edema measurment, and 2,3,5-triphenyltetrazolium chloride staining were performed to elucidate the neuroprotective effects of resveratrol. Phospho-Akt and phospho-GSK-3β expression levels were measured using Western blot analysis. MCAO injury led to severe neurobehavioral deficit, infraction, and histopathological changes in cerebral cortex. However, resveratrol treatment alleviated these changes caused by MCAO injury. Moreover, MCAO injury induced decreases in phospho-Akt and phospho-GSK-3β protein levels, whereas resveratrol attenuated these decreases. Phosphorylations of Akt and GSK-3β act as a critical role for the suppression of apoptotic cell death. Thus, our finding suggests that resveratrol attenuates neuronal cell death in MCAO-induced cerebral ischemia and Akt/GSK-3β signaling pathway contributes to the neuroprotective effect of resveratrol.
Prognostic value of trafficking of regulatory T cells to tumors in head and neck cancer patients.
Authors: Chang Hyun , Hong Hyun Jun , Kim Yongho
Published: October 2019

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Background: The prognostic value of regulatory T cells (Tregs) in head and neck squamous cell carcinoma (HNSCC) remains unknown. We analyzed the prognostic effect of Tregs in HNSCC with immune activity scores, which reflect the activity status of the seven-step cancer-immunity cycle. Methods: We correlated the 23 immune activity scores and clinicopathologic features of The Cancer Genome Atlas (TCGA) HNSCC using multivariate Cox regression analyses and Kaplan-Meier survival curves. The processed data of immune activity scores were obtained from TIP online tool and the clinicopathologic data were downloaded from TCGA HNSCC database. Results: Immune activity scores of “trafficking of Tregs to tumors” was significantly associated with overall survival (OS) and progression-free survival (PFS). Low activity scores of “trafficking of Tregs to tumors” resulted in shorter OS and PFS. In multivariate analysis, low scores predicted poor OS (adjusted HR = 1.87, 95% CI 1.34-2.60 ; P < 0.001) and were related with unfavorable PFS (adjusted HR = 2.04, 95% CI 1.45-2.86 ; P < 0.001). Conclusions: Immune activity scores of “trafficking of Tregs to tumors” was independent significant prognostic factor in HNSCC. Therefore, assessment of immune activity scores may be useful tools for predicting prognosis in these patients.