bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a calcified odontogenic hamartoma following avulsion of a permanent central incisor
Authors: Procópio Stefânia Werneck , Matos Hiorran Coelho de Almeida , de Oliveira Pedro Lima Emmerich , de Andrade Bruno Augusto Benevenuto , Agostini Michelle , Esteves Jonatas Caldeira , de Campos Paulo Ricardo Barros , de Souza Margareth Maria Gomes , Maia Lucianne Cople
Published: October 2019

The avulsion of a permanent immature tooth is a serious condition and a real emergency in dentistry. The management of a traumatized avulsed tooth is always a challenge to the clinician. This case report concerns the development of a calcified odontogenic hamartoma after the avulsion of an immature central incisor in an eight‐year‐old female. The patient presented for the treatment four months after the avulsion. Her intraoral examination showed complete healing of the area but an atypical appearance of the alveolar area of the missing tooth was observed in the periapical radiograph. A new radiographic scan performed six months later revealed the formation of a radiopaque irregular structure at the cervical level of the alveolar ridge at the site of the missing tooth. Surgical removal was performed, and the histopathological examination revealed a hamartomatous proliferation of odontogenic tissue with calcification. After healing, the lateral incisor was orthodontically moved mesially and restored to resemble the central incisor. An orthodontic device was installed to improve function and aesthetics of the patient.
Outcomes of treatment with dose‐adjusted EPOCH‐R or R‐CHOP in primary mediastinal large B‐cell lymphoma
Authors: Malenda Agata , Kołkowska‐Leśniak Agnieszka , Puła Bartosz , Długosz‐Danecka Monika , Chełstowska Monika , Końska Agnieszka , Giza Agnieszka , Lech‐Marańda Ewa , Jurczak Wojciech , Warzocha Krzysztof
Published: October 2019

Background

The standard first‐line treatment for primary mediastinal B‐cell lymphoma (PMBCL) patients is rituximab‐based immunochemotherapy; however, this is not due to the result of randomized clinical trials.

Aims

We retrospectively investigated 53 PMBCL patient outcomes treated either with R‐CHOP‐21 or DA‐EPOCH‐R‐28. The primary endpoint was overall survival (OS). Secondary endpoints were complete remission (CR), overall response rate (ORR), progression‐free survival (PFS), and treatment‐related complications.

Results

Treatment with R‐CHOP‐21 resulted in a 92.0% ORR (60% CR), while DA‐EPOCH‐R yielded a 92.6% ORR (70.4% CR). There were no differences in the occurrence of grade 3‐4 hematological adverse events, but grade 1‐2 cardiologic complications (P = .003) were observed more frequently in the DA‐EPOCH‐R arm. Median PFS and OS were not achieved. The differences in estimated 12‐month PFS in R‐CHOP and DA‐EPOCH‐R group (87% vs 73.9%) and OS (100% vs 92%) were insignificant. Patients treated with R‐CHOP‐21 and autologous hematopoietic stem cell transplantation (auto‐HSCT) had an improved OS (P = .03) but not PFS (P = .43) compared to those treated solely with R‐CHOP‐21. No differences in PFS or OS were observed between patients treated with R‐CHOP‐21/auto‐HSCT and DA‐EPOCH‐R.

Conclusion

The results of this study suggest that R‐CHOP‐21 may be an alternative to DA‐EPOCH‐R treatment for PMBCL patients.
Experiences from Southeast Asia on nursing education, practice, mobility and influencing policy
Authors: Kunaviktikul W. , Turale S. , Petrini M.A. , Tungpunkom P. , Avant K.C.
Published: October 2019

In this report from the field, we describe the challenges and opportunities for nursing practice and education, and ways to improve nurse mobility across Asia. We also explain the collaboration within the Southeast and East Asian Nursing Education and Research Network to influence policy development and review.

The collaborative process was supported by evidence drawn from discussions at Network meetings, and with nursing and other leaders, an examination of literature and policy documents, and member surveys. We reviewed the region’s regulatory statutes which all support diversity in the nursing workforce.

The Southeast Asian Nursing Education and Research Network was established in 2015 to support policy development around the upgrading of nurse education, clinical competencies and research capacity, in hospital and primary health care; and facilitating the movement of nurses across national boundaries. Most countries have tried to address policy gaps and their efforts to implement changes are seen in policy expansion and development at the national level.

We focus on two policies from the Association of Southeast Asian Nations from 2006 and 2012, that cover nurse mobility, information exchange, nurse capacity building and education and mutual professional recognition of nurses’ credentials. However, we found significant variances in education, regulatory policies and clinical competencies that have restricted, and continue to restrict policy implementation.

Nursing in South‐East Asia has made significant progress in upgrading standards for education by increasing bachelor degree bridging programs, master and doctoral degrees. Participating countries have passed legislation on licensure, competencies and credentialing of internationally qualified nurses wishing to practice in various contexts. However, much work remains to be done.

Implications for nursing policy, education and practice

Governing bodies determine entry into practice law which requires dialogue to enhance policies for domestic and international practitioners for mutual exchange and recognition. Nursing practice and education are under government regulatory bodies but require new policies and laws to ensure adequate educational requirements for safe quality practice.
Diabetes and Younger Age Are Vital and Independent Risk Factors for Acute Pancreatitis in Patients with Severe Hypertriglyceridemia
Authors: Li Qiang , Hou Chaoqun , Peng Yunpeng , Zhu Xiaole , Shi Chenyuan , Zhang Kai , Tu Min , Guo Feng , Huang Dongya , Miao Yi
Published: October 2019

Background. The incidence of hypertriglyceridemia-induced acute pancreatitis (HIAP) is increasing worldwide, and now it is the third leading cause of acute pancreatitis in the United States. But, there are only 5% of patients with severe hypertriglyceridemia (>1000 mg/dl) which might generate acute pancreatitis. In order to explore which part of the patients is easy to develop into pancreatitis, a case-control study was performed by us to consider which patient population tend to develop acute pancreatitis in patients with severe hypertriglyceridemia. To perform a retrospective case-control study, we identified severe hypertriglyceridemia patients without AP (HNAP) and with HIAP with a fasting triglyceride level of >1000 mg/dl from The First Affiliated Hospital of Nanjing Medical University during January 1, 2014, to December 31, 2016. Baseline patient characteristics, comorbidities, and risk factors were recorded and evaluated by the univariate and multivariate logistic regression analysis for HIAP and HNAP patients. A total of 124 patients with severe hypertriglyceridemia were included in this study; of which, 62 patients were in the HIAP group and 62 were in the HNAP group. Univariate logistic regression analysis showed that there was no gender difference in both groups; however, there were more younger patients in the HIAP group than in the HNAP group (Pvalue < 0.001), and the HIAP group had low level of high-density lipoprotein compared to the HNAP group (P<0.05). Meanwhile, the presence of pancreatitis was associated with higher level of glycemia and a history of diabetes (P<0.05). Multivariate logistic regression analysis indicated that a history of diabetes and younger age were independent risk factors for acute pancreatitis in patients with severe hypertriglyceridemia. Uncontrolled diabetes and younger age are potential risk factors in patients with severe hypertriglyceridemia to develop acute pancreatitis.
A Sparse Representation Method for Coherent Sources Angle Estimation with Uniform Circular Array
Authors: Su Xiaolong , Liu Zhen , Liu Tianpeng , Peng Bo , Chen Xin , Li Xiang
Published: October 2019

Coherent source localization is a common problem in signal processing. In this paper, a sparse representation method is considered to deal with two-dimensional (2D) direction of arrival (DOA) estimation for coherent sources with a uniform circular array (UCA). Considering that objective function requires sparsity in the spatial dimension but does not require sparsity in time, singular value decomposition (SVD) is employed to reduce computational complexity and ℓ2 norm is utilized to renew objective function. After the new objective function is constructed to evaluate residual and sparsity, a second-order cone (SOC) programming is employed to solve convex optimization problem and obtain 2D spatial spectrum. Simulations show that the proposed method can deal with the case of coherent source localization, which has higher resolution than 2D MUSIC method and does not need to estimate the number of coherent sources in advance.
A Thermal Damage Constitutive Model for Oil Shale Based on Weibull Statistical Theory
Authors: Zhao Guijie , Chen Chen , Yan Huan
Published: October 2019

In this work, we first studied the thermal damage to typical rocks, assuming that the strength of thermally damaged rock microelements obeys a Weibull distribution and considering the influence of temperature on rock mechanical parameters; under the condition that microelement failure conforms to the Drucker–Prager criterion, the statistical thermal damage constitutive model of rocks after high‐temperature exposure was established. On this basis, conventional triaxial compression tests were carried out on oil shale specimens heated to different temperatures, and according to the results of these tests, the relationship between the temperature and parameters in the statistical thermal damage constitutive model was determined, and the thermal damage constitutive model for oil shale was established. The results show that the thermal damage in oil shale increases with the increase of temperature; the damage variable is largest at 700°C, reaching 0.636; from room temperature to 700°C, the elastic modulus and Poisson’s ratio decrease by 62.66% and 64.57%, respectively; the theoretical stress‐strain curve obtained from the model is in good agreement with the measured curves; the maximum difference between the two curves before peak strength is only 5 × 10−4; the model accurately reflects the deformation characteristics of oil shale at high temperature. The research results are of practical significance to the underground in situ thermal processing of oil shale.
Visual Outcomes and Prognostic Factors of Intralenticular Foreign Bodies in a Tertiary Hospital in North China
Authors: Han Shaolei , Wang Tingting , Jia Jinchen , Sun Suhuan , Fan Yiming , Yang Guoxing , Yang Zanzhang
Published: October 2019

Purpose. The aim of this study is to describe the epidemiological and visual outcomes and to identify the main prognostic factors of intralenticular foreign body (ILFB) injuries. Methods. We performed a retrospective review of 21 patients (21 eyes) referred to Hebei Eye Hospital in North China from January 2012 to December 2017, who underwent surgical removal of ILFBs and associated ocular trauma repairs. Data regarding the patient demographics, cause of the injury, nature of the ILFB, clinical features, time interval between the injury and the ILFB removal, time interval between the presentation and the surgery, and the initial and final best-corrected visual acuities (BCVAs) were analyzed, and the main prognostic factors were identified. Results. Male adults were most affected by ILFBs (90.5%). The mean age of the patients was 41.5 years (median: 46 years, range: 21 to 60 years). None of the patients were wearing goggles at the time of the injury. The most common ILFB cause was hammering the metal (57.1%), and most of the ILFBs were metallic (71.4%). After medical treatment, the final BCVA was improved significantly (Z = 2.49, P=0.015). There was a significant association between the ILFBs with posterior segment injuries and the final BCVA (χ2 = 10.03, P=0.01). Those factors showing no statistical association with the final BCVA included the age (χ2 = 0.36, P=1.0), gender (χ2 = 0.52, P=1.0), nature of the ILFB (χ2 = 1.11, P=0.54), entrance wound location (χ2 = 2.85, P=0.25), and time interval between the injury and the ILFB removal (χ2 = 1.87, P=0.23). Conclusion. This is the first local study to explore the epidemiology of ILFB injuries and to identify the main prognostic factors. There was a significant association between the ILFBs with posterior segment injuries and the final BCVA. Improved public awareness and strengthened education regarding safety are the key approaches to reduce the incidence of eye injuries.
Direct Anterior Approach for One-Stage Bilateral Total Hip Arthroplasty in an ASA 3 Wheelchair-Dependent Woman
Authors: Barvelink B. (Britt) , Hooghof J. T. (Arjan) , Brokelman R. B. G. (Roy)
Published: October 2019

This case report involves a 79-year-old wheelchair-dependent woman with bilateral destructive coxarthrosis, requiring total hip arthroplasty (THA). Mobilization and transfers were unbearable due to the bilateral involvement of her hips. Performing unilateral THA would not be sufficient due to the coexisting pain from the contralateral side. Therefore, the decision was made to perform bilateral THA in one stage using the direct anterior approach (DAA). One-stage bilateral THA (1-SBTHA) using the DAA in ASA 3 patients is not previously described in the literature. The procedure was completed as planned, without any major perioperative complications. Eight weeks postoperatively, the patient was able to mobilize unaccompanied using a walker. She regained her mobility and independence. This outcome suggests that 1-SBTHA using DAA can be considered for disabling coxarthrosis in carefully selected ASA 3 patients. DAA is the superior approach for 1-SBTHA, due to decreased muscle damage leading to early mobilization with improved gait. Another benefit of DAA is that both hips can be draped simultaneously without repositioning the patient during the procedure.
Minimum Detour Index of Tricyclic Graphs
Authors: Fang Wei , Cai Zheng-Qun , Li Xiao-Xin
Published: October 2019

The detour index of a connected graph is defined as the sum of the detour distances (lengths of longest paths) between unordered pairs of vertices of the graph. The detour index is used in various quantitative structure-property relationship and quantitative structure-activity relationship studies. In this paper, we characterize the minimum detour index among all tricyclic graphs, which attain the bounds.
Reflector-Backed Antenna for UWB Medical Applications with On-Body Investigations
Authors: Kissi Chaïmaâ , Särestöniemi Mariella , Kumpuniemi Timo , Myllymäki Sami , Sonkki Marko , Srifi Mohamed Nabil , Jantunen Heli , Pomalaza-Raez Carlos
Published: October 2019

A recent reflector-backed antenna model is proposed in this paper for wireless capsule endoscopy localization. The antenna is designed to operate at the lowest 802.15.6 mandatory UWB (ultrawideband) channel, i.e., 4 GHz center frequency with 500 MHz bandwidth. The antenna achieves a good directivity and radiates well over the frequency band of interest. The proposed antenna was constructed within three successive steps. Initially, a planar omnidirectional antenna was designed of 3.15 dBi gain at 4 GHz. Since the antenna aims to operate as a receiving antenna, good directivity is preferred. Thus, an air-filled cavity was included backing the planar antenna to bolster the directivity toward the radiating element. The cavity-backed antenna has a measured gain of 6.4 dBi. The antenna was evaluated next to the homogenous and multilayer models. Then, the antenna design was optimized, by reducing its size, to a reflector-backed antenna structure reaching a maximum gain of 5.3 dBi, which is still promising for the regarded application. The body effect on the antenna matching was evaluated by means of multilayer and voxel models simulating the human body. This was followed by on-body measurements involving real subject. The depth of in-body propagation, from skin to small intestine, was studied using the multilayer and voxel models. Simulations were run using the CST Microwave Studio tool. While prototyping, free-space and on-body measurements took place at University of Oulu, Finland.
Glycemic and Insulinemic Responses of Vegetables and Beans Powders Supplemented Chapattis in Healthy Humans: A Randomized, Crossover Trial
Authors: Akhtar Saeed , Layla Anam , Sestili Piero , Ismail Tariq , Afzal Khurram , Rizvanov Albert A. , Asad Muhammad Hassham Hassan Bin
Published: October 2019

Vegetables and beans are nutrient-dense foods with innate potential to mediate diabetes in a variety of cultures. The present study aims at evaluating vegetables and beans for assessing their glycemic index and response in raising glucose levels in human model. Powdered formulations of vegetables and beans were designed to modulate glycemic response of carbohydrate-rich staples. A randomized, crossover trial was conducted in healthy young adults (n=24) who were challenged with vegetable powder-supplemented chapatti (VPSC), bean powder-supplemented chapatti (BPSC) and all-purpose wheat flour chapatti (APFC) to evaluate their postprandial glucose (PPG) and postprandial insulin (PPI) responses. In comparison with APFC, feeding VPSC and BPSC to healthy volunteers anticipated significant reduction in PPG (44% reduction in incremental area under the curve (AUC) for VPSC and 46% reduction in incremental AUC for BPSC, p=0.005). Likewise, significant reduction in PPI levels was observed for VPSC (59%, p=0.012) and BPSC (47%, p=0.002) compared to APFC-treated group. The study concludes wheat flour enrichment with vegetables and beans powder as a viable approach to develop cost effective and culturally acceptable low glycemic foods bearing acceptable sensory attributes.
Ganglionic Long-Term Potentiation in Prehypertensive and Hypertensive Stages of Spontaneously Hypertensive Rats Depends on GABA Modulation
Authors: Martínez Luis A. , Cifuentes Fredy , Morales Miguel A.
Published: October 2019

The sympathetic nervous system (SNS) regulates body functions in normal and pathological conditions and is characterized by the presence of a neuroplastic phenomenon, termed ganglionic long-term potentiation (gLTP). In hypertension, either in spontaneously hypertensive rats (SHR) or in humans, sympathetic hyperfunction, such as elevated SNS outflow and changes in synaptic plasticity have been described. Because enhanced SNS outflow is detected in the hypertensive stage and, more importantly, in the prehypertensive phase of SHR, here we explored whether synaptic plasticity, particularly gLTP, was modified in the superior cervical ganglia (SCG) of prehypertensive SHR. Furthermore, considering that GABA modulates sympathetic synaptic transmission and gLTP in Wistar rats, we studied whether GABA might modulate gLTP expression in SHR. We characterized gLTP in the SCG of young prehypertensive 6-week-old (wo) and adult hypertensive (12 wo) SHR and in the SCG of Wistar Kyoto (WKy) normotensive control rats of the same ages. We found that gLTP was expressed in 6 wo SHR, but not in 12 wo rats. By contrast, in WKy, gLTP was expressed in 12 wo, but not in 6 wo rats. We also found that gLTP depends on GABA modulation, as blockade of GABA-A subtype receptors with its antagonist bicuculline unmasked gLTP expression in adult SHR and young WKy. We propose that (1) activity-dependent changes in synaptic efficacy are altered not only during hypertension but also before its onset and (2) GABA may play a modulatory role in the changes in synaptic plasticity in SHR, because the blockade of GABA-A receptors unmasked the expression of gLTP. These early changes in neuroplasticity and GABA modulation of gLTP could be part of the sympathetic hyperfunction observed in hypertension.
First Steps in Porting the LFRic Weather and Climate Model to the FPGAs of the EuroExa Architecture
Authors: Ashworth Mike , Riley Graham D. , Attwood Andrew , Mawer John
Published: October 2019

In recent years, there has been renewed interest in the use of field-programmable gate arrays (FPGAs) for high-performance computing (HPC). In this paper, we explore the techniques required by traditional HPC programmers in porting HPC applications to FPGAs, using as an example the LFRic weather and climate model. We report on the first steps in porting LFRic to the FPGAs of the EuroExa architecture. We have used Vivado High-Level Syntheusywwi to implement a matrix-vector kernel from the LFRic code on a Xilinx UltraScale+ development board containing an XCZU9EG multiprocessor system-on-chip. We describe the porting of the code, discuss the optimization decisions, and report performance of 5.34 Gflop/s with double precision and 5.58 Gflop/s with single precision. We discuss sources of inefficiencies, comparisons with peak performance, comparisons with CPU and GPU performance (taking into account power and price), comparisons with published techniques, and comparisons with published performance, and we conclude with some comments on the prospects for future progress with FPGA acceleration of the weather forecast model. The realization of practical exascale-class high-performance computinems requires significant improvements in the energy efficiency of such systems and their components. This has generated interest in computer architectures which utilize accelerators alongside traditional CPUs. FPGAs offer huge potential as an accelerator which can deliver performance for scientific applications at high levels of energy efficiency. The EuroExa project is developing and building a high-performance architecture based upon ARM CPUs with FPGA acceleration targeting exascale-class performance within a realistic power budget.
Thermoelectric Effect of Buckypaper/Copper Assembly
Authors: Pinheiro Paula Fabíola Pantoja , Ferreira Luiza de Marilac Pantoja , Rodrigues Fabrício Augusto dos Santos , Oliveira José Carlos da Silva , Rodriguez Anselmo Fortunato Ruiz , Sousa Mário Edson Santos de , Reis Marcos Allan Leite dos
Published: October 2019

Carbon nanotubes (CNTs) exhibit excellent electrical and thermal properties that have been used in several device assemblies, such as electrode sheets made from an aggregate of CNTs, also called as buckypaper (BP). Despite that, the properties of single CNTs are reduced when randomly assembled to form a BP. In this way, this study investigated the thermoelectric effect of a BP electrode assembled on a copper electrode with an active area of 4.0 cm2. The micrographs were obtained by scanning electron microscopy and show morphology agglomerated of multiwalled CNTs, which permeated into the filter paper, forming a thickness of 67.33 μm. Moreover, indoor/outdoor tests were performed approaching the BP electrode from a heat source. Thus, the electrical responses in function of temperature variation show maximum thermovoltages of 9.0 mV and 40.73 mV from indoor and outdoor tests, respectively. Finally, an average Seebeck coefficient for the BP/copper electrodes array of 35.34 ± 6.0 mV/K was estimated from 298 to 304 K. These findings suggest that this assembly will be easily applied in thermoelectric device concepts.
Exosomal miRNA: Small Molecules, Big Impact in Colorectal Cancer
Authors: Vautrot Valentin , Chanteloup Gaëtan , Elmallah Mohammed , Cordonnier Marine , Aubin François , Garrido Carmen , Gobbo Jessica
Published: October 2019

Colorectal cancer (CRC) is one of the major causes of cancer-related deaths worldwide. Tumor microenvironment (TME) contains many cell types including stromal cells, immune cells, and endothelial cells. The TME modulation explains the heterogeneity of response to therapy observed in patients. In this context, exosomes are emerging as major contributors in cancer biology. Indeed, exosomes are implicated in tumor proliferation, angiogenesis, invasion, and premetastatic niche formation. They contain bioactive molecules such as proteins, lipids, and RNAs. More recently, many studies on exosomes have focused on miRNAs, small noncoding RNA molecules able to influence protein expression. In this review, we describe miRNAs transported by exosomes in the context of CRC and discuss their influence on TME and their potential as circulating biomarkers. This overview underlines emerging roles for exosomal miRNAs in cancer research for the near future.
Optimized Parameters of Diffusion-Weighted MRI for Prediction of the Response to Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer
Authors: Li Jie , Wang Jia , Pang Jing , Cao Shougen , Chen Jingjing , Xu Wenjian
Published: October 2019

Aim. To identify the optimal diffusion-weighted MRI-derived parameters for predicting the response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer. Methods. This prospective study enrolled 92 patients who underwent neoadjuvant chemoradiotherapy. Diffusion-weighted MRI sequences with two b-value combinations of b (0, 800) and b (0, 1000) were acquired before the start of neoadjuvant chemoradiotherapy and surgery. The pathological tumor regression grade was obtained according to the Mandard criteria, recommended by the seventh edition of the American Joint Committee on Cancer, to act as the reference standard. Pathological good responders (pathological tumor regression grade 1-2) were compared with poor responders (pathological tumor regression grade 3–5). Results. The good responder group contained 37 (40.2%) patients and the poor responder group 55 (59.8%) patients. Both before and after neoadjuvant chemoradiotherapy, the mean ADC value for b = 1000 was significantly higher than that for b = 800. In the two patient groups, the post-ADC value and ΔADC for b = 800 were significantly lower than those for b = 1000, but percentages of ADC increase for b = 800 and b = 1000 showed no significant difference. Conclusions. The percentage of ADC increase, as an optimized predictor unaffected by different b-values, may have a significant role in differentiating those patients with a good response to N-CRT from those with a poor response.
Kynurenine, a Tryptophan Metabolite That Increases with Age, Induces Muscle Atrophy and Lipid Peroxidation
Authors: Kaiser Helen , Yu Kanglun , Pandya Chirayu , Mendhe Bharati , Isales Carlos M. , McGee-Lawrence Meghan E. , Johnson Maribeth , Fulzele Sadanand , Hamrick Mark W.
Published: October 2019

The cellular and molecular mechanisms underlying loss of muscle mass with age (sarcopenia) are not well-understood; however, heterochronic parabiosis experiments show that circulating factors are likely to play a role. Kynurenine (KYN) is a circulating tryptophan metabolite that is known to increase with age and is a ligand of the aryl hydrocarbon receptor (Ahr). Here, we tested the hypothesis that KYN activation of Ahr plays a role in muscle loss with aging. Results indicate that KYN treatment of mouse and human myoblasts increased levels of reactive oxygen species (ROS) 2-fold and KYN treatment in vivo reduced muscle size and strength and increased muscle lipid peroxidation in young mice. PCR array data indicate that muscle fiber size reduction with KYN treatment reduces protein synthesis markers whereas ubiquitin ligase gene expression is not significantly increased. KYN is generated by the enzyme indoleamine 2,3-dioxygenase (IDO), and aged mice treated with the IDO inhibitor 1-methyl-D-tryptophan showed an increase in muscle fiber size and muscle strength. Small-molecule inhibition of Ahr in vitro, and Ahr knockout in vivo, did not prevent KYN-induced increases in ROS, suggesting that KYN can directly increase ROS independent of Ahr activation. Protein analysis identified very long-chain acyl-CoA dehydrogenase as a factor activated by KYN that may increase ROS and lipid peroxidation. Our data suggest that IDO inhibition may represent a novel therapeutic approach for the prevention of sarcopenia and possibly other age-associated conditions associated with KYN accumulation such as bone loss and neurodegeneration.
History and Structure in the Thought of René Zavaleta
Authors: Tapia Mealla Luis
Published: October 2019

René Zavaleta set out to deepen the explanation of the history of Bolivia by developing a set of ideas about long-term structures of pre-Hispanic and colonial origin and their forms of overlap. This paper analyses the conceptual structure of Zavaleta’s proposal and the place of history within it.
The Monograph Tradition and Chinese Scholarship: Beginning with the “Best Young Scholar’s Monograph Prize in the Social Sciences of Practice”
Authors: Huang Philip C. C.
Published: October 2019

This article first explains why our “Best Young Scholar’s Monograph Prize in the Social Sciences of Practice” selection committee has chosen the three books International Law and Late Qing China: Texts, Events, and Politics, Rural Development in Contemporary China: Micro Case Examples and Macro Changes, and Urbanizing Children: Identity Production and Political Socialization of Peasant-Worker Sons and Daughters for the award, and then goes on to discuss how monograph production is faced with deeply contradictory forces in the scholarly environment of China today when compared with the American scholarly environment, to explain the purpose of the prize.
Crustacean classification: on-going controversies and unresolved problems*
Authors: BOXSHALL GEOFF A.
Published: October 2019

The journey from Linnaeus’s original treatment to modern crustacean systematics is briefly characterised. Progress in our understanding of phylogenetic relationships within the Crustacea is linked to continuing discoveries of new taxa, to advances in theory and to improvements in methodology. Six themes are discussed that serve to illustrate some of the major on-going controversies and unresolved problems in the field as well as to illustrate changes that have taken place since the time of Linnaeus. These themes are: 1. the treatment of parasitic Crustacea, 2. the affinities of the Remipedia, 3. the validity of the Entomostraca, 4. exopodites and epipodites, 5. using larval characters in estimating phylogenetic relationships, and 6. fossils and the crustacean stem-lineage. It is concluded that the development of the stem lineage concept for the Crustacea has been dominated by consideration of taxa known only from larval or immature stages. This has limited our understanding of key events in the origin of crown group Crustacea.
The smaller arachnid orders: diversity, descriptions and distributions from Linnaeus to the present (1758 to 2007)*
Authors: HARVEY MARK S.
Published: October 2019

Carolus Linnaeus’ contribution to the study of the smaller arachnid orders was modest with the description of four taxa: the pseudoscorpions Acarus cancroides and A. scorpioides, the whip scorpion Phalangium caudatum, and the whip spider P. reniforme. Since then, more than 5,100 species have been named in eight orders by a plethora of researchers. Trends in species descriptions over time are explored; the presence of different accumulation curves for some orders is thought to be due to advances in the study of morphology combined with a greater focus on collecting small arachnids in tropical ecoregions. Pseudoscorpion species richness is examined against log-transformed area data for all countries of the world. Anomalies, such as the poor representation of pseudoscorpion diversity in some large countries such as China, appear to be due to a low number of active researchers.
Archives of a small planet: The significance of museum collections and museum-based research in invertebrate taxonomy*
Authors: WINSTON JUDITH E.
Published: October 2019

Museum natural science collections are valuable, in many cases irreplaceable, and vital to research in many disciplines including taxonomy. Since 96% of known multicellular animals belong to one or another of the 34  invertebrate phyla, the value of those collections for invertebrate taxonomy (of both living and fossil taxa) is even higher.  Systematic work that does not rely on museum specimens to verify or falsify the identities of the taxa studied is not science. Whether the techniques used are molecular or morphological, high tech analysis, or careful observation, systematics is the primary and most essential use of museum invertebrate collections. Their value and the case for their support for this primary and many other compelling reasons has been argued eloquently time after time, yet support still lags far behind needs.
Eleven new species and new records of the Tachinus nepalensis Ullrich group of the subgenus Tachinoderus Motschulsky from China, Vietnam and Laos (Coleoptera: Staphylinidae: Tachyporinae)
Authors: CHANG YUAN , LI LI-ZHEN , YIN ZI-WEI , SCHÜLKE MICHAEL
Published: October 2019

Eleven new species of the Tachinus nepalensis Ullrich group of the subgenus Tachinoderus Motschulsky are described from China, Vietnam and Laos: T. asperius Chang, Li & Yin, sp. nov. (Yunnan), T. biangulatus Chang, Li, Yin & Schülke, sp. nov. (Shaanxi, Sichuan), T. bimorphus Chang, Li, Yin & Schülke, sp. nov. (Yunnan, Xizang), T. breviculus Chang, Li, Yin & Schülke, sp. nov. (Sichuan, Yunnan), T. chengzhifeii Chang, Li, Yin & Schülke, sp. nov. (Shaanxi, Zhejiang, Hubei, Fujian, Guangxi, Chongqing, Sichuan, Yunnan, Vietnam: Sa Pa), T. granosus Chang, Li, Yin & Schülke, sp. nov. (Shaanxi, Gansu, Sichuan), T. maculosus Chang, Li, Yin & Schülke, sp. nov. (Yunnan), T. meniscus Chang, Li, Yin & Schülke, sp. nov. (Hunan, Guangdong, Guangxi, Yunnan), T. qian Chang, Li & Yin, sp. nov. (Guizhou), T. songxiaobini Chang, Li & Yin, sp. nov. (Yunnan), and T. yunnanensis Chang, Li, Yin & Schülke, sp. nov. (Yunnan; Laos: Phongsaly). Main characters distinguishing species are the shapes of the terminal tergites and sternites of both sexes, and morphological differences in the aedeagi. New collecting data for eight known species: T. beckeri Ullrich, T. grandicollis (Bernhauer), T. laosensis Katayama & Li, T. naomii Li, T. nigriceps Sharp, T. pseudobirmanus Schülke, T. sugayai Schülke and T. yushanensis Campbell are given. Tachinus laosensis Katayama & Li is recorded from China for the first time. An identification key to and distributional maps of the Chinese species of the T. nepalensis group are provided.
A new species and additional records of brachypterous Paederus (Coleoptera, Staphylinidae) of mainland China and Taiwan
Authors: CHENG ZHI-FEI , PENG ZHONG
Published: October 2019

Material of the paederine genus Paederus Fabricius, 1775 of mainland China and Taiwan was examined. In total, seven species are recognized, among which one is described here as new: P. (Gnathopaederus) zhangmuensis sp. n. (Xizang: Zhangmu). New provincial records are provided for P. jianyueae Peng and Li, 2014 from Fujian.
Pre-Transplant Variables Affecting the Outcome of Submyeloablative Allogeneic HSCT in Uniformly Treated Patients with Hematologic Malignancies.
Authors: Mehta Jayesh , Singhal S. , Tallman M. , Williams S. , Winter J. , Evens A. , Grinblatt D. , Kaminer L. , Gordon L.
Published: October 2019

The outcome of 63 consecutive submyeloablative allografts (27–66 y, median 52) performed for hematologic malignancies after 100 mg/m2 melphalan without (n=21; prior autograft) or with (n=42; no prior autograft) 50 mg/kg cyclophosphamide was analyzed to study the effect of pre-transplant characteristics. GVHD prophylaxis comprised cyclosporine-mycophenolate (n=37; HLA-identical sibling donors) or tacrolimus-mycophenolate (n=26, 1-locus mismatched sibling or 9–10/10 allele-matched unrelated). No growth factors were administered routinely post-transplant and supportive care was uniform. 14 patients experienced transplant-related mortality (TRM), and 32 relapsed. 24 relapsing patients died, and 7 of the other 8 are alive in CR or with declining disease. The following factors were analyzed in a Cox model for their effect on TRM and relapse: chemosensitive (n=25) vs refractory disease (n=38), age ≤55 (n=44) vs >55 (n=19), normal (n=32) vs abnormal (n=31) LDH, HLA match (n=56) vs mismatch (n=7), prior autograft or not, performance status 0–1 (n=47) vs 2–3 (n=16).

Outcome Favorable factor RR (95% CI) P TRM Age ≤55 0.20 (0.04–0.86) 0.03 HLA matched 0.21 (0.05–0.89) 0.04 Performance status 0-1 0.25 (0.06–0.99) 0.05 Relape Chemosensitive disease 0.28 (0.11–0.73) 0.01 Fig 1 shows TRM for patients with 0, 1 or 2 high-risk factors for TRM. Fig 1 shows TRM for patients with 0, 1 or 2 high-risk factors for TRM. Fig 2 shows overall survival (OS) for patients with 0 or 1 high-risk factors for TRM by disease chemosensitivity. Fig 2 shows overall survival (OS) for patients with 0 or 1 high-risk factors for TRM by disease chemosensitivity.

Table 2 shows the causes of death by risk factors for TRM and disease chemosensitivity.

Group (n) Alive TRM Death from disease A: 2 risk factors for TRM (7) 1 (14%) 5 (71%) 1 (14%) B: 1 risk factor for TRM + Refractory (19) 2 (11%) 6 (32%) 11 (58%) C: 1 risk factor for TRM + Sensitive (9) 5 (56%) 1 (11%) 3 (33%) D: 0 risk factor for TRM + Refractory (12) 3 (25%) 1 (8%) 8 (67%) E: 0 risk factor for TRM + Sensitive (16) 13 (81%) 1 (6%) 2 (13%)

These data suggest that while the current treatment approach is optimal for patients falling in Group E, modified approaches are needed for other patients. Based on the causes of failure, the following modifications appear to be warranted. Group A: A completely non-ablative regimen to reduce toxicity. Group B: A completely non-ablative regimen to reduce toxicity with augmentation of graft-vs-tumor effects by elective donor leukocyte infusions and/or abbreviated immunosuppression. Group C: Augmentation of graft-vs-tumor effects by elective donor leukocyte infusions and/or abbreviated immunosuppression. Group D: Conventional-intensity rather than reduced-intensity allogeneic HSCT.
Thalidomide and Dexamethasone Is an Effective Salvage Regimen for Myeloma Patients Relapsing after Autologous Transplant.
Authors: Palumbo Antonio , Falco Patrizia , Ambrosini Maria Teresa , Caravita Tommaso , Musto Pellegrino , Petrucci Maria Teresa , Pregno Patrizia , Avonto Ilaria , Bertola Alessandra , Bringhen Sara , Cavallo Federica , Ciccone Giovannino , Boccadoro Mario
Published: October 2019

PURPOSE: High-dose therapy followed by autologous stem cell transplantation (AT) is the standard treatment for newly diagnosed multiple myeloma patients. Which is the best treatment option for patients relapsing after AT has not been defined. To address this issues the efficacy of Thalidomide and Dexamethasone (TD), AT and Conventional Chemotherapy (CC) was evaluated.

MATERIALS AND METHODS: We retrospective analysed the outcome of 90 multiple myeloma patients, median age 61, range 34–77, who received a first salvage treatment between January 1999 and September 2003. All patients received AT at diagnosis. Relapse was defined as introduction of therapeutic modality that was different from maintenance treatment.

After a median time from diagnosis of 32 months, 43 patients were treated with TD (Thalidomide 100 mg/day associated with DEX 40 mg on days 1-4 each month), after a median time from diagnosis of 29 months, 28 patients were treated at first relapse with AT (86% single MEL100, 11% double MEL100, 4% single MEL200), and after a median time from diagnosis of 32 months, 19 patients were treated with CC (32% Doxorubicin, Cyclophosphamide, Etoposide, Cisplatinum combination chemotherapy, 26% Doxorubicin containing regimens, 26% Cyclophosphamide containing regimens, 11% other therapies).

Data were analysed when the median follow-up from the start of salvage TD was 30 months (range 4.5–45), from the start of salvage AT was 18 months (range 3.5–24) and from the start of salvage CC was 21 months (range 2–19.5).

End points of the study were response, progression free survival (PFS) from first relapse and overall survival (OS) from first relapse and from diagnosis.

RESULTS: Patients characteristics were similar among different groups. At relapse the response rate after TD was: 19% near complete remission (nCR) (absence of M-Protein detected by electrophoresis), 28% partial response (PR) (M-Protein reduction 50–99%), 35% stable disease (SD) (M-Protein reduction 0–49%) and 19% progressive disease (PD). After AT was: 11% nCR, 71% PR, 11% SD, 7% PD; and after CC was: 16% PR, 32% SD and 53% PD. Response rate was significantly lower for patients receiving salvage CC in comparison with AT and TD (p<0.001).

The median PFS from relapse was 20.3 months for TD, 9 months for AT and 4.5 months for CC (p<0.001). The OS from relapse at 50 months was 58% for TD, 13% for AT and 21% for CC (p = 0.008). The median OS from diagnosis was 116.34 months for TD, 41.3 months for AT and 59.5 months for CC (p<0.001).

The multivariate analysis indicates that TD, β2 microglobulin and age were the only independent risk factors associated with improved outcome.

CONCLUSION: In conclusion, TD improved PFS and OS in myeloma patients relapsing after autologous transplant.
A Novel Orally Available Proteasome Inhibitor NPI-0052 Induces Killing in Multiple Myeloma (MM) Cells Resistant to Conventional and Bortezomib Therapies.
Authors: Chauhan Dharminder , Li Guilan , Podar Klaus , Hideshima Teru , Shrigarpure Reshma , Catley Laurence , Mitsiades Constantine , Munshi Nikhil , Sclossman Robert , Bahjat Rena , Neuteboom Saskia , Richardson Paul , Palladino Michael , Anderson Kenneth C.
Published: October 2019

The recent success of bortezomib/proteasome inhibitor PS-341 (VelcadeTm) provides evidence that proteasome inhibitors can be safely utilized clinically. Specifically, bortezomib is currently being used to treat MM patients (pts) who have relapsed after initial therapy and refractory to current therapy and is under evaluation for treatment of newly diagnosed pts. Although bortezomib kills MM cells, prolonged exposure is associated with attendant toxicity and development of bortezomib-resistance. Here we show that a novel non-peptide proteasome inhibitor NPI-0052 triggers apoptosis even in bortezomib-resistant patient MM cells, without affecting the viability of normal cells. NPI-0052 overcomes MM cell-resistance to conventional therapies including melphalan (LR5), doxorubicin (Dox-40), dexamethasone (MM.1R, U266, RPMI-8226) and retains its anti-tumor activity in cells harboring two major mechanisms of drug-resistance: overexpression of P-glycoprotein and altered topoisomerase-II activity. Importantly, NPI-0052, like bortezomib, blocks MM cell growth induced by both adhesion to bone marrow stromal cells (BMSCs) and related cytokine secretion, thereby depriving MM cells of the growth and survival advantage conferred by the BM microenvironment. Moreover, NPI-0052-triggers MM cells apoptosis despite the presence of interleukin-6 or insulin-like growth factor-1 (IGF-1), two major growth and anti-apoptotic factors for MM cells. NPI-0052 also overcomes the cytoprotective effects of anti-apoptotic proteins Bcl2 and Hsp27, as well as NF-kB-mediated growth/survival, and drug-resistance in MM cells. Initial in vivo studies in animal models using either oral or intravenous administration have established the maximum tolerated dose (MTD) based on the whole blood proteasome activity. NPI-0052 decreased proteasome activity in packed whole blood lysates in a dose dependent fashion, and these data also suggest that NPI-0052 is orally active. The mechanisms whereby NPI-0052-trigger MM cell death includes: loss of mitochondrial membrane potential; Superoxide generation; release of mitochondrial proteins cytochrome-c/Smac; and activation of caspase-8/9/3. Conversely, the pan caspase inhibitor Z-VAD-fmk abrogates NPI-0052-induced apoptosis. Finally, combining NPI-0052 and bortezomib triggers synergistic apoptosis. Together, these findings provide the framework for clinical evaluation of NPI-0052, either alone or in combination with bortezomib, to inhibit tumor cell growth, reduce bortezomib-related toxicity, overcome bortezomib-resistance, and improve patient outcome in MM.
Cell Proliferation Induced by the NPM-ALK Fusion Tyrosine Kinase of Anaplastic Large Cell Lymphoma Is Mediated by mTOR/S6K1 and MEK/ERK Signaling.
Authors: Amaravadi Ravi K. , Haq Naznin , Morris Stephan W. , Gilliland D. Gary , Sternberg David W.
Published: October 2019

The nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) fusion is the product of the t(2;5)(p23;q35) chromosomal translocation found in approximately half of anaplastic large cell lymphomas (ALCL). Moreover, this fusion kinase, as well as other ALK fusion proteins, have been found in large B-cell lymphomas. This fusion kinase has been shown to regulate multiple signal transduction pathways and to induce hematopoietic malignancy in murine models. Nonetheless, the functional role of signaling events caused by NPM-ALK expression is incompletely understood. Here we report that NPM-ALK activates the kinase S6K1 (p70/p85) and the extracellular regulated kinase (ERK1/2). In Ba/F3 murine hematopoietic cells that express NPM-ALK, S6K1 activition by NPM-ALK was sensitive to mTOR inhibition by rapamycin. However, treatment of NPM-ALK-Ba/F3 cells with the MEK inhibitor UO126 did not attenuate the activation of S6K1 by NPM-ALK. Pharmacological inhibition of either mTOR or MEK in Ba/F3 cells expressing NPM-ALK resulted in impaired cytokine-independent outgrowth of these cells. For either inhibitor, suppression of cytokine-independent outgrowth was due to impairment of cell proliferation. In contrast, cell survival signaling was not compromised by either inhibitor alone or in combination. Combined inhibition of both the mTOR/S6K1 and MEK/ERK signaling modules resulted in an additive impairment of cytokine-independent outgrowth. Moreover, rapamycin attenuated the proliferation of the human NPM-ALK-expressing ALCL cell line Karpas299. The mTOR/S6K1 and MEK/ERK signaling modules may serve as effective chemotherapeutic targets in the treatment of ALCL and other malignancies that express the activated ALK protein tyrosine kinase.