bluuebunny/crossref_metadata_2025 huggingface dataset:
Vaccine efficacy against primary and metastatic cancer with in vitro-generated CD103+conventional dendritic cells
Authors: Zhou Yifan , Slone Natalie , Chrisikos Taylor T , Kyrysyuk Oleksandr , Babcock Rachel L , Medik Yusra B , Li Haiyan S , Kleinerman Eugenie S , Watowich Stephanie S
Published: April 2020

Background

Type 1 conventional dendritic cells (cDC1s) possess efficient antigen presentation and cross-presentation activity, as well as potent T cell priming ability. Tissue-resident cDC1s (CD103+cDC1s in mice, CD141+cDC1s in humans) are linked with improved tumor control, yet the efficacy of immunotherapy using this population is understudied.

Methods

We generated murine CD103+cDC1s in vitro and examined their expression of cDC1-related factors, antigen cross-presentation activity, and accumulation in tumor-draining lymph nodes (TdLNs). The antitumor efficacy of the in vitro-generated CD103+cDC1s was studied in murine melanoma and osteosarcoma models. We evaluated tumor responses on vaccination with CD103+cDC1s, compared these to vaccination with monocyte-derived DCs (MoDCs), tested CD103+cDC1 vaccination with checkpoint blockade, and examined the antimetastatic activity of CD103+cDC1s.

Results

In vitro-generated CD103+cDC1s produced cDC1-associated factors such as interleukin-12p70 and CXCL10, and demonstrated antigen cross-presentation activity on stimulation with the toll-like receptor 3 agonist polyinosinic:polycytidylic acid (poly I:C). In vitro-generated CD103+cDC1s also migrated to TdLNs following poly I:C treatment and intratumoral delivery. Vaccination with poly I:C-activated and tumor antigen-loaded CD103+cDC1s enhanced tumor infiltration of tumor antigen-specific and interferon-γ+CD8+T cells, and suppressed melanoma and osteosarcoma growth. CD103+cDC1s showed superior antitumor efficacy compared with MoDC vaccination, and led to complete regression of 100% of osteosarcoma tumors in combination with CTLA-4 antibody-mediated checkpoint blockade. In vitro-generated CD103+cDC1s effectively protected mice from pulmonary melanoma and osteosarcoma metastases.

Conclusions

Our data indicate an in vitro-generated CD103+cDC1 vaccine elicits systemic and long-lasting tumor-specific T cell-mediated cytotoxicity, which restrains primary and metastatic tumor growth. The CD103+cDC1 vaccine was superior to MoDCs and enhanced response to immune checkpoint blockade. These results indicate the potential for new immunotherapies based on use of cDC1s alone or in combination with checkpoint blockade.
Gastrointestinal bleeding during acute ischaemic stroke hospitalisation increases the risk of stroke recurrence
Authors: Du Wanliang , Zhao Xingquan , Wang Yilong , Pan Yuesong , Liu Gaifen , Wang Anxin , Ji Ruijun , Liu Liping , Gu Hongqiu , Dong Kehui , Wang Penglian , Wang Yongjun
Published: April 2020

Objective

Gastrointestinal (GI) bleeding in patients who had a stroke is strongly associated with a higher risk of death and loss of independence. However, it is unknown whether GI bleeding increases risk for recurrence of stroke. In this study, we assess the potential relationship between GI bleeding and stroke recurrence in patients within 12 months of an acute ischaemic stroke (AIS), using the China National Stroke Registry (CNSR).

Methods

This study included 22 216 patients who had an ischaemic stroke included in the CNSR from 2007 to 2008. We analysed baseline patient characteristics, GI bleeding and outcomes of patients who had an AIS, specifically stroke recurrence at 3, 6 and 12 months. We used multivariable logistic regression to evaluate a possible association between GI bleeding and stroke recurrence.

Results

Of the 12 415 patients included in our study, 12.3%, 15.5% and 17.7% had a stroke recurrence at 3, 6 and 12 months, respectively. GI bleeding was an independent stroke recurrence risk factor in patients after ischaemic stroke at 3 months (adjusted OR 1.481, 95% CI 1.118 to 1.962), 6 months (adjusted OR 1.448, 95% CI 1.106 to 1.896) and 12 months (adjusted OR 1.350; 95% CI 1.034 to 1.763).

Conclusion

GI bleeding was associated with the increased risk of stroke recurrence after an AIS.
Semi-Active Control for Benchmark Building Using Innovative TMD with MRE Isolators
Authors: Guan Xinchun , Zhang Jingcai , Li Hui , Ou Jinping
Published: April 2020

Tuned Mass Damper (TMD) with magneto-rheological elastomer isolators (MRE-TMD) is a novel control device for suppressing structural vibration caused by earthquakes. It is a nonlinear hybrid vibration absorber and the stiffness & damping can be controlled by changing the current of isolators’ coil. Using MRE-TMD as an adaptive frequency TMD to mitigate vibration and treating it as only a passive damper is the focus of most nowadays researches. In this paper, semi-active control theory is introduced to the MRE-TMD-structure system which means that the control force can be obtained through variable stiffness & damping technology, and MRE-TMD is a semi-active damper instead of a passive one. A control system sketch, as well as principles and control strategies of a semi-active MRE-TMD-structure system for vibration control is designed. An improved limited sliding (ILSL) algorithm based on linear quadratic optimal theory is also introduced. Numeric simulations of a five-story benchmark building model equipped with semi-active MRE-TMD subjected to several benchmark earthquake records are conducted to investigate the control performance of the proposed semi-active MRE-TMD. Control force characteristics of the structural MRE-TMD systems are also evaluated. The results indicate that semi-active MRE-TMD can provide control force to the system and it shows superior ability to suppress the structural vibrations of comparing to the passive MRE-TMD.
Parent Knowledge of Screening and Genetic Testing in Retinoblastoma
Authors: Xiao Wei , Ji Xian , Ye Huijing , Zeng Huiqi , Gao Yang , Chen Rongxin , Chen Xiaoyun , Mao Yuxiang , Yang Huasheng
Published: April 2020

Purpose. To evaluate parent knowledge of screening and genetic testing for retinoblastoma and its potential correlation with demographics, clinical features, and socioeconomical factors. Methods. It was a cross-sectional study conducted at the ocular oncology unit of a tertiary ophthalmic center in Southern China. A face-to-face interview was administered to parents of retinoblastoma children during hospitalization. Parent knowledge was assessed using the sum score of a 7-item questionnaire. Demographics and socioeconomic status were collected from the interview, and clinical data were retrieved from the medical records. Results. A total of 126 parents of retinoblastoma children were included. Parents accurately answered 66.7% to 84.9% of each item in the questionnaire. Only 37 (29.4%) parents correctly answered all 7 questions. Parent knowledge was positively correlated with education, but it was not associated with patients’ laterality, sex, or household income. Physicians and the Internet were the major sources of parental health-related information. During the median follow-up of 492 days, 13 (61.9%) of 21 patients in the full-score group without genetic testing at baseline actually conducted testing during follow-up compared to 29 of 67 (43.3%) in the less-than-full-score group (P=0.136). Conclusion. Overall parent knowledge about retinoblastoma screening and genetic testing was moderate. Higher education was associated with greater parent knowledge. Future studies should validate our findings in other populations, especially in those with different cultural background and healthcare systems.
Detection of 5 Kinds of Genes Related to Plasmid-Mediated Quinolone Resistance in Four Species of Nonfermenting Bacteria with 2 Drug Resistant Phenotypes
Authors: Ming De-Song , Chen Qing-Qing , Chen Xiao-Ting
Published: April 2020

Objective. This study aimed to detect 5 kinds of genes related to plasmid-mediated quinolone resistance in four species of nonfermenting bacteria with 2 drug resistance phenotypes (multidrug resistance and pandrug resistance), which were Acinetobacter baumannii (Ab), Pseudomonas aeruginosa (Pa), Stenotrophomonas maltophilia (Sm), and Elizabethkingia meningoseptica (Em). Methods. The Phoenix NMIC/ID-109 panel and API 20NE panel were applied to 19 isolated strains, including 6 Ab strains (2 strains with multidrug resistance and 4 strains with pandrug resistance), 6 Pa strains (3 strains with multidrug resistance and 3 strains with pandrug resistance), 4 Sm strains (2 strains with multidrug resistance and 2 strains with pandrug resistance), and 3 Cm strains (2 strains with multidrug resistance and 1 strain with pandrug resistance). After strain identification and drug susceptibility test, PCR was applied to detect 5 genes related to plasmid-mediated quinolone resistance. The genes detected were quinolone resistance A (qnrA), aminoglycoside acetyltransferase ciprofloxacin resistance variant, acc(6′)-Ib-cr, and 3 integrons (intI1, intI2, and intI3). The amplified products were analyzed by 1% agarose gel electrophoresis and sequenced. Sequence alignment was carried out using the bioinformatics technique. Results. Of 19 strains tested, 8 strains carried acc(6′)-Ib-cr and 6 of them were of pandrug resistance phenotype (3 Ab strains, 2 Pa strains, and 1 Sm strain). The carrying rate of acc(6′)-Ib-cr was 60.0% for strains of pandrug resistance (6/10). Two strains were of multidrug resistance (1 Ab strain and 1 Pa strain), and the carrying rate of acc(6′)-Ib-cr was 22.0% (2/9). The carrying rate was significantly different between strains of multidrug resistance and pandrug resistance (P<0.05). The class 1 integron was detected in 11 strains, among which 6 strains were of pandrug resistance (3 Ab strains, 2 Pa strains, and 1 Sm strain). The carrying rate of the class 1 integron was 60.0% (6/10). Five strains were of multidrug resistance (3 Pa strains, 1 Ab strain, and 1 Em strain), and the carrying rate was 55.6% (5/9). The carrying rate of the class 1 integron was not significantly different between strains of multidrug resistance and pandrug resistance (P>0.05). Both acc(6′)-Ib-cr and intI1 were detected in 6 strains, which were negative for qnrA, intI2, and intI3. Conclusion. Quinolone resistance of isolated strains was related to acc(6′)-Ib-cr and intI1 but not to qnrA, intI2, or intI3. The carrying rate of acc(6′)-Ib-cr among the strains of pandrug resistance was much higher than that among the strains of multidrug resistance. But, the strains of two drug resistant phenotypes were not significantly different in the carrying rate of intI1. The detection rates of the two genes were high and similar in Ab and Pa strains. 1 Em strain carried the class 1 integron.
Older Age Is Associated with Decreased Levels of VDR, CYP27B1, and CYP24A1 and Increased Levels of PTH in Human Parathyroid Glands
Authors: Jiang Yi , Liao Liyan , Li Jina , Wang Larry , Xie Zhongjian
Published: April 2020

Parathyroid glands contain the vitamin D receptor (VDR) and 25-hydroxyvitamin D-1α-hydroxylase (CYP27B1) and 24-hydroxylase (CYP24A1), which catalyze the production and degradation of 1,25-dihydroxyvitamin D [1,25(OH)2D], respectively. Previous studies have shown that the serum level of intact parathyroid hormone (iPTH) increases with age. We hypothesized that the expression of CYP27B1 or VDR in parathyroid glands decreases with age, which might account for the increased serum levels of iPTH due to decreased suppression of parathyroid hormone (PTH) secretion by 1,25(OH)2D in older people. To test this hypothesis, we examined relative expression levels of VDR, CYP27B1, CYP24A1, and PTH in specimens from parathyroid glands unintentionally removed during thyroidectomy for 70 patients varying in age from 10 to 70 years. The results showed that there was an inverse correlation between age and VDR, CYP27B1, and CYP24A1 expression (p<0.05). A significant positive correlation between PTH expression levels and age was also observed (p<0.05). These data indicate that older age is associated with decreased levels of VDR, CYP27B1, and CYP24A1 and increased levels of PTH in human parathyroid glands.
Guided Periodontal Surgery: Association of Digital Workflow and Piezosurgery for the Correction of a Gummy Smile
Authors: Deliberador Tatiana Miranda , Weiss Suyany Gabriely , Neto Alexandre Teixeira Domingues , Zetola Isabela Zago , Prix Maria Eduarda Santana , Júnior Darlan Rigo , Martins Heloysa Hoffman , Storrer Carmen Lucia Mueller
Published: April 2020

Digital flow has become a part of currently practiced dentistry. Virtual planning ensures predictable aesthetic and functional rehabilitation, painless postoperative recovery, and better communication with patients, thus meeting their expectations. The purpose of this case report is to demonstrate the digital planning for the correction of a gummy smile with a personalized preparation using a piezoelectric surgical guide (PerioGuide) for gingival contouring and flapless osteotomy. The guide was designed using Nemo Studio software, based on the patient’s facial aesthetic analysis, through photos, videos, and facial scanning. These images were aligned with the scan and placed over the cone beam computed gingival tomography for prediction of results, based not only on the distance from the cementoenamel junction to the bone crest but also on the best gingival margin contour according to virtual aesthetic planning. Digital planning, combined with the use of a piezoelectric device, allows for a flapless guided surgical technique for gingival contouring and osteotomy. As a result, the surgical procedure is safer, faster, and more predictable with better postoperative outcomes.
Renal Squamous Cell Carcinoma with Staghorn Calculus
Authors: Kasahara Ryo , Kawahara Takashi , Tajiri Ryosuke , Uemura Hiroji , Kitami Kazuo
Published: April 2020

A 70-year-old Japanese woman was referred to our department due to general fatigue and a persistent low fever. We performed percutaneous nephrostomy and administered antibiotics for the pyelonephritis due to her left staghorn calculus. After the infection had been brought under control and her general condition improved, we performed nephrectomy. A pathologic examination revealed renal squamous cell carcinoma (SCC) in addition to xanthogranulomatous inflammation. Seventeen days after the operation, computed tomography demonstrated local recurrence of the tumor; therefore, she received palliative care. Two months after her operation, she died of renal SCC.
Excessive Leukocytosis Leading to a Diagnosis of Aggressive Thyroid Anaplastic Carcinoma: A Case Report and Relevant Review
Authors: Polymeris Antonis , Kogia Christina , Ioannidis Dimitrios , Lilis Dimitrios , Drakou Maria , Maounis Nicoletta , Kaklamanis Loukas , Tseleni-Balafouta Sofia
Published: April 2020

Introduction: Leukocytosis and particularly neutrophilia are usually caused by acute infection, inflammation, and myeloproliferative neoplasms. However, leukocytosis can also occur in patients with malignancy either due to bone marrow metastases or in the context of a paraneoplastic syndrome. Case Presentation: An 86-year-old female was admitted to our hospital due to marked leukocytosis (white blood cells [WBC] >40,000/μL), neutrophilia, and monocytosis. She was afebrile and reported hoarseness and mild difficulty swallowing. Upon physical examination, lung auscultation revealed inspiratory wheezing and a non-tender mass was observed in the anterior midline of the neck. Blasts and immature WBC were not found, and polymerase chain reaction for the detection of BCR/ABL gene was negative. A mass (5.4 cm in diameter) of abnormal parenchymal composition with calcifications occupying the right lobe, was seen on thyroid ultrasound. Cytology, after fine-needle aspiration, showed an anaplastic thyroid carcinoma (ATC). The cervical and chest computed tomography scan revealed a low-density lesion with calcifications that shifts and presses the trachea and multiple lung nodular lesions bilaterally. Since the case was inoperable and the airway was severely obstructed, a DUMON stent was placed. Biopsy of specimens from the trachea lesion revealed a tumor with significant atypical cells and focal squamoid features. The patient’s WBC increased to 72,470/μL. Additionally, interleukin-6 (IL-6) was markedly elevated (20.2 pg/mL). The patient passed away due to respiratory arrest 55 days after her initial admission. Discussion: Excessive leukocytosis in a patient, having excluded infectious disease and myelodysplastic syndrome, could represent a manifestation of a paraneoplastic syndrome due to various cytokines secretion from the tumor. In our case, ATC synthesized and secreted IL-6, which seems to be the cause of severe leukocytosis.
MetaChem: An Algebraic Framework for Artificial Chemistries
Authors: Rainford Penelope Faulkner , Sebald Angelika , Stepney Susan
Published: April 2020

We introduce MetaChem, a language for representing and implementing artificial chemistries. We motivate the need for modularization and standardization in representation of artificial chemistries. We describe a mathematical formalism for Static Graph MetaChem, a static-graph-based system. MetaChem supports different levels of description, and has a formal description; we illustrate these using StringCatChem, a toy artificial chemistry. We describe two existing artificial chemistries—Jordan Algebra AChem and Swarm Chemistry—in MetaChem, and demonstrate how they can be combined in several different configurations by using a MetaChem environmental link. MetaChem provides a route to standardization, reuse, and composition of artificial chemistries and their tools.
Naming God: Exodus 3:14-15 in Augustine’s Enarrationes in Psalmos
Authors: Glowasky Michael
Published: April 2020

Augustine discusses Exodus 3:14-15 on 49 different occasions in his written corpus, 14 of which are found in his Enarrationes in Psalmos. Scholars have been quick to note the importance of God’s self-disclosure as I AM in verse 14 for Augustine’s conception of the divine as esse. However, far less attention has been paid to the place of verse 15 in Augustine’s thought, despite his claim that this verse reveals God’s “other name” (aliud nomen): the God of Abraham, Isaac and Jacob. In this article, I discuss four key passages from his Enarrationes in Psalmos – two from the redemptive-historical psalms and two from the psalms of ascent – where Augustine addresses the relationship between the two divine names God reveals to Moses in Exodus 3:14-15. In these four passages, I suggest, Augustine presents temporality and materiality as ongoing necessities for the knowledge of God, despite what he appears to suggest elsewhere.
Revisit of European-Asiatic connections in Tayloria rudolphiana (Splachnaceae, Bryophyta) based on molecular data and new morphological evidence

Authors: YI YAN-JUN , XIAO XIAO-XUAN , XU XIAO-XIA , HE SI
Published: April 2020

A molecular study of a rare moss, Tayloria rudolphiana has revealed a first new occurrence of this species in Central China after its first collecting more than 100 years ago from southwestern Yunnan Province. The phylogenetic analyses based on rps4 and trnL-F sequences along with its morphological features affirm the taxonomic identity of this new population, representing the latest evidence of European-Asiatic connections of this species. Photographic images detailing key morphological characters and a full description of the species are provided. The taxonomic problems of this species within China are discussed.
Description of two new species of Prodontorhabditis Timm, 1961 (Nematoda: Rhabditidae) from India
Authors: MUMTAZ SABIA , FATIMA HIBA , JAMAL WAJIH , AHLAWAT SHIKHA , TAHSEEN QUDSIA , AHMAD IRFAN
Published: April 2020

Two new species, Prodontorhabditis robustus sp. n. and P. grandistoma sp. n. are described and illustrated from rotting banana rhizome and decaying organic matter respectively. P. robustus sp. n. is characterized by thin and slender females with L= 490–625 µm; a= 25.8–34.7; b= 4.9–6.4; c= 2.4–3.7, an arched cheilostom with curved walls bearing basal dorsal and subventral denticles at the same level, males with 20–23 µm long, robust spicules with prominent dorsal velum and lateral spurs at its bifurcated distal tip and gubernaculum with attenuated proximal end. P. grandistoma sp. n. is characterized by plump females with L= 440–552 µm; a= 23.9–25.5; b= 4.4–5.7; c= 2.9–4.2, a long, narrow stoma of length 6–7 times diameter; the cheilostom straight but, wider anteriorly with a basal dorsal denticle and anterior subventral denticles, rectum with dilated lumen, males with 17–20 µm long, relatively slender spicules and a terminally indented bursa. This is the first report of Prodontorhabditis species from India. An updated list of species, a key to their identification and a compendium of their morphometrics and diagnostic features is presented.
A taxonomic study on the Bornean and Philippines Sword-tailed Crickets in the genus Rhicnogryllus Chopard, 1925 (Orthoptera: Trgonidiidae; Trigonidiinae)
Authors: TAN MING KAI , BAROGA-BARBECHO JESSICA B. , JAPIR RAZY , CHUNG ARTHUR Y. C. , WAHAB RODZAY BIN HAJI ABDUL , YAP SHERYL A.
Published: April 2020

Rhicnogryllus Chopard, 1925 is a small and relatively unknown group of Sword-tailed Cricket of the subfamily Trigonidiinae. This genus currently comprises 12 species from Asia, Africa (including Madagascar), South America and the Pacific. Species have been recognised by the presence of parallel and elevated veins in both males (which lack stridulatory organs) and females. However, this approach to classifying Trigonidiinae may be outdated and examination of male genitalia can offer better insights into the generic status of these species and how they are related or unrelated. By comparing male genitalia of new materials and old specimens, we describe a new species from the Philippines: Rhicnogryllus? paetensis n. sp., which is similar to the type species. Our hypothesis is that Rhicnogryllus is a non-monophyletic and artificial genus, and that the genus should comprise only Southeast Asian members (since the type species Rhicnogryllus fascipes Chopard, 1925 is known from the Philippines). We are cautiously against describing new genus to avoid adding more confusion until a comprehensive revision to the subfamily and Rhicnogryllus has been undertaken.
Stylogomphus thongphaphumensis (Odonata: Anisoptera: Gomphidae), a new gomphid dragonfly and the first record of S. malayanus Sasamoto, 2001 from Thailand
Authors: CHAINTHONG DAMRONG , SARTORI MICHEL , BOONSOONG BOONSATIEN
Published: April 2020

Stylogomphus thongphaphumensis sp. nov. is described from a type series of specimens reared from larvae (holotype ♂, Huai Khayeng, Thong Pha Phum district, Kanchanaburi Province; 14°36′20″N 98°34′38″E, 206 m a.s.l., larva collected on 14.XII.2014; adult emerged on 30.IV.2015). All larvae were collected from the same locality in western Thailand. Description of the larva (based on preserved exuviae) is provided as well. The adult of this species can be distinguished from other Stylogomphus Fraser, 1922, by the morphology of the male anal appendages, pterothoracic pattern, abdominal pattern, male genitalia and female valvula vulvae (detail provided in the differential diagnosis below). This is the first species of Stylogomphus to be described from Thailand. This study also reports the first record of Stylogomphus malayanus Sasamoto, 2001, from Thailand.
Two-Silicon-Nanocrystal Layer Memory Structure with Improved Retention Characteristics
Authors: Nassiopoulou A. G. , Salonidou A.
Published: April 2020

It was demonstrated in the literature that the use of self-aligned doubly-stacked Si dots improves retention characteristics of a nanocrystal memory. In this paper, we show that a similar effect may be obtained by using two distinct layers of silicon nanocrystals within the gate dielectric
of the MOS structure, if the nanocrystal density in each layer is high enough (above 1012 dots/cm2) so as to get an average effect of at least one smaller dot underneath each larger one. The relative distance of the layers and their position from the silicon substrate
and the gate metal are critical for optimum memory operation. Two different double-nanocrystal-layer structures were investigated. In the first structure the two nanocrystal layers were close together and they were composed of dots of different size (lower layer: 3 nm, upper layer: 5 nm),
while in the second structure the dot layers were composed of dots of equal diameter (d = 3 nm) and their inter-distance was much larger. In both cases, the retention characteristics of the structure were improved compared with a single dot layer structure. In the second case this improvement
was significantly larger than in the first case. Extrapolation of the data to ten years memory operation, showed that the charge loss after this time was only ≈ 12%.
Digital connectivity at the upstream end of value chains: A dynamic perspective on smartphone adoption amongst horticultural smallholders in Kenya
Authors: Hartmann Gideon , Nduru Gilbert , Dannenberg Peter
Published: April 2020

Driven by the rapid adoption of Internet-based technologies amongst producers in the Global South, the question of how and whether global value chain arrangements are reconfigured remains open to debate. This article addresses the changing practices of export-oriented smallholders accompanying the transition from simple phone towards smartphone use. Our dynamic approach compares cross-sectional survey data from 2013 and 2017 to answer to what extent Kenyan smallholders have adopted the Internet, which digital practices in relation to agricultural value chains they use and how this affects the inter-firm coordination between smallholders and subsequent actors. Smartphones have gained broad importance for smallholders as they are used for digital practices in value chains. Contrary to the debated dark sides of Internet connectivity, we can however not confirm sweeping digital control or value appropriation by lead firms. So far, long-established, analogue practices widely persist in arrangements between smallholders and exporters. Nevertheless, smartphones are used to nurture multilateral knowledge networks of unprecedented reach and size and further allow for incipient experiments with marketing strategies on digital marketing platforms devoted to domestic markets. We argue that these practices resemble strategic niche seeking that has to be interpreted in relation to captive export arrangements. With qualitatively and quantitatively increasing options to access and share knowledge and to market commodities, the Internet can serve to navigate the multiplicity of chain alternatives (domestic production, informal export production). Such niches should be considered as creating leverage against the take it or leave it deal of captive export production.
Quality of Life in Patients With Cancer Under Prolonged Anticoagulation for High-Risk Deep Vein Thrombosis: a Long-Term Follow-Up
Authors: Napolitano Mariasanta , Mansueto Maria Francesca , Raso Simona , Siragusa Sergio
Published: April 2020

Current guidelines recommend to prolong anticoagulant treatment in patients with cancer with venous thromboembolism (VTE); only few studies evaluated other parameters than cancer itself for selecting patients at higher risk of recurrent VTE. Long-term management of VTE is thus challenged by several controversies mainly for patients compliance. We here report results of a long-term follow-up in patients with deep vein thrombosis under anticoagulant treatment with low-molecular-weight heparin (LMWH) for residual vein thrombosis (RVT) detected at compression ultrasonography (CUS), 6 months after standard anticoagulant treatment. Patients with RVT were deemed at high risk of recurrences and included in the current observational study. They continued LMWH (reduced at 75% standard dose) for further additional 2 years after enrolment or until death. Patients were followed up every 3 months or earlier, if needed. Among ancillary study end points, there was the assessment of patients’ quality of life during daily treatment with subcutaneous injections. Quality of life was determined by the EORTC-C30 questionnaire, administered by a skilled psychologist at enrolment and every 6 months follow-up visits. Overall, 128 patients were evaluated during follow-up. Mean global EORTC-C30 score at enrollment and at 6, 12 and 24 months follow-up were 52.1, 51.4, 50.8 and 50.1, respectively. There were no statistically significant differences between scores at enrolment and at the last available follow-up (P = .1). Long-term treatment with LMWH resulted, effective and safe, it was globally well tolerated and exempt of negative impact on quality of life of the enrolled patients. Reported results support long-term anticoagulant treatment with LMWH in cancer patients at risk of recurrent VTE.
Ownership Concentration and Agency Crises in Indian Manufacturing Firms
Authors: Pandey Krishna Dayal , Sahu Tarak Nath
Published: April 2020

The study attempts to examine the dubious role of majority shareholders in internal governance in the form of moderating agency problems in Indian manufacturing firms. It uses a set of strongly balanced panel data of 91 manufacturing firms of the BSE 200 index of India from 2011–2018 and adopts panel data regression analysis to establish the relationship among the variables. The study measures ownership concentration through the Herfindahl–Hirschman Index (HHI), vertical agency crisis through assets utilization efficiency (AUE) and general and administrative expenses (G&AE) and horizontal agency crisis through return on equity (ROE). The majority owners are found neither to enhance the operating efficiency nor to minimize excessive discretionary expenses of the management. Besides, a negative impact of ownership concentration on return on equity is evidenced, which indicates increased horizontal agency crisis as a consequence of increased ownership concentration. Given the dominance of majority shareholders in the Indian manufacturing sector, it would be worthwhile for corporate policymakers to know whether these large owners act as an internal disciplinary mechanism to the management or squeeze the minority shareholders’ interest through expropriation. Finally, the study suggests stricter external regulatory and institutional specificities as an alternative mechanism to ensure better corporate governance and protection of minority shareholders’ interest.
Chimeric antigen receptor–T cells with cytokine neutralizing capacity
Authors: Tan Adrian H. J. , Vinanica Natasha , Campana Dario
Published: April 2020

Infusion of T lymphocytes expressing chimeric antigen receptors (CARs) can produce extraordinary antitumor activity in patients with leukemia, lymphoma, and myeloma. The signaling mechanisms activating T cells and provoking tumor cell killing also trigger cytokine secretion and macrophage activation, leading to cytokine release syndrome (CRS). CRS is a serious side effect of CAR–T cells, and proinflammatory interleukin-6 (IL-6) is central to its pathogenesis. To endow T cells with anti-CRS activity, we designed a nonsignaling membrane-bound IL-6 receptor (mbaIL6) constituted by a single chain variable fragment derived from an anti–IL-6 antibody linked to a transmembrane anchoring peptide. We found that mbaIL6 expressed on the surface of T cells could rapidly remove IL-6 from the culture supernatant. IL-6 removal was proportional to the number of mbaIL6+ cells, increased with T-cell proliferation, and neutralized IL-6 signaling and function. A construct encoding for mbaIL6 and an anti–CD19-41BB-CD3ζ CAR allowed simultaneous expression of both receptors. T cells with mbaIL6 and CAR neutralized macrophage-derived IL-6 while exerting powerful antitumor activity. Cytotoxicity and proliferation were identical to those of cells expressing CAR alone in vitro, and CAR–T cells were effective in xenograft models regardless of mbaIL6 expression. Levels of human IL-6 in mice, however, were greatly reduced if T cells expressed both receptors instead of CAR alone. Thus, CAR–T cells with on-board capacity to extinguish IL-6 represent a new approach to prevent CRS and suppress its severity without affecting the antitumor potential of CAR–T cells.
Efficacy of ruxolitinib in subcutaneous panniculitis-like T-cell lymphoma and hemophagocytic lymphohistiocytosis
Authors: Lévy Romain , Fusaro Mathieu , Guerin Frédéric , Chetouani Ahmed , Moshous Despina , Fischer Alain , de Saint Basile Geneviève , Sepulveda Fernando E. , Neven Bénédicte
Published: April 2020

Key Points

First evidence of ruxolitinib efficacy for subcutaneous panniculitis-like T-cell lymphoma with hemophagocytic lymphohistiocytosis. Supporting rationale for ruxolitinib use, not more aggressive treatment, in this context, questioning this condition’s neoplastic nature.
Application of the Chinese version of the addiction profile index (API) in drug users: an analysis of validity and measurement invariance across genders
Authors: Gao Huiyuan , Liu Meizhu , Luo Xu , Zhang Jun , Cai Taisheng
Published: April 2020

Background

In China, substance use disorders represent a significant burden on public health and the economy. However, while the range of drugs and drug markets expands and diversifies, the instruments available to evaluate users’ dependence statuses from multiple dimensions have become insufficient. Accordingly, the present study presents the Chinese version of the Addiction Profile Index (API), explores its reliability and validity, and investigates the measurement invariance between males and females with substance use disorders.

Methods

The API, a self-report questionnaire, was administered to 2252 people with substance use disorders who were undergoing treatment in compulsory detoxification institutions located in five provinces in China (943 females; mean age = 33.5 years old, SD = 8.6). Additionally, to ensure the authenticity of the collected data, the study’s volunteers completed the Drug Use Disorders Identification Test (DUDIT), DUDIT-Extended (DUDIT-E), and the Health Scale for Drug Abusers (HSDA).

Results

The revised API, with its updated substance list, featured 34 items. The new four-factor model, incorporating behavioral symptoms of dependence, impact on social life, cravings, and motivations for detoxification, explained 55.30% of the total variance, indicating a good fit. Moreover, Cronbach’s α and mean item coefficient values showed good internal consistency reliability. Regarding criterion validity, the revised factors were moderately to highly correlated with their corresponding subscales in the DUDIT, DUDIT-E, and HSDA. In addition, the multigroup confirmatory factor analysis demonstrated that a measurement invariance of the revised four-factor model across genders was supported, fully assuming different degrees of invariance. The three factors of symptoms, social life, and motivation exhibited significant differences between male and female participants in the t test results (p < 0.01).

Conclusions

The Chinese version of the API shows good psychometric properties in terms of reliability and validity, and exhibits measurement equivalence across the genders. Therefore, it could be used to comprehensively assess the severity of drug dependence in people with substance use disorders.
The use of digitally collected patient-reported outcome measures for newly operated patients with total knee and hip replacements to improve post-treatment recovery: study protocol for a randomized controlled trial
Authors: Kuklinski David , Oschmann Laura , Pross Christoph , Busse Reinhard , Geissler Alexander
Published: April 2020

Background

The number of total knee replacements (TKRs) and total hip replacements (THRs) has been increasing noticeably in high-income countries, such as Germany. In particular, the number of revisions is expected to rise because of higher life expectancy and procedures performed on younger patients, impacting the budgets of health-care systems. Quality transparency is the basis of holistic patient pathway optimization. Nevertheless, a nation-wide cross-sectoral assessment of quality from a patient perspective does not yet exist. Several studies have shown that the use of patient-reported outcome measures (PROMs) is effective for measuring quality and monitoring post-treatment recovery. For the first time in Germany, we test whether early detection of critical recovery paths using PROMs after TKR/THR improves the quality of care in a cost-effective way and can be recommended for implementation into standard care.

Methods/design

The study is a two-arm multi-center patient-level randomized controlled trial. Patients from nine hospitals are included in the study. Patient-centered questionnaires are employed to regularly measure digitized PROMs of TKR/THR patients from the time of hospital admission until 12 months post-discharge. An expert consortium has defined PROM alert thresholds at 1, 3, and 6 months to signal critical recovery paths after TKR/THR. An algorithm alerts study assistants if patients are not recovering in line with expected recovery paths. The study assistants contact patients and their physicians to investigate and, if needed, adjust the post-treatment protocol. When sickness funds’ claims data are added, the cost-effectiveness of the intervention can be analyzed.

Discussion

The study is expected to deliver an important contribution to test PROMs as an intervention tool and examine the determinants of high-quality endoprosthetic care. Depending on a positive and cost-effective impact, the goal is to transfer the study design into standard care. During the trial design phase, several insights have been discovered, and there were opportunities for efficient digital monitoring limited by existing legacy care models. Digitalization in hospital processes and the implementation of digital tools still represent challenges for hospital personnel and patients. Furthermore, data privacy regulations and the separation between the in- and outpatient sector are roadblocks to effectively monitor and assess quality along the full patient pathway.

Trial registration

German Clinical Trials Register: DRKS00019916. Registered November 26, 2019 – retrospectively registered.
Profound remission in Crohn’s disease requiring no further treatment for 3–23 years: a case series
Authors: Agrawal Gaurav , Clancy Annabel , Huynh Roy , Borody Thomas
Published: April 2020

Background

Crohn’s disease (CD) is rising in incidence and has a high morbidity and increased mortality. Current treatment use immunosuppressives but efficacy is suboptimal, and relapse is common. It has been shown that there is an imbalance present in the gut microbiome (dysbiosis) in CD with a possible infective aetiology—Mycobacterium avium subsp. paratuberculosis (MAP) being the most proposed. Antibacterial therapy and Faecal Microbiota Transplantation (FMT) are emerging treatments which can result in clinical and endoscopic remission, if employed correctly. The objective of this study was to report on the treatment and clinical outcomes of patients with CD in prolonged remission.

Results

Ten patients were identified to have achieved prolonged remission for 3–23 years (median 8.5 years). Of these, 7/10 took targeted Anti-MAP therapy (AMAT) for a median 36 months and then ceased AMAT treatment. After stopping AMAT five patients underwent Faecal Microbiota Transplantation (FMT) (average four infusions). In 4/7, AMAT was combined with infliximab (mean of six infusions) that was withdrawn within 6 months after fistulae resolution. One patient achieved deep mucosal healing with AMAT alone. Of the 3/10 patients not prescribed AMAT, one had a combination of anti-inflammatory agents and a single antibiotic (metronidazole) followed by FMT. The other two received only FMT for Clostridioides difficile Infection.

Conclusions

Prolonged remission has been achieved for 3–23 years with individualised treatments, with the majority using AMAT ± infliximab and FMT. Treatment with antibiotics and/or FMT provides a potential new avenue for treatment of CD. These findings should stimulate thinking, investigations and better therapy against MAP and the dysbiosis of the gut flora, to enable higher rates of prolonged remission.
Distribution of genes related to Type 6 secretion system and lipooligosaccharide that induced ganglioside mimicry among Campylobacter jejuni isolated from human diarrhea in Thailand
Authors: Serichantalergs Oralak , Wassanarungroj Patcharawalai , Khemnu Nuanpan , Poly Frédéric , Guerry Patricia , Bodhidatta Ladaporn , Crawford John , Swierczewski Brett
Published: April 2020

Background

Campylobacter jejuni(C. jejuni) is one of the most common bacteria responsible for human gastroenteritis worldwide. The mode of human transmission is foodborne infections due to consumption of contaminated food, especially poultry. Type 6 secretion systems (T6SS) were described recently asCampylobactervirulence mechanisms. Furthermore, infection sequelae associated with neurological disorders like Guillain–Barré (GBS) and Miller Fisher (MF) syndromes can become serious health problems in some patients afterCampylobactergastroenteritis. Our objective was to determine the distribution of these virulence genes amongC. jejuniisolated from stool of human diarrhea.

Methods

A total of 524C. jejunistrains from travelers and pediatric cases of acute diarrhea in Thailand were selected for this study. All isolates belonged to one of 20 known capsule types and all were assayed by PCR for T6SS, a hemolysin co-regulated protein (hcp) gene, and GBS-associated genes (cgtA,cgtB,cstIIHS19andcstIIHS2) which are involved in sialic acid production in the lipooligosaccharide (LOS) cores ofC. jejuni. The distribution of these genes are summarized and discussed.

Results

Of all isolates with these 20 capsule types identified, 328 (62.6%) were positive forhcp, ranging from 29.2 to 100% among 10 capsule types. The GBS-associated LOS genes were detected among 14 capsule type isolates with 24.4% and 23.3% ofC. jejuniisolates possessed eithercstIIHS19or all three genes (cgtA,cgtBandcstIIHS19), which were classified as LOS classes A and B whereas 9.2% ofC. jejuniisolates possessingcstIIHS2were classified as LOS class C. TheC. jejuniisolates of LOS A, B, and C together accounted for 56.9% of the isolates among 14 different capsule types while 31.1% of allC. jejuniisolates did not possess any GBS-associated genes. No significant difference was detected fromC. jejuniisolates possessing GBS-associated LOS genes among travelers and children, but changes between those withhcpwere significant (p < 0.05).

Conclusions

Our results suggested a high diversity ofhcpand GBS-associated LOS genes among capsule types ofC. jejuniisolated from Thailand.
The predictive value of tumor mutation burden for immune checkpoint inhibitors therapy in non-small cell lung cancer is affected by patients’ age
Authors: Wu Yongfeng , Xu Jinming , Xu Jiawei , Wang Yiqing , Wang Luming , Lv Wang , Hu Jian
Published: April 2020

High tumor mutation burden (TMB), which is associated with increased tumor immunogenicity, has been identified to predict improved response to immune checkpoint inhibitors (ICIs) therapy in non-small cell lung cancer (NSCLC). As host immunity is also significant to eliminate cancer cells, however, its clinical impact on cancer immunotherapy is still largely unknown. Here we explored the influence of age, which is an important characteristic to evaluate immune response of patients, on TMB-based predictive system for ICIs therapy in NSCLC. Our results showed that high TMB was capable of predicting better durable clinical benefit (DCB) in agelow group, while it was insignificant in agehigh group. Besides, the predictive power of TMB for progression-free survival (PFS) and overall survival (OS) was better in agelow group than in agehigh group. Our study illustrated that the predictive value of TMB for ICIs therapy was better in young patients than in elderly patients in NSCLC.
Improvements of poly(3-hydroxybutyrate) production in an air-lift reactor using simple production media
Authors: Ortiz-Veizán Nancy , Daga-Quisbert Jeanett , Perez-Zabaleta Mariel , Guevara-Martínez Mónica , Larsson Gen , Quillaguamán Jorge
Published: April 2020

Background

Halomonas boliviensis is a halophilic microorganism that accumulates poly(3-hydroxybutyrate) (PHB) using different carbons sources when nitrogen is depleted from the culture medium. This work presents an improved production of PHB using an air-lift reactor (ALR) that was fed with a concentrated solution of a carbon source, and was supplemented with an adequate airflow rate.

Results

Simple production media were used to study PHB production by H. boliviensis in an ALR. Glucose was first used as the main carbon source and was fed during the exponential phase of cell growth. The maximum CDW and PHB content were 31.7 g/L and 51 wt%, respectively, when the airflow rate entering the reactor varied between 0.5 and 1.2 L/min. Changing the air inflow to 0.5–0.9 L/min resulted in an improvement in PHB accumulation (62 wt%). A cultivation was performed by using the latter range of airflow rate and feeding glucose only when nitrogen was depleted from the medium; a considerable enhancement in PHB content (72 wt%) and CDW (27 g/L) was achieved under these conditions. Moreover, PHB was also produced using molasses as the main carbon source. Residual cell mass was about the same to that achieved with glucose, however the PHB content (52 wt%) was lower.

Conclusions

PHB production by H. boliviensis in an ALR using a simple medium is possible. CDW and PHB content in H. boliviensis can be improved with respect to batch cultivations previously reported when a carbon source is fed to the reactor. The best strategy for the production of PHB consisted of starting the cultivation in a batch mode while glutamate was present in the medium; glucose should be fed when glutamate is depleted from the medium to keep an excess of the carbon source during the synthesis of PHB.
Automation of marine seismic data processing
Authors: Long Andrew , Martin Tony
Published: April 2020

Marine seismic data sets contain highly redundant information. Data analytics and machine learning-based solutions should provide opportunities to reduce turnaround and improve confidence levels in output data volumes. A proof-of-concept (POC) thrust regime example from Indonesia illustrates that parameter testing can almost be eliminated if existing project parameter data can be mined from a database. Where quality control (QC) is required for complex challenges such as noise removal, supervised classifiers are a platform that can enable rapid global quantitative decisions based on relevant data attributes, moving behind the subjective art of observational QC. Finally, many early processing steps depend on reasonable knowledge of the velocity model in addition to the explicit dependence of imaging steps. A POC Monte Carlo-based model building exercise in West Africa used an efficient tomographic platform to demonstrate that turnaround can be reduced from 90 days to only a few days, even when the starting model was significantly wrong. These examples illustrate that a lot is already within our reach, and the development of embedded feedback loops will improve the level of automation further, particularly if humans can learn to let the data speak for itself.
Seismic Soundoff
Authors: Geary Andrew
Published: April 2020

The following is an excerpt from SEG's podcast, Seismic Soundoff. In this episode, host Andrew Geary previews Dave Monk's upcoming Distinguished Instructor Short Course and book titled, “Survey design and seismic acquisition for land, marine, and in-between in light of new technology and techniques.” In this engaging conversation, Dave and Andrew discuss how full-waveform inversion impacts survey design, the research breakthroughs needed for the next evolution of seismic surveys, and one group that may not realize that this course is for them. Listen to the full episode at https://seg.org/podcast/post/8946 .