bluuebunny/crossref_metadata_2025 huggingface dataset:
B-cell–autonomous somatic mutation deficit following bone marrow transplant
Authors: Glas Annuska M. , van Montfort Erwin H. N. , Storek Jan , Green Emily-Gene N. , Drissen Roy P. M. , Bechtold Viviane J. , Reilly J. Zachary , Dawson Monja A. , Milner Eric C. B.
Published: October 2019

Hematopoietic stem cell transplantation is characterized by a prolonged period of humoral immunodeficiency. We have previously shown that the deficiencies are probably not due to the failure to utilize the appropriate V regions in the pre-immune repertoire. However, a striking observation, which correlated with the absence of immunoglobulin IgD− cells and was consistent with a defect in antigen-driven responses, was that rearrangements in bone marrow transplant (BMT) recipients exhibited much less somatic mutation than did rearrangements obtained from healthy subjects. In this paper, we present evidence suggesting that naive B cells obtained from BMT recipients lack the capacity to accumulate somatic mutations in a T-cell–dependent manner compared with healthy subjects. This appears to be a B-cell–autonomous deficit because T cells from some patients, which were not able to support the accumulation of mutations in autologous naive B cells, were able to support accumulation of mutations in heterologous healthy-subject naive B cells.
Wild-type HFE protein normalizes transferrin iron accumulation in macrophages from subjects with hereditary hemochromatosis
Authors: Montosi Giuliana , Paglia Paola , Garuti Cinzia , Guzman Carlos A. , Bastin Judy M. , Colombo Mario P. , Pietrangelo Antonello
Published: October 2019

Hereditary hemochromatosis (HC) is one of the most common single-gene hereditary diseases. A phenotypic hallmark of HC is low iron in reticuloendothelial cells in spite of body iron overload. Most patients with HC have the same mutation, a change of cysteine at position 282 to tyrosine (C282Y) in the HFE protein. The role of HFE in iron metabolism and the basis for the phenotypic abnormalities of HC are not understood. To clarify the role of HFE in the phenotypic expression of HC, we studied monocytes–macrophages from subjects carrying the C282Y mutation in the HFE protein and clinically expressing HC and transfected them with wild-type HFE by using an attenuated Salmonella typhimurium strain as a gene carrier. The Salmonella system allowed us to deliver genes of interest specifically to monocytes–macrophages with high transduction efficiency. The accumulation of 55Fe delivered by55Fe-Tf was significantly lower in macrophages from patients with HC than from controls expressing wild-type HFE. Transfection of HC macrophages with the HFE gene resulted in a high level of expression of HFE protein at the cell surface. The accumulation of 55Fe delivered by 55Fe-Tf was raised by 40% to 60%, and this was reflected by an increase in the55Fe-ferritin pool within the HFE-transfected cells. These results suggest that the iron-deficient phenotype of HC macrophages is a direct effect of the HFE mutation, and they demonstrate a role for HFE in the accumulation of iron in these cells.
Graft-versus-host disease and donor-directed hemagglutinin titers after ABO-mismatched related and unrelated marrow allografts: evidence for a graft-versus-plasma cell effect
Authors: Mielcarek Marco , Leisenring Wendy , Torok-Storb Beverly , Storb Rainer
Published: October 2019

The gradual disappearance of host antidonor isohemagglutinins after major ABO-mismatched hematopoietic stem cell (HSC) allografts has been attributed to the gradual destruction of host plasma cells by graft-versus-host effects. To corroborate this hypothesis, we retrospectively analyzed results from 383 major or major/minor ABO-mismatched unrelated and related HSC allografts performed between 1983 and 1998. All patients were conditioned by high-dose pretransplant therapy and given methotrexate/cyclosporine for graft-versus-host disease (GvHD) prophylaxis. Of the 383 patients, 155 had HLA-matched related and 228 had unrelated grafts. We asked whether unrelated recipients experienced a more rapid disappearance of isohemagglutinins than related recipients, and whether, within the groups of related and unrelated recipients, the titer disappeared faster in patients with GvHD than in those without GvHD. The median time to reach undetectable antidonor IgG and IgM titers was significantly shorter in unrelated recipients (46 versus 61 days; P = .016). In addition, related recipients with GvHD had a 2.2-fold increased likelihood (1.12-4.39,95% CI; P = .02) of reaching undetectable titers within 100 days than patients without GvHD. The persistence of antidonor isohemagglutinins led to significantly increased red blood cell (RBC) transfusion requirements in the ABO-mismatched related patients compared with ABO-matched counterparts. However, time to neutrophil and platelet engraftment, incidence of GvHD, and survival were not influenced by ABO incompatibility. In conclusion, our results corroborate the hypothesis that the rate of disappearance of antidonor isohemagglutinins after ABO-mismatched allogeneic HSC grafts is influenced by the degree of genetic disparity between donor and recipient, suggesting a graft-versus-plasma cell effect.
Successful in vivo purging of CD34-containing peripheral blood harvests in mantle cell and indolent lymphoma: evidence for a role of both chemotherapy and rituximab infusion
Authors: Magni Michele , Di Nicola Massimo , Devizzi Liliana , Matteucci Paola , Lombardi Fabrizio , Gandola Lorenza , Ravagnani Fernando , Giardini Roberto , Dastoli Giuseppe , Tarella Corrado , Pileri Alessandro , Bonadonna Gianni , Gianni Alessandro M.
Published: October 2019

Elimination of tumor cells (“purging”) from hematopoietic stem cell products is a major goal of bone marrow–supported high-dose cancer chemotherapy. We developed an in vivo purging method capable of providing tumor-free stem cell products from most patients with mantle cell or follicular lymphoma and bone marrow involvement. In a prospective study, 15 patients with CD20+ mantle cell or follicular lymphoma, bone marrow involvement, and polymerase chain reaction (PCR)–detectable molecular rearrangement received 2 cycles of intensive chemotherapy, each of which was followed by infusion of a growth factor and 2 doses of the anti-CD20 monoclonal antibody rituximab. The role of rituximab was established by comparison with 10 control patients prospectively treated with an identical chemotherapy regimen but no rituximab. The CD34+ cells harvested from the patients who received both chemotherapy and rituximab were PCR-negative in 93% of cases (versus 40% of controls;P = .007). Aside from providing PCR-negative harvests, the chemoimmunotherapy treatment produced complete clinical and molecular remission in all 14 evaluable patients, including all 6 with mantle cell lymphoma (versus 70% of controls). In vivo purging of hematopoietic progenitor cells can be successfully accomplished in most patients with CD20+ lymphoma, including mantle cell lymphoma. The results depended on the activity of both chemotherapy and rituximab infusion and provide the proof of principle that in vivo purging is feasible and possibly superior to currently available ex vivo techniques. The high short-term complete-response rate observed suggests the presence of a more-than-additive antilymphoma effect of the chemoimmunotherapy combination used.
Inactivation of a GFP retrovirus occurs at multiple levels in long-term repopulating stem cells and their differentiated progeny
Authors: Klug Christopher A. , Cheshier Samuel , Weissman Irving L.
Published: October 2019

Hematopoietic stem cell gene therapy holds promise for the treatment of many hematologic disorders. One major variable that has limited the overall success of gene therapy to date is the lack of sustained gene expression from viral vectors in transduced stem cell populations. To understand the basis for reduced gene expression at a single-cell level, we have used a murine retroviral vector, MFG, that expresses the green fluorescent protein (GFP) to transduce purified populations of long-term self-renewing hematopoietic stem cells (LT-HSC) isolated using the fluorescence-activated cell sorter. Limiting dilution reconstitution of lethally irradiated recipient mice with 100% transduced, GFP+ LT-HSC showed that silencing of gene expression occurred rapidly in most integration events at the LT-HSC level, irrespective of the initial levels of GFP expression. When inactivation occurred at the LT-HSC level, there was no GFP expression in any hematopoietic lineage clonally derived from silenced LT-HSC. Inactivation downstream of LT-HSC that stably expressed GFPin long-term reconstituted animals was restricted primarily to lymphoid cells. These observations suggest at least 2 distinct mechanisms of silencing retrovirally expressed genes in hematopoietic cells.
Clinical importance of minimal residual disease in childhood acute lymphoblastic leukemia
Authors: Coustan-Smith Elaine , Sancho Jose , Hancock Michael L. , Boyett James M. , Behm Frederick G. , Raimondi Susana C. , Sandlund John T. , Rivera Gaston K. , Rubnitz Jeffrey E. , Ribeiro Raul C. , Pui Ching-Hon , Campana Dario
Published: October 2019

By using rapid flow cytometric techniques capable of detecting one leukemic cell in 104 normal cells, we prospectively studied minimal residual disease (MRD) in 195 children with newly diagnosed acute lymphoblastic leukemia (ALL) in clinical remission. Bone marrow aspirates (n = 629) were collected at the end of remission induction therapy and at 3 intervals thereafter. Detectable MRD (ie, ≥0.01% leukemic mononuclear cells) at each time point was associated with a higher relapse rate (P < .001); patients with high levels of MRD at the end of the induction phase (≥1%) or at week 14 of continuation therapy (≥0.1%) had a particularly poor outcome. The predictive strength of MRD remained significant even after adjusting for adverse presenting features, excluding patients at very high or very low risk of relapse from the analysis, and considering levels of peripheral blood lymphoblasts at day 7 and day 10 of induction therapy. The incidence of relapse among patients with MRD at the end of the induction phase was 68% ± 16% (SE) if they remained with MRD through week 14 of continuation therapy, compared with 7% ± 7% if MRD became undetectable (P = .035). The persistence of MRD until week 32 was highly predictive of relapse (all 4 MRD+patients relapsed vs 2 of the 8 who converted to undetectable MRD status; P = .021). Sequential monitoring of MRD by the method described here provides highly significant, independent prognostic information in children with ALL. Recent improvements in this flow cytometric assay have made it applicable to more than 90% of all new patients.
Sequence properties of certain GC rich avian genes, their origins and absence from genome assemblies: case studies
Authors: Beauclair Linda , Ramé Christelle , Arensburger Peter , Piégu Benoît , Guillou Florian , Dupont Joëlle , Bigot Yves
Published: October 2019

Background

More and more eukaryotic genomes are sequenced and assembled, most of them presented as a complete model in which missing chromosomal regions are filled by Ns and where a few chromosomes may be lacking. Avian genomes often contain sequences with high GC content, which has been hypothesized to be at the origin of many missing sequences in these genomes. We investigated features of these missing sequences to discover why some may not have been integrated into genomic libraries and/or sequenced.

Results

The sequences of five red jungle fowl cDNA models with high GC content were used as queries to search publicly available datasets of Illumina and Pacbio sequencing reads. These were used to reconstruct the leptin, TNFα, MRPL52, PCP2 and PET100 genes, all of which are absent from the red jungle fowl genome model. These gene sequences displayed elevated GC contents, had intron sizes that were sometimes larger than non-avian orthologues, and had non-coding regions that contained numerous tandem and inverted repeat sequences with motifs able to assemble into stable G-quadruplexes and intrastrand dyadic structures. Our results suggest that Illumina technology was unable to sequence the non-coding regions of these genes. On the other hand, PacBio technology was able to sequence these regions, but with dramatically lower efficiency than would typically be expected.

Conclusions

High GC content was not the principal reason why numerous GC-rich regions of avian genomes are missing from genome assembly models. Instead, it is the presence of tandem repeats containing motifs capable of assembling into very stable secondary structures that is likely responsible.
Parsing the synonymous mutations in the maize genome: isoaccepting mutations are more advantageous in regions with codon co-occurrence bias
Authors: Chu Duan , Wei Lai
Published: October 2019

Background

Synonymous mutations do not change amino acids but do sometimes change the tRNAs (anticodons) that decode a particular codon. An isoaccepting codon is a synonymous codon that shares the same tRNA. If a mutated codon could base pair with the same anticodon as the original, the mutation is termed an isoaccepting mutation. An interesting but less-studied type of codon bias is codon co-occurrence bias. There is a trend to cluster the isoaccepting codons in the genome. The proposed advantage of codon co-occurrence bias is that the tRNA released from the ribosome E site could be quickly recharged and subsequently decode the following isoaccepting codons. This advantage would enhance translation efficiency. In plant species, whether there are signals of positive selection on isoaccepting mutations in the codon co-occurred regions has not been studied.

Results

We termed polymorphic mutations in coding regions using publicly available RNA-seq data in maize (Zea mays). Next, we classified all synonymous mutations into three categories according to the context, i.e., the relationship between the focal codon and the previous codon, as follows: isoaccepting, nonisoaccepting and nonsynonymous. We observed higher fractions of isoaccepting mutations in the isoaccepting context. If we looked at the minor allele frequency (MAF) spectrum, the isoaccepting mutations have a higher MAF in the isoaccepting context than that in other regions, and accordingly, the nonisoaccepting mutations have a higher MAF in the nonisoaccepting context.

Conclusion

Our results indicate that in regions with codon co-occurrence bias, natural selection maintains this pattern by suppressing the nonisoaccepting mutations. However, if the consecutive codons are nonisoaccepting, mutations tend to switch these codons to become isoaccepting. Our study demonstrates that the codon co-occurrence bias in the maize genome is selectively maintained by natural selection and that the advantage of this trend could potentially be the rapid recharging and reuse of tRNAs to increase translation efficiency.
Effects of computer-assisted navigation versus the conventional technique for total knee arthroplasty on levels of plasma thrombotic markers: a prospective study
Authors: Siu Ka-Kit , Wu Kwan-Ting , Ko Jih-Yang , Wang Feng-Sheng , Chou Wen-Yi , Wang Ching-Jen , Kuo Shu-Jui
Published: October 2019

Background

Venous thromboembolism (VTE) is a major sequela after total knee arthroplasty (TKA). We prospectively compared the differences in the perioperative plasma d-dimer and fibrinogen levels between the individuals undergoing TKA via computer-assisted navigation and via a conventional method as the surrogate comparison for VTE. There were 174 patients fulfilling the inclusion criteria and providing valid informed consent between September 2011 and November 2013. There were 69 females and 20 males in the navigation-assisted group (median age: 71.00 years), while the conventional group was composed of 59 females and 26 males (median age: 69.00 years). Blood samples were obtained prior to and at 24 and 72 h after surgery for measurement of the levels of plasma d-dimer and fibrinogen.

Results

A significantly lower plasma d-dimer level 24 h after TKA (p = 0.001) and a milder postoperative surge 24 h after TKA (p = 0.002) were observed in patients undergoing navigation-assisted TKA. The proportions of subjects exceeding the plasma d-dimer cut-off values of 7.5, 8.6 and 10 mg/L 24 h after TKA were all significantly higher in the conventional group than in the navigation-assisted group (p = 0.024, 0.004, and 0.004, respectively).

Conclusions

A lower plasma d-dimer level and a milder surge in the plasma d-dimer level were observed in patients undergoing navigation-assisted TKA in comparison with patients undergoing conventional TKA 24 h after surgery. These findings may supplement the known advantages of navigation-assisted TKA.
Is there any association between gut microbiota and type 1 diabetes? A systematic review
Authors: Jamshidi Parnian , Hasanzadeh Saba , Tahvildari Azin , Farsi Yeganeh , Arbabi Mahta , Mota João Felipe , Sechi Leonardo A. , Nasiri Mohammad Javad
Published: October 2019

Introduction

Type 1 diabetes (T1D) is the second most common autoimmune disease among children. There is evidence suggesting that dysbiosis of some gut colonizing bacteria are associated with the pathogenesis of T1D. However, these studies are still controversial and a systematic review was conducted to evaluate the association between gut microbiota and T1D.

Methods

A systematic search was carried out in Medline (Via Pubmed) and Embase from January 2000 to January 2019 for all original cross-sectional, cohort, case–control or nested case–control studies investigating the association between gut microbiota and T1D.

Results

Of 568 articles identified, 26 studies met the inclusion criteria. The total population study of these articles consists of 2600 children (under 18 years old) and 189 adults. Among the included studies, 24 articles confirmed the association between gut microbiota dysbiosis and T1D. The most common bacterial alterations in T1D patients includedBacteroidesspp.,Streptococcusspp.,Clostridiumspp.,Bifidobacteriumspp.,Prevotellaspp.,Staphylococcusspp.,Blautiaspp.,Faecalibacteriumspp.,Roseburiaspp., andLactobacillusspp.

Conclusion

Our study showed a significant association between alterations in intestinal microbial composition and T1D; however, in some articles, it is not clear which one happens first. Investigation of altered gut microbiota can help in the early detection of T1D before seropositivity. Targeted microbiome modulation can be a novel potential therapeutic strategy.
Impact of solar radiation and environmental temperature on Art Nouveau glass windows
Authors: Palomar Teresa , Silva Miguel , Vilarigues Marcia , Pombo Cardoso Isabel , Giovannacci David
Published: October 2019

This work presents the results of the evaluation of two Art Nouveau glass windows from the Casa-Museu Dr. Anastácio Gonçalves (Lisbon, Portugal) with IR-thermography during the summer solstice. According to the measurements, the surface temperature of glass depended on the outdoor environmental temperature and, mainly, on the direct solar radiation. Colored glasses presented a higher surface temperature due to the absorption of their chromophores at near-IR wavelengths. Enamels and grisailles showed higher surface temperatures than their support glasses due to both their chemical composition and color. The protective glazing, with small slits in one of the window panels, induced a hot-air pocket in its upper part due to the insufficient ventilation.
A novel customized ceramic bracket for esthetic orthodontics: in vitro study
Authors: Yang Liu , Yin Guangfu , Liao Xiaoming , Yin Xing , Ye Niansong
Published: October 2019

Background

This study aims to develop a novel process to establish a standardized manufacturing technique of customized esthetic ceramic bracket system (CCB) which could be endowed with individual color and shape to satisfy patients’ individual demands. Material characteristics and mechanical parameters of CCB were evaluated.

Subjects and methods

CCB virtual models were designed individually according to patient’s teeth morphology and clinical demands. 3D printing technology, lost-wax technology, and selected glass-ceramic ingots were employed to fabricate CCB. Scanning electron microscopy (SEM) analyses were performed to characterize the surface morphology of CCB and commercially available brackets (Clarity Advanced; Crystalline VII; Inspire ICE; Damon Q). Static and kinetic frictional resistance (FR), shear bond strength (SBS) and adhesive remnant index (ARI) scores were recorded. One-way analyses of variance (ANOVA) and post-hoc Tukey’s HSD multiple tests were used for statistical analyses.

Results

Multi-color and multi-transparency raw materials facilitated CCB with a wide range of color options and controllable optical properties to satisfy different esthetic demands of individual orthodontic patients. CCB presented same level of FR as commercially available ceramic brackets did. No significant differences (P ≥ 0.05) of SBS were observed among CCB-ES (treated silane), Clarity Advanced and Crystalline VII groups, and CCB-E (no silane) attained the highest ARI mean score 3. In the preliminary clinical trial, CCB presented excellent color-matching and shape-matching appearances similar to natural teeth, which made it highly invisible from social intercourse distance.

Conclusions

CCB were demonstrated to be an applicable labial orthodontic bracket system with optimized esthetics and biomechanics. We envision that it would be an ideal alternative for patients who pursue esthetic orthodontic treatment but were not likely to take lingual appliances or clear aligners.
Exotic parrots breeding in urban tree cavities: nesting requirements, geographic distribution, and potential impacts on cavity nesting birds in southeast Florida
Authors: Diamond Joshua M. , Ross Michael S.
Published: October 2019

Background

Exotic parrots have established breeding populations in southeast Florida, including several species that nest in tree cavities. We aimed to determine the species identity, nest site requirements, relative nest abundance, geographic distribution, and interactions of parrots with native cavity-nesting bird species.

Methods

We searched Miami-Dade County, Florida, and nearby areas for natural cavities and holes excavated by woodpeckers, recording attributes of potential nest trees. We inspected all cavities with an elevated video inspection system to determine occupancy by parrots or other birds. We mapped nearly 4000 citizen science observations of parrots in our study area corresponding to our study period, and used these to construct range maps, comparing them to our nesting observations.

Results

Not all parrots reported or observed in our study area were actively breeding. Some parrots were observed at tree cavities, which previous studies have suggested is evidence of reproduction, but our inspections with an elevated video inspection system suggest they never initiated nesting attempts. Several parrot species did successfully nest in tree cavities, Red-masked Parakeets (Psittacara erythrogenys) and Orange-winged Parrots (Amazona amazonica) being the most common (n = 7 and 6 nests, respectively). These two parrots had similar nesting requirements, but Orange-winged Parrots use nests with larger entrance holes, which they often enlarge. Geographic analysis of nests combined with citizen science data indicate that parrots are limited to developed areas. The most common parrots were less abundant cavity nesters than the native birds which persist in Miami’s urban areas, and far less abundant than the invasive European Starling (Sturnus vulgaris).

Conclusions

Exotic parrots breeding elsewhere in the world have harmed native cavity-nesting birds through interference competition, but competitive interference in southeast Florida is minimized by the urban affinities of parrots in this region. The relative abundance and geographic distribution suggest that these parrots are unlikely to invade adjacent wilderness areas.
Protocol of a randomized, double-blind, placebo-controlled, parallel-group, multicentre study of the efficacy and safety of nicotinamide in patients with Friedreich ataxia (NICOFA)
Authors:   the EFACTS or NICOFA study group, Reetz Kathrin , Hilgers Ralf-Dieter , Isfort Susanne , Dohmen Marc , Didszun Claire , Fedosov Kathrin , Kistermann Jennifer , Mariotti Caterina , Durr Alexandra , Boesch Sylvia , Klopstock Thomas , Rodríguez de Rivera Garrido Francisco Javier , Schöls Ludger , Klockgether Thomas , Pandolfo Massimo , Korinthenberg Rudolf , Lavin Philip , Molenberghs Geert , Libri Vincenzo , Giunti Paola , Festenstein Richard , Schulz Jörg B.
Published: October 2019

Introduction

Currently, no treatment that delays with the progression of Friedreich ataxia is available. In the majority of patients Friedreich ataxia is caused by homozygous pathological expansion of GAA repeats in the first intron of the FXN gene. Nicotinamide acts as a histone deacetylase inhibitor. Dose escalation studies have shown, that short term treatment with dosages of up to 4 g/day increase the expression of FXN mRNA and frataxin protein up to the levels of asymptomatic heterozygous gene carriers. The long-term effects and the effects on clinical endpoints, activities of daily living and quality of life are unknown.

Methods

The aim of the NICOFA study is to investigate the efficacy and safety of nicotinamide for the treatment of Friedreich ataxia over 24 months. An open-label dose adjustment wash-in period with nicotinamide (phase A: weeks 1–4) to the individually highest tolerated dose of 2–4 g nicotinamide/day will be followed by a 2 (nicotinamide group): 1 (placebo group) randomization (phase B: weeks 5–104). In the nicotinamide group, patients will continue with their individually highest tolerated dose between 2 and 4 g/d per os once daily and the placebo group patients will be receiving matching placebo. Safety assessments will consist of monitoring and recording of all adverse events and serious adverse events, regular monitoring of haematology, blood chemistry and urine values, regular measurement of vital signs and the performance of physical examinations including cardiological signs. The primary outcome is the change in the Scale for the Assessment and Rating of Ataxia (SARA) over time as compared with placebo in patients with Friedreich ataxia based on the linear mixed effect model (LMEM) model. Secondary endpoints are measures of quality of life, functional motor and cognitive measures, clinician’s and patient’s global impression-change scales as well as the up-regulation of the frataxin protein level, safety and survival/death.

Perspective

The NICOFA study represents one of the first attempts to assess the clinical efficacy of an epigenetic therapeutic intervention for this disease and will provide evidence of possible disease modifying effects of nicotinamide treatment in patients with Friedreich ataxia.

Trial registration

EudraCT-No.: 2017-002163-17, ClinicalTrials.govNCT03761511.
FOLFOXIRI Plus Panitumumab As First-Line Treatment of RAS Wild-Type Metastatic Colorectal Cancer: The Randomized, Open-Label, Phase II VOLFI Study (AIO KRK0109)
Authors: Modest Dominik P. , Martens Uwe M. , Riera-Knorrenschild Jorge , Greeve Jobst , Florschütz Axel , Wessendorf Swen , Ettrich Thomas , Kanzler Stephan , Nörenberg Dominik , Ricke Jens , Seidensticker Max , Held Swantje , Buechner-Steudel Petra , Atzpodien Jens , Heinemann Volker , Seufferlein Thomas , Tannapfel Andrea , Reinacher-Schick Anke C. , Geissler Michael
Published: October 2019

PURPOSE

This trial investigated the addition of panitumumab to triplet chemotherapy with fluorouracil/folinic acid, oxaliplatin, and irinotecan (FOLFOXIRI) in a two-to-one randomized, controlled, open-label, phase II trial in patients with untreated RAS wild-type (WT) metastatic colorectal cancer.

PATIENTS AND METHODS

The primary end point was objective response rate (ORR) according to RECIST (version 1.1). The experimental arm (modified FOLFOXIRI [mFOLFOXIRI] plus panitumumab) was considered active if the ORR was ≥ 75%. The experimental ORR was compared with an estimated ORR of 60% based on historical data, verified by a randomized control group (FOLFOXIRI). The power of the trial was 80%, with a potential type I error of 0.05. Secondary end points included secondary resection rate, toxicity, progression-free survival, and overall survival.

RESULTS

A total of 63 patients were randomly assigned to the experimental arm and 33 patients to the control arm. The ORR of the mFOLFOXIRI plus panitumumab arm exceeded 75% and was higher when compared with that of FOLFOXIRI (87.3% v 60.6%; odds ratio, 4.469; 95% CI, 1.61 to 12.38; P = .004). The secondary resection rate was improved with the addition of panitumumab (33.3% v 12.1%; P = .02). Progression-free survival was similar in the study arms, whereas overall survival showed a trend in favor of the panitumumab-containing arm (hazard ratio for death, 0.67; 95% CI, 0.41 to 1.11; P = .12).

CONCLUSION

The addition of panitumumab to mFOLFOXIRI in patients with RAS WT metastatic colorectal cancer improved the ORR and rate of secondary resection of metastases and represents a treatment option in selected and fit patients in need of highly active first-line therapy. Future studies should determine whether the addition of panitumumab to mFOLFOXIRI prolongs survival.
The Law of the Urban Common(s)
Authors: Marella Maria Rosaria
Published: October 2019

Cities are quintessentially human and collective products. All urban space is the product of social cooperation. Therefore not just the “public” space but the metropolis as a whole must be considered as a commons. This assumption is not neutral from a legal point of view. It raises the question of whether private property of urban land is compatible with the conception of urban space as commons. The answer depends on how much we can push on the disintegration of property to expand the perspective of collective entitlements on urban resources against the commodification and new enclosures of urban space. Drawing on a legal realist approach to property, it is possible to dissolve the unitary conception of ownership into a bundle of rights. This article is a first attempt to enfranchise urban property as a legal form from its fate of being a mere boundary between the haves and the have-nots and revisit its role in the construction of social relations of production within the metropolis.
Pancreatic Heterotopia Found in the Gastric Antrum Mistaken for Malignancy
Authors: Berry Rani , Rahal Harman K. , Ho Wendy
Published: October 2019

Pancreatic heterotopia is a rare and often incidental finding in clinical practice. The term refers to pancreatic tissue distinct from the normal pancreas and with its own ductal and vascular supply. Usually asymptomatic, ectopic tissue is still prone to infection and may cause clinical complications when mistaken for malignancy or abscess. We describe a 32-year-old woman who presented with epigastric discomfort, initially thought to be a gastric outlet mass concerning for gastric malignancy vs an intraabdominal infection. She was eventually found to have an umbilicated submucosal lesion in the gastric antrum consistent with pancreatic heterotopia. Given the young age and sex of the patient, the differential diagnosis remained broad, underscoring the high risk of mismanagement of pancreatic heterotopia secondary to infrequency of this condition as a presenting diagnosis.
Histofluorometric assessment of insulin content in the endocrine tissue of the rat pancreas in the postreanimation period
Authors: Kikimbayeva A. A. , Andreyeva A. P. , Aubakirov A. B. , Bazhanov A. N. , Lebedev A. S.
Published: October 2019

Histofluorometric measurement of insulin was carried out in В cells of the rat pancreas after pseudoisocyanine staining of slices in various terms of the postreanimation period following 10-min clinical death after V.G. Korpachev. The studies showed that the reanimation factor enhanced insulin release into the blood and changed the morphology of islet endocrine tissue of the gland. Hypoxia promoted transformation of mixed acinar insular, acinar glandular, and ductal epithelial cells into insulin-producing cells in experimental animals. Histofluorometric analysis of assessing insulin content in histological preparations gives reliable data on the production of this hormone in the glandular B-cells.
The mediating effect of psychological ownership on human resources management bundle and job satisfaction ownership
Authors: Masnita Yolanda , Puspitasari Pipie , Risqiani Renny
Published: October 2019

AMO (ability, motivation, and opportunity) is one of the measurements used in Human Resource Management and for explaining the Innovation of Human Resources Management Bundle (IHRMB) that can affect job satisfaction and welfare. It explained that if a skilled, motivated employees will have the opportunity to contribute by using their knowledge and competencies. They will feel having a maximum job satisfaction. This study examine the role of psychological ownership for organizations (PO-O) in mediating the effect of IHRMB on the Job Satisfaction of bank employees (bankers). With a purposive sampling of inclusion criteria, a questionnaire was given to 100 bankers, testing the hypothesis with SEM. The results show that IHRMB affects PO-O and Job Satisfaction. The IHRMB is prepared at the end of the year to be able to have the right strategy for employees the following year, in addition to being a connector between the owner of the company to employees through a collection of innovations summarized in the IHRMB as well as providing opportunities for employees to be able to provide ideas that will support the company's progress. PO-O does not mediate the effect of IHRMB on Job Satisfaction because IHRMB is a control tool for management and company owners to review overall company performance.
A Duel of Dreams
Authors: Backiel Linda
Published: October 2019

Naomi Klein's The Battle for Paradise (Haymarket, 2018) describes a duel of dreams for post-Hurricane María Puerto Rico. On the one hand, networks of resistance and resilience sprang up around the island in the wake of the collapse of not just trees and houses, but infrastructure and government. On the other, a small group of super rich speculators and futurists were poised to cash in on what Puerto Rico's then-Governor Ricardo Rosselló described as an opportunity to "sort of restart and upgrade" a nation he shamelessly called a "blank canvas." Rosselló was forced out of office on July 24, 2019, by mass protests, in large part thanks to the networks of resistance and resilience that came to life when the government essentially disappeared after the 2017 hurricanes.
On Some Mutual Positions of Hyperplanes in a Finite-Dimensional Affine Space
Authors: Kharazishvili Alexander
Published: October 2019

Several combinatorial questions and facts connected with certain types of mutual positions of finitely many hyperplanes in a finite-dimensional affine space are considered. An application of one of such facts to a multi-dimensional version of the well-known Sylvester theorem is presented.
Controllability of Sobolev Type Semilinear Functional Differential and Integrodifferential Inclusions with an Unbounded Delay
Authors: Chang Yong-Kui , Li Wan-Tong
Published: October 2019

In this paper, sufficient conditions are established for the controllability of Sobolev type semilinear functional differential and integrodifferential inclusions with an unbounded delay in Banach spaces. The main results are obtained by using the fixed point theorem for condensing maps due to Martelli.
Removal efficiency of nitrate, phosphate, fecal and total coliforms by horizontal subsurface flow-constructed wetland from domestic wastewater
Authors: Kalankesh Laleh R. , Rodríguez-Couto Susana , Dadban Shahama Yousef , Asgarnia Hossein Ali
Published: October 2019

Background: Constructed wetlands are systems designed based on the utilization of natural processes, including vegetation, soil, and their associated microbial assemblage to assist in treating different types of wastewater. Methods: Two local Appalachian plants (Louis latifolia and Phragmites australis) were planted into smallscale constructed wetlands to treat domestic wastewater in the North of Iran. The influent wastewater and the effluent from each wetland were sampled daily for 120 days. Experiments were conducted based on the mean ± standard deviation (SD) by analysis of variance (ANOVA). Results: It was found that nitrate, phosphate, fecal and total coliforms were reduced by 84.4%, 94.4%, 96.3%, 93.9% for P. australis and 73.3%, 64.0%, 94.4%, 92.1% for L. latifolia, respectively. Conclusion: According to the results, by using the HF-CW technology with L. latifolia and P. australis plants, the treated wastewater fully meets the wastewater discharge parameters of WHO standards.
Chromium removal and water recycling from electroplating wastewater through direct osmosis: Modeling and optimization by response surface methodology
Authors: Naghdali Zohreh , Sahebi Soleyman , Ghanbari Reza , Mousazadeh Milad , Jamali Hamzeh Ali
Published: October 2019

Background: Considering the carcinogenic effects of heavy metals, such as chromium, it is essential to remove these elements from water and wastewater. Direct osmosis is a new membrane technology, which can be a proper alternative to conventional chromium removal processes. Methods: The wastewater samples were collected from an electroplating unit, located in Alborz industrial city, Qazvin, Iran. Magnesium chloride was used as the draw solution, and a semipermeable membrane (Aquaporin) was used in this study. The experiments were designed, using response surface methodology (RSM) and central composite design (CCD) with draw solution concentration (0.5- 1.5 M), feed solution concentration (4-12 mg/L), and experiment time (30-90 minutes) as variable factors. The chromium concentration and water flux were also measured, based on atomic absorption spectrophotometry and water flux equation, respectively. Results: Direct osmosis was highly efficient in chromium removal and water recycling. Water flux and chromium removal efficiency were 15.6 LMH and 85.58%, respectively, under optimal conditions (draw solution = 1.27 mol/L, feed solution = 4 mg/L, and experiment time = 90 min). In terms of validity, the results predicted by the quadratic polynomial model were in good agreement with the responses reported in the laboratory. Conclusion: In direct osmosis, the use of magnesium chloride as the draw solution resulted in the acceptable chromium removal from electroplating wastewater. Using this method, chromium concentration in wastewater reduced to a level lower than the discharge standards, established by Iran’s Department of Environment.
Investigation of heavy metals concentration in soil around a Pb-Zn mine and ecological risk assessment
Authors: Baghaie Amir Hossein , Aghili Forough
Published: October 2019

Background: Soil pollution with heavy metals seriously threatens soil quality, food safety, and humanhealth. This study was conducted to determine the soil pollution level and ecological risk assessmentof different heavy metals in agricultural soils around Nakhlak Pb-Zn mine, located in Anarak district,Nain county of Isfahan province.Methods: A total of 50 soil samples were collected from agricultural land around Nakhlak mine andanalyzed to determine the concentrations of Pb, Cd, Zn, Ni, Cu, and Mn. The geo-accumulation index(Igeo), enrichment factor (EF), and potential ecological-risk index (Er) were used to assess the level ofsoil pollution with heavy metals.Results: The mean concentrations of Pb, Cd, Zn, Ni, Cu, and Mn were 355, 2.72, 347, 26, 36, and505 mg/kg, respectively, which were higher than the background values of world soils. Based on theIgeo index, the study area was moderately to heavily contaminated with Pb and Zn, uncontaminated tomoderate contaminated with Cd and Cu, and uncontaminated with Mn and Ni. According to the EFvalues, the study soil was moderately contaminated with Mn, Ni, and Cu, significantly contaminatedwith Cd and Zn, and highly enriched with Pb. The RI values showed a moderate level of heavy metalscontamination in the study soil.Conclusion: According to the results, the ecological risk of heavy metals for ecosystem in agriculturallands around Nakhlak Pb-Zn mine is moderate. However, the contamination status should be consideredperiodically.
Removal of Acid Orange 7 dye from wastewater using combination of ultraviolet radiation, ultrasonic method, and MgO nanoparticles
Authors: Talaiekhozani Amirreza , Heydari Chaleshtori Abbas , Banisharif Farhad , Eskandari Zeinab , Nasiri Mohammad , Aminsharei Farham , Park Junboum , Rezania Shahabaldin , Bazrafshan Maryam
Published: October 2019

Background: Industrial dyes are toxic and carcinogenic, therefore, they should be removed from
wastewater. The aim of this study was to investigate the removal of acid orange 7 Dye from wastewater
using ultraviolet (UV) radiation, MgO nanoparticles, ultrasonic method alone and in combination with
each other.
Methods: The effects of some factors such as temperature, pH, hydraulic retention time (HRT), UV
power, and concentration of MgO nanoparticles on the removal of Acid Orange 7 dye from synthetic
wastewater using different methods were investigated. Also, adsorption isotherms for MgO nanoparticles
and kinetics for UV radiation were investigated.
Results: The optimum HRT was 55 minutes while the temperature was not effective in dye removal
using the ultrasonic method. Under optimum conditions for UV irradiation method (HRT = 70
minutes, UV power = 170 mW/cm2, and temperature = 10˚C), 58% of the dye was removed. However,
under optimum conditions for MgO nanoparticles method (HRT = 15 minutes, temperature = 20˚C,
and ratio of MgO nanoparticles to the initial dye concentration = 67.2), 82% of the dye was removed.
By combining these methods, the dye removal efficiency was significantly increased. The combination
of ultrasonic method and MgO nanoparticles had no significant effect on increasing the dye removal
efficiency from wastewater. It was revealed that dye removal using UV radiation can be described by
the first-order kinetics.
Conclusion: According to the results, UV radiation has a synergistic effect on the dye adsorption
process by MgO nanoparticles. Therefore, the combination of these methods can be effective for the
removal of dye from wastewater.
Minorities’ Diminished Returns of Educational Attainment on Hospitalization Risk: National Health Interview Survey (NHIS)
Authors: Assari Shervin , Bazargan Mohsen
Published: October 2019

Background: As suggested by the Minorities’ Diminished Returns (MDRs) theory, educational attainment shows a weaker protective effect for racial and ethnic minority groups compared to non-Hispanic Whites. This pattern, however, is never shown for hospitalization risk. Objectives: This cross-sectional study explored racial and ethnic variations in the association between educational attainment and hospitalization in the United States. Methods: Data came from the National Health Interview Survey (NHIS 2015). The total sample was 28,959 American adults. Independent variable was educational attainment. The main outcome was hospitalization during the last 12 months. Age, gender, employment, marital status, region, obesity, and number of cardiovascular conditions were covariates. Race and ethnicity were the effect modifiers. Logistic regression models were utilized to analyze the data. Results: From all participants, 16.2% were Black and 11.6% were Hispanic with a mean age of 51 years. Overall, higher education levels were associated with lower odds of hospitalization, independent of all confounders. Educational attainment showed significant interactions with race (odds ratio [OR] =1.04, 95% CI = 1.01-1.08) and ethnicity (OR = 1.04, 95% CI =1.01-1.07) on hospitalization, indicating smaller protective effects of educational attainment on hospitalization of Hispanics and Blacks than nonHispanic Whites. Conclusion: The protective effects of educational attainment on population health are smaller for Blacks and Hispanics compared to non-Hispanic Whites. To prevent health disparities, the diminished returns of educational attainment should be minimized for racial and ethnic minorities. To do so, there is a need for innovative and bold economic, public, and social policies that do not limit themselves to equalizing socioeconomic status, but also help minorities leverage their available resources and gain tangible outcomes.
Factors Associated with Enrolment of Households in Nepal’s National Health Insurance Program
Authors: Ghimire Prabesh , Sapkota Vishnu Prasad , Poudyal Amod Kumar
Published: October 2019

Background: Nepal has made remarkable efforts towards social health protection over the past several years. In 2016, the Government of Nepal introduced a National Health Insurance Program (NHIP) with an aim to ensure equitable and universal access to healthcare by all Nepalese citizens. Following the first year of operation, the scheme has covered 5 percent of its target population. There are wider concerns regarding the capacity of NHIP to achieve adequate population coverage and remain viable. In this context, this study aimed to identify the factors associated with enrolment of households in the NHIP. Methods: A cross-sectional household survey using face to face interview was carried out in 2 Palikas (municipalities) of Ilam district. 570 households were studied by recruiting equal number of NHIP enrolled and non-enrolled households. We used Pearson’s chi-square test and binary logistic regression to identify the factors associated with household’s enrolment in NHIP. All statistical analyses were performed using IBM SPSS version 23 software. Results: Enrolment of households in NHIP was found to be associated with ethnicity, socio-economic status, past experience of acute illness in family and presence of chronic illness. The households that belonged to higher socio-economic status were about 4 times more likely to enrol in the scheme. It was also observed that households from privileged ethnic groups such as Brahmin, Chhetri, Gurung, and Newar were 1.7 times more likely to enrol in NHIP compared to those from underprivileged ethnic groups such as janajatis (indigenous people) and dalits (the oppressed). The households with illness experience in 3 months preceding the survey were about 1.5 times more likely to enrol in NHIP compared to households that did not have such experience. Similarly, households in which at least one of the members was chronically ill were 1.8 times more likely to enrol compared to households with no chronic illness. Conclusion: Belonging to the privileged ethnic group, having a higher socio-economic status, experiencing an acute illness and presence of chronically ill member in the family are the factors associated with enrolment of households in NHIP. This study revealed gaps in enrolment between rich-poor households and privileged-underprivileged ethnic groups. Extension of health insurance coverage to poor and marginalized households is therefore needed to increase equity and accelerate the pace towards achieving universal health coverage.
Dificuldades vivenciadas pelos estudantes de enfermagem durante a sua formação
Authors: Amorim Caroline Bettanzos , Oliveira Matheus Ferreira de , Barlem Edison Luiz Devos , Mattos Larissa Merino de
Published: October 2019

Objetivo: conhecer as dificuldades enfrentadas pelos estudantes de enfermagem durante a sua formação. Método: estudo qualitativo do tipo exploratório-descritivo, desenvolvido com 18 estudantes de enfermagem de uma universidade pública no sul do Brasil. Os dados foram coletados entre março a abril de 2017, por meio de entrevistas semiestruturadas audiogravadas e analisados através da análise textual discursiva. A pesquisa obteve parecer favorável, sob o número 14/2017 do Comitê de Ética em Pesquisa na Área da Saúde. Resultados: emergiram três categorias: dificuldades relacionais e pessoais; estrutura física deficitária; dificuldades relacionadas ao processo de ensino e aprendizagem. Considerações Finais: a constante e acelerada busca por um ensino de excelência expõe o estudante as diversas situações de conflitos individuais e coletivos que podem levar ao desgaste físico e psicológico.