bluuebunny/crossref_metadata_2025_split huggingface dataset:
TGFβ and CIS Inhibition Overcomes NK-cell Suppression to Restore Antitumor Immunity
Authors: Souza-Fonseca-Guimaraes Fernando , Rossi Gustavo R. , Dagley Laura F. , Foroutan Momeneh , McCulloch Timothy R. , Yousef Jumana , Park Hae-Young , Gunter Jennifer H. , Beavis Paul A. , Lin Cheng-Yu , Hediyeh-Zadeh Soroor , Camilleri Tania , Davis Melissa J. , Huntington Nicholas D. 
Published: June 2022

Abstract

Antibodies targeting “immune checkpoints” have revolutionized cancer therapy by reactivating tumor-resident cytotoxic lymphocytes, primarily CD8+ T cells. Interest in targeting analogous pathways in other cytotoxic lymphocytes is growing. Natural killer (NK) cells are key to cancer immunosurveillance by eradicating metastases and driving solid tumor inflammation. NK-cell antitumor function is dependent on the cytokine IL15. Ablation of the IL15 signaling inhibitor CIS (Cish) enhances NK-cell antitumor immunity by increasing NK-cell metabolism and persistence within the tumor microenvironment (TME). The TME has also been shown to impair NK-cell fitness via the production of immunosuppressive transforming growth factor β (TGFβ), a suppression which occurs even in the presence of high IL15 signaling. Here, we identified an unexpected interaction between CIS and the TGFβ signaling pathway in NK cells. Independently, Cish- and Tgfbr2-deficient NK cells are both hyperresponsive to IL15 and hyporesponsive to TGFβ, with dramatically enhanced antitumor immunity. Remarkably, when both these immunosuppressive genes are simultaneously deleted in NK cells, mice are largely resistant to tumor development, suggesting that combining suppression of these two pathways might represent a novel therapeutic strategy to enhance innate anticancer immunity.
Evaluation of the DLL3-targeting Antibody–Drug Conjugate Rovalpituzumab Tesirine in Preclinical Models of Neuroblastoma
Authors: Krytska Kateryna , Casey Colleen E. , Pogoriler Jennifer , Martinez Daniel , Rathi Komal S. , Farrel Alvin , Berko Esther R. , Tsang Matthew , Sano Renata R. , Kendsersky Nathan , Erickson Stephen W. , Teicher Beverly A. , Isse Kumiko , Saunders Laura , Smith Malcolm A. , Maris John M. , Mossé Yael P. 
Published: June 2022

Neuroblastomas have neuroendocrine features and often show similar gene expression patterns to small cell lung cancer including high expression of delta-like ligand 3 (DLL3). Here we determine the efficacy of rovalpituzumab tesirine (Rova-T), an antibody–drug conjugated (ADC) with a pyrrolobenzodiazepine dimer toxin targeting DLL3, in preclinical models of human neuroblastoma.We evaluated DLL3 expression in RNA-sequencing datasets and performed IHC on neuroblastoma patient-derived xenograft (PDX), human neuroblastoma primary tumor and normal childhood tissue microarrays. We then evaluated the activity of Rova-T against 11 neuroblastoma PDX models using varying doses and schedules and compared antitumor activity with expression levels.DLL3 mRNA was differentially overexpressed in neuroblastoma at comparable levels to small cell lung cancer, as well as Wilms and rhabdoid tumors. DLL3 protein was robustly expressed across the neuroblastoma PDX array, but membranous staining was variable. The human neuroblastoma array, however, showed staining in only 44% of cases, whereas no significant staining was observed in the normal childhood tissue array. Rova-T showed a clear dose–response effect across the 11 models tested, with a single dose inducing a complete or partial response in 3 of 11 and stable disease in another 3 of 11 models. No overt signs of toxicity were observed, and there was no treatment-related mortality. Strong membranous staining was necessary, but not sufficient, for antitumor activity.Rova-T has activity in a subset of neuroblastoma preclinical models, but heterogeneous expression in these models and the near absence of expression seen in human tumors suggests that any DLL3-targeting clinical trial should be only performed with a robust companion diagnostic to evaluate DLL3 expression for patient selection.Significance:GD2-directed antibody therapy is standard of care for high-risk neuroblastoma; therapy is toxic, and relapses often occur. DLL3, an inhibitory Notch ligand, is overexpressed in several neuronal cancers. A DLL3-targeting ADC showed objective activity only in neuroblastoma models with high DLL3 expression. These data provide vigilance about clinical development of DLL3 immunotherapies for neuroblastoma.
Decision‐Making in Seeking Emergency Care for Stroke Symptoms
Authors: Andersson Jenny , Jakobsson Sofie , Rejnö Åsa , Hansson Per‐Olof , Nielsen Susanne J. , Björck Lena 
Published: June 2022

Background
Previous studies have shown that rapid treatment for stroke, especially ischemic stroke, reduces mortality and disability. The focus has mainly been on reducing time from arrival at hospital to start of treatment. However, the main reason for delay is often time from symptom onset to arrival at hospital. This study therefore aimed to explore decision‐making processes after the onset of stroke symptoms in patients experiencing a first‐time stroke.

Methods
We included 36 patients aged 18 and older, all of whom were hospitalized with a first‐time stroke between October 2018 and April 2020. All patients were interviewed once within 4 weeks of symptom onset and before hospital discharge. Eligible patients were identified retrospectively through a targeted review of medical records. The data were collected and analyzed according to the grounded theory methodology.

Results
In total, 43 potential patients were identified and asked to participate. Overall, 36 patients were included in the study: 17 women (median age 77.0 years, interquartile range 17.5) and 19 men (median age 65.7 years, interquartile range 17.2). All interviewees felt fear, and this affected their decision to seek emergency care. The decision‐making processes were described by the core category of “Acting on fear.” The reason for feeling frightened determined the actions taken. The reasons were sorted into 3 main categories: (1) “seeking care”–recognized stroke symptoms and acted immediately; (2) “pending and reluctance”–suspected stroke but awaited to seek care; and (3) “seeking an explanation”–confused by symptoms.

Conclusion
We found that decision‐making when experiencing stroke symptoms was complex. All patients felt fear, which determined their actions. Some patients knew about stroke symptoms and acted immediately. Others suspected stroke but still chose to wait, whereas others were confused and tried to find answers. These results could contribute to form future awareness campaigns.
Reassessing Moscow Conceptualism: The View from the Nest
Authors: Nicholas Mary A. 
Published: June 2022

Abstract
This essay argues for a radical reassessment of Moscow Conceptualism to incorporate the underappreciated Nest, the group of artists Gennady Donskoy, Mikhail Roshal, and Victor Skersis active in Moscow from 1974 to 1979. The Nest's emphasis on models of shared artistic investigation, audience autonomy, and unconstructed aesthetic response helped reshape Moscow Conceptualism in the late 1970s and early 1980s, making their experience essential to understanding both the era and the works of particular artists they influenced, including Yuri Albert, Vadim Zakharov, Nadezhda Stolpovskaya, and others. The Nest's focus on alternative media and new genres, particularly on unstructured performative works, helped transform Moscow's unofficial art world, freeing it from lingering insularity and modernist conventions.
Neo-Aramaic as a source of hitherto unattested Aramaic words and meanings
Authors: Mutzafi Hezy 
Published: June 2022

Abstract
The spectrum of Neo-Aramaic languages and dialects, spoken in an arch of language-islets that stretch from south-western Syria to south-western Iran, exhibits rich lexical repositories inherited from early layers of the Aramaic language. Within this wealthy lexical legacy, some genuine Aramaic lexical items are not attested in any of the literary Aramaic sources, hence it is only by virtue of these modern lexical manifestations that the existence of the ancient Aramaic antecedents of these words can be inferred or reconstructed. Such historical lacunae concern also meanings that must be of considerable antiquity, yet these meanings, pertaining to well-known Aramaic words, have no evidence in literary Aramaic, having surfaced only in the modern era. This article discusses ten selected cases of pre-modern Aramaic words and meanings that were discovered by etymological and comparative examination of their modern reflexes in North-Eastern Neo-Aramaic (NENA), Western Neo-Aramaic and Ṭuroyo.
Going Mobile to Address Emerging Climate Equity Needs in the Heterogeneous Urban Environment
Authors: Lamer Katia , Luke Edward P. , Walsh Brian , Andrade Steven , Mages Zackary , Zhu Zeen , Leghart Erin , Treserras Bernat P. , Emrick Ann , Kollias Pavlos , Vogelmann Andrew , Schoonen Martin 
Published: June 2022

Abstract
The Brookhaven National Laboratory Center for Multiscale Applied Sensing (CMAS) aims to address environmental equity needs in the context of a changing climate. As a first step toward this goal, the center developed a one-of-a-kind observatory tailored to the study of highly heterogeneous urban environments. This article describes the features of the mobile observatory that enable its rapid deployment either on or off the power grid, as well as its instrument payload. Beyond its unique design, the observatory optimizes data collection within the obstacle-laden urban environment using a new smart sampling paradigm. This setup facilitated the collection of previously poorly documented environmental properties, including wind profiles throughout the atmospheric column. The mobile observatory captured unique observations during its first few intensive observation periods. Vertical air motion and infrared temperature measurements collected along the faces of the supertall One Vanderbilt skyscraper in Manhattan, NY, reveal how solar and anthropogenic heating affect wind flow and thus the venting of heat, pollution, and contaminants in urban street canyons. Also, air temperature measurements collected during travel along a 150-km transect between Upton and Manhattan, NY, offer a high-resolution view of the urban heat island and reveal that temperature disparities also exist within the city across different neighborhoods. Ultimately, the datasets collected by CMAS are poised to help guide equitable urban planning by highlighting existing disparities and characterizing the impact of urban features on the urban microclimate with the goal of improving human comfort.
The International Hip Dysplasia Institute (IHDI) classification is more informative than the Tönnis classification
Authors: Sand Adam , Tiderius Carl Johan , Düppe Henrik , Wenger Daniel 
Published: June 2022

Background A new, supposedly more reproducible radiographic classification, set to replace the Tönnis classification of hip dislocations, was proposed in 2015: the International Hip Dysplasia Institute (IHDI) classification. Purpose To compare the IHDI classification with the Tönnis classification when evaluating the severity of hip dislocations as well as their respective inter- and intra-observer reliability. Material and Methods Since January 2000, Swedish-born children with a hip dislocation were prospectively registered. From this registry, radiographs of 97 hips in 79 patients (91% girls; median age = 7 months), born in 2000–2009, were analyzed. Two observers, one consultant and one resident, classified each hip both by IHDI and Tönnis twice. Results The IHDI classification had a more even distribution of grades with the majority in grade 2–3. The Tönnis classification graded the majority (77%) of the patients as grade 2 and equally among the other grades. There was moderate inter-observer agreement using both methods calculated with Kappa, 0.61 (95% confidence interval [CI] = 0.44–0.79) for Tönnis and 0.62 (95% CI = 0.49–0.74) for IHDI. The resident calculated Tönnis with weak intra-observer reliability of 0.57 (95% CI = 0.40–0.74) compared to high intra-observer reliability of 0.86 (95% CI = 0.74–0.98) for the consultant. Both observers graded IHDI with high intra-observer reliability. Conclusion IHDI is more discriminative than the Tönnis classification when evaluating the severity of a hip dislocation in infants.
Polyurethane and its composites derived from bio-sources: Synthesis, characterization and adsorption studies
Authors: Vijayan Jyothy G , Chandrashekar Akshatha , AG Jineesh , Prabhu T Niranjana , Kalappa Prashantha 
Published: June 2022

Polyols from chaulmoogra seed oil and grape seed oil were prepared by epoxidation and ring opening of oxirane ring using lactic acid in nitrogen atmosphere with a control over their functionality. Nanocellulose was derived from Desmostachya Bipinnata grass leaves and further surface functionalized. Modified nanocellulose was used as filler to prepare porous flexible bio-based polyurethane nanocomposites via in-situ polymerization. Adsorption of malachite green (MG) dye from wastewater using the prepared polyurethane composites was carried out. The effect of varying factors such as weight percentage of filers (modified nanocellulose), dosage of the adsorbent, pH, temperature and time on the MG adsorption have been studied experimentally. Material characterization for prepared materials was carried out using FTIR, NMR, TGA, DSC, and SEM along with other physical and chemical methods. FTIR results indicated the presence of peaks at 1704 cm−1 for –C=O stretching vibrations from urethane groups, 1531 cm−1 for –NH bending, 1232 cm−1 for –C–N stretching and 1105 cm−1 for –C–O stretching in the urethane group (–NHCOO–) thus, indicating the formation of urethane linkage in the polyurethane. Polyols with functionality around 2.8 were obtained from the oils, which has contributed to forming flexible polyurethanes. Morphological studies indicate the nano fibrillation of cellulose and closed-cell porosity in polyurethane and its composites. The flexible porous PU and its nanocellulose composites displayed improved thermal stability from 256.3°C to 270.5°C. Taguchi’s L27 orthogonal array have been applied for experimental design and optimization and the results were analyzed using ANOVA for raw and S/N ratio. It was found that pH is the most influential factor for adsorption lead by quantity of nanocellulose, time, dosage of the adsorbent and temperature.
Impact of closed-incision negative pressure wound dressings on surgical site infection following groin incisions in vascular surgery; a single-centre experience
Authors: Barry Ian Patrick , Turley Luke P , Gwilym Brenig L , Bosanquet David C , Richards Toby 
Published: June 2022

Objectives Surgical site infection (SSI) is a common complication in vascular surgery, and is associated with increased patient morbidity, readmission and reintervention. The aim of this study was to assess the impact of closed-incision negative pressure wound therapy (CiNPWT) upon rate of SSI and length of hospital stay. Methods This study was reported in line with the STROBE guidelines. We assessed the baseline incidence of SSI from a 12-month retrospective cohort and, following a change in practice intervention with CiNPWT, compared to a 6-month prospective cohort. The primary endpoint was incidence of SSI (according to CDC-NHSN guidelines) while secondary endpoints included length of hospital stay, readmission, reintervention and Days Alive and Out of Hospital (DAOH) to 90-days. Results A total of 127 groin incisions were performed: 76 (65 patients) within the retrospective analysis and 51 (42 patients) within the prospective analysis (of whom 69% received CiNPWT). The primary endpoint of SSI was seen in 21.1% of the retrospective cohort and 9.8% of the prospective cohort ( p = .099). Readmission was found to be significantly associated with the retrospective cohort ( p = .016) while total admission (inclusive of re-admission) was significantly longer in those in the retrospective cohort ( p = .013). DAOH-90 was 83 days (77–85) following introduction of the CiNPWT protocol as compared to the retrospective cohort (77 days (64–83), p = .04). Conclusion Introduction of CiNPWT was associated with a reduced length of hospital stay and improved DAOH-90. Further trials on CINPWT should include patient-centred outcomes and healthcare cost analysis.
Real-life short-term effectiveness of anti-osteoporotic treatments: a longitudinal cohort study
Authors: Adami Giovanni , Gavioli Irene , Rossini Maurizio , Viapiana Ombretta , Orsolini Giovanni , Benini Camilla , Bertoldo Eugenia , Fracassi Elena , Gatti Davide , Fassio Angelo 
Published: June 2022

Introduction: Randomized clinical trials have shown that anti-osteoporotic treatments can increase bone mineral density (BMD) and reduce the incidence of fragility fractures. However, data on the real-life effectiveness of anti-osteoporotic medications are still scarce. Methods: We conducted a cohort study on women at high risk of fracture. We retrieved clinical and densitometric data from the DeFRA database, which derives from the DeFRA tool, a web-based fracture risk assessment tool. Multivariable Cox regression survival models were employed to analyze the effectiveness of different anti-osteoporotic drugs on fracture. In sensitivity analyses, we conducted 1:1 propensity score matching analyses. Results: Data on 50,862 women were available. Among these, 3574 individuals had at least two consecutive visits. The crude fracture rate was 91.9/1000 person-year for non-treated patients. The crude fracture rate in bisphosphonate users was 72.1/1000 person-year, in denosumab users was 58.2/1000 person-year, and in teriparatide users was 19.3/1000 person-year. Overall, we found that bisphosphonate use was associated with a 30% lower risk of fracture compared to no treatment [adjusted hazard ratio (aHR): 0.70, 95% confidence interval (CI): 0.50–0.98]. Treatment with denosumab and teriparatide were associated with 60% and 90% lower risk of fracture, respectively (aHR: 0.43, 95% CI: 0.24–0.75 and aHR: 0.09, 95% CI: 0.01–0.70). Bisphosphonate use was associated with a lower risk of fracture only after 1 year of treatment. Conclusion: In conclusion, we found that all anti-osteoporotic medications considered in the study effectively reduced the risk of fracture in the real-life. The effect of bisphosphonate on fracture risk was apparent only after the first year of treatment. Our findings do not support the use of bisphosphonates in patients at imminent risk of fracture.
Use of Bayes factors to evaluate the effects of host genetics, litter and cage on the rabbit cecal microbiota
Authors: Velasco-Galilea María , Piles Miriam , Ramayo-Caldas Yuliaxis , Varona Luis , Sánchez Juan Pablo 
Published: June 2022

Abstract
Background
The rabbit cecum hosts and interacts with a complex microbial ecosystem that contributes to the variation of traits of economic interest. Although the influence of host genetics on microbial diversity and specific microbial taxa has been studied in several species (e.g., humans, pigs, or cattle), it has not been investigated in rabbits. Using a Bayes factor approach, the aim of this study was to dissect the effects of host genetics, litter and cage on 984 microbial traits that are representative of the rabbit microbiota.

Results
Analysis of 16S rDNA sequences of cecal microbiota from 425 rabbits resulted in the relative abundances of 29 genera, 951 operational taxonomic units (OTU), and four microbial alpha-diversity indices. Each of these microbial traits was adjusted with mixed linear and zero-inflated Poisson (ZIP) models, which all included additive genetic, litter and cage effects, and body weight at weaning and batch as systematic factors. The marginal posterior distributions of the model parameters were estimated using MCMC Bayesian procedures. The deviance information criterion (DIC) was used for model comparison regarding the statistical distribution of the data (normal or ZIP), and the Bayes factor was computed as a measure of the strength of evidence in favor of the host genetics, litter, and cage effects on microbial traits. According to DIC, all microbial traits were better adjusted with the linear model except for the OTU present in less than 10% of the animals, and for 25 of the 43 OTU with a frequency between 10 and 25%. On a global scale, the Bayes factor revealed substantial evidence in favor of the genetic control of the number of observed OTU and Shannon indices. At the taxon-specific level, significant proportions of the OTU and relative abundances of genera were influenced by additive genetic, litter, and cage effects. Several members of the genera Bacteroides and Parabacteroides were strongly influenced by the host genetics and nursing environment, whereas the family S24-7 and the genus Ruminococcus were strongly influenced by cage effects.

Conclusions
This study demonstrates that host genetics shapes the overall rabbit cecal microbial diversity and that a significant proportion of the taxa is influenced either by host genetics or environmental factors, such as litter and/or cage.
Comparative genomics analysis and virulence-related factors in novel Aliarcobacter faecis and Aliarcobacter lanthieri species identified as potential opportunistic pathogens
Authors: Chuan Jiacheng , Belov Anatoly , Cloutier Michel , Li Xiang , Khan Izhar U. H. , Chen Wen 
Published: June 2022

Abstract
Background
Emerging pathogenic bacteria are an increasing threat to public health. Two recently described species of the genus Aliarcobacter, A. faecis and A. lanthieri, isolated from human or livestock feces, are closely related to Aliarcobacter zoonotic pathogens (A. cryaerophilus, A. skirrowii, and A. butzleri). In this study, comparative genomics analysis was carried out to examine the virulence-related, including virulence, antibiotic, and toxin (VAT) factors in the reference strains of A. faecis and A. lanthieri that may enable them to become potentially opportunistic zoonotic pathogens.

Results
Our results showed that the genomes of the reference strains of both species have flagella genes (flaA, flaB, flgG, flhA, flhB, fliI, fliP, motA and cheY1) as motility and export apparatus, as well as genes encoding the Twin-arginine translocation (Tat) (tatA, tatB and tatC), type II (pulE and pulF) and III (fliF, fliN and ylqH) secretory pathways, allowing them to secrete proteins into the periplasm and host cells. Invasion and immune evasion genes (ciaB, iamA, mviN, pldA, irgA and fur2) are found in both species, while adherence genes (cadF and cj1349) are only found in A. lanthieri. Acid (clpB), heat (clpA and clpB), osmotic (mviN), and low-iron (irgA and fur2) stress resistance genes were observed in both species, although urease genes were not found in them. In addition, arcB, gyrA and gyrB were found in both species, mutations of which may mediate the resistance to quaternary ammonium compounds (QACs). Furthermore, 11 VAT genes including six virulence (cadF, ciaB, irgA, mviN, pldA, and tlyA), two antibiotic resistance [tet(O) and tet(W)] and three cytolethal distending toxin (cdtA, cdtB, and cdtC) genes were validated with the PCR assays. A. lanthieri tested positive for all 11 VAT genes. By contrast, A. faecis showed positive for ten genes except for cdtB because no PCR assay for this gene was available for this species.

Conclusions
The identification of the virulence, antibiotic-resistance, and toxin genes in the genomes of A. faecis and A. lanthieri reference strains through comparative genomics analysis and PCR assays highlighted the potential zoonotic pathogenicity of these two species. However, it is necessary to extend this study to include more clinical and environmental strains to explore inter-species and strain-level genetic variations in virulence-related genes and assess their potential to be opportunistic pathogens for animals and humans.