bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of short-term heating on bioefficacy of deltamethrin-coated long-lasting insecticidal nets
Authors: Bubun Nakei , Freeman Timothy W. , Laman Moses , Karl Stephan 
Published: August 2021

AbstractWe recently reported that long-lasting insecticidal nets (LLINs) distributed in Papua New Guinea (PNG) between 2013 and 2019, exhibited severely diminished efficacy to knock down and kill susceptible Anopheles mosquitoes. This coincided with a rise in malaria observed in PNG since 2015. Here we show that LLIN bioefficacy is increased by heating LLINs prior to WHO cone bioassays.Unused LLINs with low bioefficacy, delivered to PNG in 2019, were heated to 120°C for 5 minutes. Cone bioassays were performed before and at 1 h, 7 days and 30 days after heating. This led to a significant increase in 24 h mortality (17% to 61%) and 60 min knock down (31% to 72%). The effect was sustained over 30 days.Bioassays are crucial in quality assurance of LLIN products. Our findings indicate that bioassay results can easily be manipulated. This may have implications for quality assurance procedures used to assess LLINs.
Longitudinal Associations between Hair Cortisol, PTSD Symptoms, and Sleep Disturbances in a Sample of Firefighters with Duty-related Trauma Exposure
Authors: Sopp M. R. , Michael T. , Lass-Hennemann J. , Haim-Nachum S. , Lommen M. J. J. 
Published: August 2021

AbstractSeveral studies have found evidence of altered cortisol levels in patients with posttraumatic stress disorder (PTSD). Based on these findings, it is assumed that these patients may show signs of cortisol dysregulation after trauma. Posttrauma cortisol levels are thus considered a potential biomarker of PTSD. However, longitudinal studies using indicators of long-term cortisol secretion (such as hair cortisol concentrations; HCC) are scarce. The current study investigated prospective associations between HCC and PTSD symptoms in a sample of Dutch firefighters taking into account varying levels of work-related trauma severity. In addition, we assessed posttraumatic sleep disturbances as a secondary outcome measure to investigate whether effects generalize to this frequent comorbidity of PTSD. Three hundred seventy-one Dutch firefighters with a mean of 14.01 years of work experience were included in the analyses. Baseline assessment included the collection of hair samples and the measurement of work-related trauma severity, PTSD symptoms, and sleep disturbances. PTSD symptoms and sleep disturbance were re-assessed after six and twelve months. Multilevel analyses indicate a significant positive correlation between HCC and baseline PTSD symptoms in those with average or above-average work-related trauma severity. A similar pattern was evident for posttraumatic sleep disturbances at baseline. Moreover, higher HCC predicted more posttraumatic sleep disturbances after 6 months in participants with above-average work-related trauma severity. No other associations emerged for PTSD symptoms or posttraumatic sleep disturbances at six or twelve months. As such, our study supports the existence of a cross-sectional association between HCC and trauma symptoms, which may vary for different levels of subjective trauma severity. The longitudinal stability of this association should be reinvestigated by future research.
Serum miRNA-based signature indicates radiation exposure and dose in humans: a multicenter diagnostic biomarker study
Authors: Nowicka Zuzanna , Tomasik Bartłomiej , Kozono David , Stawiski Konrad , Johnson Thomas , Haas-Kogan Daphne , Ussowicz Marek , Chowdhury Dipanjan , Fendler Wojciech 
Published: August 2021

AbstractMouse and non-human primate models showed that serum miRNAs may be used to predict the biological impact of radiation doses. We hypothesized that these results can be translated to humans treated with total body irradiation (TBI), and that miRNAs may be used as clinically feasible biodosimeters. To test this hypothesis, serial serum samples were obtained from 25 patients who underwent allogeneic stem-cell transplantation and profiled for miRNA expression using next-generation sequencing. Circulating exosomes were extracted, their miRNA content sequenced and cross-referenced with the total miRNA fraction. Finally, miRNAs with diagnostic potential were quantified with qPCR and an artificial neural network model was created and validated on an independent group of 12 patients with samples drawn under the same protocol. Differential expression results were largely consistent with previous studies and allowed us to build an 8-miRNA-based model that showed AUC of 0.97 (95%CI 0.89-1.00) and validate it using qPCR in an independent validation set where it showed accuracy >91% for detecting exposure and 87.5% for differentiating between lethal and non-lethal doses. MiRNAs used in the model were miR-150-5p, miR-126-5p, miR-375, miR-215-5p, miR-144-5p, miR-122-5p, miR-320d and miR-10b-5p. Additionally, miRNAs with detectable expression in this and two prior animal sets almost perfectly separated the irradiated from non-irradiated samples in mice, macaques and humans, validating the miRNAs as radiation-responsive through evolutionarily conserved transcriptional regulation mechanisms. We conclude that serum miRNAs reflect radiation exposure and dose for humans undergoing TBI and may be used as functional biodosimeters for precise identification of people exposed to clinically significant radiation doses.
Real-time Continuous Measurement of Lactate through a Minimally-invasive Microneedle Biosensor: a Phase I Clinical Study
Authors: Ming DK , Jangam S , Gowers SAN , Wilson R , Freeman DME , Boutelle MG , Cass AEG , O’Hare D , Holmes AH 
Published: August 2021

AbstractIntroductionDetermination of blood lactate levels supports decision-making in a range of medical conditions. Invasive blood-sampling and laboratory access are often required, and measurements provide a static profile at each instance. We conducted a Phase I clinical study validating performance of a microneedle patch for minimally-invasive, continuous lactate measurement in healthy volunteers.MethodsFive healthy adult participants wore a solid microneedle biosensor on their forearms and undertook aerobic exercise for 30 minutes. The microneedle biosensor quantifies lactate concentrations in interstitial fluid (ISF) within the dermis continuously and in real-time. Outputs were captured as sensor current and compared with lactate concentrations from venous blood and microdialysis.ResultsThe biosensor was well-tolerated. Participants generated a median peak venous lactate of 9.25 mmol/L (Interquartile range, 6.73 to 10.71). Microdialysate concentrations of lactate closely correlated with blood. Microneedle biosensor current followed venous lactate concentrations and dynamics, with good agreement seen in all participants. There was an estimated lag-time of 5 minutes (IQR -4 to 11 minutes) between microneedle and blood lactate measurements.ConclusionThis study provides first-in-human data on use of a minimally-invasive microneedle biosensor for continuous lactate measurement, providing dynamic monitoring. The platform offers distinct advantages to frequent blood sampling in a wide range of clinical settings, especially where access to laboratory services is limited or blood sampling is infeasible.
Discordant humoral and T cell immune responses to SARS-CoV-2 vaccination in people with multiple sclerosis on anti-CD20 therapy
Authors: Gadani Sachin P. , Reyes-Mantilla Maria , Jank Larissa , Harris Samantha , Douglas Morgan , Smith Matthew D. , Calabresi Peter A. , Mowry Ellen M. , Fitzgerald Kathryn C. , Bhargava Pavan 
Published: August 2021

AbstractBackgroundSphingosine-1-phosphate receptor (S1P) modulators and antiCD20 therapies impair humoral responses to SARS-CoV-2 mRNA vaccines. Whether disease modifying therapies (DMTs) for multiple sclerosis (MS) also impact T cell immune response to vaccination is unknown.MethodsIn 101 people with MS, we measured humoral responses via an immunoassay to measure IgG against the COVID-19 spike S1 glycoprotein in serum. We also measured T cell responses using FluoroSpot assay for interferon gamma (IFN-γ) (Mabtech,Sweden) using cryopreserved rested PBMCs and then incubated in cRPMI with 1µg/ml of pooled peptides spanning the entire spike glycoprotein (Genscript, 2 pools; 158 peptides each). Plates were read on an AID iSpot Spectrum to determine number of spot forming cells (SFC)/106PBMCs. We tested for differences in immune responses across DMTs using linear models.FindingsHumoral responses were detected in 22/39 (56.4%) participants on anti-CD20 and in 59/63 (93.6%) participants on no or other DMTs. In a subset with immune cell phenotyping (n=88; 87%), T cell responses were detected in 76/88 (86%), including 32/33 (96.9%) participants on anti-CD20 therapies. AntiCD20 therapies were associated with an increase in IFN-γ SFC counts relative to those on no DMT or other DMTs (for antiCD20 vs. no DMT: 425.9% higher [95%CI: 109.6%, 1206.6%] higher; p<0.001; for antiCD20 vs. other DMTs: 289.6% [95%CI: 85.9%, 716.6%] higher; p<0.001).InterpretationWe identified a robust T cell response in individuals on anti-CD20 therapies despite a reduced humoral response to SARS-CoV-2 vaccination. Follow up studies are needed to determine if this translates to protection against COVID-19 infection.
Loss of ACKR4 in tumor cells dysregulates dendritic cell migration to tumor-draining lymph nodes and T-cell priming
Authors: Wangmo Dechen , Premsrirut Prem K. , Yuan Ce , Morris William S. , Zhao Xianda , Subramanian Subbaya 
Published: August 2021

ABSTRACTColorectal cancer (CRC) is one of the most common malignancies in both morbidity and mortality. Immune checkpoint blockade (ICB) treatments have been successful in a portion of mismatch repair-deficient (dMMR) CRC patients but failed in the mismatch repair-proficient (pMMR) CRC patients. Atypical Chemokine Receptor 4 (ACKR4) is known for regulating dendritic cell (DC) migration. However, the roles of ACKR4 in CRC development and immunoregulation are unclear. By analyzing human CRC tissues, transgenic animals, and genetically modified CRC cells lines, our study revealed an important function of ACKR4 in maintaining CRC immune response. Loss of ACKR4 in CRC is associated with poor immune infiltration in the tumor microenvironment. More importantly, loss of ACKR4 in CRC tumor cells, rather than stromal cells, restrains the DC migration and antigen presentation to the tumor-draining lymph nodes (TdLNs). Tumors with ACKR4 knockdown become less sensitive to immune checkpoint blockades. Finally, we identified that microRNA-552 negatively regulates ACKR4 expression in human CRC. Taken together, our work identifies a critical mechanism for the maintenance of the DC-mediated T-cell priming in the TdLNs. These new findings demonstrate a novel mechanism leading to immunosuppression and ICB treatment resistance in CRC tumors.LAY SUMMARYOur study demonstrated that Atypical Chemokine Receptor 4 (ACKR4) is downregulated in human colorectal cancer (CRC) tissues compared with normal colon tissues. Loss of ACKR4 in human CRC tissues is associated with a weak anti-tumor immune response. Knockdown of ACKR4 in tumor cells impairs the dendritic cell migration from the tumor tissue to the tumor-draining lymph nodes (TdLNs), causing inadequate tumor-specific T-cell expanding and insensitivity to immune checkpoint blockades. However, loss of ACKR4 in tumor stromal cells does not significantly affect anti-tumor immunity. In human CRC tumors, high expression of microRNA-552 is a mechanism leading to ACKR4 downregulation. Our study revealed a novel mechanism that leads to the poor immune response in a subset of CRC tumors and will contribute to the framework for identifying new therapies against this deadly tumor.
Comparing SARS-CoV-2 natural immunity to vaccine-induced immunity: reinfections versus breakthrough infections
Authors: Gazit Sivan , Shlezinger Roei , Perez Galit , Lotan Roni , Peretz Asaf , Ben-Tov Amir , Cohen Dani , Muhsen Khitam , Chodick Gabriel , Patalon Tal 
Published: August 2021

AbstractBackgroundReports of waning vaccine-induced immunity against COVID-19 have begun to surface. With that, the comparable long-term protection conferred by previous infection with SARS-CoV-2 remains unclear.MethodsWe conducted a retrospective observational study comparing three groups: (1)SARS-CoV-2-naïve individuals who received a two-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 vaccine, (2)previously infected individuals who have not been vaccinated, and (3)previously infectedandsingle dose vaccinated individuals. Three multivariate logistic regression models were applied. In all models we evaluated four outcomes: SARS-CoV-2 infection, symptomatic disease, COVID-19-related hospitalization and death. The follow-up period of June 1 to August 14, 2021, when the Delta variant was dominant in Israel.ResultsSARS-CoV-2-naïve vaccinees had a 13.06-fold (95% CI, 8.08 to 21.11) increased risk for breakthrough infection with the Delta variant compared to those previously infected, when the first event (infection or vaccination) occurred during January and February of 2021. The increased risk was significant (P<0.001) for symptomatic disease as well. When allowing the infection to occur at any time before vaccination (from March 2020 to February 2021), evidence of waning natural immunity was demonstrated, though SARS-CoV-2 naïve vaccinees had a 5.96-fold (95% CI, 4.85 to 7.33) increased risk for breakthrough infection and a 7.13-fold (95% CI, 5.51 to 9.21) increased risk for symptomatic disease. SARS-CoV-2-naïve vaccinees were also at a greater risk for COVID-19-related-hospitalizations compared to those that were previously infected.ConclusionsThis study demonstrated that natural immunity confers longer lasting and stronger protection against infection, symptomatic disease and hospitalization caused by the Delta variant of SARS-CoV-2, compared to the BNT162b2 two-dose vaccine-induced immunity. Individuals who were both previously infected with SARS-CoV-2 and given a single dose of the vaccine gained additional protection against the Delta variant.
Immune and malignant cell phenotypes of ovarian cancer are determined by distinct mutational processes
Authors: Vázquez-García Ignacio , Uhlitz Florian , Ceglia Nicholas , Lim Jamie L.P. , Wu Michelle , Mohibullah Neeman , Ruiz Arvin Eric B. , Boehm Kevin M. , Bojilova Viktoria , Fong Christopher J. , Funnell Tyler , Grewal Diljot , Havasov Eliyahu , Leung Samantha , Pasha Arfath , Patel Druv M. , Pourmaleki Maryam , Rusk Nicole , Shi Hongyu , Vanguri Rami , Williams Marc J. , Zhang Allen W. , Broach Vance , Chi Dennis , Da Cruz Paula Arnaud , Gardner Ginger J. , Kim Sarah H. , Lennon Matthew , Roche Kara Long , Sonoda Yukio , Zivanovic Oliver , Kundra Ritika , Viale Agnes , Derakhshan Fatemeh N. , Geneslaw Luke , Maroldi Ana , Nunez Rahelly , Pareja Fresia , Stylianou Anthe , Vahdatinia Mahsa , Bykov Yonina , Grisham Rachel N. , Liu Ying L. , Lakhman Yulia , Nikolovski Ines , Kelly Daniel , Gao Jianjiong , Schietinger Andrea , Hollmann Travis J. , Bakhoum Samuel F. , Soslow Robert A. , Ellenson Lora H. , Abu-Rustum Nadeem R. , Aghajanian Carol , Friedman Claire F. , McPherson Andrew , Weigelt Britta , Zamarin Dmitriy , Shah Sohrab P. 
Published: August 2021

ABSTRACTHigh-grade serous ovarian cancer (HGSOC) is an archetypal cancer of genomic instability patterned by distinct mutational processes, intratumoral heterogeneity and intraperitoneal spread. We investigated determinants of immune recognition and evasion in HGSOC to elucidate co- evolutionary processes underlying malignant progression and tumor immunity. Mutational processes and anatomic sites of tumor foci were key determinants of tumor microenvironment cellular phenotypes, inferred from whole genome sequencing, single-cell RNA sequencing, digital histopathology and multiplexed immunofluorescence of 160 tumor sites from 42 treatment-naive HGSOC patients. Homologous recombination-deficient (HRD)-Dup (BRCA1 mutant-like) and HRD- Del (BRCA2 mutant-like) tumors harbored increased neoantigen burden, inflammatory signaling and ongoing immunoediting, reflected in loss of HLA diversity and tumor infiltration with highly- differentiated dysfunctional CD8+ T cells. Foldback inversion (FBI, non-HRD) tumors exhibited elevated TGFβ signaling and immune exclusion, with predominantly naive/stem-like and memory T cells. Our findings implicate distinct immune resistance mechanisms across HGSOC subtypes which can inform future immunotherapeutic strategies.HIGHLIGHTSMulti-region, multi-modal profiling of malignant and immune cell phenotypes in ovarian cancerAnatomic site specificity is a determinant of cancer cell and intratumoral immune phenotypesTumor mutational processes impact mechanisms of immune control and immune evasionSpatial topology of HR-deficient tumors is defined by immune interactions absent from immune inert HR-proficient subtypes
Microplastic consumption induces inflammatory signatures in the colon and prolongs a viral arthritis
Authors: Rawle Daniel J. , Dumenil Troy , Tang Bing , Bishop Cameron , Yan Kexin , Le Thuy T. , Suhrbier Andreas 
Published: August 2021

ABSTRACTGlobal microplastic (MP) contamination and the effects on the environment are well described. However, the potential for MP consumption to affect human health remains controversial. Mice consuming ≈80 µg/kg/day of 1 µm polystyrene MPs via their drinking water for a month showed no weight loss, nor were MPs detected in organs. The microbiome was also unchanged. MP consumption did lead to small transcriptional changes in the colon suggesting plasma membrane perturbations and mild inflammation. Mice were challenged with the arthritogenic chikungunya virus, with MP consumption leading to a significantly prolonged arthritic foot swelling that was associated with elevated Th1, NK cell and neutrophil signatures. Immunohistochemistry also showed a significant increase in the ratio of neutrophils to monocyte/macrophages. The picture that emerges is reminiscent of enteropathic arthritis, whereby perturbations in the colon are thought to activate innate lymphoid cells that caninter aliamigrate to joint tissues to promote inflammation.
Spatial transcriptomics reveals antiparasitic targets associated with essential behaviors in the human parasiteBrugia malayi
Authors: Airs Paul M. , Vaccaro Kathy , Gallo Kendra J. , Dinguirard Nathalie , Heimark Zachary W. , Wheeler Nicolas J. , He Jiaye , Weiss Kurt R. , Schroeder Nathan E. , Huisken Jan , Zamanian Mostafa 
Published: August 2021

ABSTRACTLymphatic filariasis (LF) is a chronic debilitating neglected tropical disease (NTD) caused by mosquito-transmitted nematodes that afflicts over 60 million people. Control of LF relies on routine mass drug administration with antiparasitics that clear circulating larval parasites but are ineffective against adults. The development of effective adulticides is hampered by a poor understanding of the processes and tissues driving parasite survival in the host. The adult filariae head region contains essential tissues that control parasite feeding, sensory, secretory, and reproductive behaviors, which express promising molecular substrates for the development of antifilarial drugs, vaccines, and diagnostics. We have adapted spatial transcriptomic approaches to map gene expression patterns across these prioritized but historically intractable head tissues. Spatial and tissue-resolved data reveal distinct biases in the origins of known drug targets and secreted antigens. These data were used to identify potential new drug and vaccine targets, including putative hidden antigens expressed in the alimentary canal, and to spatially associate receptor subunits belonging to druggable families. Spatial transcriptomic approaches provide a powerful resource to aid gene function inference and seed antiparasitic discovery pipelines across helminths of relevance to human and animal health.
Interleukin-11 plays a key role in human and mouse alcohol-related liver disease
Authors: Effenberger Maria , Grabherr Felix , Schaefer Benedikt , Grander Christoph , Mayr Lisa , Schwärzler Julian , Enrich Barbara , Moser Patrizia , Fink Julia , Pedrini Alisa , Jaschke Nikolai , Freund Martin , Loizides Alexander , Bale Reto , Putzer Daniel , Widjaja Anissa A , Schafer Sebastian , Cook Stuart A , Zoller Heinz , Oberhuber Georg , Adolph Timon E , Tilg Herbert 
Published: August 2021

AbstractBackgroundAlcoholic hepatitis (AH) reflects acute exacerbation of alcoholic liver disease (ALD) and is a growing healthcare burden worldwide with limited treatment options. Interleukin-11 (IL-11) is a pro-fibrotic, pro-inflammatory cytokine with increasingly recognized toxicities in parenchymal and epithelial cells.AimThe aim of this study was to explore the prognostic value of IL-11 serum levels in patients suffering from AH and cirrhosis of various etiology and to understand the role of IL-11 in experimental ALD.MethodsIL-11 serum concentration and tissue expression was determined in a cohort comprising 50 patients with AH, 110 patients with cirrhosis and 19 healthy volunteers. Findings were replicated in an independent patient cohort including 186 patients. Ethanol-fed wildtype mice were treated with a neutralizing murine IL-11 receptor-antibody (anit-IL11RA) and thereafter examined for severity signs and markers of ALD.ResultsHuman IL-11 serum concentration and liver tissue expression increased with severity of liver disease and were most pronounced in AH. In a multivariate Cox-regression, a serum level above 6.4 picograms/milliliter was a MELD independent risk factor for transplant-free liver disease survival in patients with compensated and decompensated cirrhosis. Findings were confirmed in an independent cohort. In mice, severity of alcohol-induced liver inflammation was positively correlated to enhanced hepatic IL-11 expression. Pretreatment with a neutralizing anti-IL11RA inhibited hepatic inflammation and mice were protected from ethanol-induced liver injury. In comparison to IgG-control, ethanol-fed mice treated with anti-IL11RA showed decreased steatosis, hepatic neutrophil infiltration, and expression of pro-inflammatory cytokines.ConclusionIL-11 plays a crucial role in the pathogenesis of ALD and could serve as an independent prognostic factor for transplant-free survival. Blocking IL-11 signaling might be a therapeutic option in human ALD, particularly AH.
24-nt phasiRNAs move from tapetal to meiotic cells in maize anthers
Authors: Zhou Xue , Huang Kun , Teng Chong , Abdelgawad Ahmed , Batish Mona , Meyers Blake C. , Walbot Virginia 
Published: August 2021

SummaryIn maize, 24-nt phased, secondary small interfering RNAs (phasiRNAs) are abundant in meiotic stage anthers, but their distribution and functions are not precisely known.Using laser capture microdissection, we analyzed tapetal cells, meiocytes, and other somatic cells at several stages of anther development to establish the timing of 24-PHAS precursor transcripts and the 24-nt phasiRNA products.By integrating RNA and small RNA profiling plus single-molecule and small RNA FISH (smFISH or sRNA-FISH) spatial detection, we demonstrate that the tapetum is the primary site of 24-PHAS precursor and Dcl5 transcripts and the resulting 24-nt phasiRNAs. Interestingly, 24-nt phasiRNAs accumulate in all cell types, with the highest levels in meiocytes, followed by tapetum.Our data support the conclusion that 24-nt phasiRNAs are mobile from tapetum to meiocytes and to other somatic cells. We discuss possible roles for 24-nt phasiRNAs in anther cell types.