bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toxic stress-specific cytoprotective responses regulate learned behavioral decisions in C. elegans
Authors: Hajdú Gábor , Gecse Eszter , Taisz István , Móra István , Sőti Csaba 
Published: February 2021

Abstract
Background
Recognition of stress and mobilization of adequate “fight-or-flight” responses is key for survival and health. Previous studies have shown that exposure of Caenorhabditis elegans to pathogens or toxins simultaneously stimulates cellular stress and detoxification responses and aversive behavior. However, whether a coordinated regulation exists between cytoprotective stress responses and behavioral defenses remains unclear.

Results
Here, we show that exposure of C. elegans to high concentrations of naturally attractive food-derived odors, benzaldehyde and diacetyl, induces toxicity and food avoidance behavior. Benzaldehyde preconditioning activates systemic cytoprotective stress responses involving DAF-16/FOXO, SKN-1/Nrf2, and Hsp90 in non-neuronal cells, which confer both physiological (increased survival) and behavioral tolerance (reduced food avoidance) to benzaldehyde exposure. Benzaldehyde preconditioning also elicits behavioral cross-tolerance to the structurally similar methyl-salicylate, but not to the structurally unrelated diacetyl. In contrast, diacetyl preconditioning augments diacetyl avoidance, weakens physiological diacetyl tolerance, and does not induce apparent molecular defenses. The inter-tissue connection between cellular and behavioral defenses is mediated by JNK-like stress-activated protein kinases and the neuropeptide Y receptor NPR-1. Reinforcement of the stressful experiences using spaced training forms stable stress-specific memories. Memory retrieval by the olfactory cues leads to avoidance of food contaminated by diacetyl and context-dependent behavioral decision to avoid benzaldehyde only if there is an alternative, food-indicative odor.

Conclusions
Our study reveals a regulatory link between conserved cytoprotective stress responses and behavioral avoidance, which underlies “fight-or-flight” responses and facilitates self-protection in real and anticipated stresses. These findings imply that variations in the efficiency of physiological protection during past episodes of stress might shape current behavioral decisions.

Graphical abstract
The Southern European Atlantic Diet and all-cause mortality in older adults
Authors: Carballo-Casla Adrián , Ortolá Rosario , García-Esquinas Esther , Oliveira Andreia , Sotos-Prieto Mercedes , Lopes Carla , Lopez-Garcia Esther , Rodríguez-Artalejo Fernando 
Published: February 2021

Abstract
Background
The Southern European Atlantic Diet (SEAD) is the traditional diet of Northern Portugal and North-Western Spain. Higher adherence to the SEAD has been associated with lower levels of some cardiovascular risk factors and reduced risk for myocardial infarction, but whether this translates into lower all-cause mortality is uncertain. We hence examined the association between adherence to the SEAD and all-cause mortality in older adults.

Methods
Data were taken from the Seniors-ENRICA-1 cohort, which included 3165 individuals representative of the non-institutionalized population aged ≥ 60 years in Spain. Food consumption was assessed with a validated diet history, and adherence to the SEAD was measured with an index comprising 9 food components: fresh fish, cod, red meat and pork products, dairy products, legumes and vegetables, vegetable soup, potatoes, whole-grain bread, and wine. Vital status was ascertained with the National Death Index of Spain. Statistical analyses were performed with Cox regression models and adjusted for the main confounders.

Results
During a median follow-up of 10.9 years, 646 deaths occurred. Higher adherence to the SEAD was associated with lower all-cause mortality (fully adjusted hazard ratio [95% confidence interval] per 1-SD increment in the SEAD score 0.86 [0.79, 0.94]; p-trend < 0.001). Most food components of the SEAD showed some tendency to lower all-cause mortality, especially moderate wine consumption (hazard ratio [95% confidence interval] 0.71 [0.59, 0.86]). The results were robust in several sensitivity analyses. The protective association between SEAD and all-cause death was of similar magnitude to that found for the Mediterranean Diet Adherence Screener (hazard ratio [95% confidence interval] per 1-SD increment 0.89 [0.80, 0.98]) and the Alternate Healthy Eating Index (0.83 [0.76, 0.92]).

Conclusions
Adherence to the SEAD is associated with a lower risk of all-cause death among older adults in Spain.
A case of congenital ureteral atresia causing rare upper and lower urinary tract manifestations in a puppy: a case report
Authors: Zalek Megan , Shah Rohan , Bolton Timothy 
Published: February 2021

AbstractBackgroundUreteral atresia is the congenital absence of a ureteral opening, resulting in a blind-ended ureter that fails to terminate at the urinary bladder. Consequently, severe hydroureter and hydronephrosis occur ipsilateral to the atresic ureter. However, hydronephrosis contralateral to severe hydroureter, although reported in humans, is not documented in the dog. Additionally, ureteral atresia has not been reported as a cause for lower urinary tract signs directly related to extramural urinary bladder compression. This report aims to describe these unique manifestations of this congenital urinary tract disease, as well as follow-up findings after successful treatment.Case presentationA 4-month-old male Husky puppy was evaluated for pollakiuria, stranguria, and urine dribbling of 1-month duration. During the physical examination, a mass was palpated in the mid-abdomen. Diagnostic imaging and cystoscopy findings were diagnostic for right-sided ureteral atresia with secondary hydroureter and hydronephrosis. The severe right hydroureter caused lower urinary tract signs and contralateral hydronephrosis secondary to regional compression of the left distal ureter and urinary bladder. A right-sided ureteronephrectomy was performed, resolving the stranguria and pollakiuria. Significant reduction in the contralateral (left) hydronephrosis also occurred.Clinical RelevanceUreteral atresia should be considered as a differential diagnosis for lower urinary tract signs and/or bilateral hydronephrosis in a young dog. Reporting this case expands our knowledge of congenital lower urinary tract disease and the etiology of their manifestations in dogs. Surgical resolution of the congenital ureteral abnormality can result in preservation of renal function in the contralaterally obstructed kidney.
Biomarker profiling for risk of future heart failure (HFpEF) development
Authors: Watson Chris J. , Gallagher Joe , Wilkinson Mark , Russell-Hallinan Adam , Tea Isaac , James Stephanie , O’Reilly James , O’Connell Eoin , Zhou Shuaiwei , Ledwidge Mark , McDonald Ken 
Published: February 2021

Abstract
Background
The purpose of this study was to investigate the utility of BNP, hsTroponin-I, interleukin-6, sST2, and galectin-3 in predicting the future development of new onset heart failure with preserved ejection fraction (HFpEF) in asymptomatic patients at-risk for HF.

Methods
This is a retrospective analysis of the longitudinal STOP-HF study of thirty patients who developed HFpEF matched to a cohort that did not develop HFpEF (n = 60) over a similar time period. Biomarker candidates were quantified at two time points prior to initial HFpEF diagnosis.

Results
HsTroponin-I and BNP at baseline and follow-up were statistically significant predictors of future new onset HFpEF, as was galectin-3 at follow-up and concentration change over time. Interleukin-6 and sST2 were not predictive of future development of new onset HFpEF in this study. Unadjusted biomarker combinations of hsTroponin-I, BNP, and galectin-3 could significantly predict future HFpEF using both baseline (AUC 0.82 [0.73,0.92]) and follow-up data (AUC 0.86 [0.79,0.94]). A relative-risk matrix was developed to categorize the relative-risk of new onset of HFpEF based on biomarker threshold levels.

Conclusion
We provided evidence for the utility of BNP, hsTroponin-I, and Galectin-3 in the prediction of future HFpEF in asymptomatic event-free populations with cardiovascular disease risk factors.
Vpx enhances innate immune responses independently of SAMHD1 during HIV-1 infection
Authors: Cingöz Oya , Arnow Nicolas D. , Puig Torrents Mireia , Bannert Norbert 
Published: February 2021

Abstract
Background
The genomes of HIV-2 and some SIV strains contain the accessory gene vpx, which carries out several functions during infection, including the downregulation of SAMHD1. Vpx is also commonly used in experiments to increase HIV-1 infection efficiency in myeloid cells, particularly in studies that investigate the activation of antiviral pathways. However, the potential effects of Vpx on cellular innate immune signaling is not completely understood. We investigated whether and how Vpx affects ISG responses in monocytic cell lines and MDMs during HIV-1 infection.

Results
HIV-1 infection at excessively high virus doses can induce ISG activation, although at the expense of high levels of cell death. At equal infection levels, the ISG response is potentiated by the presence of Vpx and requires the initiation of reverse transcription. The interaction of Vpx with the DCAF1 adaptor protein is important for the enhanced response, implicating Vpx-mediated degradation of a host factor. Cells lacking SAMHD1 show similarly augmented responses, suggesting an effect that is independent of SAMHD1 degradation. Overcoming SAMHD1 restriction in MDMs to reach equal infection levels with viruses containing and lacking Vpx reveals a novel function of Vpx in elevating innate immune responses.

Conclusions
Vpx likely has as yet undefined roles in infected cells. Our results demonstrate that Vpx enhances ISG responses in myeloid cell lines and primary cells independently of its ability to degrade SAMHD1. These findings have implications for innate immunity studies in myeloid cells that use Vpx delivery with HIV-1 infection.
What do service providers in Southern Ethiopia say about barriers to using youth-friendly sexual and reproductive health services for adolescents?: Qualitative study
Authors: Habtu Yitagesu , Kaba Mirgissa , Mekonnen Hussein 
Published: February 2021

Abstract
Background
In Ethiopia, the utilization coverage of adolescent-friendly health services (AFSRHs) ranged only from 9 to 55% and it was the lowest of all Sub-Saharan African countries in 2016. Little is known why adolescents were not accessing the existing services to the side of healthcare providers.

Objective
The aim of this study is to explore contextual perceived and actual barriers to accessing AFSRHs by adolescents in Southern Ethiopia.

Methods
Phenomenological study design supplemented with observation was used to explore perceived and actual barriers to accessing AFSRHs in 2020. Criterion sampling was used to select study participants. In-depth interviews with healthcare providers and non-specialist sexual and reproductive healthcare providers were conducted. Transcribed interviews and observations were imported to Open Code 4.02 for coding, categorizing, and creating themes. Finally, barriers to accessing existing services were explained using thematic analysis.

Results
The study explores contextual barriers to accessing sexual and reproductive health services in five emergent themes. According to providers’ points of view, the barriers include ranging from providers (e.g. poor providers’ competency), health facilities (e.g. supply constraints and unsupportive environment), adolescents (e.g. perceived lack of information and attitude towards SRHs), community (e.g. lack of parental and social support), and broader health system (e.g. poor implementation and multi-sectorial engagement).

Conclusion
As to providers, adolescents face multiple barriers to accessing youth friendly sexual and reproductive health services. Healthcare facilities and all levels of the healthcare system should implement varieties of approaches to increase access to the services for adolescents. Given the lack of progress in utilization of adolescents- youth friendly sexual and reproductive services, the existing strategy should be re-evaluated and new interventions at all levels of the healthcare system are needed. Moreover, implementation research is required at system level factors.
A qualitative exploration of contraceptive use and discontinuation among women with an unmet need for modern contraception in Kenya
Authors: Ontiri Susan , Mutea Lilian , Naanyu Violet , Kabue Mark , Biesma Regien , Stekelenburg Jelle 
Published: February 2021

Abstract
Background
Addressing the unmet need for modern contraception underpins the goal of all family planning and contraception programs. Contraceptive discontinuation among those in need of a method hinders the attainment of the fertility desires of women, which may result in unintended pregnancies. This paper presents experiences of contraceptive use, reasons for discontinuation, and future intentions to use modern contraceptives.

Methods
Qualitative data were collected in two rural counties in Kenya in 2019 from women with unmet need for contraception who were former modern contraceptive users. Additional data was collected from male partners of some of the women interviewed. In-depth interviews and focus group discussions explored previous experience with contraceptive use, reasons for discontinuation, and future intentionality to use. Following data collection, digitally recorded data were transcribed verbatim, translated, and coded using thematic analysis through an inductive approach.

Results
Use of modern contraception to prevent pregnancy and plan for family size was a strong motivator for uptake of contraceptives. The contraceptive methods used were mainly sourced from public health facilities though adolescents got them from the private sector. Reasons for discontinued use included side effects, method failure, peer influence, gender-based violence due to covert use of contraceptives, and failure within the health system. Five reasons were provided for those not willing to use in the future: fear of side effects, cost of contraceptive services, family conflicts over the use of modern contraceptives, reduced need, and a shift to traditional methods.

Conclusion
This study expands the literature by examining reasons for contraceptive discontinuation and future intentionality to use among women in need of contraception. The results underscore the need for family planning interventions that incorporate quality of care in service provision to address contraceptive discontinuation. Engaging men and other social influencers in family planning programs and services will help garner support for contraception, rather than focusing exclusively on women. The results of this study can inform implementation of family planning programs in Kenya and beyond to ensure they address the concerns of former modern contraception users.
Impacts of pine plantations on carbon stocks of páramo sites in southern Ecuador
Authors: Quiroz Dahik Carlos , Crespo Patricio , Stimm Bernd , Mosandl Reinhard , Cueva Jorge , Hildebrandt Patrick , Weber Michael 
Published: February 2021

AbstractBackgroundSince the 1990’s, afforestation programs in the páramo have been implemented to offset carbon emissions through carbon sequestration, mainly using pine plantations. However, several studies have indicated that after the establishment of pine plantations in grasslands, there is an alteration of carbon pools including a decrease of the soil organic carbon (SOC) pool. The aim of this study is to investigate the impact of the establishment of pine plantations on the carbon stocks in different altitudes of the páramo ecosystem of South Ecuador.ResultsAt seven locations within an elevational gradient from 2780 to 3760 m a.s.l., we measured and compared carbon stocks of three types of land use: natural grassland, grazed páramo, andPinus patulaSchlltdl. & Cham. plantation sites. For a more accurate estimation of pine tree carbon, we developed our own allometric equations. There were significant (p < 0.05) differences between the amounts of carbon stored in the carbon pools aboveground and belowground for the three types of land use. In most of the locations, pine plantations revealed the highest amounts of aboveground and belowground carbon (55.4 and 6.9 tC/ha) followed by natural grassland (23.1 and 2.7 tC/ha) and grazed páramo sites (9.1 and 1.5 tC/ha). Concerning the SOC pools, most of the locations revealed significant lower values of plantations’ SOC in comparison to natural grassland and grazed páramo sites. Higher elevation was associated with lower amounts of pines’ biomass.ConclusionsEven though plantations store high amounts of carbon, natural páramo grassland can also store substantial amounts above and belowground, without negatively affecting the soils and putting other páramo ecosystem services at risk. Consequently, plans for afforestation in the páramo should be assessed case by case, considering not only the limiting factor of elevation, but also the site quality especially affected by the type of previous land use.
Protein signature of human skin fibroblasts allows the study of the molecular etiology of rare neurological diseases
Authors: Hentschel Andreas , Czech Artur , Münchberg Ute , Freier Erik , Schara-Schmidt Ulrike , Sickmann Albert , Reimann Jens , Roos Andreas 
Published: February 2021

Abstract
Background
The elucidation of pathomechanisms leading to the manifestation of rare (genetically caused) neurological diseases including neuromuscular diseases (NMD) represents an important step toward the understanding of the genesis of the respective disease and might help to define starting points for (new) therapeutic intervention concepts. However, these “discovery studies” are often limited by the availability of human biomaterial. Moreover, given that results of next-generation-sequencing approaches frequently result in the identification of ambiguous variants, testing of their pathogenicity is crucial but also depending on patient-derived material.

Methods
Human skin fibroblasts were used to generate a spectral library using pH8-fractionation of followed by nano LC-MS/MS. Afterwards, Allgrove-patient derived fibroblasts were subjected to a data independent acquisition approach. In addition, proteomic signature of an enriched nuclear protein fraction was studied. Proteomic findings were confirmed by immunofluorescence in a muscle biopsy derived from the same patient and cellular lipid homeostasis in the cause of Allgrove syndrome was analysed by fluorescence (BODIPY-staining) and coherent anti-Stokes Raman scattering (CARS) microscopy.

Results
To systematically address the question if human skin fibroblasts might serve as valuable biomaterial for (molecular) studies of NMD, we generated a protein library cataloguing 8280 proteins including a variety of such linked to genetic forms of motoneuron diseases, congenital myasthenic syndromes, neuropathies and muscle disorders. In silico-based pathway analyses revealed expression of a diversity of proteins involved in muscle contraction and such decisive for neuronal function and maintenance suggesting the suitability of human skin fibroblasts to study the etiology of NMD. Based on these findings, next we aimed to further demonstrate the suitability of this in vitro model to study NMD by a use case: the proteomic signature of fibroblasts derived from an Allgrove-patient was studied. Dysregulation of paradigmatic proteins could be confirmed in muscle biopsy of the patient and protein-functions could be linked to neurological symptoms known for this disease. Moreover, proteomic investigation of nuclear protein composition allowed the identification of protein-dysregulations according with structural perturbations observed in the muscle biopsy. BODIPY-staining on fibroblasts and CARS microscopy on muscle biopsy suggest altered lipid storage as part of the underlying disease etiology.

Conclusions
Our combined data reveal that human fibroblasts may serve as an in vitro system to study the molecular etiology of rare neurological diseases exemplified on Allgrove syndrome in an unbiased fashion.
Emergency physician’s dispatch by a paramedic-staffed emergency medical communication centre: sensitivity, specificity and search for a reference standard
Authors: Chappuis Victor Nathan , Deham Hélène , Cottet Philippe , Gartner Birgit Andrea , Sarasin François Pierre , Niquille Marc , Suppan Laurent , Larribau Robert 
Published: February 2021

Abstract
Background
Some emergency medical systems (EMS) use a dispatch centre where nurses or paramedics assess emergency calls and dispatch ambulances. Paramedics may also provide the first tier of care “in the field”, with the second tier being an Emergency Physician (EP).
In these systems, the appropriateness of the decision to dispatch an EP to the first line at the same time as the ambulance has not often been measured. The main objective of this study was to compare dispatching an EP as part of the first line emergency service with the severity of the patient’s condition. The secondary objective was to highlight the need for a recognized reference standard to compare performance analyses across EMS.

Methods
This prospective observational study included all emergency calls received in Geneva’s dispatch centre between January 1st, 2016 and June 30th, 2019. Emergency medical dispatchers (EMD) assigned a level of risk to patients at the time of the initial call. Only the highest level of risk led to the dispatch of an EP. The severity of the patient’s condition observed in the field was measured using the National Advisory Committee for Aeronautics (NACA) scale. Two reference standards were proposed by dichotomizing the NACA scale. The first compared NACA≥4 with other conditions and the second compared NACA≥5 with other conditions. The level of risk identified during the initial call was then compared to the dichotomized NACA scales.

Results
97′861 assessments were included. Overall prevalence of sending an EP as first line was 13.11, 95% CI [12.90–13.32], and second line was 2.94, 95% CI [2.84–3.05]. Including NACA≥4, prevalence was 21.41, 95% CI [21.15–21.67], sensitivity was 36.2, 95% CI [35.5–36.9] and specificity 93.2 95% CI [93–93.4]. The Area Under the Receiver-Operating Characteristics curve (AUROC) of 0.7507, 95% CI [0.74734–0.75397] was acceptable. Looking NACA≥5, prevalence was 3.09, 95% CI [2.98–3.20], sensitivity was 64.4, 95% CI [62.7–66.1] and specificity 88.5, 95% CI [88.3–88.7]. We found an excellent AUROC of 0.8229, 95% CI [0.81623–0.82950].

Conclusion
The assessment by Geneva’s EMD has good specificity but low sensitivity for sending EPs. The dichotomy between immediate life-threatening and other emergencies could be a valid reference standard for future studies to measure the EP’s dispatching performance.