bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost-effectiveness of improvement strategies for reperfusion treatments in acute ischemic stroke: a systematic review
Authors: Nguyen Chi Phuong , Maas Willemijn J. , van der Zee Durk-Jouke , Uyttenboogaart Maarten , Buskens Erik , Lahr Maarten M. H. ,   on behalf of the CONTRAST consortium
Published: March 2023

Abstract
Background
Reducing delays along the acute stroke pathway significantly improves clinical outcomes for acute ischemic stroke patients eligible for reperfusion treatments. The economic impact of different strategies reducing onset to treatment (OTT) is crucial information for stakeholders in acute stroke management. This systematic review aimed to provide an overview on the cost-effectiveness of several strategies to reduce OTT.

Methods
A comprehensive literature search was conducted in EMBASE, PubMed, and Web of Science until January 2022. Studies were included if they reported 1/ stroke patients treated with intravenous thrombolysis and/or endovascular thrombectomy, 2/ full economic evaluation, and 3/ strategies to reduce OTT. The Consolidated Health Economic Evaluation Reporting Standards statement was applied to assess the reporting quality.

Results
Twenty studies met the inclusion criteria, of which thirteen were based on cost-utility analysis with the incremental cost-effectiveness ratio per quality-adjusted life year gained as the primary outcome. Studies were performed in twelve countries focusing on four main strategies: educational interventions, organizational models, healthcare delivery infrastructure, and workflow improvements. Sixteen studies showed that the strategies concerning educational interventions, telemedicine between hospitals, mobile stroke units, and workflow improvements, were cost-effective in different settings. The healthcare perspective was predominantly used, and the most common types of models were decision trees, Markov models and simulation models. Overall, fourteen studies were rated as having high reporting quality (79%-94%).

Conclusions
A wide range of strategies aimed at reducing OTT is cost-effective in acute stroke care treatment. Existing pathways and local characteristics need to be taken along in assessing proposed improvements.
The CARAMAL study could not assess the effectiveness of rectal artesunate in treating suspected severe malaria
Authors: Watson James A. , Peto Thomas J. , White Nicholas J. 
Published: March 2023

AbstractCARAMAL was a large observational study which recorded mortality in children with suspected severe malaria before and after the roll-out of rectal artesunate in Nigeria, Uganda and the Democratic Republic of the Congo. The results of CARAMAL have had a huge impact on public health policy leading to a World Health Organization moratorium on the roll-out of rectal artesunate. The conclusion reported in the abstract uses strong causal language, stating that “pre-referral RAS [rectal artesunate suppositories] had no beneficial effect on child survival”. We argue that this causal interpretation of the study results is not justified. Data from the CARAMAL study inform chiefly on the strengths and weaknesses of referral systems in these three countries and do not inform reliably as to the beneficial effect of providing access to a known life-saving treatment.
The prognostic value of gastroesophageal reflux disorder in interstitial lung disease related hospitalizations
Authors: Alqalyoobi Shehabaldin , Little Bertis Brit , Oldham Justin M. , Obi Ogugua Ndili 
Published: March 2023

Abstract
Background
Gastroesophageal reflux disease (GERD) is a common comorbidity in patients with interstitial lung disease (ILD). We built and validated a model using the national inpatient sample (NIS) database to assess the contributory role of GERD in ILD-related hospitalizations mortality.

Methods
In this retrospective analysis, we extracted ILD-related hospitalizations data between 2007 and 2019 from the NIS database. Univariable logistic regression was used for predictor selection. Data were split into the training and validation cohorts (0.6 and 0.4, respectively). We used decision tree analysis (classification and regression tree, CART) to create a predictive model to explore the role of GERD in ILD-related hospitalizations mortality. Different metrics were used to evaluate our model. A bootstrap-based technique was implemented to balance our training data outcome to improve our model metrics in the validation cohort. We conducted a variance-based sensitivity analysis to evaluate GERD's importance in our model.

Findings
The model had a sensitivity of 73.43%, specificity of 66.15%, precision of 0.27, negative predictive value (NPV) of 93.62%, accuracy of 67.2%, Matthews Correlation Coefficient (MCC) of 0.3, F1 score of 0.4, and area under the curve (AUC) for the receiver operating characteristic (ROC) curve of 0.76. GERD did not predict survival in our cohort. GERD contribution to the model was ranked the eleventh among twenty-nine variables included in this analysis (importance of 0.003, normalized importance of 5%). GERD was the best predictor in ILD-related hospitalizations who didn’t receive mechanical ventilation.

Interpretations
GERD is associated with mild ILD-related hospitalization. Our model-performance measures suggest overall an acceptable discrimination. Our model showed that GERD does not have a prognostic value in ILD-related hospitalization, indicating that GERD per se might not have any impact on mortality in hospitalized ILD patients.
Unmet healthcare needs and health inequalities in people with spinal cord injury: a direct regression inequality decomposition
Authors: Oña Ana , Athanasios Kyriakides , Tederko Piotr , Escorpizo Reuben , Arora Mohit , Sturm Christian , Yang Shujuan , Barzallo Diana Pacheco 
Published: March 2023

AbstractBackgroundInequality in health is a prevalent and growing concern among countries where people with disabilities are disproportionately affected. Unmet healthcare needs explain a large part of the observed inequalities between and within countries; however, there are other causes, many non-modifiable, that also play a role.AimThis article explores the difference in health across income levels in populations with spinal cord injury (SCI). SCI is of special interest in the study of health systems, as it is an irreversible, long-term health condition that combines a high level of impairment with subsequent comorbidities.MethodsWe estimated the importance of modifiable and non-modifiable factors that explain health inequalities through a direct regression approach. We used two health outcomes: years living with the injury and a comorbidity index. Data come from the International Spinal Cord Injury Survey (InSCI), which has individual data on people with SCI in 22 countries around the world. Due to the heterogeneity of the data, the results were estimated country by country.ResultsOn average, the results exhibit a prevalence of pro-rich inequalities, i.e., better health outcomes are more likely observed among high-income groups. For the years living with the injury, the inequality is mostly explained by non-modifiable factors, like the age at the time of the injury. In contrast, for the comorbidity index, inequality is mostly explained by unmet healthcare needs and the cause of the injury, which are modifiable factors.ConclusionsA significant portion of health inequalities is explained by modifiable factors like unmet healthcare needs or the type of accident. This result is prevalent in low, middle, and high-income countries, with pervasive effects for vulnerable populations like people with SCI, who, at the same time are highly dependent on the health system. To reduce inequity, it is important not only to address problems from public health but from inequalities of opportunities, risks, and income in the population.Highlights• Better health status is evident among high-income groups, which is reflected in pro-rich inequalities.• Age at the time of the injury is the most important factor to explain inequalities in years living with the injury.• Unmet health care needs are the most important factor to explain inequalities in comorbidities.• The inequality in health varies by country dependent upon socioeconomic factors.
Genetically engineered CXCR4-modified exosomes for delivery of miR-126 mimics to macrophages alleviate periodontitis
Authors: Luo Haotian , Chen Danying , Li Ruoyu , Li Runze , Teng Yungshan , Cao Yang , Zou Xuenong , Wang Weicai , Zhou Chen 
Published: March 2023

AbstractBiofilm-related diseases are a group of diseases that tolerate antimicrobial chemotherapies and therefore are refractory to treatment. Periodontitis, a non-device chronic biofilm disease induced by dental plaque, can serve as an excellent in vivo model to study the important effects of host factors on the biofilm microenvironment. Macrophage activity is one of the key factors that modulate the progression of inflammation-driven destruction in periodontitis; therefore it is an important host immunomodulatory factor. In this study, the reduction of microRNA-126 (miR-126) with the recruitment of macrophages in periodontitis was confirmed in clinical samples, and a strategy for targeted delivery of miR-126 to macrophages was explored. Exosomes overexpressing the C-X-C motif chemokine receptor 4 (CXCR4) loaded with miR-126 (CXCR4-miR126-Exo) was successfully constructed, which reduced off-target delivery to macrophages and regulated macrophages toward the anti-inflammatory phenotype. In vivo local injection of CXCR4-miR126-Exo into sites of periodontitis in rats effectively reduced bone resorption and osteoclastogenesis and inhibited the progression of periodontitis. These results provide new insights for designing novel immunomodulatory factor targeted delivery systems to treat periodontitis and other biofilm-related diseases.
Associations of alcohol consumption with breast tissue composition
Authors: Yaghjyan Lusine , Heng Yujing J. , Baker Gabrielle M. , Rosner Bernard A. , Tamimi Rulla M. 
Published: March 2023

Abstract
Background
We investigated the associations of alcohol with percentage of epithelium, stroma, fibroglandular tissue (epithelium + stroma), and fat in benign breast biopsy samples.

Methods
We included 857 cancer-free women with biopsy-confirmed benign breast disease within the Nurses’ Health Study (NHS) and NHSII cohorts. Percentage of each tissue was measured on whole slide images using a deep-learning algorithm and then log-transformed. Alcohol consumption (recent and cumulative average) was assessed with semi-quantitative food frequency questionnaires. Regression estimates were adjusted for known breast cancer risk factors. All tests were 2-sided.

Results
Alcohol was inversely associated with % of stroma and fibroglandular tissue (recent ≥ 22 g/day vs. none: stroma: β = − 0.08, 95% Confidence Interval [CI] − 0.13; − 0.03; fibroglandular: β = − 0.08, 95% CI − 0.13; − 0.04; cumulative ≥ 22 g/day vs. none: stroma: β = − 0.08, 95% CI − 0.13; − 0.02; fibroglandular: β = − 0.09, 95% CI − 0.14; − 0.04) and positively associated with fat % (recent ≥ 22 g/day vs. none: β = 0.30, 95% CI 0.03; 0.57; cumulative ≥ 22 g/day vs. none: β = 0.32, 95% CI 0.04; 0.61). In stratified analysis, alcohol consumption was not associated with tissue measures in premenopausal women. In postmenopausal women, cumulative alcohol use was inversely associated with % of stroma and fibroglandular tissue and positively associated with fat % (≥ 22 g/day vs. none: stroma: β = − 0.16, 95% CI − 0.28; − 0.07; fibroglandular: β = − 0.18, 95% CI − 0.28; − 0.07; fat: β = 0.61, 95% CI 0.01; 1.22), with similar results for recent alcohol use.

Conclusion
Our findings suggest that alcohol consumption is associated with smaller % of stroma and fibroglandular tissue and a greater % of fat in postmenopausal women. Future studies are warranted to confirm our findings and to elucidate the underlying biological mechanisms.
Tick-borne pathogens and body condition of cattle in smallholder rural livestock production systems in East and West Africa
Authors: Heylen Dieter J. A. , Kumsa Bersissa , Kimbita Elikira , Frank Mwiine Nobert , Muhanguzi Dennis , Jongejan Frans , Adehan Safiou Bienvenu , Toure Alassane , Aboagye-Antwi Fred , Ogo Ndudim Isaac , Juleff Nick , Crafford Dionne , Fourie Josephus , Labuchange Michel , Madder Maxime 
Published: March 2023

AbstractBackgroundThe majority of the African population lives in rural areas where they heavily depend on crop and livestock production for their livelihoods. Given their socio-economic importance, we initiated a standardized multi-country (Benin, Burkina Faso, Ghana, Nigeria, Ethiopia Tanzania and Uganda) surveillance study to assess the current status of important tick-borne haemoparasites (TBHPs) of cattle.MethodsWe assessed pathogen prevalences (Anaplasma marginale, Anaplasma centrale, Babesia bigemina, Babesia bovis, Ehrlichia ruminantium, andTheileria parva) in the blood of 6447 animals spread over fourteen districts (two districts per country). In addition, we screened for intrinsic (sex, weight, body condition) and extrinsic (husbandry, tick exposure) risk factors as predictors of infections with TBHPs.ResultsThere was a large macro-geographic variation observed inA. marginale, B. bigemina, B. bovisandE. ruminantiumprevalences. Most correlated with the co-occurrence of their specific sets of vector-competent ticks. Highest numbers of infected cattle were found in Ghana and Benin, and lowest in Burkina Faso. WhileT. parvawas seldomly found (Uganda only: 3.0%),A. marginalewas found in each country with a prevalence of at least 40%.Babesia bovisinfected individuals had lower body condition scores. Age (as estimated via body weight) was higher inA. marginaleinfected cattle, but was negatively correlated withB. bigeminaandE. ruminantiumprevalences.Ehrlichia ruminantiuminfection was more often found in males, andA. marginalemore often in transhumance farming. High levels of co-infection, especially the combinationA. marginale × B. bigemina, were observed in all countries, except for Uganda and Burkina Faso.Babesia bigeminawas more or less often observed than expected by chance, when cattle were also co-infected withE. ruminantiumorA. marginale, respectively.ConclusionsTick-borne pathogens of cattle are ubiquitous in African’s smallholder cattle production systems. Our standardized study will help a wide range of stakeholders to provide recommendations for TBHP surveillance and prevention in cattle, especially forB. boviswhich heavily impacts production and continues its spread over the African continent via the invasiveRhipicephalus microplustick.Graphical Abstract
Detection of Virulence and β-lactamase resistance genes of non-typhoidal Salmonella isolates from human and animal origin in Egypt "one health concern"
Authors: Diab Mohamed S. , Thabet Asmaa S. , Elsalam Mohamed Abd , Ewida Rania M. , Sotohy Sotohy A. 
Published: March 2023

Abstract
Background
Non-typhoidal Salmonella (NTS) is a major foodborne zoonotic pathogen worldwide. In the current study, Various NTS strains were isolated from (cows, milk and dairy products in addition to humans) in New Valley and Assiut Governorate, Egypt. NTS were firstly serotyped and tested by antibiotic sensitivity test. Secondly, some virulence genes and Antibiotic resistance genes have been identified by using PCR. Finally, Phylogenesis was performed depending on the invA gene, for two S. typhimurium isolates (one of animal origin and the other of human origin for evaluating zoonotic potential).

Results
Out of 800 examined samples, the total number of isolates was 87 (10.88%), which were classified into 13 serotypes, with the most prevalent being S. Typhimurium and S. enteritidis. Both bovine and human isolates showed the highest resistance to clindamycin and streptomycin, with 90.80% of the tested isolates exhibiting MDR. The occurrence of the invA gene was 100%, while 72.22%, 30.56%, and 94.44% of the examined strains were positive for stn, spvC, and hilA genes, respectively. Additionally, blaOXA-2 was detected in 16.67% (6/ 36) of the tested isolates, while blaCMY-1 was detected in 30.56% (11of 36) of the tested isolates. Phylogenesis revealed a high degree of similarity between the two isolates.

Conclusions
The high occurrence of MDR strains of NTS in both human and animal samples with high degree of genetic similarity, shows that cows, milk and milk product may be a valuable source of human infection with NTS and interfere with treatment procedures.
Isolation and multilocus sequence typing of Borrelia burgdorferi from Ixodes scapularis collected from dogs in Ontario, Canada
Authors: Nichol Grace K. , Weese J. Scott , Clow Katie M. 
Published: March 2023

Abstract
Objective
To identify the multilocus sequence typing (MLST) sequence types of Borrelia burgdorferi from Ixodes scapularis in Ontario, Canada.

Results
One hundred and eighty-five I. scapularis ticks were submitted from 134 dogs via participating clinics from April 1, 2019, to March 31, 2020. Seventeen MLST sequence types of B. burgdorferi were detected from fifty-eight cultured isolates from 21 ticks. The most common MLST sequence types were 12 and 16. Mixed infections of two MLST sequence types were detected in four ticks. Three sequence types (48, 317, 639) were new detections in Ontario.
Clinical outcomes of dupilumab therapy in chronic rhinosinusitis with nasal polyps in a Canadian tertiary care rhinology practice
Authors: Grose Elysia , Li Alyssa Y. , Lee John M. 
Published: March 2023

Abstract
Background
In 2020, dupilumab became the first monoclonal antibody therapy to be approved by Health Canada for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP). The primary aim of this study was to characterize the outcomes in an initial cohort of patients with CRSwNP who have undergone dupilumab therapy.

Methods
A retrospective study was conducted of patients with CRSwNP who were treated with dupilumab. Demographic information, comorbidities, number of previous surgeries, and insurance information were collected. The primary outcome were changes in the sinonasal outcome test (SNOT-22) scores from baseline to timepoints after receiving dupilumab.

Results
Forty-eight patients were considered for dupilumab therapy, and 27 (56%) received coverage or were able to fund the medication independently. Patients waited an average of 3.6 months to obtain access to the medication. The mean age of the patients was 43. Forty-one percent (11/27) of patients had aspirin exacerbated respiratory disease, and 96% (26/27) had a diagnosis of asthma. The mean length of time on dupilumab was 12.1 months. The baseline SNOT-22 score was 60.6. The mean decrease at 1 month, 3 months, 6 months, and 12 months after starting dupilumab was 8.8, 26.5, 42.8, and 33.8, respectively. There were no serious adverse events.

Conclusion
Patients treated with dupilumab in a Canadian tertiary care rhinology clinic demonstrated substantial clinical improvement as measured by disease-specific sinonasal outcomes. Further studies are needed to determine the longer-term effectiveness and adverse event profile of this novel therapy.
N-methyl-d-aspartate receptors induce M1 polarization of macrophages: Feasibility of targeted imaging in inflammatory response in vivo
Authors: Jeon Hui-Jeon , Byun Jun-Kyu , Lee Sang Bong , Son Kwang Hee , Lim Ji-Youn , Lee Da Sol , Kim Kil Soo , Park Jin Woo , Shin Gyeong Rim , Kim Ye Jin , Jin Jonghwa , Kim Daehoon , Kim Dong-Ho , Yu Ji Hoon , Choi Yeon-Kyung , Park Keun-Gyu , Jeon Yong Hyun 
Published: March 2023

Abstract
Background
N-methyl-d-aspartate receptors (NMDARs) are considered to be involved in several physiological and pathophysiological processes in addition to the progression of neurological disorders. However, how NMDARs are involved in the glycolytic phenotype of M1 macrophage polarization and the possibility of using them as a bio-imaging probe for macrophage-mediated inflammation remain unclear.

Methods
We analyzed cellular responses to NMDAR antagonism and small interfering RNAs using mouse bone marrow-derived macrophages (BMDMs) treated with lipopolysaccharide (LPS). An NMDAR targeting imaging probe, N-TIP, was produced via the introduction of NMDAR antibody and the infrared fluorescent dye FSD Fluor™ 647. N-TIP binding efficiency was tested in intact and LPS-stimulated BMDMs. N-TIP was intravenously administered to mice with carrageenan (CG)- and LPS-induced paw edema, and in vivo fluorescence imaging was conducted. The anti-inflammatory effects of dexamethasone were evaluated using the N-TIP-mediated macrophage imaging technique.

Results
NMDARs were overexpressed in LPS-treated macrophages, subsequently inducing M1 macrophage polarization. Mechanistically, NMDAR-mediated Ca2+ accumulation resulted in LPS-stimulated glycolysis via upregulation of PI3K/AKT/mTORC1 signaling. In vivo fluorescence imaging with N-TIP showed LPS- and CG-induced inflamed lesions at 5 h post-inflammation, and the inflamed lesions could be detected until 24 h. Furthermore, our N-TIP-mediated macrophage imaging technique helped successfully visualize the anti-inflammatory effects of dexamethasone in mice with inflammation.

Conclusion
This study demonstrates that NMDAR-mediated glycolysis plays a critical role in M1 macrophage-related inflammation. Moreover, our results suggest that NMDAR targeting imaging probe may be useful in research on inflammatory response in vivo.