bluuebunny/crossref_metadata_2025_split huggingface dataset:
Flu Induced Acute Chest Syndrome in Sickle Cell Disease Mice
Authors: Kaminski Tomasz Waldemar , Katoch Omika , Sundd Prithu 
Published: December 2023

Background: Sickle cell disease (SCD) affects over ~8 million people world-wide. Acute chest syndrome, a type of acute lung injury (ALI) is a major cause of mortality among SCD patients. Flu is an acute respiratory disease primarily caused by the influenza A virus (IAV), which is typically a self-resolving upper airway inflammation. However, epidemiological evidence suggests that flu can result in severe ACS in SCD patients. Although flu associates with a 50-fold higher risk of ICU admission among SCD than non-SCD humans, the etiological mechanism underlying the flu severity in SCD remains unknown.
Aim: To determine whether a mild dose of IAV promotes severe lung injury in SCD mice.
Methods: We have developed a model of A/PR/8/34 (H1N1) IAV induced respiratory infection in knock-in, humanized SCD mice. Mice were intranasally inoculated with a mild dose of IAV. The body weight was measured every day for three weeks after intranasal IAV administration followed by assessment of lung injury at day 10 and 14 post infection. Severity of lung injury was evaluated using histological scoring and oxygen saturation measurements. Real-time intravital ( in vivo) multi-photon-excitation fluorescence microscopy (MPE) was used to assess thrombo-inflammation and vascular leakage in the lung of mice at 10 and 14 days post IAV-infection.
Results: Over the first 8 days post-IAV infection, both SCD and control mice manifested comparable levels of mild lung injury and a mild drop in body weight (15%). Unlike the control mice that started to recover, the lung injury and drop in body weight continued to worsen in SCD mice at 8-10 days post IAV infection. By day 14 post IAV infection, the lung injury was resolved and body weight was recovered in control mice, while SCD mice still manifested severe lung injury and ~20% drop in body weight. Intravital lung microscopy revealed large areas with vascular occlusion, ischemia, neutrophil infiltration and vascular leakage in the lung of SCD mice 10 days post infection, however, such pathophysiology was rarely present in the lung of control mice at 10 days post infection.
Conclusions: Our current findings are the first to suggest that the inflammatory milieu in SCD mice promotes a severe non-resolving ALI following an IAV infection, which otherwise leads to a mild self-resolving lung inflammation in control mice.
Neurocognitive Improvement with Hydroxyurea Therapy in Children with Sickle Cell Anemia in Uganda: Interim Analysis at Month 18
Authors: Naggayi Shubaya Kasule , Kalibala Dennis , Opoka Robert , Rosano Caterina , Munube Deogratias , Kasirye Phillip , Mupere Ezekiel , Mboizi Vincent , Ssenkusu John , Green Nancy S. , Idro Richard , Bangirana Paul 
Published: December 2023

Introduction: Cerebrovascular injury can lead to neurocognitive impairment in children with sickle cell anemia (SCA). The prospective impact of hydroxyurea therapy on neurocognitive function has not been previously reported in a large sample of children with SCA in sub-Saharan Africa. We assessed the impact of hydroxyurea therapy at the trial's18-month midpoint on neurocognitive function compared to baseline assessments and to non-SCA controls.
Methods: A sample of267 children with SCA, ages 3 to 9 years, were randomly selected for screening and enrollment from eligible patients who attended the Mulago Hospital Sickle Cell Clinic (MHSCC). BRAIN SAFE II is an open label hydroxyurea treatment trial with escalation to maximal tolerated dose. Primary outcomes are stroke, stroke risk and neurocognitive assessment. Controls were aged 3 to 12 years and siblings/relatives of participants with SCA.Attention, cognition and executive function were assessed for all participants by age-appropriate neurocognitive testing. Controlsestablished test z-scores for each age. Baseline (month 0) SCA group z-scores were compared to the controls and to the SCA sample at trial month 18.
Results: At trial baseline, SCA trial participants (n=267) were younger than the control group (mean age 5.1±1.7 vs. 7.1± 3.9 years, p&lt;0.001), had lower weight-for-age ( p=0.03) and had similar socio-economic score and caregiver age and educational attainment. Participants had lower z-scores in attention (p&lt;0.001) and neurocognitive ability (p&lt;0.001), and in executive function ( p=0.001) in a total of 15 of 17 subtests. After 18 months of hydroxyurea therapy (mean dose 25.4mg/kg) for all active SCA participants (95.1%) (n=254), significant improvements in z-scores were seen at 18 months in attention ( p&lt;0.001), all 4 subtests for cognitive ability ( p&lt;0.001) and in 3 of 6 subtests of executive function ( p=0.003 to &lt;0.001).
Conclusion: After 18 months of hydroxyurea therapy reaching MTD dosing, children showed significant improvements in attention and cognition, with more modest improvements in executive function. Their scores moved closer to those from non-SCA controls in most subtests. These findings suggest that hydroxyurea therapy may play an important role in enhancing overall neurocognitive function in children with SCA. Trial procedures are ongoing to assess the effects from longer-term therapy.
Racial Disparities in Hospital Outcomes of Autologous Stem Cell Transplantation for Multiple Myeloma: A Comparative NIS 2016 to 2020 Database Study
Authors: Neupane Niraj , Srivastava Arnav , Sanjeevi Aditya , Agrawal Shubham , Mahmoud Amir , Shah Anish , Budhathoki Pravash , Kharel Himal , Joshi Utsav , Dhakal Binod 
Published: December 2023

Objective:
Due to the paucity of data and the difference in-hospital outcomes in the two most common races in America remains controversial. This study aims to compare hospital outcomes in multiple myeloma patients undergoing autologous stem cell transplantation (ASCT) between White and Black patients using data from the National Inpatient Sample (NIS) from 2016 to 2020.
Methods:
A retrospective analysis of the NIS database was conducted using International Classification of Diseases (ICD-10) codes to identify patients who underwent ASCT for multiple myeloma. STATA version MP14.2 was used for analysis. We used Fischer's exact test to compare proportions, the student's t-test to compare continuous variables, and multivariate regression analysis to calculate the adjusted odds ratio after controlling age, gender, primary payer, and CCI. Following are included in transplant complications (transplant rejection, failure, transplant infection).
Results:
Among 31,389 hospitalizations, 19,065 (60.74%) were whites, and 6,110 (19.47%) were blacks. The mean age was 62 in whites and 59 in blacks (P &lt; 0.001). Most patients were male, constituting 59.46% among Whites and 71.11% among Blacks. A significantly higher proportion of blacks had comorbidities compared to whites, including CKD (18.9% vs. 14.98%), diabetes mellitus (25.94% vs. 14.29%), obesity (16.35% vs. 11.6%), and mean Charlson Comorbidity Index (2.51 vs. 2.42, P &lt; 0.001). On multivariate analysis compared to whites, blacks had a non-significant difference in the risk of acute kidney injury (adjusted odds ratio [AOR]: 0.94, 95% confidence interval [CI]: 0.76-1.17, P =0.58), cardiac arrest (AOR: 0.71, 95% CI: 0.16-3.20, P = 0.71), and blood transfusion (AOR: 1.11, 95% CI: 0.89-1.37, P = 0.36). Additionally, there was no significant difference in the average length (16.53 vs. 16.52, P = 0.85) and total cost ($195,971 vs. $196,300, P = 0.76) of hospital stay between blacks and whites. However, blacks had significantly lower transplant complications (AOR: 0.56, 95% CI: 0.37-0.87, P = 0.01), ICU admission (AOR: 0.58, 95% CI: 0.35-0.97, P = 0.04) and in-hospital mortality (AOR: 0.28, 95% CI: 0.09-0.91, P = 0.03) compared to whites.
Conclusion:
According to our study, blacks who underwent ASCT for multiple myeloma had better outcomes than Whites. Despite having a higher mean age and more comorbidities, this finding emphasizes the importance of conducting additional research and providing personalized interventions to enhance patient outcomes. It also suggests the potential for more black Americans to undergo ASTCT and benefit from it while avoiding delays and improving overall survival rates.
Efficacy and Safety of Isavuconazole in the Treatment of Invasive Fungal Disease in Patients with Hematological Disorders
Authors: Pan Pan , Pang Aiming , Jiang Erlie 
Published: December 2023

Objective: Invasive fungal disease (IFD) poses a significant threat to patients suffering from hematological disorders with high morbidity and mortality. isavuconazole has shown promising efficacy and safety in treating IFD caused by various pathogens including but not limited to Aspergillus and Mucor species in the previous studies. Thus, this retrospective single-arm case analysis study was conducted to evaluate the efficacy and safety of isavuconazole in patients with hematological disorders.
Method: This study included 12 patients diagnosed with IFD (including proven/probable/possible IFD) between August 2022 and March 2023 who underwent isavuconazole treatment for a minimum duration of 7 days. Only patients who received itraconazole monotherapy were involved, with 4 of whom taking initial treatment while 8 receiving isavuconazole as salvage therapy.
Results: Among the 12 patients included in this study, 7 were diagnosed with invasive aspergillosis and 5 were diagnosed with invasive mucormycosis. The median duration of isavuconazole treatment was 43.5 (11-86) days. At the conclusion of the treatment, the overall response (OR) rate for all patients was 67% (8/12), with a complete response rate of 42% (5/12) and a partial response rate of 25% (3/12). Among patients receiving initial treatment, 75% (3/4) patients achieved OR, while 62.5% (5/8) patients approached OR among those receiving salvage therapy. Importantly, only 1 patient experienced an increase in transaminases without demand to discontinuing isavuconazole treatment. Besides, no patients withdraw isavuconazole therapy due to other adverse reactions.
Conclusions: The study results demonstrate that isavuconazole exhibits both effect and safety in the treatment of invasive fungal disease in patients with hematological disorders. Furthermore, there are indications that initial antifungal treatment with itraconazole may yield higher response rates.
Macrophage Immune Checkpoint for Immunotherapy of Osteosarcoma
Authors: Suh Jin Kyung , Lee Jun Ah , Ko Yunmi , Park Meerim , Park Hyeon Jin 
Published: December 2023

Purpose: Macrophages account for the majority of immune cells infiltrated in sarcoma tissues. CD47 is a “don't eat me” signal expressed on the cell surface. We tested a feasibility of CD47, a macrophage immune checkpoint, for immunotherapy of osteosarcoma.
Methods: Twenty-four biopsy samples of osteosarcoma patients younger than 20 years were retrospectively analyzed for CD47 protein expression by immunohistochemistry. Relationships between CD47 expression and clinicopathologic characteristics were evaluated. Two osteosarcoma cell lines, KHOS/NP and MG63, were analyzed for CD47 expression by western blotting and flowcytometry. Efficacies of CD47 antibody (B6-H12) on the phagocytic activity of M1-type macrophages, differentiated from peripheral blood monocytes, were evaluated.
Results: CD47 protein was expressed in 5 (20.8%) samples and in three osteosarcoma cell lines. Positive staining for CD47 was related to the presence of metastasis at diagnosis ( P=0.04). Patients with tumors stained positive for CD47 tended to be older than those with tumors stained negative (16.5±6.2 years vs. 15.7±3.0 years, P=0.07). However, sex, tumor size, histologic response to preoperative chemotherapy were not associated with CD47 protein expression.
Influence of CD47 antibody (B6-H12) on cell viability varied between KHOS/NP and MG63 cells. Phagocytic activity of M1-type macrophage on osteosarcoma cells was higher in cells pretreated with CD47 antibody, compared to cells not treated (4.52% vs. 2.02%). However, CD47 antibody pretreatment did not influence the viability of osteosarcoma cells.
Conclusion: The association between CD47 protein expression on biopsy tissues and clinical characteristics suggest a possibility of CD47 as a new target for immunotherapy of osteosarcoma. As we observed a discrepancy between phagocytic activity and cell viability, future studies needs to focus on coupling the macrophage phagocytosis and effector T cell function.
Headaches during pregnancy and the risk of subsequent stroke
Authors: Nam Ki-Woong , Ha Sungyeon , Oh Min-Jeong , Oh Kyungmi , Kim Chi Kyung , Cho Geum Joon , Kim Young Seo , Bushnell Cheryl D. 
Published: December 2023

Abstract
Background
Primary headache disorder is a known risk factor for stroke in women and usually improves during the first trimester of pregnancy. However, despite this, some women develop headaches during pregnancy (G-HA), and the effect of this headache on subsequent stroke is unknown. In this study, we evaluated the association between G-HA and stroke after delivery in women.

Methods
Based on the Korean National Health Insurance Service database, we included women hospitalized for delivery between 2012 and 2013. G-HA was defined as a headache diagnosed during pregnancy. Primary outcome was any stroke that occurred during the observational periods from delivery to December 31, 2020. All diseases were identified based on data registered in the database using the International Classification of Disease-10th Revision-Clinical Modification codes.

Results
Of 906,187 pregnant women, G-HA was found in 56,813 (6.3%). During the observational periods, the G-HA ( +) group had a significantly higher risk of any stroke [adjusted hazard ratio (aHR) = 1.59, 95% confidence interval (CI): 1.30–1.95], ischemic stroke (aHR = 1.50, 95% CI: 1.12–2.01), hemorrhagic stroke (aHR = 1.63, 95% CI: 1.23–2.15), and intracerebral hemorrhage (aHR = 1.63, 95% CI: 1.19–2.23) than the G-HA (-) group. When analyzed considering the interaction with history of headache disorder, G-HA showed a significant association with hemorrhagic stroke, but lost its effect on ischemic stroke.

Conclusions
We demonstrated that G-HA was associated with subsequent stroke occurrence after delivery. However, the relationship between G-HA and ischemic stroke is mitigated by a history of pre-pregnancy headache disorder.
How to improve public transport usage in a medium-sized city: key factors for a successful bus system
Authors: Al Suleiman Shireen , Cortez Adriana , Monzón Andrés , Lara Antonio 
Published: December 2023

AbstractIn recent years, the promotion and use of public transport (PT) has become key to overcoming the negative impacts of mobility, such as traffic congestion, high pollution (GHG), and traffic accidents. Improving users’ satisfaction and increasing the attractiveness of buses play an essential role in increasing PT patronage. Whilst most of the literature concentrates on large and complex bus systems, less attention has been paid to European medium-sized cities, the region’s most common urban configuration, where public transport mainly depends on bus services. To this end, a survey campaign was conducted on passengers of urban buses in Oviedo, Spain, a representative medium-sized city. An Exploratory Factor Analysis (EFA) was used to identify key user satisfaction factors. In this case, three factors were the most important: comfort and information, service performance, and integration. That was complemented by the overall satisfaction (OS) with services, which was used for ranking the importance of the factors using an ordinal logistic regression model; comfort and information appear as the most important. These findings can serve bus operators to identify service-related attributes that need more attention or investment to increase users’ satisfaction and to make the service attractive to potential users.
GC heterogeneity reveals sequence-structures evolution of angiosperm ITS2
Authors: Liu Yubo , Liang Nan , Xian Qing , Zhang Wei 
Published: December 2023

Abstract
Background
Despite GC variation constitutes a fundamental element of genome and species diversity, the precise mechanisms driving it remain unclear. The abundant sequence data available for the ITS2, a commonly employed phylogenetic marker in plants, offers an exceptional resource for exploring the GC variation across angiosperms.

Results
A comprehensive selection of 8666 species, comprising 165 genera, 63 families, and 30 orders were used for the analyses. The alignment of ITS2 sequence-structures and partitioning of secondary structures into paired and unpaired regions were performed using 4SALE. Substitution rates and frequencies among GC base-pairs in the paired regions of ITS2 were calculated using RNA-specific models in the PHASE package. The results showed that the distribution of ITS2 GC contents on the angiosperm phylogeny was heterogeneous, but their increase was generally associated with ITS2 sequence homogenization, thereby supporting the occurrence of GC-biased gene conversion (gBGC) during the concerted evolution of ITS2. Additionally, the GC content in the paired regions of the ITS2 secondary structure was significantly higher than that of the unpaired regions, indicating the selection of GC for thermodynamic stability. Furthermore, the RNA substitution models demonstrated that base-pair transformations favored both the elevation and fixation of GC in the paired regions, providing further support for gBGC.

Conclusions
Our findings highlight the significance of secondary structure in GC investigation, which demonstrate that both gBGC and structure-based selection are influential factors driving angiosperm ITS2 GC content.
Association between living arrangements and health risk behaviors among the Hakka older adults in Fujian, China
Authors: Liu Xiaojun , Zhang Lingling , Chang Huajing , Chen Mengshi , Huang Yimin 
Published: December 2023

Abstract
Background
Behavioral lifestyles are important social determinants of health. The impact of changes in living arrangements on behavioral lifestyles is currently under-explored. This study aims to examine the association between living arrangements and health risk behaviors among the Hakka older adults.

Methods
Data were extracted from China’s Health-Related Quality of Life Survey for Older Adults 2018. Living arrangements were divided into five categories: living alone, living with spouse only, living with child, mixed habitation, and others. Five health risk behaviors, including unhealthy dietary patterns, drinking, smoking, irregular sleep practices, and physical inactivity were measured. Logistic regression analysis was used to assess the association between living arrangements and specific health risk behaviors, and generalized linear models were established to test the association between living arrangements and the number of health risk behaviors.

Results
A total of 1,262 Hakka older adults were included in this study. Compared to those living alone, those living with spouse only were less likely to have unhealthy dietary patterns (OR = 0.45, P < 0.05) and drinking (OR = 0.50, P < 0.05), those living with the child were less likely to experience unhealthy dietary patterns (OR = 0.35, P < 0.001), drinking (OR = 0.32, P < 0.001), smoking (OR = 0.49, P < 0.05), and physical inactivity (OR = 0.13, P < 0.01). Moreover, those who were living with child (β = -0.78, P < 0.001) or mixed habitation (β = -0.33, P < 0.05) tended to engage in fewer health risk behaviors than those living alone.

Conclusions
This study suggests significant differences in health risk behaviors among the Hakka older adults with different living arrangements. Living with the child could reduce the occurrence of health risk behaviors in the Hakka older adults and thus maintain their health status.
Effects of inappropriate cause-of-death certification on mortality from cardiovascular disease and diabetes mellitus in Tonga
Authors: Figueroa Carah A. , Linhart Christine L. , Dearie Catherine , Fusimalohi Latu E. , Kupu Sioape , Morrell Stephen L. , Taylor Richard J. 
Published: December 2023

Abstract
Background
Cardiovascular disease (CVD) and diabetes mellitus are major health issues in Tonga and other Pacific countries, although mortality levels and trends are unclear. We assess the impacts of cause-of-death certification on coding of CVD and diabetes as underlying causes of death (UCoD).

Methods
Tongan records containing cause-of-death data (2001–2018), including medical certificates of cause-of-death (MCCD), had UCoD assigned according to International Classification of Diseases 10th revision (ICD-10) coding rules. Deaths without recorded cause were included to ascertain total mortality. Diabetes and hypertension causes were reallocated from Part 1 of the MCCD (direct cause) to Part 2 (contributory cause) if potentially fatal complications were not recorded, and an alternative UCoD was assigned. Proportional mortality by cause based on the alternative UCoD were applied to total deaths then mortality rates calculated by age and sex using census/intercensal population estimates. CVD and diabetes mortality rates for unaltered and alternative UCoD were compared using Poisson regression.

Results
Over 2001–18, in ages 35–59 years, alternative CVD mortality was higher than unaltered CVD mortality in men (p = 0.043) and women (p = 0.15); for 2010–18, alternative versus unaltered measures in men were 3.3/103 (95%CI: 3.0–3.7/103) versus 2.9/103 (95%CI: 2.6–3.2/103), and in women were 1.1/103 (95%CI: 0.9–1.3/103) versus 0.9/103 (95%CI: 0.8–1.1/103). Conversely, alternative diabetes mortality rates were significantly lower than the unaltered rates over 2001–18 in men (p < 0.0001) and women (p = 0.013); for 2010–18, these measures in men were 1.3/103 (95%CI: 1.1–1.5/103) versus 1.9/103 (95%CI: 1.6–2.2/103), and in women were 1.4/103 (95%CI: 1.2–1.7/103) versus 1.7/103 (95%CI: 1.5–2.0/103). Diabetes mortality rates increased significantly over 2001–18 in men (unaltered: p < 0.0001; alternative: p = 0.0007) and increased overall in women (unaltered: p = 0.0015; alternative: p = 0.014).

Conclusions
Diabetes reporting in Part 1 of the MCCD, without potentially fatal diabetes complications, has led to over-estimation of diabetes, and under-estimation of CVD, as UCoD in Tonga. This indicates the importance of controlling various modifiable risks for atherosclerotic CVD (including stroke) including hypertension, tobacco use, and saturated fat intake, besides obesity and diabetes. Accurate certification of diabetes as a direct cause of death (Part 1) or contributory factor (Part 2) is needed to ensure that valid UCoD are assigned. Examination of multiple cause-of-death data can improve understanding of the underlying causes of premature mortality to better inform health planning.