bluuebunny/crossref_metadata_2025_split huggingface dataset:
Geographic accessibility and hospital competition for emergency blood transfusion services in Bungoma, Western Kenya
Authors: Mumo Eda , Agutu Nathan O. , Moturi Angela K. , Cherono Anitah , Muchiri Samuel K. , Snow Robert W. , Alegana Victor A. 
Published: March 2023

Abstract
Background
Estimating accessibility gaps to essential health interventions helps to allocate and prioritize health resources. Access to blood transfusion represents an important emergency health requirement. Here, we develop geo-spatial models of accessibility and competition to blood transfusion services in Bungoma County, Western Kenya.

Methods
Hospitals providing blood transfusion services in Bungoma were identified from an up-dated geo-coded facility database. AccessMod was used to define care-seeker’s travel times to the nearest blood transfusion service. A spatial accessibility index for each enumeration area (EA) was defined using modelled travel time, population demand, and supply available at the hospital, assuming a uniform risk of emergency occurrence in the county. To identify populations marginalized from transfusion services, the number of people outside 1-h travel time and those residing in EAs with low accessibility indexes were computed at the sub-county level. Competition between the transfusing hospitals was estimated using a spatial competition index which provided a measure of the level of attractiveness of each hospital. To understand whether highly competitive facilities had better capacity for blood transfusion services, a correlation test between the computed competition metric and the blood units received and transfused at the hospital was done.

Results
15 hospitals in Bungoma county provide transfusion services, however these are unevenly distributed across the sub-counties. Average travel time to a blood transfusion centre in the county was 33 min and 5% of the population resided outside 1-h travel time. Based on the accessibility index, 38% of the EAs were classified to have low accessibility, representing 34% of the population, with one sub-county having the highest marginalized population. The computed competition index showed that hospitals in the urban areas had a spatial competitive advantage over those in rural areas.

Conclusion
The modelled spatial accessibility has provided an improved understanding of health care gaps essential for health planning. Hospital competition has been illustrated to have some degree of influence in provision of health services hence should be considered as a significant external factor impacting the delivery, and re-design of available services.
Multifunctional porous poly (L-lactic acid) nanofiber membranes with enhanced anti-inflammation, angiogenesis and antibacterial properties for diabetic wound healing
Authors: Yu Hao , Li Yijia , Pan Yining , Wang Hongning , Wang Wei , Ren Xiaobin , Yuan Hang , Lv Ziru , Zuo Yijia , Liu Zhirong , Lin Wei , Yao Qingqing 
Published: March 2023

AbstractWith increased diabetes incidence, diabetic wound healing is one of the most common diabetes complications and is characterized by easy infection, chronic inflammation, and reduced vascularization. To address these issues, biomaterials with multifunctional antibacterial, immunomodulatory, and angiogenic properties must be developed to improve overall diabetic wound healing for patients. In our study, we prepared porous poly (L-lactic acid) (PLA) nanofiber membranes using electrospinning and solvent evaporation methods. Then, sulfated chitosan (SCS) combined with polydopamine-gentamicin (PDA-GS) was stepwise modified onto porous PLA nanofiber membrane surfaces. Controlled GS release was facilitated via dopamine self-polymerization to prevent early stage infection. PDA was also applied to PLA nanofiber membranes to suppress inflammation. In vitro cell tests results showed that PLA/SCS/PDA-GS nanofiber membranes immuomodulated macrophage toward the M2 phenotype and increased endogenous vascular endothelial growth factor secretion to induce vascularization. Moreover, SCS-contained PLA nanofiber membranes also showed good potential in enhancing macrophage trans-differentiation to fibroblasts, thereby improving wound healing processes. Furthermore, our in vitro antibacterial studies against Staphylococcus aureus indicated the effective antibacterial properties of the PLA/SCS/PDA-GS nanofiber membranes. In summary, our novel porous PLA/SCS/PDA-GS nanofiber membranes possessing enhanced antibacterial, anti-inflammatory, and angiogenic properties demonstrate promising potential in diabetic wound healing processes.
Acute subdural haematoma exacerbates cerebral blood flow disorder and promotes the development of intraoperative brain bulge in patients with severe traumatic brain injury
Authors: Zhang Shangming , Chen Qizuan , Xian Liang , Chen Yehuang , Wei Liangfeng , Wang Shousen 
Published: March 2023

Abstract
Background
Decompressive craniectomy (DC) is a routine procedure used for the treatment of severe traumatic brain injury (TBI) with concomitant acute subdural haematoma (SDH). However, certain patients are prone to developing malignant brain bulge during DC, which prolongs the operative time and worsens patient outcomes. Previous studies have shown that malignant intraoperative brain bulge (IOBB) may be associated with excessive arterial hyperaemia caused by cerebrovascular system disorders. Through a clinical retrospective analysis and prospective observations, we found that the cerebral blood flow of patients who possessed risk factors manifested high resistance and low flow velocity, which severely affected brain tissue perfusion and resulted in the occurrence of malignant IOBB. In the current literature, rat models of severe brain injury-associated brain bulge have rarely been reported.

Methods
To gain an in-depth understanding of cerebrovascular changes and the cascade of responses related to brain bulge, we introduced acute SDH into the Marmarou model for the preparation of a rat model of high intracranial pressure (ICP) to simulate the pathological conditions experienced by patients with severe brain injury.

Results
With the introduction of a 400-µL haematoma, significant dynamic changes occurred in ICP, mean arterial pressure, and relative blood perfusion rate of the cerebral cortical vessels. ICP increased to 56.9 ± 2.3 mmHg, mean arterial pressure showed reactive decrease, and the blood flow of cerebral cortical arteries and veins on the non-SDH-affected side decreased to < 10%. These changes could not fully recover even after DC. This resulted in generalised damage to the neurovascular unit and a lag effect to the venous blood reflux, which triggered malignant IOBB formation during DC.

Conclusion
An excessive increase in ICP causes cerebrovascular dysfunction and brings about a cascade of damage to brain tissue, which forms the basis for the development of diffuse brain swelling. The subsequent heterogeneous responses of the cerebral arteries and veins during craniotomy may be the main cause of primary IOBB. Clinicians should pay particular attention to the redistribution of CBF to various vessels when performing DC in patients with severe TBI.
How are adolescents engaged in obesity and chronic disease prevention policy and guideline development? A scoping review
Authors: Mandoh Mariam , Redfern Julie , Mihrshahi Seema , Cheng Hoi Lun , Phongsavan Philayrath , Partridge Stephanie R. 
Published: March 2023

Abstract
Background
Adolescent consumer engagement is widely accepted, with global calls to meaningfully involve adolescents for effective and tailored policy and guideline development. However, it is still unclear if and how adolescents are engaged. The aim of this review was to determine if and how adolescents meaningfully participate in policy and guideline development for obesity and chronic disease prevention.

Methods
A scoping review was conducted guided by the Arksey and O’Malley six stage framework. Official government websites for Australia, Canada, United Kingdom, and United States including intergovernmental organizations (World Health Organisation and United Nations) were examined. Universal databases Tripdatabase and Google advanced search were also searched. Current and published international and national obesity or chronic disease prevention policies, guidelines, strategies, or frameworks that engaged adolescents aged 10–24 years in meaningful decision-making during the development process were included. The Lansdown-UNICEF conceptual framework was used to define mode of participation.

Results
Nine policies and guidelines (n = 5 national, n = 4 international) engaged adolescents in a meaningful capacity, all focused on improving ‘health and well-being’. Demographic characteristics were poorly reported, still most ensured representation from disadvantaged groups. Adolescents were primarily engaged in consultative modes (n = 6), via focus groups and consultation exercises. Predominantly in formative phases e.g., scoping the topic or identifying needs (n = 8) and to a lesser extent in the final stage of policy and guideline development e.g., implementation or dissemination (n = 4). No policy or guideline engaged adolescents in all stages of the policy and guideline development process.

Conclusion
Overall, adolescent engagement in obesity and chronic disease prevention policy and guideline development is consultative and rarely extends throughout the entire development and implementation process.
Photon-counting CT of elbow joint fractures: image quality in a simulated post-trauma setting with off-center positioning
Authors: Sonnow Lena , Salimova Nigar , Behrendt Lea , Wacker Frank K. , Örgel Marcus , Plagge Jochen , Weidemann Friederike 
Published: March 2023

Abstract
Background
Photon-counting detector computed tomography (PCD-CT) has the potential to provide superior image quality compared to energy-integrating detector computed tomography (EID-CT). We compared the two systems for elbow imaging in off-center arm positioning, 90° flexion, and cast fixation in a simulated post-trauma setting.

Methods
The institutional review board approved the study protocol. In a cadaver study, an olecranon fracture was artificially created in ten whole arm specimens. Two different scanning positions were evaluated: (a) arm overhead; and (b) arm on top of the abdomen of a whole-body phantom. The ultra-high resolution mode with three dose protocols and two reconstruction kernels was applied. Two blinded radiologists independently evaluated fracture and trabecular bone delineation. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and cortical sharpness measurements were performed. Cohen κ correlations, Mann-Whitney U and Wilcoxon signed rank tests were used. A p value lower than 0.05 was considered statistically significant.

Results
Dose-equivalent PCD-CT scans were rated better for fracture and trabecular bone evaluation (p < 0.001). SNR, CNR, and cortical sharpness were higher for all diagnostic (Br76) PCD-CT images (p < 0.001). The arm position had less effect on image quality in the PCD-CT compared to the EID-CT. The use of a sharp bone kernel (Br89) improved image quality ratings for PCD-CT. In the low-dose scan mode, PCD-CT resulted in more diagnostic scans (75%) compared to EID-CT (19%).

Conclusions
PCD-CT provided superior objective and subjective image quality for fracture and trabecular bone structures delineation of the elbow compared to EID-CT in a typical post-trauma setting.

Key points
• Photon-counting detector computed tomography (PCD-CT) preserved high image quality in elbow imaging with off-center positions.
• PCD-CT was advantageous for bone evaluation in trauma elbows.
• PCD-CT ultra-high-resolution mode and very sharp reconstruction kernels facilitated higher image quality.
Effectiveness and safety of intravenous golimumab with and without concomitant methotrexate in patients with rheumatoid arthritis in the prospective, noninterventional AWARE study
Authors: Broadwell Aaron , Schechtman Joy , Conaway Douglas , Kivitz Alan , Shiff Natalie J. , Black Shawn , Xu Stephen , Langholff Wayne , Schwartzman Sergio , Curtis Jeffrey R. 
Published: March 2023

Abstract
Background
Biologic therapies are often prescribed for patients with rheumatoid arthritis (RA) who have inadequate responses to or are intolerant of methotrexate (MTX) and patients with poor prognostic indicators. This post hoc analysis evaluated effectiveness and safety of intravenous golimumab + MTX vs golimumab without MTX in RA patients.

Methods
AWARE, a real-world, prospective and pragmatic, Phase 4 study, compared effectiveness and safety of golimumab and infliximab in biologic-naïve and biologic-experienced patients. All treatment decisions were at the discretion of the treating rheumatologist. Effectiveness was evaluated by mean change in CDAI scores at Months 6 and 12. Safety was monitored through approximately 1 year.

Results
Among 685 golimumab-treated patients, 420 (61%) received concomitant MTX during the study and 265 (39%) did not receive MTX after enrollment; 63% and 72%, respectively, discontinued the study. Relative to golimumab without MTX, golimumab + MTX patients had shorter mean disease duration (8.7 vs 10.0 years) and a lower proportion received prior biologics (60% vs 72%); mean ± standard deviation (SD) baseline CDAI scores were similar (30.8 ± 15.1 and 32.6 ± 15.4). Mean ± SD changes from baseline in CDAI scores at Months 6 and 12, respectively, were similar with golimumab + MTX (− 10.2 ± 14.2 and − 10.8 ± 13.8) and golimumab without MTX (− 9.6 ± 12.9 and − 9.9 ± 13.1). The incidence of adverse events/100 patient-years (PY) (95% confidence interval [CI]) was 155.6 (145.6, 166.1) for golimumab + MTX and 191.2 (176.2, 207.1) for golimumab without MTX; infections were the most common type. The incidence of infusion reactions/100PY (95% CI) was 2.1 (1.1, 3.6) for golimumab + MTX versus 5.1 (2.9, 8.3) for golimumab without MTX; none were considered serious. For golimumab + MTX versus golimumab without MTX, rates/100PY (95% CI) of serious infections, opportunistic infections, and malignancies were 2.6 (1.5, 4.3) versus 7.0 (4.4, 10.6), 0.9 (0.3, 2.0) versus 2.6 (1.1, 5.0), and 3.0 (1.7, 4.7) versus 1.0 (0.2, 2.8), respectively.

Conclusions
Mean change in CDAI score in the golimumab without MTX group was generally similar to that of the golimumab + MTX group through 1 year, regardless of prior biologic therapy. Adverse events were consistent with the known IV golimumab safety profile. These results provide real world evidential data that may assist healthcare providers and patients with RA in making informed treatment decisions.
Trial registration: clinicaltrials.gov NCT02728934 05/04/2016.
In vitro synergistic effect of hesperidin and doxorubicin downregulates epithelial-mesenchymal transition in highly metastatic breast cancer cells
Authors: Amalina Nur Dina , Salsabila Irfani Aura , Zulfin Ummi Maryam , Jenie Riris Istighfari , Meiyanto Edy 
Published: March 2023

Abstract
Background
We previously reported that in highly metastatic breast cancer cells, doxorubicin (DOX) at non-toxic concentrations promoted cell migration and invasion. Hesperidin (30, 5, 9-dihydroxy-40-methoxy-7-orutinosyl flavanone) is a flavonoid glycoside isolated from citrus/lemon plant that possesses a cytotoxic effect in several cancer cells. In this study, we investigate whether DOX efficacy is enhanced by hesperidin (Hsd) and the molecular pathway involved in highly metastatic breast cancer, 4T1.

Methods
Combined cytotoxicity of Hsd and DOX was evaluated with MTT assay and was analyzed using Chou-Talalay’s method. To better understand the underlying mechanism, several factors, including apoptosis and cell cycle arrest were analyzed by flow cytometry. In addition, antimigration activity was evaluated by scratch wound healing assay, MMP-9 expression by ELISA and gelatin zymography, and Rac-1 protein level using western blot. The data on survival rate and expression level of MMP-9 and Rac-1 were obtained from Gene Expression OMNIBUS (GEO).

Results
Under MTT assay, Hsd showed a cytotoxic effect in a concentration-dependent manner with an IC50 value of 284 µM on 4T1 cells. Hsd synergistically enhanced the cytotoxic effect of DOX which seemed to correlate with an increase in apoptotic cell death, G2/M cell cycle arrest and blocked the migration of 4T1 cells. At 10 nM, doxorubicin induced lamellipodia formation, and increased the level of Rac-1 and metalloproteinase-9 (MMP-9) expression. Interestingly, combined treatment of DOX and Hsd dramatically downregulated the expression of MMP-9 and Rac-1. These results indicated that Hsd block the cell migration induced by DOX under in vitro studies.

Conclusion
These findings strongly suggest that Hsd possesses a potential synergistic effect that can be developed to enhance the anticancer efficacy of DOX and reduce the risks of chemotherapy use in highly metastatic breast cancer.
Evaluating the non-invasive tools for assessment of liver fibrosis in children with intrahepatic cholestasis prior to partial biliary diversion: tertiary-center experience
Authors: El-din Hadeer Mohamed Nasr , Adel Noha , EL-koofy Nehal , Obeida Alaa , Kaddah Sherif , EL-Tagy Gamal , Mohamed Wesam 
Published: March 2023

Abstract
Background
The liver biopsy is an essential element of evaluating progression of liver disease in children with Progressive Familial Intrahepatic Cholestasis (PFIC) and Allagille Syndrome (AGS). Several noninvasive techniques, including radiological imaging and blood biomarkers assay, can be used to evaluate liver stiffness.

Objectives
To identify whether liver Transient elastography (FibroScan) and AST/PLT Ratio Index (APRI) could be reliable tools to assess the degree of fibrosis prior to partial biliary diversion (PBD).

Methods
A prospective cohort in which all patients with PFIC and AGS who underwent PBD from July 2019 to July 2021 were included. Preoperative liver functions, pelvic-abdominal ultrasonography and FibroScan assessments were performed while intraoperative liver biopsy was obtained.

Results
Eight patients with chronic cholestatic liver disease who were candidates for PBD due to intractable pruritus were enrolled, including PFIC (n = 6; 75%), and AGS (n = 2; 25%). The liver FibroScan results were similar to the liver biopsy histopathological assessment in 87.5% of cases. APRI ranged from 0.1 to 3.2 (median = 1.2). In four cases (50%), APRI was consistent with histological evaluation of liver samples. The FibroScan results were in concordance with APRI results in three patients (37.5%).

Conclusion
The current cohort demonstrated that fibroScan was consistent with histopathology in 87.5% of patients, highlighting its value in determining the degree of liver fibrosis prior to surgery, whereas the APRI was only consistent with histopathology in half of cases.
University Governance and the Culture of Dissent in Eighteenth-Century Charcas
Authors: Serulnikov Sergio 
Published: March 2023

Abstract
The article analyzes how the University of Charcas participated in public affairs in Chuquisaca (present-day Sucre) during the late colonial era. I show that following the Jesuit expulsion in the 1760s, the claustro (academic senate) became a center of university life. This body held annual elections to appoint the rector and passed governing rules for the university that allocated academic chairs based on public tenders. The faculty forcefully defended their newly gained autonomy from ecclesiastical and royal authorities, and its representative practices were instrumental in consolidating a culture of dissent that helped destabilize the unanimity principle underlying the monarchical imaginary, a principle that deemed nonconforming opinions a societal pathology incompatible with the sovereign's will and the common good. The rise of this contentious politics helped set the conditions for Chuquisaca's general uprising after the French invasion of Spain in 1808.
Comparison Between the Supracerebellar Infratentorial and Precuneal Interhemispheric, Transtentorial Approaches to the Cerebellomesencephalic Fissure: An Anatomoradiological Study and Illustrative Cases
Authors: Alexander A. Yohan , Agosti Edoardo , Leonel Luciano C. P. C. , Lanzino Giuseppe , Peris-Celda Maria 
Published: March 2023

BACKGROUND:
The dorsal brainstem and cerebellomesencephalic fissure are challenging surgical targets. To afford a preferentially craniocaudal trajectory to this region, the precuneal interhemispheric transtentorial approach (PCIT) has been proposed.

OBJECTIVE:
To didactically describe and compare exposures and anatomic indications of the supracerebellar infratentorial approach (SCIT) and PCIT to the cerebellomesencephalic fissure.

METHODS:
Nine formalin-fixed, latex-injected cadaveric head specimens were used to perform a midline SCIT and bilateral PCITs and measure the distance of each approach. Twenty-four formalin-fixed specimens were used to measure the distance from the most posterior cortical bridging vein entering the superior sagittal sinus to the calcarine sulcus and the torcula. Fifty-one magnetic resonance images were reviewed to calculate the angle of each approach. Three illustrative surgical cases were described.

RESULTS:
Mean distances from the brain or cerebellar surface to the operative target of the PCIT and SCIT were 7.1 cm (range: 5-7.7 cm) and 5.5 cm (range: 3.8-6.2 cm), respectively. The SCIT provided direct access to structures of the quadrigeminal cistern bilaterally. The PCIT provided access from the ipsilateral inferior colliculus to the ipsilateral infratrochlear zone. The PCIT's benefit was the direct access it provided to the cerebellomesencephalic fissure because of its superior to inferior trajectory.

CONCLUSION:
The PCIT is indicated for unilateral lesions of the cerebellomesencephalic fissure and dorsal brainstem that harbor a craniocaudal long axis and do not have a superior extension beyond the superior colliculi. The SCIT is beneficial for lesions that extend bilaterally, have an anteroposterior long axis, or involve the Galenic complex.
Molecular profiling of the vestibular lamina highlights a key role for Hedgehog signalling
Authors: Qiu Tengyang , Hutečková Barbora , Seppala Maisa , Cobourne Martyn T. , Chen Zhi , Hovořáková Mária , Buchtová Marcela , Tucker Abigail S. 
Published: March 2023

ABSTRACTThe vestibular lamina (VL) forms the oral vestibule, creating a gap between the teeth, lips and cheeks. In a number of ciliopathies, formation of the vestibule is defective, leading to the creation of multiple frenula. In contrast to the neighbouring dental lamina, which forms the teeth, little is known about the genes that pattern the VL. Here, we establish a molecular signature for the usually non-odontogenic VL in mice and highlight several genes and signalling pathways that may play a role in its development. For one of these, the Sonic hedgehog (Shh) pathway, we show that co-receptors Gas1, Cdon and Boc are highly expressed in the VL and act to enhance the Shh signal from the forming incisor region. In Gas1 mutant mice, expression of Gli1 was disrupted and the VL epithelium failed to extend due to a loss of proliferation. This defect was exacerbated in Boc/Gas1 double mutants and could be phenocopied using cyclopamine in culture. Signals from the forming teeth, therefore, control development of the VL, coordinating the development of the dentition and the oral cavity.