bluuebunny/crossref_metadata_2025_split huggingface dataset:
The knock-on effects of COVID-19 pandemic on the supply and availability of generic medicines in Ethiopia: mixed methods study
Authors: Mekonnen Zeleke , Melaku Tsegaye , Tucho Gudina Terefe , Mecha Mohammed , Årdal Christine , Jahre Marianne 
Published: May 2023

Abstract
Background
COVID-19 pandemic posed a major impact on the availability and affordability of essential medicines. This study aimed to assess the knock-on effects of the COVID-19 pandemic on the supply availability of non-communicable chronic disease (NCD) medicines and paracetamol products in Ethiopia.

Methods
A mixed methods study was conducted to assess the supply and availability of twenty-four NCD drugs and four paracetamol products listed on the national essential medicines list for hospitals. Data were collected from twenty-six hospitals located in seven zones of Oromia region in the southwestern part of Ethiopia. We extracted data on drug availability, cost and stock out for these drugs between May 2019 and December 2020. The quantitative data were entered into Microsoft Excel and exported to statistical package software for social science (SPSS) version 22 (IBM Corporation, Armonk, NY, USA) software for analysis.

Results
The overall mean availability of selected basket medicines was 63.4% (range 16.7% to 80.3%) during the pre-COVID-19 time. It was 46.3% (range 2.8% to 88.7) during the pandemic. There was a relative increase in the availability of two paracetamol products [paracetamol 500 mg tablet (67.5% versus 88.7%) and suppository (74.5% versus 88%)] during the pandemic. The average monthly orders fill rates for the selected products range from 43 to 85%. Pre-COVID-19, the average order fill rate was greater or equal to 70%. However, immediately after the COVID-19 case notification, the percentage of order(s) filled correctly in items and quantities began decreasing. Political instability, shortage of trained human resources, currency inflation, and limited drug financing were considered as the major challenges to medicine supply.

Conclusion
The overall stock out situation in the study area has worsened during COVID-19 compared to pre-COVID-19 time. None of the surveyed chronic disease basket medicines met the ideal availability benchmark of 80% in health facilities. However, availability of paracetamol 500 mg tablet surprisingly improved during the pandemic. A range of policy frameworks and options targeting inevitable outbreaks should exist to enable governments to ensure that medicines for chronic diseases are consistently available and affordable.
Identification of genetic mechanisms underlying lipid metabolism-mediated tumor immunity in head and neck squamous cell carcinoma
Authors: Liu Shaokun , Wang Shuning , Wang Zhenlin 
Published: May 2023

Abstract
Objective
To identify the genetic mechanisms underlying lipid metabolism-mediated tumor immunity in head and neck squamous carcinoma (HNSC).

Materials and methods
RNA sequencing data and clinical characteristics of HNSC patients were procured from The Cancer Genome Atlas (TCGA) database. Lipid metabolism-related genes were collected from KEGG and MSigDB databases. Immune cells and immune-related genes were obtained from the TISIDB database. The differentially expressed genes (DEGs) in HNSC were identified and weighted correlation network analysis (WGCNA) was performed to identify the significant gene modules. Lasso regression analysis was performed to identify hub genes. The differential gene expression pattern, diagnostic values, relationships with clinical features, prognostic values, relationships with tumor mutation burden (TMB), and signaling pathways involved, were each investigated.

Results
One thousand six hundred sixty-eight DEGs were identified as dysregulated between HNSC tumor samples and healthy control head and neck samples. WGCNA analysis and Lasso regression analysis identified 8 hub genes, including 3 immune-related genes (PLA2G2D, TNFAIP8L2 and CYP27A1) and 5 lipid metabolism-related genes (FOXP3, IL21R, ITGAL, TRAF1 and WIPF1). Except CYP27A1, the other hub genes were upregulated in HNSC as compared with healthy control samples, and a low expression of these hub genes indicated a higher risk of death in HNSC. Except PLA2G2D, all other hub genes were significantly and negatively related with TMB in HNSC. The hub genes were implicated in several immune-related signaling pathways including T cell receptor signaling, Th17 cell differentiation, and natural killer (NK) cell mediated cytotoxicity.

Conclusion
Three immune genes (PLA2G2D, TNFAIP8L2, and CYP27A1) and immune-related pathways (T cell receptor signaling, Th17 cell differentiation, and natural killer (NK) cell mediated cytotoxicity) were predicted to play significant roles in the lipid metabolism-mediated tumor immunity in HNSC.
Long-term effectiveness of benralizumab in severe eosinophilic asthma patients treated for 96-weeks: data from the ANANKE study
Authors: Vultaggio Alessandra , Aliani Maria , Altieri Elena , Bracciale Pietro , Brussino Luisa , Caiaffa Maria Filomena , Cameli Paolo , Canonica Giorgio Walter , Caruso Cristiano , Centanni Stefano , D’Amato Maria , De Michele Fausto , Del Giacco Stefano , Di Marco Fabiano , Menzella Francesco , Pelaia Girolamo , Rogliani Paola , Romagnoli Micaela , Schino Pietro , Senna Gianenrico , Benci Marco , Boarino Silvia , Schroeder Jan Walter 
Published: May 2023

Abstract
Background
The efficacy of benralizumab has been broadly demonstrated in severe eosinophilic asthma (SEA), but only few real-life studies evaluated its long-term effects. Here we present novel data from the ANANKE study in which a large cohort of SEA patients was treated for up to 96 weeks.

Methods
ANANKE (NCT04272463) is an observational retrospective Italian study investigating the key characteristics of SEA patients (collected during the 12 months prior to benralizumab initiation) and the clinical outcomes during benralizumab treatment (annual exacerbation rate [AER], lung function, asthma control, OCS use, healthcare resource utilization). A post hoc analysis was also conducted in groups of patients based on history of previous biologic therapy (bio-experienced versus naïve patients). Analyses were descriptive only.

Results
Before benralizumab initiation, evaluable SEA patients (N = 162, 61.1% females, mean age 56.0 ± 12.7) showed a median blood eosinophil count (BEC) of 600 cells/mm3 (IQR: 430–890). Patients experienced frequent exacerbations (annualized exacerbation rate [AER]: 4.10, severe AER: 0.98), with impaired lung function and poor asthma control (median ACT score: 14) despite 25.3% reported oral corticosteroid (OCS) use. Nasal polyposis was present in 53.1% patients; 47.5% patients were atopic. After 96 weeks since the start of benralizumab, nearly 90% patients were still on treatment; benralizumab dramatically decreased exacerbations (AER: − 94.9%; severe AER: − 96.9%), improved respiratory parameters (median increase in pre-bronchodilator forced expiratory volume [pre-BD FEV1]: + 400 mL) and asthma control (median ACT score: 23) while eliminating OCS in 60% patients. Importantly, benralizumab effects were either maintained or progressively improved over time, accompanied by a nearly complete depletion of BEC. Benralizumab reduced AER both in naïve (any AER: − 95.9%; severe AER: − 97.5%) and bio-experienced patients (any AER: − 92.4%; severe AER: − 94.0%).

Conclusions
Profound and sustained improvements in all asthma outcomes were observed with benralizumab. The correct identification of patients’ eosinophilic-driven asthma phenotype was essential to ensure the achievement of such remarkable results.
Trial registration: ClinicalTrials.gov Identifier: NCT04272463.
The phospholipid transporter PITPNC1 links KRAS to MYC to prevent autophagy in lung and pancreatic cancer
Authors: Entrialgo-Cadierno Rodrigo , Cueto-Ureña Cristina , Welch Connor , Feliu Iker , Macaya Irati , Vera Laura , Morales Xabier , Michelina Sandra Vietti , Scaparone Pietro , Lopez Ines , Darbo Elodie , Erice Oihane , Vallejo Adrian , Moreno Haritz , Goñi-Salaverri Ainhoa , Lara-Astiaso David , Halberg Nils , Cortes-Dominguez Ivan , Guruceaga Elizabeth , Ambrogio Chiara , Lecanda Fernando , Vicent Silve 
Published: May 2023

Abstract
Background
The discovery of functionally relevant KRAS effectors in lung and pancreatic ductal adenocarcinoma (LUAD and PDAC) may yield novel molecular targets or mechanisms amenable to inhibition strategies. Phospholipids availability has been appreciated as a mechanism to modulate KRAS oncogenic potential. Thus, phospholipid transporters may play a functional role in KRAS-driven oncogenesis. Here, we identified and systematically studied the phospholipid transporter PITPNC1 and its controlled network in LUAD and PDAC.

Methods
Genetic modulation of KRAS expression as well as pharmacological inhibition of canonical effectors was completed. PITPNC1 genetic depletion was performed in in vitro and in vivo LUAD and PDAC models. PITPNC1-deficient cells were RNA sequenced, and Gene Ontology and enrichment analyses were applied to the output data. Protein-based biochemical and subcellular localization assays were run to investigate PITPNC1-regulated pathways. A drug repurposing approach was used to predict surrogate PITPNC1 inhibitors that were tested in combination with KRASG12C inhibitors in 2D, 3D, and in vivo models.

Results
PITPNC1 was increased in human LUAD and PDAC, and associated with poor patients’ survival. PITPNC1 was regulated by KRAS through MEK1/2 and JNK1/2. Functional experiments showed PITPNC1 requirement for cell proliferation, cell cycle progression and tumour growth. Furthermore, PITPNC1 overexpression enhanced lung colonization and liver metastasis. PITPNC1 regulated a transcriptional signature which highly overlapped with that of KRAS, and controlled mTOR localization via enhanced MYC protein stability to prevent autophagy. JAK2 inhibitors were predicted as putative PITPNC1 inhibitors with antiproliferative effect and their combination with KRASG12C inhibitors elicited a substantial anti-tumour effect in LUAD and PDAC.

Conclusions
Our data highlight the functional and clinical relevance of PITPNC1 in LUAD and PDAC. Moreover, PITPNC1 constitutes a new mechanism linking KRAS to MYC, and controls a druggable transcriptional network for combinatorial treatments.

Graphical Abstract
Serum lipidomics reveals phosphatidylethanolamine and phosphatidylcholine disorders in patients with myocardial infarction and post-myocardial infarction-heart failure
Authors: Rong Jidong , He Tianmu , Zhang Jianyong , Bai Zhixun , Shi Bei 
Published: May 2023

Abstract
Background
Myocardial infarction (MI) and post-MI-heart failure (pMIHF) are a major cause of death worldwide, however, the underlying mechanisms of pMIHF from MI are not well understood. This study sought to characterize early lipid biomarkers for the development of pMIHF disease.

Methods
Serum samples from 18 MI and 24 pMIHF patients were collected from the Affiliated Hospital of Zunyi Medical University and analyzed using lipidomics with Ultra High Performance Liquid Chromatography and Q-Exactive High Resolution Mass Spectrometer. The serum samples were tested by the official partial least squares discriminant analysis (OPLS-DA) to find the differential expression of metabolites between the two groups. Furthermore, the metabolic biomarkers of pMIHF were screened using the subject operating characteristic (ROC) curve and correlation analysis.

Results
The average age of the 18 MI and 24 pMIHF participants was 57.83 ± 9.28 and 64.38 ± 10.89 years, respectively. The B-type natriuretic peptide (BNP) level was 328.5 ± 299.842 and 3535.96 ± 3025 pg/mL, total cholesterol(TC) was 5.59 ± 1.51 and 4.69 ± 1.13 mmol/L, and blood urea nitrogen (BUN) was 5.24 ± 2.15 and 7.20 ± 3.49 mmol/L, respectively. In addition, 88 lipids, including 76 (86.36%) down-regulated lipids, were identified between the patients with MI and pMIHF. ROC analysis showed that phosphatidylethanolamine (PE) (12:1e_22:0) (area under the curve [AUC] = 0.9306) and phosphatidylcholine (PC) (22:4_14:1) (AUC = 0.8380) could be potential biomarkers for the development of pMIHF. Correlation analysis showed that PE (12:1e_22:0) was inversely correlated with BNP and BUN, but positively correlated with TC. In contrast, PC (22:4_14:1) was positively associated with both BNP and BUN, and was negatively associated with TC.

Conclusions
Several lipid biomarkers were identified that could potentially be used to predict and diagnose patients with pMIHF. PE (12:1e_22:0) and PC (22:4_14:1) could sufficiently differentiate between patients with MI and pMIHF.
Noninvasive right ventricular work in patients with atrial septal defects: a proof-of-concept study
Authors: Wu Jian , Huang Xinyi , Chen Weibin , Tang Yiruo , Chen Xu , Wang Xinyu , Jing Bo , Sun Yuanyuan , Huang Kunhui , Gao Qiumei , Liu Xueming , Su Maolong 
Published: May 2023

Abstract
Background
Noninvasive right ventricular (RV) myocardial work (RVMW) determined by echocardiography is a novel indicator used to estimate RV systolic function. To date, the feasibility of using RVMW has not been verified in assessing RV function in patients with atrial septal defect (ASD).

Methods
Noninvasive RVMW was analysed in 29 ASD patients (median age, 49 years; 21% male) and 29 age- and sex-matched individuals without cardiovascular disease. The ASD patients underwent echocardiography and right heart catheterization (RHC) within 24 h.

Results
The RV global work index (RVGWI), RV global constructive work (RVGCW), and RV global wasted work (RVGWW) were significantly higher in the ASD patients than in the controls, while there was no significant difference in RV global work efficiency (RVGWE). RV global longitudinal strain (RV GLS), RVGWI, RVGCW, and RVGWW demonstrated significant correlations with RHC-derived stroke volume (SV) and SV index. The RVGWI (area under receiver operating characteristic curve [AUC] = 0.895), RVGCW (AUC = 0.922), and RVGWW (AUC = 0.870) could be considered good predictors of ASD and were superior to RV GLS (AUC = 0.656).

Conclusion
The RVGWI, RVGCW, and RVGWW could be used to assess RV systolic function and are correlated with RHC-derived SV and SV index in patients with ASD.

Graphical Abstract
CD16 CAR-T cells enhance antitumor activity of CpG ODN-loaded nanoparticle-adjuvanted tumor antigen-derived vaccinevia ADCC approach
Authors: Zhang Xiaofei , Hu Qin , He Xuesong , Cui Xinyue , Liang Zhaoyuan , Wang Li , Deng Xiongwei , Zhang Ze , Sheng Wang , Han Xiaodong D. 
Published: May 2023

Abstract
Background
Combinatorial immunotherapy strategies for enhancing the responsiveness of immune system have shown great promise for cancer therapy. Engineered nanoformulation incorporated toll-like receptor (TLR) 9 agonist CpG ODN has shown more positive results in suppressing tumor growth and can significantly enhance other immunotherapy activity with combinatorial effects due to the innate and adaptive immunostimulatory effects of CpG.

Results
In the present work, protamine sulfate (PS) and carboxymethyl β-glucan (CMG) were used as nanomaterials to form nanoparticles through a self-assembly approach for CpG ODN encapsulation to generate CpG ODN-loaded nano-adjuvant (CNPs), which was subsequently mixed with the mixture of mouse melanoma-derived antigens of tumor cell lysates (TCL) and neoantigens to develop vaccine for anti-tumor immunotherapy. The obtained results showed that CNPs was able to effectively deliver CpG ODN into murine bone marrow-derived dendritic cells (DC) in vitro, and remarkably stimulate the maturation of DC cells with proinflammatory cytokine secretion. In addition, in vivo analysis showed that CNPs enhanced anti-tumor activity of PD1 antibody and CNPs-adjuvanted vaccine based on the mixture antigens of melanoma TCL and melanoma-specific neoantigen could not only induce anti-melanoma cellular immune responses, but also elicit melanoma specific humoral immune responses, which significantly inhibited xenograft tumor growth. Furthermore, CD16 CAR-T cells were generated by expressing CD16-CAR in CD3+CD8+ murine T cells.

Conclusion
Our results eventually showed that anti-melanoma antibodies induced by CNPs-adjuvanted TCL vaccines were able to collaborate with CD16-CAR-T cells to generate an enhanced targeted anti-tumor effects through ADCC (antibody dependent cell cytotoxicity) approach. CD16 CAR-T cells has thus a great potential to be an universal promising strategy targeting on solid tumor synergistic immunotherapy via co-operation with TCL-based vaccine.
Quality of routine health data at the onset of the COVID-19 pandemic in Ethiopia, Haiti, Laos, Nepal, and South Africa
Authors: Ayele Wondimu , Gage Anna , Kapoor Neena R. , Kassahun Gelaw Solomon , Hensman Dilipkumar , Derseh Mebratie Anagaw , Nega Adiam , Asai Daisuke , Molla Gebeyaw , Mehata Suresh , Mthethwa Londiwe , Mfeka-Nkabinde Nompumelelo Gloria , Joseph Jean Paul , Pierre Daniella Myriam , Thermidor Roody , Arsenault Catherine 
Published: May 2023

Abstract
Background
During the COVID-19 pandemic, governments and researchers have used routine health data to estimate potential declines in the delivery and uptake of essential health services. This research relies on the data being high quality and, crucially, on the data quality not changing because of the pandemic. In this paper, we investigated those assumptions and assessed data quality before and during COVID-19.

Methods
We obtained routine health data from the DHIS2 platforms in Ethiopia, Haiti, Lao People’s Democratic Republic, Nepal, and South Africa (KwaZulu-Natal province) for a range of 40 indicators on essential health services and institutional deaths. We extracted data over 24 months (January 2019–December 2020) including pre-pandemic data and the first 9 months of the pandemic. We assessed four dimensions of data quality: reporting completeness, presence of outliers, internal consistency, and external consistency.

Results
We found high reporting completeness across countries and services and few declines in reporting at the onset of the pandemic. Positive outliers represented fewer than 1% of facility-month observations across services. Assessment of internal consistency across vaccine indicators found similar reporting of vaccines in all countries. Comparing cesarean section rates in the HMIS to those from population-representative surveys, we found high external consistency in all countries analyzed.

Conclusions
While efforts remain to improve the quality of these data, our results show that several indicators in the HMIS can be reliably used to monitor service provision over time in these five countries.
Study on wild medicinal plant resources and their applied ethnology in multiethnic areas of the Gansu–Ningxia–Inner Mongolia intersection zone
Authors: Xie Jian , Luo Chaoqun , Yang Xingwu , Ren Yan , Zhang Xingsheng , Chen Haoran , Zhao Yongxia , Liu Sha , Wu Faming 
Published: May 2023

Abstract
Introduction
This study conducted an ethnobotanical survey of wild medicinal plants in the multi-ethnic areas of Gansu–Ningxia–Inner Mongolia intersection zone. Traditional knowledge of medicinal plant use in the region was compiled to identify important medicinal plants currently used for treating relevant diseases and to determine species with potential for development.

Methods
Key informant interviews, semi-structured interviews, participatory rural appraisal methods, and ethnobotanical quantitative evaluation were used to investigate and study the traditional knowledge of local residents' use of wild medicinal plants in the region. The relative importance of the referenced plants was assessed, as well as the prominent species widely used in medicinal applications.

Results
The study found that the region has a total of 204 wild medicinal plant resources, belonging to 149 genera of 51 families. Among these resources, a total of 50 commonly used plants were identified (44 of which were herbs, some of which were multi-origin), belonging to 27 families, with the most species found in the Asteraceae family, with 11 species. These herbs are mainly used for preventing and treating colds and nourishing health, followed by treatment of fever, stomach problems, and bleeding. The most frequently used medicinal plant in the region is “Ai”, which includes Artemisia argyi Lévl. et Van. and Artemisia kanashiroi Kitam. All respondents provided information about the use of this medicinal plant to varying degrees, followed by Artemisia annua Linn., Ephedra sinica Stapf, Taraxacum mongolicum Hand.-Mazz., Sonchus arvensis Linn., Artemisia capillaris Thunb., among others.

Conclusion
Our investigation gained a wealth of traditional knowledge about the use of wild herbs, using wild herbs, which plays an important role in the lives of local residents. Especially, the herbs and application methods used for treating colds, bleeding, and stomach problems are worthy of further research and development.
Study protocol for a multicenter, multinational, observational registry of epidemiology, treatment and outcome of patients with Robin sequence
Authors: Oechsle Anna-Lisa , Wiechers Cornelia , Abadie Veronique , Abel Francois , Breugem Corstiaan , Poets Christian F. 
Published: May 2023

Abstract
Background
Robin sequence (RS) is a congenital condition characterized by micrognathia, glossoptosis and upper airway obstruction. Diagnosis and treatment are characterized by heterogeneity, resulting in a lack of uniformly collected data.

Methods
We have set up a prospective, observational, multicenter, multinational registry aimed at obtaining routine clinical data from RS patients receiving different treatment approaches and enabling an assessment of outcomes obtained through different therapeutic approaches. Patient enrolment has started in January 2022. Disease characteristics, adverse events and complications depending on the different diagnostic and treatment approaches and their effects on neurocognition, growth, speech development and hearing outcome are evaluated using routine clinical data. In addition to characterizing the patient population and comparing outcomes achieved with different treatment approaches, the registry will evolve to focus on endpoints such as quality of life and long-term developmental status.

Discussion
This registry will provide data on different treatment approaches collected during routine care with diverse framework conditions and will allow assessing diagnostic and therapeutic outcomes of children with RS. These data, urgently demanded by the scientific community, may contribute to refining and personalizing existing therapeutic approaches and increase knowledge about the long-term outcome of children born with this rare condition.

Trial registration
DRKS00025365.