bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Cameroon Health Research and Evidence Database (CAMHRED): tools and methods for local evidence mapping
Authors: Ongolo-Zogo Clémence , El-Khechen Hussein , Morfaw Frederick , Djiadjeu Pascal , Zani Babalwa , Darzi Andrea , Nji Paul Wankah , Nyambi Agatha , Youta Andrea , Zaman Faiyaz , Youmbi Cheikh Tchouambou , Siani Ines Ndzana , Mbuagbaw Lawrence 
Published: June 2023

Abstract
Background
Local evidence is important for contextualized knowledge translation. It can be used to adapt global recommendations, to identify future research priorities and inform local policy decisions. However, there are challenges in identifying local evidence in a systematic, comprehensive, and timely manner. There is limited guidance on how to map local evidence and provide it to users in an accessible and user-friendly way. In this study, we address these issues by describing the methods for the development of a centralized database of health research evidence for Cameroon and its applications for research prioritization and decision making.

Methods
We searched 10 electronic health databases and hand-searched the archives of non-indexed African and Cameroonian journals. We screened titles, abstracts, and full texts of peer reviewed journal articles published between 1999 and 2019 in English or French that assess health related outcomes in Cameroonian populations. We extracted relevant study characteristics based on a pre-established guide. We developed a coding scheme or taxonomy of content areas so that local evidence is mapped to corresponding domains and subdomains. Pairs of reviewers coded articles independently and resolved discrepancies by consensus. Moreover, we developed guidance on how to search the database, use search results to create evidence maps and conduct knowledge gap analyses.

Results
The Cameroon Health Research and Evidence Database (CAMHRED) is a bilingual centralized online portal of local evidence on health in Cameroon from 1999 onwards. It currently includes 4384 studies categorized into content domains and study characteristics (design, setting, year and language of publication). The database is searchable by keywords or through a guided search. Results including abstracts, relevant study characteristics and bibliographic information are available for users to download. Upon request, guidance on how to optimize search results for applications like evidence maps and knowledge gap analyses is also available.

Conclusions
CAMHRED (https://camhred.org/) is a systematic, comprehensive, and centralized resource for local evidence about health in Cameroon. It is freely available to stakeholders and provides an additional resource to support their work at various levels in the research process.
Scutellaria baicalensis enhances 5-fluorouracil-based chemotherapy via inhibition of proliferative signaling pathways
Authors: Liu Haizhou , Liu Hui , Zhou Zhiyi , Chung Jessica , Zhang Guojing , Chang Jin , Parise Robert A. , Chu Edward , Schmitz John C. 
Published: June 2023

AbstractFluoropyridine-based chemotherapy remains the most widely used treatment for colorectal cancer (CRC). In this study, we investigated the mechanism by which the natural product Scutellaria baicalensis (Huang Qin; HQ) and one of its main components baicalin enhanced 5-fluorouracil (5-FU) antitumor activity against CRC. Cell proliferation assays, cell cycle analysis, reverse-phase protein array (RPPA) analysis, immunoblot analysis, and qRT-PCR were performed to investigate the mechanism(s) of action of HQ and its active components on growth of CRC cells. HQ exhibited in vitro antiproliferative activity against drug resistant human CRC cells, against human and mouse CRC cells with different genetic backgrounds and normal human colon epithelial cells. In vivo animal models were used to document the antitumor activity of HQ and baicalin. The mechanism of growth inhibitory activity of HQ is due to inhibition of proliferative signaling pathways including the CDK-RB pathway. In addition, HQ enhanced the antitumor effects of 5-FU and capecitabine in vivo. Furthermore, we identified baicalin as an active component of HQ. The combination of baicalin and 5-FU demonstrated synergistic activity against 5-FU-resistant RKO-R10 cells. The combination significantly inhibited in vivo tumor growth greater than each treatment alone. RPPA results showed that the signaling pathway alterations in CRC cells were similar following HQ and baicalin treatment. Together, these results indicate that HQ and its component baicalin enhance the effect of 5-fluorouracil-based chemotherapy via inhibition of CDK-RB pathway. These findings may provide the rational basis for developing agents that can overcome the development of cellular drug resistance.
Induction of filopodia formation by α-Actinin-2 via RelA with a feedforward activation loop promoting overt bone marrow metastasis of gastric cancer
Authors: Wang Caiqin , Xie Bo , Yin Shi , Cao Jianghua , Huang Junhao , Jin Longyang , Du Ge , Zhai Xiaohui , Zhang Rongqin , Li Shanshan , Cao Taiyuan , Yu Hongen , Fan Xinjuan , Yang Zuli , Peng Junsheng , Xiao Jian , Lian Lei 
Published: June 2023

Abstract
Background
Bone marrow metastasis (BMM) is underestimated in gastric cancer (GC). GC with BMM frequently complicate critical hematological abnormalities like diffused intravascular coagulation and microangiopathic hemolytic anemia, which constitute a highly aggressive GC (HAGC) subtype. HAGC present a very poor prognosis with peculiar clinical and pathological features when compared with not otherwise specified advanced GC (NAGC). But the molecular mechanisms underlying BMM from GC remain rudimentary.

Methods
The transcriptomic difference between HAGC and NAGC were analyzed. Genes that were specifically upregulated in HAGC were identified, and their effect on cell migration and invasion was studied. The function of ACTN2 gene were confirmed by GC cell lines, bone-metastatic animal model and patients’ tissues. Furthermore, the molecular mechanism of ACTN2 derived-BMM was explored by multiple immunofluorescence staining, western blot, chromatin immunoprecipitation, and luciferase reporter assays.

Results
We elucidated the key mechanisms of BMM depending on the transcriptomic difference between HAGC and NAGC. Five genes specifically upregulated in HAGC were assessed their effect on cell migration and invasion. The ACTN2 gene encoding protein α-Actinin-2 was detected enhanced the metastatic capability and induced BMM of GC cells in mouse models. Mechanically, α-Actinin-2 was involved in filopodia formation where it promoted the Actin filament cross-linking by replacing α-Actinin-1 to form α-Actinin-2:α-Actinin-4 complexes in GC cells. Moreover, NF-κB subunit RelA and α-Actinin-2 formed heterotrimers in the nuclei of GC cells. As a direct target of RelA:α-Actinin-2 heterotrimers, the ACTN2 gene was a positive auto-regulatory loop for α-Actinin-2 expression.

Conclusions
We demonstrated a link between filopodia, BMM and ACTN2 activation, where a feedforward activation loop between ACTN2 and RelA is established via actin in response to distant metastasis. Given the novel filopodia formation function and the new mechanism of BMM in GC, we propose ACTN2 as a druggable molecular vulnerability that may provide potential therapeutic benefit against BMM of GC.
Comparison of serum acylcarnitine levels in patients with myalgic encephalomyelitis/chronic fatigue syndrome and healthy controls: a systematic review and meta-analysis
Authors: Jinushi Ryuhei , Masuda Sakue , Tanisaka Yuki , Nishiguchi Sho , Shionoya Kento , Sato Ryo , Sugimoto Kei , Shin Takahiro , Shiomi Rie , Fujita Akashi , Mizuide Masafumi , Ryozawa Shomei 
Published: June 2023

Abstract
Background
Myalgic encephalomyelitis/chronic fatigue syndrome/systemic exertion intolerance disease (ME/CFS/SEID) is a condition diagnosed primarily based on clinical symptoms, including prolonged fatigue and post-exertional malaise; however, there is no specific test for the disease. Additionally, diagnosis can be challenging since healthcare professionals may lack sufficient knowledge about the disease. Prior studies have shown that patients with ME/CFS/SEID have low serum acylcarnitine levels, which may serve as a surrogate test for patients suspected of having this disease. This systematic review and meta-analysis aimed to investigate the differences in serum acylcarnitine levels between patients with ME/CFS/SEID and healthy controls.

Methods
This systematic review was conducted using PubMed and Ichushi-Web databases. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, we included all studies from the databases’ inception until February 17, 2023, that evaluated blood tests in both patients with ME/CFS/SEID and healthy control groups. The primary endpoint was the difference in serum acylcarnitine levels between the two groups.

Results
The electronic search identified 276 studies. Among them, seven met the eligibility criteria. The serum acylcarnitine levels were analyzed in 403 patients with ME/CFS/SEID. The patient group had significantly lower serum acylcarnitine levels when compared with the control group, and the statistical heterogeneity was high.

Conclusion
The patient group had significantly lower serum acylcarnitine levels when compared with the control group. In the future, the measurement of serum acylcarnitine levels, in addition to clinical symptoms, may prove to be a valuable diagnostic tool for this condition.
Comparative phylogenetic analysis and transcriptomic profiling of Dengue (DENV-3 genotype I) outbreak in 2021 in Bangladesh
Authors: Sarkar Md. Murshed Hasan , Rahman M. Shaminur , Islam M. Rafiul , Rahman Arafat , Islam Md. Shariful , Banu Tanjina Akhtar , Akter Shahina , Goswami Barna , Jahan Iffat , Habib Md. Ahashan , Uddin Mohammad Mohi , Mia Md. Zakaria , Miah Md. Ibrahim , Shaikh Aftab Ali , Khan Md. Salim 
Published: June 2023

AbstractBackgroundThe next-generation sequencing (NGS) technology facilitates in-depth study of host-pathogen metatranscriptome. We, therefore, implicated phylodynamic and transcriptomic approaches through NGS technology to know/understand the dengue virus (DENV) origin and host response with dengue fever.MethodsIn this study, blood serum RNA was extracted from 21 dengue patients and 3 healthy individuals. Total transcriptomic data were analyzed for phylogenetic, phylodynamic, differential express gene (DEG), and gene ontology (GO) using respective bioinformatics tools.ResultsThe viral genome sequence revealed dengue viral genome size ranges 10647 to 10707 nucleotide. Phylogenetic and phylodynamic analysis showed that the 2021 epidemic isolates were DENV-3 genotype-I and maintained as a new clade in compared to 2019 epidemic. Transcriptome analysis showed a total of 2686 genes were DEG in dengue patients compared to control with a q-value < 0.05. DESeq2 plot counts function of the top 24 genes with the smallest q-values of differential gene expression of RNA-seq data showed that 11 genes were upregulated, whereas 13 genes were downregulated. GO analysis showed a significant upregulation (p = < 0.001) in a process of multicellular organismal, nervous system, sensory perception of chemical stimulus, and G protein-coupled receptor signaling pathways in the dengue patients. However, there were a significant downregulation (p = < 0.001) of intracellular component, cellular anatomical entity, and protein-containing complex in dengue patients. Most importantly, there was a significant increase of a class of immunoregulatory proteins in dengue patients in compared to the controls, with increased GO of immune system process. In addition, upregulation of toll receptor (TLR) signaling pathways were found in dengue patients. These TLR pathways were particularly involved for the activation of innate system coupled with adaptive immune system that probably involved the rapid elimination of dengue virus infected cells. These differentially expressed genes could be further investigated for target based prophylactic interventions for dengue.ConclusionThis is a first report describing DENV complete genomic features and differentially expressed genes in patients in Bangladesh. These genes may have diagnostic and therapeutic values for dengue infection. Continual genomic surveillance is required to further investigate the shift in dominant genotypes in relation to viral pathogenesis.
Cross-reactive immune responses to monkeypox virus induced by MVA vaccination in mice
Authors: Gao Feixia , He Cheng , Liu Min , Yuan Ping , Tian Shihua , Zheng Mei , Zhang Linya , Zhou Xu , Xu Fangjingwei , Luo Jian , Li Xiuling 
Published: June 2023

AbstractMpox (monkeypox) infection cases increased recently in non-Mpox outbreak areas, potentially causing an international threat. The desire to defend against a potential outbreak has led to renewed efforts to develop Mpox vaccines. In this report, mice were immunized with various doses of modified vaccinia virus Ankara (MVA) to evaluate the cross-reactive immune response of MVA immunization against protective antigens of the current monkeypox virus. We demonstrated that MVA induced specific antibodies against protective antigens (A29, A35, B6, M1, H3, and I1), mediating the neutralization abilities against the MVA and the monkeypox virus (MPXV). Moreover, recombinant protective antigens of the MPXV elicited cross-binding and cross-neutralizing activities for MVA. Hence, the MVA induced cross-reactive immune responses, which may guide future efforts to develop vaccines against the recent MPXV. Notably, compared to the other protective antigens, the predominant A29 and M1 antigens mediated higher cross-neutralizing immune responses against the MVA, which could serve as antigen targets for novel orthologous orthopoxvirus vaccine.
A review of social media platform policies that address cannabis promotion, marketing and sales
Authors: Berg Carla J. , LoParco Cassidy R. , Cui Yuxian , Pannell Alexandria , Kong Grace , Griffith Lynniah , Romm Katelyn F. , Yang Y. Tony , Wang Yan , Cavazos-Rehg Patricia A. 
Published: June 2023

Abstract
Background
Cannabis marketing exposure via social media may impact use in youth and young adults. Most states with recreational cannabis lack policies regarding social media-based marketing. Thus, we examined such policies among prominent platforms, particularly those popular among youth and young adults.

Methods
In September-October 2022, 3 research team members extracted policies applying to the general community, advertising, and any specific content regarding drug-related content for 11 social media sites: Discord, Facebook, Instagram, Pinterest, Reddit, Snapchat, TikTok, Tumblr, Twitch, Twitter, and YouTube. Using inductive thematic analysis, they then dual-coded restrictions on cannabis-related content (e.g., paid advertising, unpaid promotion, sales). Descriptive analyses were conducted.

Results
Ten (all except TikTok) referenced cannabis/marijuana, 7 (all except Discord, Instagram, TikTok, and YouTube) distinguished different cannabis-derived products, and 5 (Reddit, Snapchat, TikTok, Tumblr, Twitter) noted jurisdictional differences in cannabis regulations/legality. All prohibited sales, 9 (all except Snapchat and Tumblr) prohibited paid advertising, and 4 (Discord, Reddit, Snapchat, TikTok) prohibited unpaid promotion (e.g., user-generated content). All restricted underage access to cannabis-related content. However, policies varied and were ambiguous regarding how “promotion” was defined, whether/how jurisdictional differences in legality were addressed, how businesses may interact on social media, barriers implemented to inhibit the facilitation of sales, and enforcement protocols.

Conclusions
Social media policies regarding cannabis marketing are ambiguous and may facilitate cannabis marketing, promotion, sales, and underage exposure, thus compounding concerns regarding insufficient governmental regulations. Greater specificity in social media cannabis-related policies and enforcement is needed.
Impact of planning organ at risk volume margins and matching method on late gastrointestinal toxicity in moderately hypofractionated IMRT for locally advanced pancreatic ductal adenocarcinoma
Authors: Ogawa Ayaka , Yoshimura Michio , Nakamura Mitsuhiro , Adachi Takanori , Iwai Takahiro , Ashida Ryo , Mizowaki Takashi 
Published: June 2023

Abstract
Background
This study examined the differences in late gastrointestinal (GI) toxicities in moderately hypofractionated intensity-modulated radiation therapy (IMRT) for locally advanced pancreatic ductal adenocarcinoma (LA-PDAC) by changing the planning organs at risk volume (PRV) margin and the target matching method and assessed the causes of adverse events.

Methods
We examined 37 patients with LA-PDAC who underwent moderately hypofractionated IMRT between 2016 and 2020 at our institution; 23 patients were treated with wide PRV margins and soft tissue matching (Protocol A) and 14 with narrow PRV margins and fiducial marker matching (Protocol B). The GI toxicities, local control (LC) rate, and overall survival (OS) were assessed for each protocol. The initially planned and daily doses to the gross tumor volume (GTV), stomach, and duodenum, reproduced from cone-beam computed tomography, were evaluated.

Results
The late GI toxicity rate of grades 3–4 was higher in Protocol B (42.9%) than in Protocol A (4.3%). Although the 2-year LC rates were significantly higher in Protocol B (90.0%) than in Protocol A (33.3%), no significant difference was observed in OS rates. In the initial plan, no deviations were found for the stomach and duodenum from the dose constraints in either protocol. In contrast, daily dose evaluation for the stomach to duodenal bulb revealed that the frequency of deviation of V3 Gy per session was 44.8% in Protocol B, which was significantly higher than the 24.3% in Protocol A.

Conclusions
Reducing PRV margins with fiducial marker matching increased GI toxicities in exchange for improved LC. Daily dose analysis indicated the trade-off between the GTV dose coverage and the irradiated doses to the GI. This study showed that even with strict matching methods, the PRV margin could not be reduced safely because of GI inter-fractional error, which is expected to be resolved with online adaptive radiotherapy.
A classification algorithm based on dynamic ensemble selection to predict mutational patterns of the envelope protein in HIV-infected patients
Authors: Fili Mohammad , Hu Guiping , Han Changze , Kort Alexa , Trettin John , Haim Hillel 
Published: June 2023

Abstract
Background
Therapeutics against the envelope (Env) proteins of human immunodeficiency virus type 1 (HIV-1) effectively reduce viral loads in patients. However, due to mutations, new therapy-resistant Env variants frequently emerge. The sites of mutations on Env that appear in each patient are considered random and unpredictable. Here we developed an algorithm to estimate for each patient the mutational state of each position based on the mutational state of adjacent positions on the three-dimensional structure of the protein.

Methods
We developed a dynamic ensemble selection algorithm designated k-best classifiers. It identifies the best classifiers within the neighborhood of a new observation and applies them to predict the variability state of each observation. To evaluate the algorithm, we applied amino acid sequences of Envs from 300 HIV-1-infected individuals (at least six sequences per patient). For each patient, amino acid variability values at all Env positions were mapped onto the three-dimensional structure of the protein. Then, the variability state of each position was estimated by the variability at adjacent positions of the protein.

Results
The proposed algorithm showed higher performance than the base learner and a panel of classification algorithms. The mutational state of positions in the high-mannose patch and CD4-binding site of Env, which are targeted by multiple therapeutics, was predicted well. Importantly, the algorithm outperformed other classification techniques for predicting the variability state at multi-position footprints of therapeutics on Env.

Conclusions
The proposed algorithm applies a dynamic classifier-scoring approach that increases its performance relative to other classification methods. Better understanding of the spatiotemporal patterns of variability across Env may lead to new treatment strategies that are tailored to the unique mutational patterns of each patient. More generally, we propose the algorithm as a new high-performance dynamic ensemble selection technique.
Panax notoginseng alleviates oxidative stress through miRNA regulations based on systems biology approach
Authors: Tang Yun , Chen Yi-Gang , Huang Hsi-Yuan , Li Shang-Fu , Zuo Hua-Li , Chen Ji-Hang , Li Li-Ping , Mao Run-Bo , Lin Yang-Chi-Dung , Huang Hsien-Da 
Published: June 2023

Abstract
Background
Herbal medicine Sanqi (SQ), the dried root or stem of Panax notoginseng (PNS), has been reported to have anti-diabetic and anti-obesity effects and is usually administered as a decoction for Chinese medicine. Alternative to utilizing PNS pure compound for treatment, we are motivated to propose an unconventional scheme to investigate the functions of PNS mixture. However, studies providing a detailed overview of the transcriptomics-based signaling network in response to PNS are seldom available.

Methods
To explore the reasoning of PNS in treating metabolic disorders such as insulin resistance, we implemented a systems biology-based approach with RNA sequencing (RNA-seq) and miRNA sequencing data to elucidate key pathways, genes and miRNAs involved.

Results
Functional enrichment analysis revealed PNS up-regulating oxidative stress-related pathways and down-regulating insulin and fatty acid metabolism. Superoxide dismutase 1 (SOD1), peroxiredoxin 1 (PRDX1), heme oxygenase-1 (Hmox1) and glutamate cysteine ligase (GCLc) mRNA and protein levels, as well as related miRNA levels, were measured in PNS treated rat pancreatic β cells (INS-1). PNS treatment up-regulated Hmox1, SOD1 and GCLc expression while down-regulating miR-24-3p and miR-139-5p to suppress oxidative stress. Furthermore, we verified the novel interactions between miR-139-5p and miR-24-3p with GCLc and SOD1.

Conclusion
This work has demonstrated the mechanism of how PNS regulates cellular molecules in metabolic disorders. Therefore, combining omics data with a systems biology strategy could be a practical means to explore the potential function and molecular mechanisms of Chinese herbal medicine in the treatment of metabolic disorders.
SCARB1 downregulation in adrenal insufficiency with Allgrove syndrome
Authors: Bitetto Giacomo , Lopez Gianluca , Ronchi Dario , Pittaro Alessandra , Melzi Valentina , Peverelli Erika , Cribiù Fulvia Milena , Comi Giacomo P. , Mantovani Giovanna , Di Fonzo Alessio 
Published: June 2023

Abstract
Background
Allgrove disease is a rare genetic syndrome characterized by adrenal insufficiency, alacrimia, achalasia and complex neurological involvement. Allgrove disease is due to recessive mutations in the AAAS gene, which encodes for the nucleoporin Aladin, implicated in the nucleocytoplasmic transport. The adrenal insufficiency has been suggested to rely on adrenal gland-ACTH resistance. However, the link between the molecular pathology affecting the nucleoporin Aladin and the glucocorticoid deficiency is still unknown.

Results
By analyzing postmortem patient’s adrenal gland, we identified a downregulation of Aladin transcript and protein. We found a downregulation of Scavenger receptor class B-1 (SCARB1), a key component of the steroidogenic pathway, and SCARB1 regulatory miRNAs (mir125a, mir455) in patient’s tissues. With the hypothesis of an impairment in the nucleocytoplasmic transport of the SCARB1 transcription enhancer cyclic AMP-dependent protein kinase (PKA), we detected a reduction of nuclear Phospho-PKA and a cytoplasmic mislocalization in patient’s samples.

Conclusions
These results shed a light on the possible mechanisms linking ACTH resistance, SCARB1 impairment, and defective nucleocytoplasmic transport.