bluuebunny/crossref_metadata_2025_split huggingface dataset:
The patients’ perspective on the burden of idiopathic intracranial hypertension
Authors: Witry Max , Kindler Christine , Weller Johannes , Linder Andreas , Wüllner Ullrich 
Published: July 2021

Abstract
Background
Idiopathic intracranial hypertension (IIH) is characterized by increased intracranial pressure without evidence of a tumor or any other underlying cause. Headache and visual disturbances are frequent complaints of IIH patients, but little is known about other symptoms. In this study, we evaluated the patients’ perspective on the burden of IIH.

Methods
For this cross-sectional study, we developed an online survey for patients with IIH containing standardized evaluations of headache (HIT-6), sleep (PROMIS Sleep Disturbance Scale) and depression (MDI) in relation to BMI, lumbar puncture opening pressure (LP OP) and treatment.

Results
Between December 2019 and February 2020, 306 patients completed the survey. 285 (93 %) were female, mean age was 36.6 years (± 10.8), mean BMI 34.2 (± 7.3) and mean LP OP at diagnosis was 37.8 cmH2O (± 9.5). 219 (72 %) of the participants were obese (BMI ≥ 30); 251 (82 %) reported severe impacting headaches, 140 (46 %) were suffering from sleep disturbances and 169 (56 %) from depression. Higher MDI scores correlated with higher BMI and increased sleep disturbances. Patients with a normalized LP opening pressure reported less headaches, less sleep disturbances and less depression than those with a constantly elevated opening pressure.

Conclusions
In addition to headaches and visual disturbances, sleep disturbances and depression are frequent symptoms in IIH and contribute to the patients’ burden. Structured questionnaires can help to identify IIH patients’ needs and can lead to personalized and better treatment.
Phenome-wide analysis highlights putative causal relationships between self-reported migraine and other complex traits
Authors: García-Marín Luis M. , Campos Adrián I. , Martin Nicholas G. , Cuéllar-Partida Gabriel , Rentería Miguel E. 
Published: July 2021

Abstract
Background
Migraine is a complex neurological disorder that is considered the most common disabling brain disorder affecting 14 % of people worldwide. The present study sought to infer potential causal relationships between self-reported migraine and other complex traits, using genetic data and a hypothesis-free approach.

Methods
We leveraged available summary statistics from genome-wide association studies (GWAS) of 1,504 phenotypes and self-reported migraine and inferred pair-wise causal relationships using the latent causal variable (LCV) method.

Results
We identify 18 potential causal relationships between self-reported migraine and other complex traits. Hypertension and blood clot formations were causally associated with an increased migraine risk, possibly through vasoconstriction and platelet clumping. We observed that sources of abdominal pain and discomfort might influence a higher risk for migraine. Moreover, occupational and environmental factors such as working with paints, thinner or glues, and being exposed to diesel exhaust were causally associated with higher migraine risk. Psychiatric-related phenotypes, including stressful life events, increased migraine risk. In contrast, ever feeling unenthusiastic / disinterested for a whole week, a phenotype related to the psychological well-being of individuals, was a potential outcome of migraine.

Conclusions
Overall, our results suggest a potential vascular component to migraine, highlighting the role of vasoconstriction and platelet clumping. Stressful life events and occupational variables potentially influence a higher migraine risk. Additionally, a migraine could impact the psychological well-being of individuals. Our findings provide novel testable hypotheses for future studies that may inform the design of new interventions to prevent or reduce migraine risk and recurrence.
LncRNA UCA1 promotes development of gastric cancer via the miR-145/MYO6 axis
Authors: Yang An , Liu Xin , Liu Ping , Feng Yunzhang , Liu Hongbo , Gao Shen , Huo Limin , Han Xinyan , Wang Jurong , Kong Wei 
Published: July 2021

Abstract
Background
Long noncoding RNA (lncRNA), urothelial carcinoma-associated 1 (UCA1) is aberrantly expressed in multiple cancers and has been verified as an oncogene. However, the underlying mechanism of UCA1 in the development of gastric cancer is not fully understood. In the present study, we aimed to identify how UCA1 promotes gastric cancer development.

Methods
The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data were used to analyze UCA1 and myosin VI (MYO6) expression in gastric cancer. Western blot and quantitative real-time PCR (QPCR) were performed to test the expression level of the UCA1/miR-145/MYO6 axis in gastric cancer cell lines and tissues. The roles of the UCA1/miR-145/MYO6 axis in gastric cancer in vitro and in vivo were investigated by CCK-8 assay, flow cytometry, siRNAs, immunohistochemistry, and a mouse xenograft model. The targeted relationship among UCA1, miR-145, and MYO6 was predicted using LncBase Predicted v.2 and TargetScan online software, and then verified by luciferase activity assay and RNA immunoprecipitation.

Results
UCA1 expression was higher but miR-145 expression was lower in gastric cancer cell lines or tissues, compared to the adjacent normal cell line or normal tissues. Function analysis verified that UCA1 promoted cell proliferation and inhibited cell apoptosis in the gastric cancer cells in vitro and in vivo. Mechanistically, UCA1 could bind directly to miR-145, and MYO6 was found to be a downstream target gene of miR-145. miR-145 mimics or MYO6 siRNAs could partly reverse the effect of UCA1 on gastric cancer cells.

Conclusions
UCA1 accelerated cell proliferation and inhibited cell apoptosis through sponging miR-145 to upregulate MYO6 expression in gastric cancer, indicating that the UCA1/miR-145/MYO6 axis may serve as a potential therapeutic target for gastric cancer.
Radiolabeling and PET–MRI microdosing of the experimental cancer therapeutic, MN-anti-miR10b, demonstrates delivery to metastatic lesions in a murine model of metastatic breast cancer
Authors: Le Fur Mariane , Ross Alana , Pantazopoulos Pamela , Rotile Nicholas , Zhou Iris , Caravan Peter , Medarova Zdravka , Yoo Byunghee 
Published: July 2021

Abstract
Background
In our earlier work, we identified microRNA-10b (miR10b) as a master regulator of the viability of metastatic tumor cells. This knowledge allowed us to design a miR10b-targeted therapeutic consisting of an anti-miR10b antagomir conjugated to ultrasmall iron oxide nanoparticles (MN), termed MN-anti-miR10b. In mouse models of breast cancer, we demonstrated that MN-anti-miR10b caused durable regressions of established metastases with no evidence of systemic toxicity. As a first step towards translating MN-anti-miR10b for the treatment of metastatic breast cancer, we needed to determine if MN-anti-miR10b, which is so effective in mice, will also accumulate in human metastases.

Results
In this study, we devised a method to efficiently radiolabel MN-anti-miR10b with Cu-64 (64Cu) and evaluated the pharmacokinetics and biodistribution of the radiolabeled product at two different doses: a therapeutic dose, referred to as macrodose, corresponding to 64Cu-MN-anti-miR10b co-injected with non-labeled MN-anti-miR10b, and a tracer-level dose of 64Cu-MN-anti-miR10b, referred to as microdose. In addition, we evaluated the uptake of 64Cu-MN-anti-miR10b by metastatic lesions using both in vivo and ex vivo positron emission tomography–magnetic resonance imaging (PET–MRI). A comparable distribution of the therapeutic was observed after administration of a microdose or macrodose. Uptake of the therapeutic by metastatic lymph nodes, lungs, and bone was also demonstrated by PET–MRI with a significantly higher PET signal than in the same organs devoid of metastatic lesions.

Conclusion
Our results demonstrate that PET–MRI following a microdose injection of the agent will accurately reflect the innate biodistribution of the therapeutic. The tools developed in the present study lay the groundwork for the clinical testing of MN-anti-miR10b and other similar therapeutics in patients with cancer.
Venom-gland transcriptomic, venomic, and antivenomic profiles of the spine-bellied sea snake (Hydrophis curtus) from the South China Sea
Authors: Zhao Hong-Yan , Wen Lin , Miao Yu-Feng , Du Yu , Sun Yan , Yin Yin , Lin Chi-Xian , Lin Long-Hui , Ji Xiang , Gao Jian-Fang 
Published: July 2021

Abstract
Background
A comprehensive evaluation of the -omic profiles of venom is important for understanding the potential function and evolution of snake venom. Here, we conducted an integrated multi-omics-analysis to unveil the venom-transcriptomic and venomic profiles in a same group of spine-bellied sea snakes (Hydrophis curtus) from the South China Sea, where the snake is a widespread species and might generate regionally-specific venom potentially harmful to human activities. The capacity of two heterologous antivenoms to immunocapture the H. curtus venom was determined for an in-depth evaluation of their rationality in treatment of H. curtus envenomation. In addition, a phylogenetic analysis by maximum likelihood was used to detect the adaptive molecular evolution of full-length toxin-coding unigenes.

Results
A total of 90,909,384 pairs of clean reads were generated via Illumina sequencing from a pooled cDNA library of six specimens, and yielding 148,121 unigenes through de novo assembly. Sequence similarity searching harvested 63,845 valid annotations, including 63,789 non-toxin-coding and 56 toxin-coding unigenes belonging to 22 protein families. Three protein families, three-finger toxins (3-FTx), phospholipase A2 (PLA2), and cysteine-rich secretory protein, were detected in the venom proteome. 3-FTx (27.15% in the transcriptome/41.94% in the proteome) and PLA2 (59.71%/49.36%) were identified as the most abundant families in the venom-gland transcriptome and venom proteome. In addition, 24 unigenes from 11 protein families were shown to have experienced positive selection in their evolutionary history, whereas four were relatively conserved throughout evolution. Commercial Naja atra antivenom exhibited a stronger capacity than Bungarus multicinctus antivenom to immunocapture H. curtus venom components, especially short neurotoxins, with the capacity of both antivenoms to immunocapture short neurotoxins being weaker than that for PLA2s.

Conclusions
Our study clarified the venom-gland transcriptomic and venomic profiles along with the within-group divergence of a H. curtus population from the South China Sea. Adaptive evolution of most venom components driven by natural selection appeared to occur rapidly during evolutionary history. Notably, the utility of commercial N. atra and B. multicinctus antivenoms against H. curtus toxins was not comprehensive; thus, the development of species-specific antivenom is urgently needed.
Characterization of resistance mechanisms of Enterobacter cloacae Complex co-resistant to carbapenem and colistin
Authors: Liu Shixing , Fang Renchi , Zhang Ying , Chen Lijiang , Huang Na , Yu Kaihang , Zhou Cui , Cao Jianming , Zhou Tieli 
Published: July 2021

Abstract
Background
The emergence of carbapenem-resistant and colistin-resistant ECC pose a huge challenge to infection control. The purpose of this study was to clarify the mechanism of the carbapenems and colistin co-resistance in Enterobacter cloacae Complex (ECC) strains.

Results
This study showed that the mechanisms of carbapenem resistance in this study are: 1. Generating carbapenemase (7 of 19); 2. The production of AmpC or ESBLs combined with decreased expression of out membrane protein (12 of 19). hsp60 sequence analysis suggested 10 of 19 the strains belong to colistin hetero-resistant clusters and the mechanism of colistin resistance is increasing expression of acrA in the efflux pump AcrAB-TolC alone (18 of 19) or accompanied by a decrease of affinity between colistin and outer membrane caused by the modification of lipid A (14 of 19). Moreover, an ECC strain co-harboring plasmid-mediated mcr-4.3 and blaNDM-1 has been found.

Conclusions
This study suggested that there is no overlap between the resistance mechanism of co-resistant ECC strains to carbapenem and colistin. However, the emergence of strain co-harboring plasmid-mediated resistance genes indicated that ECC is a potential carrier for the horizontal spread of carbapenems and colistin resistance.
Genome-wide analysis of MYB transcription factors and their responses to salt stress in Casuarina equisetifolia
Authors: Wang Yujiao , Zhang Yong , Fan Chunjie , Wei Yongcheng , Meng Jingxiang , Li Zhen , Zhong Chonglu 
Published: July 2021

Abstract
Background
MYB transcription factors are a kind of DNA binding protein that can specifically interact with the promoter region. Members of MYB TFs are widely involved in plant growth and development, secondary metabolism, stress response, and hormone signal transduction. However, there is no report of comprehensive bioinformatics analysis on the MYB family of Casuarina equisetifolia.

Results
In this study, bioinformatics methods were used to screen out 182 MYB transcription factors from the Casuarina equisetifolia genome database, including 69 1R-MYB, 107 R2R3-MYB, 4 R1R2R3-MYB, and 2 4R-MYB. The C. equisetifolia R2R3-MYB genes were divided into 29 groups based on the phylogenetic topology and the classification of the MYB superfamily in Arabidopsis thaliana, while the remaining MYB genes (1R-MYB, R1R2R3-MYB, and 4R-MYB) was divided into 19 groups. Moreover, the conserved motif and gene structure analysis shown that the members of the CeqMYBs were divided into the same subgroups with mostly similar gene structures. In addition, many conserved amino acids in the R2 and R3 domains of CeqMYBs by WebLogo analysis, especially tryptophan residues (W), with 3 conserved W in R2 repeat and 2 conserved W in R3 repeat. Combining promoter and GO annotation analysis, speculated on the various biological functions of CeqMYBs, thus 32 MYB genes were selected to further explore its response to salt stress by using qPCR analysis technique. Most CeqMYB genes were differentially regulated following multiple salt treatments.

Conclusions
Seven genes (CeqMYB164, CeqMYB4, CeqMYB53, CeqMYB32, CeqMYB114, CeqMYB71 and CeqMYB177) were assigned to the “response to salt stress” by GO annotation. Among them, the expression level of CeqMYB4 was up-regulated under various salt treatments, indicating CeqMYB4 might participated in the response to salt stress. Our results provide important information for the biological function of C. equisetifolia, as well as offer candidate genes for further study of salt stress mechanism.
A new likelihood model for analyses of pharmacoepidemiologic case–control studies which avoids decision rules for determining latent exposure status
Authors: Støvring Henrik , Pottegård Anton , Hallas Jesper 
Published: July 2021

Abstract
Background
Case–control studies based on pharmaco-epidemiological databases typically use decision rules to determine exposure status from information on dates of prescription redemptions, although this induces misclassification. The reverse Waiting Time Distribution has been suggested as a likelihood based model to estimate the latent exposure status, and we therefore suggest to extend this into a joint likelihood based model, which incorporates both the latent exposure status and the exposure-outcome association. This will achieve consistency and efficiency of the estimates, i.e. they can be expected to be asymptotically unbiased and have optimal precision.

Methods
We established a joint likelihood for the observed case–control status and last prescription redemption before the index date. The likelihood combines the ordinary logistic regression likelihood and the reverse Waiting Time Distribution, and allows inclusion of covariates in both parts to adjust for observed confounders. We conducted a simulation study of the new model and standard models based on decision rules for exposure and the probability of being exposed, respectively, to assess the relative bias and variability of estimates. Lastly, we applied the models to a case–control study on use of nonsteroidal anti-inflammatory drugs and risk of upper-gastrointestinal bleeding.

Results
In simulation studies the new model had low relative bias (< 1.4%) and largely retained nominal coverage probabilities (90.2% to 95.1% of nominal 95% confidence intervals), also when moderate misspecification was introduced. All standard methods generally had substantial bias (-21.1% to 17.0%) and low coverage probabilities (0.0% to 68.9%). When analyzing the empirical case–control study, the new method estimated the effect of nonsteroidal anti-inflammatory drugs on risk of with upper-gastrointestinal bleeding hospitalization to 2.52 (1.59 – 3.45), whereas the other methods had estimates ranging from 3.52 (2.19 – 5.65) to 5.17 (2.40 – 11.11).

Conclusions
Unlike standard methods, the proposed model gave nearly unbiased estimates with adequate coverage probabilities in simulation studies. The developed model demonstrates the potential for the reverse Waiting Time Distribution to be integrated with existing likelihood based analyses in pharmacoepidemiological studies.
Small intestinal follicular lymphoma induced by methotrexate: a case report
Authors: Osaki Yui , Kawaratani Hideto , Kachi Hiroki , Matsuura Kyohei , Tsuji Yuki , Ozutsumi Takahiro , Takagi Hirotetsu , Furukawa Masanori , Sawada Yasuhiko , Mitoro Akira , Yamao Junichi , Yoshiji Hitoshi 
Published: July 2021

Abstract
Background
Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is a rare but critical complication that develops in patients treated with MTX. Although MTX-LPD has been recently reported, the incidence of follicular lymphoma in the intestine is very low.

Case presentation
A 73-year-old woman who had been receiving MTX for over 10 years visited our hospital complaining of postprandial abdominal pain and nausea. Upper and lower digestive tract endoscopies did not show any abnormal findings. A patency capsule was stagnated at the proximal part of the ileum with a mild dilation on the oral side. An oral balloon endoscopy revealed shallow ulcerative lesions in the jejunum. She was diagnosed with MTX-LPD based on histopathological findings. The symptoms did not improve with the discontinuation of MTX, and the patient required partial resection of the small intestine. The test result for Epstein-Barr virus-encoded small RNA was negative. She was diagnosed with follicular lymphoma based on the histology findings of a surgical specimen. Postoperative positron emission tomography-computed tomography and bone marrow aspiration did not show any findings of lymphoma. On follow-up, no recurrence was noted four years after the surgery.

Conclusions
Herein, we report the first case of follicular lymphoma that occurred in the small intestine, negative for Epstein-Barr virus-encoded small RNA. If intestinal symptoms occur during MTX administration, it is important to directly observe by endoscopy and perform histological examination.
Successful use of montelukast in eosinophilic gastroenteritis: a case report and a literature review
Authors: El-Alali Emran A. , Abukhiran Ibrahim M. , Alhmoud Tarik Z. 
Published: July 2021

Abstract
Background
Eosinophilic gastrointestinal disorders, also known as eosinophilic gastroenteritis, are rare inflammatory conditions characterized by eosinophilic infiltration of different parts of the gastrointestinal tract, along with peripheral eosinophilia in most cases. Other known causes for gut eosinophilic infiltration must be excluded to confirm the diagnosis of eosinophilic gastroenteritis. Symptoms of the disorder depend on the affected gastrointestinal tract segment and depth of involvement. Treatment includes systemic glucocorticoids and/or dietary therapy with an empiric elimination diet. Second line therapies include the leukotriene receptor antagonist montelukast, and other anti-allergy drugs such as mast cell stabilizers (including cromolyn and the H1-antihistamine ketotifen), suplatast tosilate which is a selective Th-2 cytokines (IL-4 and IL-5) inhibitor, and the monoclonal anti-IgE antibody omalizumab. We report a case of eosinophilic gastroenteritis who was successfully treated and achieved remission with montelukast as an initial monotherapy. Upon extensive literature review, this represents the second reported adult case of eosinophilic gastroenteritis who responds to montelukast alone as a first line therapy.

Case presentation
A 49-year-old female presented with recurrent abdominal pain, vomiting, diarrhea and unexplained eosinophilia. She was diagnosed with eosinophilic gastroenteritis and was successfully treated with montelukast monotherapy. After 7 days of therapy, the patient responded well and had complete resolution of her gastrointestinal symptoms and peripheral eosinophilia. Patient remained in remission on follow-up after 12 months. We reviewed the literature for leukotriene antagonist use in the treatment of eosinophilic gastroenteritis and included the cases treated with the leukotriene antagonist montelukast as an initial therapy or as a second line therapy for refractory disease.

Conclusion
Montelukast may be an effective treatment for eosinophilic gastroenteritis, either alone or in combination with systemic steroids or ketotifen. Our patient is the second reported adult case of eosinophilic gastroenteritis who responded to montelukast alone as a first line therapy. Further studies and clinical trials are required to confirm efficacy compared to standard therapy.
The increasing use of the WHO Safe Childbirth Checklist: lessons learned at the Yaoundé Gynaeco-Obstetric and Paediatric Hospital, Cameroon
Authors: Dohbit Julius Sama , Woks Namanou Ines Emma , Koudjine Carlin Héméry , Tafen Willy , Foumane Pascal , Bella Assumpta Lucienne , Ogu Rosemary Nkemdilim , Angwafo Fru Fobuzshi 
Published: July 2021

Abstract
Background
Safe childbirth remains a daunting challenge, particularly in low-middle income countries, where most pregnancy-related deaths occur. Cameroon’s maternal mortality rate, estimated at 529 per 100,000 live births in 2017, is significantly high. The WHO Safe Childbirth Checklist (SCC) was designed to improve the quality of care provided to pregnant women during childbirth. The SCC was implemented at the Yaoundé Gynaeco-Obstetric and Paediatric Hospital to improve the quality of care during childbirth.

Methods
This study was a retrospective study to determine the adoption rate of the SCC and its association with maternal (eclampsia, perineal tears, and postpartum haemorrhage) and neonatal (stillbirth, neonatal asphyxia and neonatal death) complications. Data were collected 6 months after the introduction of the SCC. Multivariate binary logistic regression was used to analyse the association between the use of the SCC and maternofoetal complications.

Results
Out of 1611 deliveries conducted, 1001 records were found, giving a retrieval rate of 62%. Twenty-five records were excluded. During the study period, the checklists were used in 828 of 976 clinical notes, with an adoption rate of 84.8% and a utilization rate of 93.9% at 6 months. Severe preeclampsia/eclampsia was associated with the non-use of the SCC (2.1 vs 5.4%, p = 0.041). Stillbirth, neonatal asphyxia, and neonatal death rates were not significantly different between the checklist and non-checklist groups. However, for all neonatal outcomes, the proportion of complications was lower when the checklist was used.

Conclusion
The use of the SCC was associated with significantly reduced pregnancy complications, especially for reducing the rates of severe pre-eclampsia/eclampsia. The use of the SCC increased to 93.9% of all deliveries within 6 months. We advocate for the use of the WHO Safe Childbirth Checklist in maternity units.