bluuebunny/crossref_metadata_2025_split huggingface dataset:
Junctional adhesion molecule-like protein promotes tumor progression via the Wnt/β-catenin signaling pathway in lung adenocarcinoma
Authors: Wu Qian , Li Rui , Wang Qing-Xiang , Zhang Meng-Yu , Liu Ting-Ting , Qu Yi-Qing 
Published: June 2022

Abstract
Background
Lung adenocarcinoma (LUAD) is a heavy social burden worldwide. Because the mechanisms involved in LUAD remain unclear, the prognosis of LUAD remains poor. Consequently, it is urgent to investigate the potential mechanisms of LUAD. Junctional adhesion molecule-like protein (JAML), is recognized as a tumorigenesis molecule in gastric cancer. However, the role of JAML in LUAD is still unclear. Here we aimed to evaluate the role of JAML in LUAD.

Methods
qRT-PCR, Western blotting and immunohistochemistry were conducted to investigate the expression of JAML in LUAD tissues. JAML was knocked down and overexpressed in LUAD cells using transient transfection by siRNA and plasmids or stable transfection by lentivirus. Proliferation potential of LUAD cells were detected by Cell Counting Kit-8, EdU incorporation and Colony formation assay. Migration and invasion abilities of LUAD cells were determined by wound healing, transwell migration and invasion assays. Cell cycle and cell apoptosis were detected by flow cytometry. The effects of JAML in vivo were studied in xenograft tumor models. Western blotting was used to explore the molecular mechanisms of JAML function. In addition, rescue experiments were performed to verify the possible mechanisms.

Results
JAML expression was elevated in LUAD tissues compared with peritumor tissues, and this upregulation was positively related to pT and pTNM. Furthermore, both in vitro and in vivo, JAML silencing markedly repressed malignant behaviors of LUAD cells and vice versa. Knockdown of JAML also mediated cell cycle arrest at G0/G1 phase and promoted apoptosis in LUAD cells. Mechanistically, silencing JAML repressed the process of epithelial-mesenchymal transition by inactivating the Wnt/β-catenin pathway in LUAD cells. Effects of JAML can be rescued by Wnt/β-catenin pathway activator in A549 cells.

Conclusions
Our data reveal the oncogenic role of JAML in LUAD, indicating that JAML may be a predictive biomarker and novel therapeutic target for LUAD.
Dengue infection triggered immune mediated necrotizing myopathy in children: a case report and literature review
Authors: Mekmangkonthong Aphirak , Amornvit Jakkrit , Numkarunarunrote Numphung , Veeravigrom Montida , Khaosut Parichat 
Published: June 2022

Abstract
Background
Immune-mediated necrotizing myopathy (IMNM) is a subgroup of idiopathic inflammatory myopathies manifesting with progressive weakness, elevated serum creatine kinase (CK) levels, and necrotizing myopathic features on muscle biopsy. There is a paucity of data on the clinical presentation of IMNM in children. We report a paediatric patient who developed anti-3-hydroxy-3-methylglutaryl-CoA reductase (anti-HMGCR)-positive necrotizing myopathy after recent dengue infection.

Case presentation
A previously healthy 9-year-old boy presented with acute proximal muscle weakness after recovery from dengue infection. Five days after the fever subsided, he could not stand from a squatting position. He denied having skin rash, arthritis, or other systemic features. He had marked elevation of CK level of 30,833 mg/dL and was put on steroid therapy. The patient initially responded to oral prednisolone, however the weakness persisted and muscle enzymes increased as steroids were decreased. He was then referred to our hospital for further assessment. Subsequent investigation revealed anti-HMGCR positivity along with specific histopathological findings consistent with IMNM. The patient was treated with six cycles of intravenous immunoglobulin (IVIG) monthly, then followed by a gradual taper of prednisolone and oral methotrexate weekly with complete recovery in motor power.

Conclusions
Our report presents a child with clinical manifestations of IMNM which can be categorized as acute onset of muscle weakness following dengue infection. Two key points supporting a diagnosis in this case are clinical response after immunosuppressive therapy and absence of rashes found in juvenile dermatomyositis.
Vascular network expansion, integrity of blood–brain interfaces, and cerebrospinal fluid cytokine concentration during postnatal development in the normal and jaundiced rat
Authors: Blondel Sandrine , Strazielle Nathalie , Amara Amel , Guy Rainui , Bain Christine , Rose Alix , Guibaud Laurent , Tiribelli Claudio , Gazzin Silvia , Ghersi-Egea Jean-François 
Published: June 2022

Abstract
Background
Severe neonatal jaundice resulting from elevated levels of unconjugated bilirubin in the blood induces dramatic neurological impairment. Central oxidative stress and an inflammatory response have been associated with the pathophysiological mechanism. Cells forming the blood–brain barrier and the choroidal blood–CSF barrier are the first CNS cells exposed to increased plasma levels of unconjugated bilirubin. These barriers are key regulators of brain homeostasis and require active oxidative metabolism to fulfill their protective functions. The choroid plexus-CSF system is involved in neuroinflammatory processes. In this paper, we address the impact of neonatal hyperbilirubinemia on some aspects of brain barriers. We describe physiological changes in the neurovascular network, blood–brain/CSF barriers integrities, and CSF cytokine levels during the postnatal period in normobilirubinemic animals, and analyze these parameters in parallel in Gunn rats that are deficient in bilirubin catabolism and develop postnatal hyperbilirubinemia.

Methods
Gunn rats bearing a mutation in UGT1a genes were used. The neurovascular network was analyzed by immunofluorescence stereomicroscopy. The integrity of the barriers was evaluated by [14C]-sucrose permeability measurement. CSF cytokine levels were measured by multiplex immunoassay. The choroid plexus-CSF system response to an inflammatory challenge was assessed by enumerating CSF leukocytes.

Results
In normobilirubinemic animals, the neurovascular network expands postnatally and displays stage-specific regional variations in its complexity. Network expansion is not affected by hyperbilirubinemia. Permeability of the blood–brain and blood–CSF barriers to sucrose decreases between one- and 9-day-old animals, and does not differ between normobilirubinemic and hyperbilirubinemic rats. Cytokine profiles differ between CSF and plasma in all 1-, 9-, and 18-day-old animals. The CSF cytokine profile in 1-day-old animals is markedly different from that established in older animals. Hyperbilirubinemia perturbs these cytokine profiles only to a very limited extent, and reduces CSF immune cell infiltration triggered by systemic exposure to a bacterial lipopeptide.

Conclusion
The data highlight developmental specificities of the blood–brain barrier organization and of CSF cytokine content. They also indicate that a direct effect of bilirubin on the vascular system organization, brain barriers morphological integrity, and inflammatory response of the choroid plexus-CSF system is not involved in the alteration of brain functions induced by severe neonatal jaundice.
Monteggia fractures: analysis of patient-reported outcome measurements in correlation with ulnar fracture localization
Authors: Tille Eric , Seidel L. , Schlüßler A. , Beyer Franziska , Kasten P. , Bota O. , Biewener A. , Nowotny J. 
Published: June 2022

Abstract
Background
Monteggia fractures and Monteggia-like lesions result after severe trauma and have high complication rates. Preliminary biomechanical studies suggested a correlation between ulnar fracture localization and clinical result.

Objectives
Key objective was to evaluate whether the site of the ulnar fracture can be correlated to clinical outcome after open reduction and internal stabilization.

Methods
In a retrospective, monocentric study 35 patients who underwent surgical treatment after suffering a Monteggia injury or Monteggia-like lesion were included. Fractures were classified according to Bado and Jupiter, the site of the fracture location at the proximal ulna and regarding the potential accompanying ligamentary injury. In a follow-up examination validated patient-reported outcome measures and functional parameters were evaluated. Furthermore, treatment strategy and complications were analysed.

Results
Mean patient age was 51.9 years (± 18.0). 69% were females (n = 24). Follow-up took place after 50.5 months (± 22.1). Fractures were classified according to Bado (I:2, II:27, III:4, IV:2). Bado II-fractures were further classified according to Jupiter (A:7, B:16, C:3, D:1). Cases were divided into subgroups depending upon the distance of the ulnar fracture site in respect to its distal endpoint (A: < 7 cm and B: > 7 cm). Average overall MEPS was 84.1 (± 19.0). Oxford elbow score and DASH were 37.2 (± 10.5) and 20.4 (± 20.5). Average extension capability reached − 7° (± 7.5). Mean flexion was 134.8° (± 19.7). Average pain according to visual analogue scale was 1.6 (± 1.9). We found no differences between the subgroups regarding the PROMs. Subgroup A displayed a worse extension capability (p = 0.027) and patients were significantly older (p < 0.01). Comparing patients with and without fracture of the radial head, we observed no differences. Patients with an accompanying injury of the coronoid process displayed higher pain levels (p = 0.011), a worse functionality (p = 0.027) and overall lower scoring in PROM.

Conclusion
The presented results suggest that in Monteggia fractures and Monteggia-like lesions, the localization of the ulna fracture can give a hint for its postoperative outcome. However, we could not confirm the hypothesis of an increasing instability in ulnar fractures located further distally (high severity of the potential ligamentous injury). Intraarticular fractures or injuries with a close relation to the joint have a worse prognosis, especially if the coronoid process is injured.
Trial registration Registration was done with ClinicalTrials.gov under NCT05325268.
Concurrent double aortic arch and circumflex aorta repair in a symptomatic child: a case report
Authors: Hurtado Christopher G. , Nelson Jennifer S. 
Published: June 2022

AbstractDouble aortic arch with circumflex aorta is a rare type of vascular ring. Symptoms result from external compression of the trachea and esophagus. The best surgical approach for patients with double arch and circumflex aorta is debated, and options include the highly complex aortic uncrossing procedure. Herein we describe the surgical treatment of a patient with concurrent double aortic arch and circumflex aorta by division of the non-dominant arch and ligamentum arteriosum, plication and posterior tacking of the diverticulum of Kommerell. This left thoracotomy approach provided complete symptom resolution.
Risk factors for miscarriage in Syrian refugee women living in non-camp settings in Jordan: results from the Women ASPIRE cross-sectional study
Authors: Khadra Maysa M. , Suradi Haya H. , Amarin Justin Z. , El-Bassel Nabila , Kaushal Neeraj , Jaber Ruba M. , Al-Qutob Raeda , Dasgupta Anindita 
Published: June 2022

Abstract
Background
Syrian refugee women face health care disparities and experience worse pregnancy outcomes, including miscarriage. We investigated risk factors for miscarriage in Syrian refugee women living in non-camp settings in Jordan to identify targets for interventions.

Methods
We analyzed data from Women ASPIRE, a cross-sectional study of gendered physical and mental health concerns of 507 Syrian refugee women (≥ 18 years old) living in non-camp settings in Jordan. We recruited women using systematic clinic-based sampling from four clinics. We limited our analyses to women who had a history of pregnancy and whose most recent pregnancy was single, took place in Jordan, and ended in term live birth or miscarriage (N = 307). We grouped the women by the primary outcome (term live birth or miscarriage) and compared the sociodemographic and clinical characteristics of the two groups. We used Pearson’s χ2 test or the Mann–Whitney U test to obtain unadjusted estimates and multivariable binomial logistic regression to obtain adjusted estimates.

Results
The most recent pregnancies of 262 women (85%) ended in term live birth and another 45 (15%) ended in miscarriage. Since crossing into Jordan, 11 women (4%) had not received reproductive health services. Of 35 women who were ≥ 35 years old, not pregnant, and did not want a (or another) child, nine (26%) did not use contraception. Of nine women who were ≥ 35 years old and pregnant, seven (78%) did not plan the pregnancy. The adjusted odds of miscarriage were higher in women who had been diagnosed with thyroid disease (aOR, 5.54; 95% CI, 1.56–19.07), had been of advanced maternal age (aOR, 5.83; 95% CI, 2.02–16.91), and had not received prenatal care (aOR, 36.33; 95% CI, 12.04–129.71). Each additional previous miscarriage predicted an increase in the adjusted odds of miscarriage by a factor of 1.94 (1.22–3.09).

Conclusions
We identified several risk factors for miscarriage in Syrian refugee women living in non-camp settings in Jordan. The risk factors may be amenable to preconception and prenatal care.
Patient selection for CAR T or BiTE therapy in multiple myeloma: Which treatment for each patient?
Authors: Kegyes David , Constantinescu Catalin , Vrancken Louise , Rasche Leo , Gregoire Celine , Tigu Bogdan , Gulei Diana , Dima Delia , Tanase Alina , Einsele Hermann , Ciurea Stefan , Tomuleasa Ciprian , Caers Jo 
Published: June 2022

AbstractMultiple myeloma (MM) is a plasma cell malignancy that affects an increasing number of patients worldwide. Despite all the efforts to understand its pathogenesis and develop new treatment modalities, MM remains an incurable disease. Novel immunotherapies, such as CAR T cell therapy (CAR) and bispecific T cell engagers (BiTE), are intensively targeting different surface antigens, such as BMCA, SLAMF7 (CS1), GPRC5D, FCRH5 or CD38. However, stem cell transplantation is still indispensable in transplant-eligible patients. Studies suggest that the early use of immunotherapy may improve outcomes significantly. In this review, we summarize the currently available clinical literature on CAR and BiTE in MM. Furthermore, we will compare these two T cell-based immunotherapies and discuss potential therapeutic approaches to promote development of new clinical trials, using T cell-based immunotherapies, even as bridging therapies to a transplant.
Efficacy and safety of piezocision in accelerating maxillary anterior teeth en-masse retraction: study protocol for a randomized controlled trial
Authors: Xu Yichen , Yu Liming , Tong Xianqin , Wang Yuhui , Li Yuanyuan , Pan Jie , Yang Yanjing , Liu Yuehua 
Published: June 2022

Abstract
Background
Orthodontic treatment is commonly more time-consuming in adults than in teenagers, especially when it comes to the maxillary en-masse retraction, which may take 9 months or even longer. As to solve this concern, orthodontists have been striving to seek new methods for shortening orthodontic treatment time. Piezocision, as a popular alternative treatment, has been widely used in different types of tooth movement. However, its effect on en-masse retraction of maxillary anterior teeth remains unclear. This randomized controlled trial intends to figure out the role piezocision plays in accelerating en-masse retraction.

Methods
This protocol is designed for a prospective, single-center, assessor-blinded and parallel-group randomized controlled trial. Twenty adult patients aged from 18 to 40 whose orthodontic treatment required bilateral maxillary first premolars extraction will be randomly assigned to the piezocision group and the control group at a ratio of 1:1. The piezocision group will undergo en-masse retraction immediately after the piezo surgery, while the control group will start en-masse retraction directly. Both groups will be followed up every 2 weeks to maintain the retraction force until the end of space closure. The space closing time is set as the primary endpoint. Meanwhile, the secondary endpoints include the change of root length, labial and palatal alveolar bone thickness, vertical bone height, probing depth of maxillary anterior teeth, cephalometric measurements, visual analogue scale, and postoperative satisfaction questionnaire.

Discussion
This study will attempt to provide more convincing evidence to verify whether piezocision will shorten the time of en-masse retraction or not. Distinguished with previous studies, our study has made some innovations in orthodontic procedure and primary outcome measurement, aiming to clarify the efficacy and safety of piezocision-assisted en-masse retraction in Chinese population.

Trial registration
Chinese Clinical Trial Registry ChiCTR 1900024297. Registered on 5 July 2019
Retinoic acid inhibits the angiogenesis of human embryonic stem cell-derived endothelial cells by activating FBP1-mediated gluconeogenesis
Authors: Yang Zhuangzhuang , Yu Miao , Li Xuechun , Tu Yuanyuan , Wang Chunyan , Lei Wei , Song Min , Wang Yong , Huang Ying , Ding Fengyue , Hao Kaili , Han Xinglong , Ni Xuan , Qu Lina , Shen Zhenya , Hu Shijun 
Published: June 2022

Abstract
Background
Endothelial cells are located in the inner lumen of blood and lymphatic vessels and exhibit the capacity to form new vessel branches from existing vessels through a process called angiogenesis. This process is energy intensive and tightly regulated. Glycolysis is the main energy source for angiogenesis. Retinoic acid (RA) is an active metabolite of vitamin A and exerts biological effects through its receptor retinoic acid receptor (RAR). In the clinic, RA is used to treat acne vulgaris and acute promyelocytic leukemia. Emerging evidence suggests that RA is involved in the formation of the vasculature; however, its effect on endothelial cell angiogenesis and metabolism is unclear.

Methods
Our study was designed to clarify the abovementioned effect with human embryonic stem cell-derived endothelial cells (hESC-ECs) employed as a cell model.

Results
We found that RA inhibits angiogenesis, as manifested by decreased proliferation, migration and sprouting activity. RNA sequencing revealed general suppression of glycometabolism in hESC-ECs in response to RA, consistent with the decreased glycolytic activity and glucose uptake. After screening glycometabolism-related genes, we found that fructose-1,6-bisphosphatase 1 (FBP1), a key rate-limiting enzyme in gluconeogenesis, was significantly upregulated after RA treatment. After silencing or pharmacological inhibition of FBP1 in hESC-ECs, the capacity for angiogenesis was enhanced, and the inhibitory effect of RA was reversed. ChIP-PCR demonstrated that FBP1 is a target gene of RAR. When hESC-ECs were treated with the RAR inhibitor BMS493, FBP1 expression was decreased and the effect of RA on angiogenesis was partially blocked.

Conclusions
The inhibitory role of RA in glycometabolism and angiogenesis is RAR/FBP1 dependent, and FBP1 may be a novel therapeutic target for pathological angiogenesis.
Pharmacological affinity fingerprints derived from bioactivity data for the identification of designer drugs
Authors: He Kedan 
Published: June 2022

AbstractFacing the continuous emergence of new psychoactive substances (NPS) and their threat to public health, more effective methods for NPS prediction and identification are critical. In this study, the pharmacological affinity fingerprints (Ph-fp) of NPS compounds were predicted by Random Forest classification models using bioactivity data from the ChEMBL database. The binary Ph-fp is the vector consisting of a compound’s activity against a list of molecular targets reported to be responsible for the pharmacological effects of NPS. Their performance in similarity searching and unsupervised clustering was assessed and compared to 2D structure fingerprints Morgan and MACCS (1024-bits ECFP4 and 166-bits SMARTS-based MACCS implementation of RDKit). The performance in retrieving compounds according to their pharmacological categorizations is influenced by the predicted active assay counts in Ph-fp and the choice of similarity metric. Overall, the comparative unsupervised clustering analysis suggests the use of a classification model with Morgan fingerprints as input for the construction of Ph-fp. This combination gives satisfactory clustering performance based on external and internal clustering validation indices.
Probabilistic metabolite annotation using retention time prediction and meta-learned projections
Authors: García Constantino A. , Gil-de-la-Fuente Alberto , Barbas Coral , Otero Abraham 
Published: June 2022

AbstractRetention time information is used for metabolite annotation in metabolomic experiments. But its usefulness is hindered by the availability of experimental retention time data in metabolomic databases, and by the lack of reproducibility between different chromatographic methods. Accurate prediction of retention time for a given chromatographic method would be a valuable support for metabolite annotation. We have trained state-of-the-art machine learning regressors using the 80, 038 experimental retention times from the METLIN Small Molecule Retention Tim (SMRT) dataset. The models included deep neural networks, deep kernel learning, several gradient boosting models, and a blending approach. 5, 666 molecular descriptors and 2, 214 fingerprints (MACCS166, Extended Connectivity, and Path Fingerprints fingerprints) were generated with the alvaDesc software. The models were trained using only the descriptors, only the fingerprints, and both types of features simultaneously. Bayesian hyperparameter search was used for parameter tuning. To avoid data-leakage when reporting the performance metrics, nested cross-validation was employed. The best results were obtained by a heavily regularized deep neural network trained with cosine annealing warm restarts and stochastic weight averaging, achieving a mean and median absolute errors of$$39.2 \pm 1.2\; s$$39.2±1.2sand$$17.2 \pm 0.9\;s$$17.2±0.9s, respectively. To the best of our knowledge, these are the most accurate predictions published up to date over the SMRT dataset. To project retention times between chromatographic methods, a novel Bayesian meta-learning approach that can learn from just a few molecules is proposed. By applying this projection between the deep neural network retention time predictions and a given chromatographic method, our approach can be integrated into a metabolite annotation workflow to obtain z-scores for the candidate annotations. To this end, it is enough that just as few as 10 molecules of a given experiment have been identified (probably by using pure metabolite standards). The use of z-scores permits considering the uncertainty in the projection when ranking candidates, and not only the accuracy. In this scenario, our results show that in 68% of the cases the correct molecule was among the top three candidates filtered by mass and ranked according to z-scores. This shows the usefulness of this information to support metabolite annotation. Python code is available on GitHub at https://github.com/constantino-garcia/cmmrt.