bluuebunny/crossref_metadata_2025_split huggingface dataset:
Knockdown of PAR2 alleviates cancer-induced bone pain by inhibiting the activation of astrocytes and the ERK pathway
Authors: Tang Yiting , Chen Yupeng , Yang Mingzhu , Zheng Qiuhui , Li Yaoyuan , Bao Yanju 
Published: May 2022

Abstract
Objective
Cancer-induced bone pain (CIBP) is a kind of pain with complex pathophysiology. Proteinase-activated receptor 2 (PAR-2) is involved in CIBP. This study explored the effects of PAR-2 on CIBP rats.

Methods
CIBP rat model was established by injecting Walker 256 rat breast cancer cells into the left tibia of female Sprague-Dawley rats and verified by tibial morphology observation, HE staining, and mechanical hyperalgesia assay. CIBP rats were injected with PAR-2 inhibitor, ERK activator, and CREB inhibitor through the spinal cord sheath on the 13th day after operation. CIBP behaviors were measured by mechanical hyperalgesia assay. On the 14th day after operation, L4-5 spinal cord tissues were obtained. PAR-2 expression, co-expression of PAR-2 and astrocyte marker GFAP, GFAP mRNA and protein levels and the ERK pathway-related protein levels were detected by Western blot, immunofluorescence double staining, RT-qPCR, and Western blot.

Results
CIBP rats had obvious mechanical hyperalgesia and thermal hyperalgesia from the 7th day after modeling; mechanical hyperalgesia threshold and thermal threshold were decreased; PAR-2 was increased in spinal cord tissues and was co-expressed with GFAP. PAR-2 silencing alleviated rat CIBP by inhibiting astrocyte activation. p-ERK/t-ERK and p-CREB/t-CREB levels in CIBP spinal cord were elevated, the ERK/CREB pathway was activated, while the ERK/CREB pathway was inhibited by PAR-2 silencing. The alleviating effect of PAR-2 inhibitor on hyperalgesia behaviors in CIBP rats were weakened by ERK activator, while were partially restored by CREB inhibitor.

Conclusions
PAR-2 knockdown inhibited the ERK/CREB pathway activation and astrocyte activation, thus alleviating CIBP in rats.
Use of massage therapy by mid-aged and older Australian women
Authors: Ladanyi Suzy , Adams Jon , Sibbritt David 
Published: May 2022

AbstractBackgroundMassage is a widely acceptable and popular form of complementary medicine (CM) among Australian women. While there is some research that reports on massage use in younger women, there is minimal research exploring massage use in the treatment of chronic illness in older women. This study provides an estimate of the prevalence of massage use, as well as identifying the characteristics significantly associated with consultation with a massage therapist, for mid-age and older Australian women.MethodsA cross-sectional sub-study was conducted on a sample of women drawn from the45 and Up Study; a large cohort study of adults aged 45 years and over.Data from 1795 women were included in the analyses and massage use was compared against measures of demographics, health status and health care utilisation.ResultsA total of 174 (7.7%) women consulted with a massage therapist in the previous 12 months. Women were more likely to consult a massage therapist if they have tertiary level education (O.R. = 1.67; 95% C.I.: 1.04, 2.65;p = 0.031), private health insurance (O.R. = 6.37; 95% C.I.: 4.41, 9.19;p < 0.001) and/or osteoarthritis (O.R. = 1.72; 95% C.I.: 1.19, 2.48;p = 0.004). They were also more likely to consult a massage therapist if they have a poorer health-related quality of life (HRQoL) (O.R. = 1.14; 95% C.I.: 1.04, 1.27;p = 0.007).ConclusionOlder, tertiary-level educated Australian women with private health insurance were more likely to use massage therapy, as were women with osteoarthritis specifically. Women with lower HRQoL were found to be more likely to use massage therapy in the treatment of their chronic illness. This research provides insight into the determinants of massage use among ageing women and is useful for governments in consideration of accessibility to holistic healthcare when developing public policy for healthcare in Australia.
Pycnogenol a promising remedy for diabetic keratopathy in experimentally induced corneal alkali burns in diabetic rats
Authors: Hamed Mohamed A. , Farag Amany , Zahran Ibrahim S. , Hafez Ahmed , Rizk Mohamed Abdo , Abass Marwa 
Published: May 2022

Abstract
Aim
This study aimed to investigate the efficiency of topically applied pycnogenol (PYC) in healing the standardized alkaline corneal ulcer in diabetic and normal rats.

Materials and methods
The corneal alkali-burn injury (CA-I) model was unilaterally developed in Wistar rats by filter paper saturated with 0.01 M of NaOH and touching the eyes for 45 s. Rats were divided into four groups: Normal control (NC), normal PYC (NPYC), diabetic control (DC), and diabetic PYC (DPYC). Both NPYC and DPYC groups were daily treated with PY eye drops three times, whereas NC and DC ones were treated with ordinary saline for six successive days.

Results
The wound healing of corneal epithelial was improved in the NPYC group compared to the NC group. Meanwhile, it was significantly improved (P < 0.05) in the DPYC group than in the DC group. Histological examination revealed that corneal re-epithelialization was more accomplished in the DPYC group than in the DC group. In addition, the inflammatory cells were augmented in the DC group more than those in the DPYC one.

Conclusion
The findings obtained revealed the efficiency of PYC for enhancing the corneal re-epithelialization and reducing the inflammatory reaction post alkali burn in rats, and thus it could be beneficially valuable as a treatment for the diabetic keratopathy.
Hemoglobin A1C as a prognostic factor and the pre-diabetic paradox in patients admitted to a tertiary care medical center intensive cardiac care unit
Authors: Lupu Lior , Taha Louay , Farkash Rivka , Bayya Feras , Karmi Mohammad , Steinmetz Yoed , Shaheen Fauzi Fadi , Perel Nimrod , Hamayel Kamal , Levi Nir , Maller Tommer , Karameh Hani , Lichewitz Gavriel , Gavish Dov , Algur Nurit , Glikson Michael , Asher Elad 
Published: May 2022

Abstract
Background
Hemoglobin A1C (HbA1c) is a form of glycated hemoglobin used to estimate glycemic control in diabetic patients. Data regarding the prognostic significance of HbA1c levels in contemporary intensive cardiac care unit (ICCU) patients is limited.

Methods
All patients admitted to the ICCU at a tertiary care medical center between January 1, 2020, and June 30, 2021, with documented admission HbA1c levels were included in the study. Patients were divided into 3 groups according to their HbA1c levels: < 5.7 g% [no diabetes mellitus (DM)], 5.7–6.4 g% (pre-DM), ≥ 6.5 g% (DM).

Results
A total of 1412 patients were included. Of them, 974 (69%) were male with a mean age of 67(± 15.7) years old. HbA1c level < 5.7 g% was found in 550 (39%) patients, 5.7–6.4 g% in 458 (32.4%) patients and ≥ 6.5 g% in 404 (28.6%) patients. Among patients who did not know they had DM, 81 (9.3%) patients had high HbA1c levels (≥ 6.5 g%) on admission. The crude mortality rate at follow-up (up to 1.5 years) was almost twice as high among patients with pre-DM and DM than in patients with no DM (10.6% vs. 5.4%, respectively, p = 0.01). Interestingly, although not statistically significant, the trend was that pre-DM patients had the strongest association with mortality rate [HR 1.83, (95% CI 0.936–3.588); p = 0.077].

Conclusions
Although an HbA1c level of ≥ 5.7 g% (pre-DM & DM) is associated with a worse prognosis in patients admitted to ICCU, pre-DM patients, paradoxically, have the highest risk for short and long-term mortality rates.
Attitudes, practices, and determinants of community care-seeking behaviours for fever/malaria episodes in the context of the implementation of multiple first-line therapies for uncomplicated malaria in the health district of Kaya, Burkina Faso
Authors: Kaboré Jean Moise Tanga , Siribié Mohamadou , Hien Denise , Soulama Issiaka , Barry Nouhoun , Nombré Yacouba , Dianda Frederic , Baguiya Adama , Tiono Alfred Bewendtaoré , Burri Christian , Tchouatieu André-Marie , Sirima Sodiomon Bienvenu 
Published: May 2022

Abstract
Background
Malaria case management relies on World Health Organization (WHO)-recommended artemisinin-based combination therapy (ACT), and a continuous understanding of local community knowledge, attitudes, and practices may be a great support for the success of malaria disease control efforts. In this context, this study aimed to identify potential facilitators or barriers at the community level to inform a health district-wide implementation of multiple first-line therapies (MFT) as a new strategy for uncomplicated malaria case management.

Methods
A community-based cross-sectional study using a mixed-method design was carried out from November 2018 to February 2019, in the health district (HD) of Kaya in Burkina Faso. Quantitative data were collected using a standardized questionnaire from 1394 individuals who had fever/malaria episodes four weeks prior to the survey. In addition, 23 focus group discussions (FGDs) were conducted targeting various segments of the community. Logistic regression models were used to assess the predictors of community care-seeking behaviours.

Results
Overall, 98% (1366/1394) of study participants sought advice or treatment, and 66.5% did so within 24 h of fever onset. 76.4% of participants preferred to seek treatment from health centres as the first recourse to care, 5.8% were treated at home with remaining drug stock, and 2.3% preferred traditional healers. Artemether-lumefantrine (AL) was by far the most used anti-malarial drug (98.2%); reported adherence to the 3-day treatment regimen was 84.3%. Multivariate analysis identified less than 5 km distance travelled for care (AOR = 2.7; 95% CI 2.1–3.7) and education/schooling (AOR = 1.8; 95% CI 1.3–2.5) as determinants of prompt care-seeking for fever. Geographical proximity (AOR = 1.5, 95% CI 1.2–2.1), having a child under five (AOR = 4.6, 95% CI 3.2–6.7), being pregnant (AOR = 6.5, 95% CI 1.9–22.5), and living in an urban area (AOR = 2.8, 95% CI 1.8–4.2) were significant predictors for visiting health centres. The FGDs showed that participants had good knowledge about malaria symptoms, prevention tools, and effective treatment. Behaviour change regarding malaria treatment and free medication for children under five were the main reasons for participants to seek care at health centres.

Conclusions
The study showed appropriate knowledge about malaria and positive community care-seeking behaviour at health centres for fever/malaria episodes. This could potentially facilitate the implementation of a MFT pilot programme in the district.
ClinicalTrials.gov Identifier: NCT04265573.
Podocyte specific deletion of PKM2 ameliorates LPS-induced podocyte injury through beta-catenin
Authors: Alquraishi Mohammed , Chahed Samah , Alani Dina , Puckett Dexter L. , Dowker Presley D. , Hubbard Katelin , Zhao Yi , Kim Ji Yeon , Nodit Laurentia , Fatima Huma , Donohoe Dallas , Voy Brynn , Chowanadisai Winyoo , Bettaieb Ahmed 
Published: May 2022

Abstract
Background
Acute kidney injury (AKI) is associated with a severe decline in kidney function caused by abnormalities within the podocytes' glomerular matrix. Recently, AKI has been linked to alterations in glycolysis and the activity of glycolytic enzymes, including pyruvate kinase M2 (PKM2). However, the contribution of this enzyme to AKI remains largely unexplored.

Methods
Cre-loxP technology was used to examine the effects of PKM2 specific deletion in podocytes on the activation status of key signaling pathways involved in the pathophysiology of AKI by lipopolysaccharides (LPS). In addition, we used lentiviral shRNA to generate murine podocytes deficient in PKM2 and investigated the molecular mechanisms mediating PKM2 actions in vitro.

Results
Specific PKM2 deletion in podocytes ameliorated LPS-induced protein excretion and alleviated LPS-induced alterations in blood urea nitrogen and serum albumin levels. In addition, PKM2 deletion in podocytes alleviated LPS-induced structural and morphological alterations to the tubules and to the brush borders. At the molecular level, PKM2 deficiency in podocytes suppressed LPS-induced inflammation and apoptosis. In vitro, PKM2 knockdown in murine podocytes diminished LPS-induced apoptosis. These effects were concomitant with a reduction in LPS-induced activation of β-catenin and the loss of Wilms’ Tumor 1 (WT1) and nephrin. Notably, the overexpression of a constitutively active mutant of β-catenin abolished the protective effect of PKM2 knockdown. Conversely, PKM2 knockdown cells reconstituted with the phosphotyrosine binding–deficient PKM2 mutant (K433E) recapitulated the effect of PKM2 depletion on LPS-induced apoptosis, β-catenin activation, and reduction in WT1 expression.

Conclusions
Taken together, our data demonstrates that PKM2 plays a key role in podocyte injury and suggests that targetting PKM2 in podocytes could serve as a promising therapeutic strategy for AKI.

Trial registration

Not applicable.
Foxtail mosaic virus-induced gene silencing (VIGS) in switchgrass (Panicum virgatum L.)
Authors: Tiedge Kira , Destremps Janessa , Solano-Sanchez Janet , Arce-Rodriguez Magda Lisette , Zerbe Philipp 
Published: May 2022

Abstract
Background
Although the genome for the allotetraploid bioenergy crop switchgrass (Panicum virgatum) has been established, limitations in mutant resources have hampered in planta gene function studies toward crop optimization. Virus-induced gene silencing (VIGS) is a versatile technique for transient genetic studies. Here we report the implementation of foxtail mosaic virus (FoMV)-mediated gene silencing in switchgrass in above- and below-ground tissues and at different developmental stages.

Results
The study demonstrated that leaf rub-inoculation is a suitable method for systemic gene silencing in switchgrass. For all three visual marker genes, Magnesium chelatase subunit D (ChlD) and I (ChlI) as well as phytoene desaturase (PDS), phenotypic changes were observed in leaves, albeit at different intensities. Gene silencing efficiency was verified by RT-PCR for all tested genes. Notably, systemic gene silencing was also observed in roots, although silencing efficiency was stronger in leaves (~ 63–94%) as compared to roots (~ 48–78%). Plants at a later developmental stage were moderately less amenable to VIGS than younger plants, but also less perturbed by the viral infection.

Conclusions
Using FoMV-mediated VIGS could be achieved in switchgrass leaves and roots, providing an alternative approach for studying gene functions and physiological traits in this important bioenergy crop.
Adrenal carcinoma: a case report
Authors: Abeynayake D. R. , V Sopan , Perera K. J. C. , Paramanantham A. , Munasinghe T. M. J. 
Published: May 2022

Abstract
Background
Adrenocortical carcinoma is a rare malignancy (0.5–2 cases/million/year) with a poor prognosis. Hypercortisolism, virilization, and compressive features are among the common presentations of adrenocortical carcinoma. Hematuria is one of the rare initial presentations of adrenocortical carcinoma reported in the literature. We report a case of adrenal carcinoma presenting with microscopic hematuria.

Case presentation
A 67-year-old Sri Lankan patient with diabetes, hypertension, and ischemic heart disease presented with an acute coronary event. During the routine evaluation, microscopic hematuria was detected without proteinuria or active sediments. She denied any painful micturition, previous similar episodes, or abdominal pain. Further evaluation revealed a hypokalemia with biochemical evidence of hypercortisolism and high testosterone levels with suppressed adrenocorticotropic hormone levels. On imaging, there was evidence of a right suprarenal mass 7 cm × 3 cm × 6 cm in size that was hypoechoic and lobulated and suggestive of a lipid-poor tumor. She underwent adrenalectomy. By the time of surgery 3 weeks later, significant weight gain with features of Cushing syndrome, including hirsutism, skin atrophy, easy bruising without virilization, and proximal myopathy, were noted. Histology identified a right-sided adrenal tumor with capsular and vascular invasion. Hypercortisolism and hematuria disappeared after surgery. The patient was referred for further oncological management.

Conclusion
This case illustrates a rare presentation of adrenal carcinoma. Awareness of this presentation may facilitate early evaluation and management.
Chemical reaction network knowledge graphs: the OntoRXN ontology
Authors: Garay-Ruiz Diego , Bo Carles 
Published: May 2022

Abstract
The organization and management of large amounts of data has become a major point in almost all areas of human knowledge. In this context, semantic approaches propose a structure for the target data, defining ontologies that state the types of entities on a certain field and how these entities are interrelated. In this work, we introduce OntoRXN, a novel ontology describing the reaction networks constructed from computational chemistry calculations. Under our paradigm, these networks are handled as undirected graphs, without assuming any traversal direction. From there, we propose a core class structure including reaction steps, network stages, chemical species, and the lower-level entities for the individual computational calculations. These individual calculations are founded on the OntoCompChem ontology and on the ioChem-BD database, where information is parsed and stored in CML format. OntoRXN is introduced through several examples in which knowledge graphs based on the ontology are generated for different chemical systems available on ioChem-BD. Finally, the resulting knowledge graphs are explored through SPARQL queries, illustrating the power of the semantic approach to standardize the analysis of intricate datasets and to simplify the development of complex workflows.

Graphical Abstract
Revision of the genus Protadelomys, a middle Eocene theridomyoid rodent: evolutionary and biochronological implications
Authors: Vianey-Liaud Monique , Hautier Lionel 
Published: May 2022

AbstractThe generic status of the species referred to Protadelomys has long been problematic. Most Protadelomys species are now considered paraphyletic, except for the type species P. cartieri and for P. lugdunensis. Here, we revised these two species from their type locality, Egerkingen (Swiss Jura) for P. cartieri and Lissieu (Rhône, France) for P. lugdunensis. For the latter species, we also consider the locality of Laprade (Tarn-et-Garonne, Quercy, France). Additionally, we revised the material attributed to Protadelomys species that is now considered paraphyletic: ?P. alsaticus from Bouxwiller (Bas-Rhin, France) and Cuzal (Lot, Quercy, France), ?P. maximini from St-Maximin (Gard, France), and ?P. nievesae from Casa Ramon (Huesca, Spain). Our detailed morphological analysis enables us to better characterize the extent of the morphological and size variability in all Protadelomys and ?Protadelomys species. We show that both P. cartieri and P. lugdunensis co-existed in Egerkingen, Lissieu, and Laprade. We also erected a new genus and species, Homœtreposciurus egerkingensis, and reported the presence of Eoelfomys from Egerkingen. Eoelfomys is here described as a new genus and species from Laprade. Size and morphological comparisons enabled us to detect large intraspecific variation in the material of ?P. alsaticus from Bouxwiller, as well as in the type population of ?P. maximini. The co-occurrence of the two Protadelomys species, at least in two localities, in addition to the revision of the features characterizing the three species of ?Protadelomys, led us to question the existence of a single evolutionary lineage (chronospecies), as previously recognized from ?P. maximini to P. lugdunensis.
The role of diffusion-weighted MR imaging in discrimination between benign and malignant axillary lymph nodes in breast cancer patients
Authors: Zahran Amany Mohammed Hussein , Maarouf Rania Aly , Hussein Ahmed , Sheha Aliaa Sayed 
Published: May 2022

Abstract
Background
Noninvasive preoperative evaluation of axillary lymph nodes proved to have a significant role not only on the protocol of treatment of breast cancer but also impact the whole life of the patient. Complications of lymph node biopsy or axillary clearance increase the need for noninvasive reliable diagnostic tool. We aimed in the current study to evaluate the role of diffusion-weighted magnetic resonance imaging (DW-MRI) and apparent diffusion coefficient (ADC) in discrimination between benign and malignant axillary lymph nodes. We included 44 suspicious lymph nodes from 29 patients. Qualitative DW-MRI was analyzed into restricted or not; ADC maps and cut-off value were calculated, and they were correlated with histopathological results, which were the gold standard tool of the current study.

Results
The cut-off value of ADC-differentiated between malignant and benign lymph nodes was 0.89 × 10−3 mm2/s. The statistical indices including the sensitivity, specificity, PPV, NPV and accuracy were 89.66%, 86.67%, 93.9, 81.2% and 87.8%, respectively, with P value < 0.001, while DW-MRI results were classified into restricted or not restricted with qualitative statistical indices of 96.6%, 80%, 90.3%, 92.3% and 90.9% for sensitivity, specificity, PPV, NPV and accuracy, respectively, with P value < 0.001.

Conclusion
DW-MRI and ADC both have significant role in discrimination between benign and malignant axillary lymph nodes increasing the accuracy of MRI examination in breast cancer patients.
In vivo dosimetry in pelvic brachytherapy
Authors: Houlihan Orla Anne , Workman Geraldine , Hounsell Alan R , Prise Kevin M , Jain Suneil 
Published: May 2022

Brachytherapy is an effective treatment in the curative management of prostate and gynaecological cancers. With advances in technology, brachytherapy has increased in complexity in recent years. Human error, equipment malfunction, patient organ motion and radioactive source displacement can result in substantial deviation of delivered dose from planned dose. To limit adverse clinical outcomes, adequate steps to improve the robustness of pathway processes, ensure the implementation of appropriate treatment margins and confirm the delivered dose must be considered. In vivo dosimetry is one such method of dose validation which, if implemented appropriately within clinical practice, is an attractive technique for reducing dosimetric uncertainties and identifying potential errors. This review aims to describe the dosimetric uncertainties and potential errors associated with brachytherapy, the potential for in vivo dosimetry in adaptive brachytherapy as a key method of dose validation, and the clinical considerations and future directions of in vivo dosimetry. Advances in knowledge This paper describes the potential role for in vivo dosimetry in the reduction of uncertainties in pelvic brachytherapy, the pertinent factors for consideration in clinical practice, and the future potential for in vivo dosimetry in the personalisation of brachytherapy.