bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acidification is required for calcium and magnesium concentration measurements in equine urine
Authors: Lapsina Sandra , Stirn Martina , Hofmann-Lehmann Regina , Schoster Angelika , Riond Barbara 
Published: January 2024

Abstract
Background
Acidification of equine urine to promote dissociation of ion complexes is a common practice for urine ion concentration measurements. The objective of this study was to evaluate the effect of acidification and storage after acidification on calcium (Ca), magnesium (Mg) and phosphate (P) concentrations and on fractional excretion (FE) of these electrolytes. Thirty-two fresh equine urine samples were analysed between December 2016 and July 2020. Complete urinalysis (stick and sediment) was performed on all samples. Ca, Mg, P and creatinine concentrations were measured in supernatant of centrifuged native urine, urine directly centrifuged after acidification and urine centrifuged 1 hour after acidification. Urine was acidified with hydrochloric acid to reach a pH of 1–2. Ca, Mg, P and creatinine concentrations were also measured in blood plasma, and fractional excretion of each electrolyte was calculated. Equality of medians was tested with Friedman tests and Bland-Altman bias plots were used to show the agreement between conditions.

Results
Acidification had a statistically significant effect on Ca and Mg concentrations, FECa and FEMg. Bland-Altman plot revealed a strong positive proportional bias between Ca concentration in native and acidified urine with a mean bias of 17.6 mmol/l. For Mg concentration, the difference between native and acidified urine was small with a mean bias of 1.8 mmol/l. The increase in FECa was clinically relevant. Storage of acidified urine had no effect on any of the measured ion concentrations. All P concentrations in native urine samples were below the detection limit of the assay and statistical analysis and calculation of FEP was not possible.

Conclusions
Urine acidification is essential for accurate measurement of Ca and Mg concentrations and therefore FE calculations in equine urine. Storage time of 1 hour after acidification does not significantly change Ca and Mg concentrations.
Identification of breast cancer subgroups and immune characterization based on glutamine metabolism-related genes
Authors: Yu Hongjing , Liu Junchen 
Published: January 2024

AbstractImmunotherapy is a promising treatment for breast cancer (BC). However, due to individual differences and tumor heterogeneity, immunotherapy is only applicable to some BC patients. Glutamine metabolism plays a role in inhibiting immunotherapy, but its role in BC is limitedly studied. Therefore, we aimed to identify different BC subgroups based on glutamine metabolism and characterize the features of different subgroups to provide guidance for personalized immunotherapy for BC patients. Using unsupervised clustering analysis, we classified BC patients in The Cancer Genome Atlas (TCGA) with glutamine metabolism-related genes and obtained low-risk (LR) and high-risk (HR) subgroups. Survival analysis revealed that prognosis of LR subgroup was notably better than HR subgroup. Through ssGSEA and CIBERSORT methods, we disclosed that infiltration levels of B cells, Mast cells, T helper cells, and Th2 cells, and Type II IFN Response immune function were notably higher in LR subgroup than in HR subgroup. The Wilcox algorithm comparison denoted that DEPTH of LR subgroup was significantly lower than HR subgroup. The TIDE of LR subgroup was significantly higher than HR subgroup. Functional annotation of differentially expressed genes revealed that channel activity and the Estrogen signaling pathway may be related to BC prognosis. Ten hub genes were selected between the subgroups through the STRING database and Cytoscape, and their correlation with drugs was predicted on the CellMiner website. This study analyzed the immune characteristics of BC subgroups based on glutamine metabolism and provided reference for prognosis prediction and personalized immunotherapy.
The use of cultured human alveolar basal cells to mimic honeycomb formation in idiopathic pulmonary fibrosis
Authors: Blumer Sabrina , Khan Petra , Artysh Nataliia , Plappert Linda , Savic Spasenija , Knudsen Lars , Jonigk Danny , Kuehnel Mark P. ,  Prasse Antje , Hostettler Katrin E. 
Published: January 2024

Abstract
Background
Honeycomb cysts (HC) within the alveolar region are distinct histopathological features in the lungs of idiopathic pulmonary fibrosis (IPF) patients. HC are lined with a single-or stratified layer of basal cells (BC), or with a bronchiolar-like epithelium composed of basal-, ciliated- and secretory epithelial cells. By using cultured IPF patient-derived alveolar BC, we aimed to establish an in vitro- and in vivo model to mimic HC formation in IPF. We (1) optimized conditions to culture and propagate IPF patient-derived alveolar BC, (2) cultured the cells on an air liquid interface (ALI) or in a three dimensional (3D) organoid model, and (3) investigated the cells` behavior after instillation into bleomycin-challenged mice.

Methods
Alveolar BC were cultured from peripheral IPF lung tissue and grown on tissue-culture treated plastic, an ALI, or in a 3D organoid model. Furthermore, cells were instilled into bleomycin-challenged NRG mice. Samples were analyzed by TaqMan RT-PCR, immunoblotting, immunocytochemistry/immunofluorescence (ICC/IF), or immunohistochemistry (IHC)/IF. Mann–Whitney tests were performed using GraphPad Prism software.

Results
Cultured alveolar BC showed high expression of canonical basal cell markers (TP63, keratin (KRT)5, KRT14, KRT17), robust proliferation, and wound closure capacity. The cells could be cryopreserved and propagated for up to four passages without a significant loss of basal cell markers. When cultured on an ALI or in a 3D organoid model, alveolar BC differentiated to ciliated- and secretory epithelial cells. When instilled into bleomycin-challenged mice, human alveolar BC cells formed HC-like structures composed of human basal-, and secretory epithelial cells within the mouse parenchyma.

Conclusion
IPF patient-derived alveolar BC on an ALI, in 3D organoids or after instillation into bleomycin-challenged mice form HC-like structures that closely resemble HC within the IPF lung. These models therefore represent powerful tools to study honeycomb formation, and its potential therapeutic inhibition in IPF.
Impact of immunohistochemical expression of kinesin family member 18A (Kif18A) and β-catenin in infiltrating breast carcinoma of no special type
Authors: Hemida Aiat Shaban , Shabaan Mohammed Ibrahim , Taha Mennatallah Ahmed , Abdou Asmaa Gaber 
Published: January 2024

Abstract
Background
KIF18A is a regulator of the cell cycle that stimulates the proliferation of cancer cells. The Wnt/β-catenin pathway is involved in different issues’ carcinogenesis and is being examined as a therapeutic target. The relationship between KIF18A and β-catenin in breast cancer was not previously investigated. Therefore, this work aims to study the immunohistochemical expression and correlation of KIF18A and β-catenin in breast-infiltrating duct carcinoma (IDC) and their relation to prognosis.

Material and methods
Slides cut from paraffin blocks of 135 IDC and 40 normal breast tissues were stained by KIF18A and β-catenin antibodies. KIF18A cytoplasmic or nucleocytoplasmic staining and β-catenin aberrant expression either nucleo-cytoplasmic or cytoplasmic staining were considered.

Results
Normal breast tissue and IDC showed a significant difference regarding KIF18A and aberrant β-catenin expression. High KIF18A and β-catenin H score values were associated with poor prognostic factors such as high grade, advanced stage, distant metastasis, high Ki67 status, and Her2neu-enriched subtype. There was a significant direct correlation between KIF18A and β-catenin as regards percent and H score values. Prolonged overall survival (OS) was significantly associated with mild intensity and low H score of KIF18A, and low β-catenin H score.

Conclusions
KIF18A could be involved in breast carcinogenesis by activating β-catenin. Overexpression of KIF18A and aberrant expression of β-catenin are considered proto-oncogenes of breast cancer development. KIF18A and β-catenin could be poor prognostic markers and predictors of aggressive behavior of breast cancer.
Progress in the clinical effects and adverse reactions of ticagrelor
Authors: Wei Peng , Wang Xiaoqing , Fu Qiang , Cao Bangming 
Published: January 2024

Abstract
Background
Ticagrelor is a novel receptor antagonist that selectively binds to the P2Y12 receptor, thereby inhibiting adenosine diphosphate (ADP)-mediated platelet aggregation. Compared to clopidogrel, ticagrelor has the advantages of a fast onset, potent effects, and a reversible platelet inhibition function, which make this drug clinically suitable for treating acute coronary syndrome (ACS), especially acute ST-segment elevation myocardial infarction (STEMI).

Objective
This review was performed to determine the basic characteristics, clinical effects, and adverse reactions of ticagrelor.

Methods
Relevant trials and reports were obtained from the MEDLINE, Embase, and Cochrane Library databases.

Results
Ticagrelor is rapidly absorbed by the body after oral administration, exhibits inherent activity without requiring metabolic activation, and binds reversibly to the P2Y12 receptor. Ticagrelor has been recommended in ACS treatment guidelines worldwide due to its advantageous pharmacological properties and significant clinical benefits. Ticagrelor inhibits platelet aggregation, inhibits inflammatory response, enhances adenosine function, and has cardioprotective effects. However, ticagrelor also causes adverse reactions such as bleeding tendency, dyspnea, ventricular pause, gout, kidney damage, and thrombotic thrombocytopenic purpura in clinical treatment. Therefore, it is necessary to pay attention to risk assessments when using ticagrelor.

Conclusion
Ticagrelor is a promising drug for the effective treatment of ACS. When using ticagrelor, individualized treatment should be provided based on the specific conditions of the patients to avoid serious adverse events.
Protein cargo in extracellular vesicles as the key mediator in the progression of cancer
Authors: Hánělová Klára , Raudenská Martina , Masařík Michal , Balvan Jan 
Published: January 2024

AbstractExosomes are small vesicles of endosomal origin that are released by almost all cell types, even those that are pathologically altered. Exosomes widely participate in cell-to-cell communication via transferring cargo, including nucleic acids, proteins, and other metabolites, into recipient cells. Tumour-derived exosomes (TDEs) participate in many important molecular pathways and affect various hallmarks of cancer, including fibroblasts activation, modification of the tumour microenvironment (TME), modulation of immune responses, angiogenesis promotion, setting the pre-metastatic niche, enhancing metastatic potential, and affecting therapy sensitivity and resistance. The unique exosome biogenesis, composition, nontoxicity, and ability to target specific tumour cells bring up their use as promising drug carriers and cancer biomarkers. In this review, we focus on the role of exosomes, with an emphasis on their protein cargo, in the key mechanisms promoting cancer progression. We also briefly summarise the mechanism of exosome biogenesis, its structure, protein composition, and potential as a signalling hub in both normal and pathological conditions.
Machine learning prediction of pathological complete response and overall survival of breast cancer patients in an underserved inner-city population
Authors: Dell’Aquila Kevin , Vadlamani Abhinav , Maldjian Takouhie , Fineberg Susan , Eligulashvili Anna , Chung Julie , Adam Richard , Hodges Laura , Hou Wei , Makower Della , Duong Tim Q. 
Published: January 2024

Abstract
Background
Generalizability of predictive models for pathological complete response (pCR) and overall survival (OS) in breast cancer patients requires diverse datasets. This study employed four machine learning models to predict pCR and OS up to 7.5 years using data from a diverse and underserved inner-city population.

Methods
Demographics, staging, tumor subtypes, income, insurance status, and data from radiology reports were obtained from 475 breast cancer patients on neoadjuvant chemotherapy in an inner-city health system (01/01/2012 to 12/31/2021). Logistic regression, Neural Network, Random Forest, and Gradient Boosted Regression models were used to predict outcomes (pCR and OS) with fivefold cross validation.

Results
pCR was not associated with age, race, ethnicity, tumor staging, Nottingham grade, income, and insurance status (p > 0.05). ER−/HER2+ showed the highest pCR rate, followed by triple negative, ER+/HER2+, and ER+/HER2− (all p < 0.05), tumor size (p < 0.003) and background parenchymal enhancement (BPE) (p < 0.01). Machine learning models ranked ER+/HER2−, ER−/HER2+, tumor size, and BPE as top predictors of pCR (AUC = 0.74–0.76). OS was associated with race, pCR status, tumor subtype, and insurance status (p < 0.05), but not ethnicity and incomes (p > 0.05). Machine learning models ranked tumor stage, pCR, nodal stage, and triple-negative subtype as top predictors of OS (AUC = 0.83–0.85). When grouping race and ethnicity by tumor subtypes, neither OS nor pCR were different due to race and ethnicity for each tumor subtype (p > 0.05).

Conclusion
Tumor subtypes and imaging characteristics were top predictors of pCR in our inner-city population. Insurance status, race, tumor subtypes and pCR were associated with OS. Machine learning models accurately predicted pCR and OS.
Characteristics of the synovial microenvironment and synovial mesenchymal stem cells with hip osteoarthritis of different bone morphologies
Authors: Yang Yang , Koga Hideyuki , Nakagawa Yusuke , Nakamura Tomomasa , Katagiri Hiroki , Takada Ryohei , Katakura Mai , Tsuji Kunikazu , Sekiya Ichiro , Miyatake Kazumasa 
Published: January 2024

Abstract
Background
Variations in bone morphology in patients with hip osteoarthritis (HOA) can be broadly categorized into three types: atrophic, normotrophic, and hypertrophic. Despite the investigations examining clinical elements, such as bone morphology, pain, and range of motion, our understanding of the pathogenesis of HOA remains limited. Previous studies have suggested that osteophytes typically originate at the interface of the joint cartilage, periosteum, and synovium, potentially implicating synovial mesenchymal stem cells (SMSCs) in the process. This study aimed to investigate the potential factors that drive the development of bone morphological features in HOA by investigating the characteristics of the synovium, differentiation potential of SMSCs, and composition of synovial fluid in different types of HOA.

Methods
Synovial tissue and fluid were collected from 30 patients who underwent total hip arthroplasty (THA) with the variable bone morphology of HOA patients. RNA sequencing analysis and quantitative reverse transcription-polymerase chain reaction (RT-qPCR) were performed to analyse the genes in the normotrophic and hypertrophic synovial tissue. SMSCs were isolated and cultured from the normotrophic and hypertrophic synovial tissues of each hip joint in accordance with the variable bone morphology of HOA patients. Cell differentiation potential was compared using differentiation and colony-forming unit assays. Cytokine array was performed to analyse the protein expression in the synovial fluid.

Results
In the RNA sequencing analysis, 103 differentially expressed genes (DEGs) were identified, predominantly related to the interleukin 17 (IL-17) signalling pathway. Using a protein–protein interaction (PPI) network, 20 hub genes were identified, including MYC, CXCL8, ATF3, NR4A1, ZC3H12A, NR4A2, FOSB, and FOSL1. Among these hub genes, four belonged to the AP-1 family. There were no significant differences in the tri-lineage differentiation potential and colony-forming capacity of SMSCs. However, RT-qPCR revealed elevated SOX9 expression levels in synovial tissues from the hypertrophic group. The cytokine array demonstrated significantly higher levels of CXCL8, MMP9, and VEGF in the synovial fluid of the hypertrophic group than in the normotrophic group, with CXCL8 and MMP9 being significantly expressed in the hypertrophic synovium.

Conclusion
Upregulation of AP-1 family genes in the synovium and increased concentrations of CXCL8, MMP9, and VEGF were detected in the synovial fluid of the hypertrophic group of HOA patients, potentially stimulating the differentiation of SMSCs towards the cartilage and thereby contributing to severe osteophyte formation.
A controlled clinical trial investigating the effects of stretching and compression exercises on electromyography of calf muscles in chronic LBP patients with a deep gluteal syndrome
Authors: Shamsi MohammadBagher , Mirzaei Maryam , Hopayian Kevork 
Published: January 2024

Abstract
Background
In deep gluteal syndrome (DGS), the piriformis muscle could impinge the sciatic nerve. The FAIR (flexion adduction internal rotation) test is a provocation test used to identify sciatic nerve irritation caused by this muscle. Compression and stretching exercises are usually prescribed to treat this syndrome. The aim of this study was to compare the effects of these two treatments on surface electromyography (sEMG) of the gastrocnemius and tibialis anterior in patients with low back pain (LBP) and DGS.

Materials and methods
Forty-five participants were allocated to three groups of stretching exercise, compression or control. In addition to 15 min of heat and 15 min of electrical nerve stimulation for pain relief, participants in the compression exercise (CE) group received self-compression exercise, those in the stretching exercise (SE) group received self-stretching exercise and those in the control group received no extra interventions. For the two intervention groups, three sets of two minutes of exercise with two minutes of rest in between were applied. The sEMG amplitude values of the gastrocnemius and tibialis anterior muscles of the affected buttock side of any one group while performing the FAIR test were compared to the others. Pain and disability were assessed and the changes were compared between the two groups.

Results
After the intervention period, no group demonstrated a change in the sEMG of the gastrocnemius or tibialis anterior muscles (p > 0.05). There was no difference in the change in this variable between groups (Mean difference (95% CI) of gastrocnemius was ranged over= -4.04 to 7.72 (-19.44 to 23.14); p = 0.603); (Mean difference (95% CI) of tibialis anterior muscles was ranged from − 2.44 to -6.43 (-18.28 to 9.31); p = 0.550).; Pain and disability also decreased significantly in all three study groups (p < 0.05). However, only the disability of patients who performed stretching exercises improved compared to the compression exercise group (Mean difference (95% CI) = -12.62 (-20.41 to -4.38); p = 0.009).

Conclusion
Neither stretching nor compression exercises altered the sEMG of the gastrocnemius and tibialis anterior muscles in patients with DGS. Furthermore, performing stretching exercises improved disability compared to the other interventions.

Trial registration
The trial was retrospectively registered in the Iranian Registry of Clinical Trials (www.irct.ir) on 10/01/2017 as IRCT201604178035N4. URL of the record: https://en.irct.ir/trial/8473.
Comparison of tracer kinetic models for 68Ga-PSMA-11 PET in intermediate-risk primary prostate cancer patients
Authors: Smith Nathaniel J. , Green Mark A. , Bahler Clinton D. , Tann Mark , Territo Wendy , Smith Anne M. , Hutchins Gary D. 
Published: January 2024

Abstract
Background
68Ga-PSMA-11 positron emission tomography enables the detection of primary, recurrent, and metastatic prostate cancer. Regional radiopharmaceutical uptake is generally evaluated in static images and quantified as standard uptake values (SUVs) for clinical decision-making. However, analysis of dynamic images characterizing both tracer uptake and pharmacokinetics may offer added insights into the underlying tissue pathophysiology. This study was undertaken to evaluate the suitability of various kinetic models for 68Ga-PSMA-11 PET analysis. Twenty-three lesions in 18 patients were included in a retrospective kinetic evaluation of 55-min dynamic 68Ga-PSMA-11 pre-prostatectomy PET scans from patients with biopsy-demonstrated intermediate- to high-risk prostate cancer. Three kinetic models—a reversible one-tissue compartment model, an irreversible two-tissue compartment model, and a reversible two-tissue compartment model, were evaluated for their goodness of fit to lesion and normal reference prostate time-activity curves. Kinetic parameters obtained through graphical analysis and tracer kinetic modeling techniques were compared for reference prostate tissue and lesion regions of interest.

Results
Supported by goodness of fit and information loss criteria, the irreversible two-tissue compartment model optimally fit the time-activity curves. Lesions exhibited significant differences in kinetic rate constants (K1, k2, k3, Ki) and semiquantitative measures (SUV and %ID/kg) when compared with reference prostatic tissue. The two-tissue irreversible tracer kinetic model was consistently appropriate across prostatic zones.

Conclusions
An irreversible tracer kinetic model is appropriate for dynamic analysis of 68Ga-PSMA-11 PET images. Kinetic parameters estimated by Patlak graphical analysis or full compartmental analysis can distinguish tumor from normal prostate tissue.
A non‐weight bearing protocol after ACL reconstruction improves static anterior tibial translation in patients with elevated slope and increased weight bearing tibial anterior translation
Authors: Romandini Iacopo , Cance Nicolas , Dan Michael J. , Pineda Tomas , Pairot de Fontenay Benoit , Demey Guillaume , Dejour David H. 
Published: January 2024

AbstractPurposeAim of this study is to evaluate the impact of a non‐weight bearing (NWB) protocol within 21 post‐operative days after anterior cruciate ligament (ACL) reconstruction on static and dynamic anterior tibial translations (SATT and DATT, respectively). The hypothesis is that delayed WB would improve ATT at 9 months follow‐up.MethodsA series of patients treated with ACL reconstruction was retrospectively reviewed, comparing a group with immediate post‐operative weight bearing (WB group) and a group without post‐operative weight bearing (NWB group). The NWB protocol was applied to patients with posterior tibial slope (PTS) ≥ 12°, pre‐operative SATT ≥ 5 mm, and/or meniscal lesions of root or radial type. SATT, and PTS were measured on 20° flexion monopodal lateral x‐rays, while DATT on Telos™ x‐rays at pre‐operative and 9‐months follow‐up.ResultsOne hundred seventy‐nine patients were included (50 NWB group, 129 WB group). The SATT worsened in the WB group with a mean increase of 0.7 mm (SD 3.1 mm), while in the NWB group, the SATT improved with a mean decrease of 1.4 mm (SD 3.1 mm) from the pre‐operative to 9 months’ follow‐up (p < 0.001). The side‐to‐side Telos™ evaluation showed a significant improvement in DATT within both the groups (p < 0.001), but there was no difference between the two groups (p = 0.99).ConclusionThe post‐operative protocol of 21 days without WB led to an improvement in SATT at 9 months without an influence on DATT, and it is recommended for patients with a SATT ≥ 5 mm and/or a PTS ≥ 12° as part of an “à la carte” approach to ACL reconstruction.Level of evidenceLevel IV, Retrospective case series