bluuebunny/crossref_metadata_2025_split huggingface dataset:
Achieving the UNAIDS 90–90-90 targets: a comparative analysis of four large community randomised trials delivering universal testing and treatment to reduce HIV transmission in sub-Saharan Africa
Authors: Sabapathy K. , Balzer L. , Larmarange J. , Block L. , Floyd S. , Iwuji C. , Wirth K. , Ayles H. , Fidler S. , Kamya M. , Petersen M. , Havlir D. , Dabis F. , Moore J. , Hayes R. 
Published: December 2022

Abstract
Background
Four large community-randomized trials examining universal testing and treatment (UTT) to reduce HIV transmission were conducted between 2012–2018 in Botswana, Kenya, Uganda, Zambia and South Africa. In 2014, the UNAIDS 90–90-90 targets were adopted as a useful metric to monitor coverage. We systematically review the approaches used by the trials to measure intervention delivery, and estimate coverage against the 90–90-90 targets. We aim to provide in-depth understanding of the background contexts and complexities that affect estimation of population-level coverage related to the 90–90-90 targets.

Methods
Estimates were based predominantly on “process” data obtained during delivery of the interventions which included a combination of home-based and community-based services. Cascade coverage data included routine electronic health records, self-reported data, survey data, and active ascertainment of HIV viral load measurements in the field.

Results
The estimated total adult populations of trial intervention communities included in this study ranged from 4,290 (TasP) to 142,250 (Zambian PopART Arm-B). The estimated total numbers of PLHIV ranged from 1,283 (TasP) to 20,541 (Zambian PopART Arm-B). By the end of intervention delivery, the first-90 target (knowledge of HIV status among all PLHIV) was met by all the trials (89.2%-94.0%). Three of the four trials also achieved the second- and third-90 targets, and viral suppression in BCPP and SEARCH exceeded the UNAIDS target of 73%, while viral suppression in the Zambian PopART Arm-A and B communities was within a small margin (~ 3%) of the target.

Conclusions
All four UTT trials aimed to implement wide-scale testing and treatment for HIV prevention at population level and showed substantial increases in testing and treatment for HIV in the intervention communities. This study has not uncovered any one estimation approach which is superior, rather that several approaches are available and researchers or policy makers seeking to measure coverage should reflect on background contexts and complexities that affect estimation of population-level coverage in their specific settings.
All four trials surpassed UNAIDS targets for universal testing in their intervention communities ahead of the 2020 milestone. All but one of the trials also achieved the 90–90 targets for treatment and viral suppression. UTT is a realistic option to achieve 95–95-95 by 2030 and fast-track the end of the HIV epidemic.
Importance of the reflective logbook in improving the residents’ perception of reflective learning in the dermatology residency program in Saudi Arabia: findings from a cross-sectional study
Authors: Alotaibi Hend M. , Alharithy Ruaa , Alotaibi Hala M. 
Published: December 2022

Abstract
Background
Reflection is an essential feature of the learning process in all medical education and training fields. While writing the logbooks has been considered to improve learners’ reflection in several disciplines, it is unknown whether writing reflective logbooks improves the learning perception of dermatology residents. Therefore, this study was carried out to assess the role of the reflective logbook in improving the residents’ perception of reflective learning in the dermatology residency program.

Methods
This cross-sectional study was conducted on 32 dermatology residents from year two (R2) to year four (R4) enrolled in different hospitals in Riyadh, Saudi Arabia. A baseline electronic survey was emailed to all residents before and after implementing the reflective logbook for six months. The survey included 28 close-ended questions assessing their point of view on a Likert scale, and responses varied from agreeing to disagreeing strongly. Frequencies and proportions were generated for the categorical variables such as sex and level of residency. The graphs were generated to assess the proportion of residents correctly responding to the knowledge questions. The data were analyzed using SPSS version 23.

Results
Almost 80% of dermatology residents considered reflection as an important element of their learning, and 47% of the residents agreed that a reflective log book increases understanding in medical education. About 44% of the residents agreed that the reflective logbook assisted in their learning, and about 19% strongly agreed on the same. However, only 37.5% agreed that logbooks helped them acquire theoretical knowledge, and 9.4% and 18.8% agreed that they helped them acquire practical and research skills, respectively. Almost 68% of the residents had support in writing the logbook, and 34.4% agreed that logbooks helped them address their patient’s needs and enhance their diagnostic skills.

Conclusion
The study findings revealed that dermatology residents perceived reflection and writing a reflective logbook as important and potentially beneficial. However, knowing the importance of reflection and what reflection means was not optimal. Not all dermatology residents were aware of the reflection and reflective logbooks as tools for reflective learning. Thereby warranting regular workshops or fostering continuous medical education on the importance of reflection.
Pharmacokinetics and pharmacodynamics of intra-articular isoflupredone following administration to horses with lipopolysaccharide-induced synovitis
Authors: Knych Heather K. , Weiner Daniel , Harrison Linda , McKemie Daniel S. 
Published: December 2022

Abstract

Background

Intra-articular corticosteroids, such as isoflupredone acetate, are commonly used in the treatment of joint inflammation, especially in performance horses. Following administration in a non-inflamed joints blood concentrations of isoflupredone were low and detectable for only a short period of time post-administration compared to synovial fluid concentrations. For some drugs, inflammation can affect pharmacokinetics, therefore, the goal of the current study was to describe the pharmacokinetics of isoflupredone acetate following intra-articular administration using a model of acute synovitis. Secondarily, pharmacodynamic effects, including effects on joint circumference, joint flexion, and lameness following intra-articular administration of isoflupredone acetate in the experimental model were described.

Methods
Sixteen horses received a single intra-articular dose of 8 mg of isoflupredone acetate or saline 12 h post-administration of lipopolysaccharide. Blood and urine samples were collected up to 72 h and synovial fluid for 28 days post-administration, drug concentrations determined by liquid chromatography- mass spectrometry and pharmacokinetic analysis performed. Joint circumference, maximum angle of pain free joint flexion and lameness were evaluated prior to and post-treatment.

Results
The maximum isoflupredone plasma concentration was 2.45 ± 0.61 ng/mL at 2.5 ± 0.75 h and concentrations were less than the limit of quantitation by 72 h. Isoflupredone was below detectable concentrations in urine by 72 h post-administration in all horses and no longer detectable in synovial fluid by 96 h post-administration. Joint circumference was significantly decreased in the isoflupredone treatment group compared to the saline group at 24 and 48 h post drug administration. Pain free joint flexion was significantly different between the saline and isoflupredone treatment groups on day 4 post-treatment.

Conclusions
Synovial fluid concentrations and maximum plasma concentrations of isoflupredone differed slightly between the current study and a previous one describing administration into a non-inflamed joint, however, the detection time of isoflupredone in blood was comparable. Effects of isoflupredone on joint circumference and degree of pain free joint flexion suggest a short duration of effect with respect to alleviation of lipopolysaccharide induced synovitis, however, results of this study support future studies of the anti-inflammatory effects of intra-articular isoflupredone acetate.
Plasma markers of COVID-19 severity: a pilot study
Authors: Beimdiek Julia , Janciauskiene Sabina , Wrenger Sabine , Volland Sonja , Rozy Adriana , Fuge Jan , Olejnicka Beata , Pink Isabell , Illig Thomas , Popov Alexander , Chorostowska Joanna , Buettner Falk F. R. , Welte Tobias 
Published: December 2022

Abstract
Background
SARS-CoV-2 infected patients show heterogeneous clinical presentations ranging from mild symptoms to severe respiratory failure and death. Consequently, various markers reflect this wide spectrum of disease presentations.

Methods
Our pilot cohort included moderate (n = 10) and severe (n = 10) COVID-19 patients, and 10 healthy controls. We determined plasma levels of nine acute phase proteins (APPs) by nephelometry, and full-length (M65), caspase-cleaved (M30) cytokeratin 18, and ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type-1 motif 13) by ELISA. In addition, we examined whole plasma N-glycosylation by capillary gel electrophoresis coupled to laser-induced fluorescence detection (CGE-LIF).

Results
When compared to controls, COVID-19 patients had significantly lower concentrations of ADAMTS13 and albumin (ALB) but higher M30, M65, α1-acid glycoprotein (AGP), α1-antitrypsin (AAT), ceruloplasmin (CP), haptoglobin (HP), and high-sensitivity C-reactive protein (hs-CRP). The concentrations of α1-antichymotrypsin (ACT), α2-macroglobulin (A2MG) and serum amyloid A (SAA) proteins did not differ. We found significantly higher levels of AAT and M65 but lower ALB in severe compared to moderate COVID-19 patients. N-glycan analysis of the serum proteome revealed increased levels of oligomannose- and sialylated di-antennary glycans and decreased non-sialylated di-antennary glycan A2G2 in COVID-19 patients compared to controls.

Conclusions
COVID-19-associated changes in levels and N-glycosylation of specific plasma proteins highlight complexity of inflammatory process and grant further investigations.
Oleic acid from cancer-associated fibroblast promotes cancer cell stemness by stearoyl-CoA desaturase under glucose-deficient condition
Authors: Hwang Sung-Hyun , Yang Yeseul , Jung Jae-Ha , Kim Yongbaek 
Published: December 2022

Abstract
Background
Cancer-associated fibroblasts (CAFs) coordinate the malignancy of cancer cells via secretory materials. Reprogrammed lipid metabolism and signaling play critical roles in cancer biology. Oleic acid (OA) serves as a source of energy under glucose-deficient conditions, but its function in cancer progression remains unclear. The present study investigated that CAFs in xenografted tumors had higher amounts of fatty acids, particularly OA, compared to normal fibroblasts, and promoted the cancer cell stemness in lung adenocarcinoma cells under glucose-deficient condition.

Methods
Xenografts were established in immunodeficient mice by injection of NCI-H460 (H460) cells. Lipids and fatty acids were evaluated using the BODIPY staining and fatty-acid methyl esters analysis. The expression levels of markers for lipid metabolism and cancer stemness were determined by western blot, flow cytometry, and real-time PCR. Cancer cell subclones against stearoyl-CoA desaturase (SCD) were produced by lentiviral vector and CRISPR/cas9 systems. The expression of SCD was examined immunochemically in human adenocarcinoma tissues, and its clinical relevance to survival rate in lung adenocarcinoma patients was assessed by Kaplan–Meier analysis.

Results
Transferred CAF-derived OA through lipid transporter upregulated SCD in cancer cells under glucose-deficient conditions, resulting in enhanced lipid metabolism and autophagosome maturation. By OA treatment under glucose deficient condition, cancer cell stemness was significantly enhanced through sequential activation of SCD, F-actin polymerization and nuclear translocation of yes-associated protein. These findings were confirmed by experiments using chemical inhibitors, SCD-overexpressing cells and SCD-knockout (KO) cells. When xenografted, SCD-overexpressing cells produced larger tumors compared with parental cells, while SCD-KO cells generated much smaller tumors. Analysis of tumor tissue microarray from lung adenocarcinoma patients revealed that SCD expression was the marker for poor prognosis involving tumor grade, clinical stage and survival rate.

Conclusion
Our data indicate that CAFs-derived OA activated lipid metabolism in lung adenocarcinoma cells under glucose-deficient conditions, subsequently enhancing stemness and progression toward malignancy.
Antenna-enhanced mid-infrared detection of extracellular vesicles derived from human cancer cell cultures
Authors: Temperini Maria Eleonora , Di Giacinto Flavio , Romanò Sabrina , Di Santo Riccardo , Augello Alberto , Polito Raffaella , Baldassarre Leonetta , Giliberti Valeria , Papi Massimiliano , Basile Umberto , Niccolini Benedetta , Krasnowska Ewa K. , Serafino Annalucia , De Spirito Marco , Di Gaspare Alessandra , Ortolani Michele , Ciasca Gabriele 
Published: December 2022

Abstract
Background
Extracellular Vesicles (EVs) are sub-micrometer lipid-bound particles released by most cell types. They are considered a promising source of cancer biomarkers for liquid biopsy and personalized medicine due to their specific molecular cargo, which provides biochemical information on the state of parent cells. Despite this potential, EVs translation process in the diagnostic practice is still at its birth, and the development of novel medical devices for their detection and characterization is highly required.

Results
In this study, we demonstrate mid-infrared plasmonic nanoantenna arrays designed to detect, in the liquid and dry phase, the specific vibrational absorption signal of EVs simultaneously with the unspecific refractive index sensing signal. For this purpose, EVs are immobilized on the gold nanoantenna surface by immunocapture, allowing us to select specific EV sub-populations and get rid of contaminants. A wet sample-handling technique relying on hydrophobicity contrast enables effortless reflectance measurements with a Fourier-transform infrared (FTIR) spectro-microscope in the wavelength range between 10 and 3 µm. In a proof-of-principle experiment carried out on EVs released from human colorectal adenocarcinoma (CRC) cells, the protein absorption bands (amide-I and amide-II between 5.9 and 6.4 µm) increase sharply within minutes when the EV solution is introduced in the fluidic chamber, indicating sensitivity to the EV proteins. A refractive index sensing curve is simultaneously provided by our sensor in the form of the redshift of a sharp spectral edge at wavelengths around 5 µm, where no vibrational absorption of organic molecules takes place: this permits to extract of the dynamics of EV capture by antibodies from the overall molecular layer deposition dynamics, which is typically measured by commercial surface plasmon resonance sensors. Additionally, the described metasurface is exploited to compare the spectral response of EVs derived from cancer cells with increasing invasiveness and metastatic potential, suggesting that the average secondary structure content in EVs can be correlated with cell malignancy.

Conclusions
Thanks to the high protein sensitivity and the possibility to work with small sample volumes—two key features for ultrasensitive detection of extracellular vesicles- our lab-on-chip can positively impact the development of novel laboratory medicine methods for the molecular characterization of EVs.

Graphical Abstract
Treg cell-derived exosomes miR-709 attenuates microglia pyroptosis and promotes motor function recovery after spinal cord injury
Authors: Xiong Wu , Li Cong , Kong Guang , Zeng Qiang , Wang Siming , Yin Guoyong , Gu Jun , Fan Jin 
Published: December 2022

AbstractNeuroinflammation is an important cause of poor prognosis in patients with spinal cord injury. pyroptosis is a new type of inflammatory cell death. Treg cells has been shown to play an anti-inflammatory role in a variety of inflammatory diseases, including inflammatory bowel disease, amyotrophic lateral sclerosis, and arthritis. However, little is known about Treg cells' potential role in pyroptosis following spinal cord injury. The aim of this research was to look into the effect of Treg cells to motor function recovery, pyroptosis and the mechanism behind it after SCI. Here, we found that pyroptosis mainly occurred in microglia on the seventh day after spinal cord injury. Konckout Treg cells resulted in widely pyroptosis and poor motor recovery after SCI. In conversely, over-infiltration of Treg cell in mice by tail vein injection had beneficial effects following SCI.Treg cell-derived exosomes promote functional recovery by inhibiting microglia pyroptosis in vivo. Bioinformatic analysis revealed that miRNA-709 was significantly enriched in Treg cells and Treg cell-secreted exosomes. NKAP has been identified as a miRNA-709 target gene. Moreover, experiments confirmed that Treg cells targeted the NKAP via exosomal miR-709 to reduce microglia pyroptosis and promote motor function recovery after SCI. More importantly, The miR-709 overexpressed exosomes we constructed significantly reduced the inflammatory response and improved motor recovery after spinal cord injury. In brief, our findings indicate a possible mechanism for communication between Treg cells and microglia, which opens up a new perspective for alleviating neuroinflammation after SCI.
Haemostasis patterns in patients with acute-on-chronic liver failure and acute decompensation of cirrhosis including thromboelastometric tests with and without the addition of Protac: a pilot study
Authors: Calvo Andrea , Torrente Miguel Angel , Görlinger Klaus , Fernandez Javier , Reverter Enric , Vidal Julia , Tassies Dolors , Colmenero Jordi , Blasi Annabel , Reverter Juan Carlos 
Published: December 2022

Abstract
Background
Thromboelastometry is considered the best method to assesses hemostasis in liver disease. Diagnostic performance could be improved by adding protein C activators such as thrombomodulin or Protac®.
We assessed changes in ROTEM parameters after the addition of Protac® in patients with acute-on-chronic liver failure (ACLF), acute decompensation (AD), and healthy individuals (HI) to define different hemostasis patterns, considering standard and velocity ROTEM parameters, and assess whether Protac® can improve the definition of the pattern.

Methods
Pre-test, we investigated whether diluted EXTEM reagent improved the effect of Protac® on the clotting time (CT)-ratio with and without Protac®. Ten ACLF and 20 AD patients and 21 HI were included in the main study.

Results
Standard EXTEM was used in the main study. INTEM CFT, INTEM A5 (inverse), and INTEM TPI (inverse) were the parameters that best differentiated liver disease from HI (ROC AUC, 0.921, 0.906, and 0.928, respectively; all P-values < 0.001). Combining INTEM CFT with EXTEM LI60-ratio only slightly improved the diagnostic performance (ROC AUC, 0.948; P < 0.001). EXTEM LI60 and INTEM maxV-t were the parameters that best differentiated between ACLF and AD patients (ROC AUC, 0.743, P = 0.033; and 0.723, P = 0.050; respectively). Combining EXTEM LI60 + INTEM maxV-t moderately improved the diagnostic performance (ROC AUC, 0.81, P < 0.001).

Conclusions
ROTEM velocity, fibrinolysis parameters and the indices calculated improve the diagnosis in combination with standard parameters (e.g., CFT and A5). Ratios calculated with and without Protac® (e.g., EXTEM LI60-ratio) only slightly increased the diagnostic performance in discriminating hemostasis patterns.
An extensive bioinformatics study on the role of mitochondrial solute carrier family 25 in PC and its mechanism behind affecting immune infiltration and tumor energy metabolism
Authors: Zhang Qiang , Tang Yubao , Sun Shuai , Xie Qiuyi , Yao Jie , Wang Xiaodong , Qian Jianjun , Li Zhennan 
Published: December 2022

Abstract
Background
Several metabolic disorders and malignancies are directly related to abnormal mitochondrial solute carrier family 25 (SLC25A) members activity. However, its biological role in pancreatic cancer (PC) is not entirely understood.

Methods
The lasso method was used to create a novel prognostic risk model for PC based on SLC25A members, and its roles in tumor immunology and energy metabolism were explored. Furthermore, co-expression networks were constructed for SLC25A11, SLC25A29, and SLC25A44. Single-cell RNA sequencing (ScRNA-seq) revealed the distribution of gene expression in PC. Tumor immune infiltration was examined with the TIMER database. Lastly, drug sensitivity was investigated, and co-transcriptional factors were predicted.

Results
In the present study, a novel prognostic risk model was established and validated for PC based on SLC25A members. The high-risk group had a lower activation of oxidative phosphorylation and a more abundant immune infiltration phenotype than the low-risk group. According to co-expression network studies, SLC25A11, SLC25A29, and SLC25A44 were involved in the energy metabolism of PC and prevented tumor growth, invasion, and metastasis. ScRNA-seq research also pointed to their contribution to the tumor microenvironment. Moreover, the recruitment of numerous immune cells was positively correlated with SLC25A11 and SLC25A44 but negatively correlated with SLC25A29. Additionally, the sensitivity to 20 Food and Drug Administration-approved antineoplastic medicines was strongly linked to the aforementioned genes, where cisplatin sensitivity increased with the up-regulation of SLC25A29. Finally, the Scleraxis BHLH Transcription Factor (SCX) and other proteins were hypothesized to co-regulate the mRNA transcription of the genes.

Conclusion
SLC25A members are crucial for tumor immune and energy metabolism in PC, and SLC25A11, SLC25A29, and SLC25A44 can be used as favorable prognostic markers. The use of these markers will provide new directions to unravel their action mechanisms in PC.
Phenotypic and functional alterations of monocyte subsets with aging
Authors: Cao Yu , Fan Yang , Li Fangyuan , Hao Yu , Kong Yaxian , Chen Chen , Hao Xing , Han Dannuo , Li Guoli , Wang Zengtao , Song Chuan , Han Junyan , Zeng Hui 
Published: December 2022

Abstract
Background
It has been widely accepted that monocytes are one of the central mediators contributing to inflammaging. However, it remains unclear whether aged monocytes, similar to aged T cells, have characteristics of hyperactivation and increased expression of co-inhibitory molecules.

Methods
Peripheral blood mononuclear cells (PBMCs) were isolated from young (21–40 years old), middle-aged (41–60 years old), and older human subjects (> 60 years old). Flow cytometry was used to monitor changes in the expression of surface molecules of monocyte subsets and cytokine-producing capacity.

Results
We observed increased tumor necrosis factor-α: TNF-α and decreased interleukin-6 (IL-6) production in monocytes from older adults compared with young and middle-aged adults. Older adults had a greater percentage of intermediate and non-classical monocyte subsets, along with increased levels of the immune activation markers human leukocyte antigen-DR (HLA-DR), and adhesion molecules cluster of differentiation molecule 11b (CD11b) and L-selectin (CD62L). Furthermore, we observed increased C–C motif chemokine receptor 2 (CCR2) expression on classical monocytes and decreased C-X3-C motif chemokine receptor 1 (CX3CR1) expression on non-classical monocytes in older adult subjects. The expression of co-inhibitory receptors was reduced on monocyte subsets in older adults.

Conclusions
Circulating monocytes in older adults exhibit increased expression of activation, adhesion, and migration markers, but decreased expression of co-inhibitory molecules.