bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chinmedomics: a potent tool for the evaluation of traditional Chinese medicine efficacy and identification of its active components
Authors: Wang Mengmeng , Yin Fengting , Kong Ling , Yang Le , Sun Hui , Sun Ye , Yan Guangli , Han Ying , Wang Xijun 
Published: March 2024

AbstractAs an important part of medical science, Traditional Chinese Medicine (TCM) attracts much public attention due to its multi-target and multi-pathway characteristics in treating diseases. However, the limitations of traditional research methods pose a dilemma for the evaluation of clinical efficacy, the discovery of active ingredients and the elucidation of the mechanism of action. Therefore, innovative approaches that are in line with the characteristics of TCM theory and clinical practice are urgently needed. Chinmendomics, a newly emerging strategy for evaluating the efficacy of TCM, is proposed. This strategy combines systems biology, serum pharmacochemistry of TCM and bioinformatics to evaluate the efficacy of TCM with a holistic view by accurately identifying syndrome biomarkers and monitoring their complex metabolic processes intervened by TCM, and finding the agents associated with the metabolic course of pharmacodynamic biomarkers by constructing a bioinformatics-based correlation network model to further reveal the interaction between agents and pharmacodynamic targets. In this article, we review the recent progress of Chinmedomics to promote its application in the modernisation and internationalisation of TCM.
A systematic review of real-world evidence (RWE) supportive of new drug and biologic license application approvals in rare diseases
Authors: Vaghela Shailja , Tanni Kaniz Afroz , Banerjee Geetanjoli , Sikirica Vanja 
Published: March 2024

Abstract
Background
Real-world evidence (RWE) generated using real-world data (RWD) presents the potential to contextualize and/or supplement traditional clinical trials for regulatory approval of rare diseases (RDs). This systematic review evaluated the use of RWD for non-oncologic RD therapies with orphan drug designation (ODD) to support efficacy outcomes in regulatory application packages to the US Food and Drug Administration (FDA). New drug applications (NDAs) and biologic license applications (BLAs) submitted between January 2017 and October 2022 were obtained from publicly available FDA drug approval websites. NDAs and BLAs of non-oncologic RD therapies were screened, and manually reviewed using RWE-related keywords. Quantitative summary of number/proportion of study types was provided, whereas qualitative synthesis focused on key categories of output assessing the use of RWD in overall drug approval process, including agency’s feedback on its strengths and key challenges.

Results
A total of 868 NDAs and BLAs were identified, of which 243 were screened for non-oncologic RDs with ODD, and 151 were subsequently reviewed for the RWD used to support efficacy outcomes. Twenty (12 NDAs, 8 BLAs) applications met the review inclusion criteria. Most (19; 95%) applications used only retrospective RWD, while one (5%) collected RWD both retrospectively and prospectively. RWD studies included natural history including registry-based/retrospective historical controls (14; 70%), retrospective medical chart-reviews (4; 20%), and external RWD controls from other studies (2; 10%). The FDA generally accepted RWD studies demonstrating a large effect size despite the noted concerns and criticisms. However, the agency expressed concerns about overall quality and comparability of RWD with trial data for some applications, including RWD study designs with respect to differences in patients’ baseline characteristics, missing information, and potential bias and measurement errors.

Conclusions
This systematic review highlights potential benefits of appropriately conducted RWE studies in RD, which can strengthen the clinical evidence for efficacy comparison and contextualization to support product approval efforts, particularly when a large magnitude of effect is observed for the new intervention. Nonetheless, quality and completeness of RWD and its comparability with trial data remain areas of concern that can serve as valuable learnings for advancing future science and regulatory approvals.
Lymphatic drainage of sinonasal malignancies and the role of sentinel node biopsies
Authors: Kashani Fatemeh , Weiss BG , Bartenstein P , Canis M , Haubner F 
Published: March 2024

Abstract
Background
Locoregional recurrence is a critical factor in the prognosis of sinonasal malignancies. Due to the rarity of these tumours, as well as the heterogeneity of histologies and anatomical subsites, there is little evidence regarding the rate and location of regional metastases in sinonasal malignancies. Elective regional lymph node dissection in the therapy of sinonasal malignancies has become controversial. On the one hand, elective regional lymph node dissection is considered to be an overtreatment in the cN0 cases. On the other hand, undetected occult lymphatic metastases are associated with a poor prognosis. In this study, we discuss the role of sentinel lymph node biopsy as a minimally invasive procedure in the treatment of sinonasal malignancies based on our two years of practical experience and the currently available data.

Results
This is a descriptive, monocentric, retrospective study, including 20 cases of cN0 malignant sinonasal neoplasm, that underwent a surgical therapy between 2020 and 2022. The following aspects were investigated: tumour entity, localisation of the primary tumour, tumoral stage, localisation of the sentinel lymph nodes, and postoperative complications. Squamous cell carcinoma was the most frequently diagnosed tumour entity (50%), followed by adenocarcinoma (20%) and malignant melanoma (15%), adenoid cystic carcinoma and mucoepidermoid carcinoma. Sentinel lymph nodes were most frequently found in the ipsilateral neck region I (45%), followed by the ipsilateral neck region II (40%). In all cases, the removed lymph nodes were free of malignancy. There were no postoperative complications due to lymph node biopsy. There were no recurrences during the study period.

Conclusion
Sentinel node biopsy could add more safety to the management of cN0 sinonasal malignancies due to its low morbidity. Whether SNB could provide an alternative to elective neck dissection in the management of SNM should be investigated in further studies.
Low CD4 + T cell count is related to specific anti-nuclear antibodies, IFNα protein positivity and disease activity in systemic lupus erythematosus pregnancy
Authors: Torell Agnes , Stockfelt Marit , Blennow Kaj , Zetterberg Henrik , Akhter Tansim , Leonard Dag , Rönnblom Lars , Pihl Sofia , Saleh Muna , Sjöwall Christopher , Strevens Helena , Jönsen Andreas , Bengtsson Anders A. , Trysberg Estelle , Majczuk Sennström Maria , Zickert Agneta , Svenungsson Elisabet , Gunnarsson Iva , Bylund Johan , Jacobsson Bo , Rudin Anna , Lundell Anna-Carin 
Published: March 2024

Abstract
Background
Lymphopenia, autoantibodies and activation of the type I interferon (IFN) system are common features in systemic lupus erythematosus (SLE). We speculate whether lymphocyte subset counts are affected by pregnancy and if they relate to autoantibody profiles and/or IFNα protein in SLE pregnancy.

Methods
Repeated blood samples were collected during pregnancy from 80 women with SLE and 51 healthy controls (HC). Late postpartum samples were obtained from 19 of the women with SLE. Counts of CD4 + and CD8 + T cells, B cells and NK cells were measured by flow cytometry. Positivity for anti-nuclear antibodies (ANA) fine specificities (double-stranded DNA [dsDNA], Smith [Sm], ribonucleoprotein [RNP], chromatin, Sjögren’s syndrome antigen A [SSA] and B [SSB]) and anti-phospholipid antibodies (cardiolipin [CL] and β2 glycoprotein I [β2GPI]) was assessed with multiplexed bead assay. IFNα protein concentration was quantified with Single molecule array (Simoa) immune assay. Clinical data were retrieved from medical records.

Results
Women with SLE had lower counts of all lymphocyte subsets compared to HC throughout pregnancy, but counts did not differ during pregnancy compared to postpartum. Principal component analysis revealed that low lymphocyte subset counts differentially related to autoantibody profiles, cluster one (anti-dsDNA/anti-Sm/anti-RNP/anti-Sm/RNP/anti-chromatin), cluster two (anti-SSA/anti-SSB) and cluster three (anti-CL/anti-β2GPI), IFNα protein levels and disease activity. CD4 + T cell counts were lower in women positive to all ANA fine specificities in cluster one compared to those who were negative, and B cell numbers were lower in women positive for anti-dsDNA and anti-Sm compared to negative women. Moreover, CD4 + T cell and B cell counts were lower in women with moderate/high compared to no/low disease activity, and CD4 + T cell count was lower in IFNα protein positive relative to negative women. Finally, CD4 + T cell count was unrelated to treatment.

Conclusion
Lymphocyte subset counts are lower in SLE compared to healthy pregnancies, which seems to be a feature of the disease per se and not affected by pregnancy. Our results also indicate that low lymphocyte subset counts relate differentially to autoantibody profiles, IFNα protein levels and disease activity, which could be due to divergent disease pathways.
Transcriptomic and proteomic profiles of fetal versus adult mesenchymal stromal cells and mesenchymal stromal cell-derived extracellular vesicles
Authors: Gençer Emine Begüm , Lor Yuk Kit , Abomaray Fawaz , El Andaloussi Samir , Pernemalm Maria , Sharma Nidhi , Hagey Daniel W , Görgens André , Gustafsson Manuela O , Le Blanc Katarina , Asad Toonsi Mawaddah , Walther-Jallow Lilian , Götherström Cecilia 
Published: March 2024

Abstract
Background
Mesenchymal stem/stromal cells (MSCs) can regenerate tissues through engraftment and differentiation but also via paracrine signalling via extracellular vesicles (EVs). Fetal-derived MSCs (fMSCs) have been shown, both in vitro and in animal studies, to be more efficient than adult MSC (aMSCs) in generating bone and muscle but the underlying reason for this difference has not yet been clearly elucidated. In this study, we aimed to systematically investigate the differences between fetal and adult MSCs and MSC-derived EVs at the phenotypic, RNA, and protein levels.

Methods
We carried out a detailed and comparative characterization of culture-expanded fetal liver derived MSCs (fMSCs) and adult bone marrow derived MSCs (aMSCs) phenotypically, and the MSCs and MSC-derived EVs were analysed using transcriptomics and proteomics approaches with RNA Sequencing and Mass Spectrometry.

Results
Fetal MSCs were smaller, exhibited increased proliferation and colony-forming capacity, delayed onset of senescence, and demonstrated superior osteoblast differentiation capability compared to their adult counterparts. Gene Ontology analysis revealed that fMSCs displayed upregulated gene sets such as “Positive regulation of stem cell populations”, “Maintenance of stemness” and “Muscle cell development/contraction/Myogenesis” in comparison to aMSCs. Conversely, aMSCs displayed upregulated gene sets such as “Complement cascade”, “Adipogenesis”, “Extracellular matrix glycoproteins” and “Cellular metabolism”, and on the protein level, “Epithelial cell differentiation” pathways. Signalling entropy analysis suggested that fMSCs exhibit higher signalling promiscuity and hence, higher potency than aMSCs. Gene ontology comparisons revealed that fetal MSC-derived EVs (fEVs) were enriched for “Collagen fibril organization”, “Protein folding”, and “Response to transforming growth factor beta” compared to adult MSC-derived EVs (aEVs), whereas no significant difference in protein expression in aEVs compared to fEVs could be detected.

Conclusions
This study provides detailed and systematic insight into the differences between fMSCs and aMSCs, and MSC-derived EVs. The key finding across phenotypic, transcriptomic and proteomic levels is that fMSCs exhibit higher potency than aMSCs, meaning they are in a more undifferentiated state. Additionally, fMSCs and fMSC-derived EVs may possess greater bone forming capacity compared to aMSCs. Therefore, using fMSCs may lead to better treatment efficacy, especially in musculoskeletal diseases.
Ground deformations associated with an overpressurized hydrothermal systems at Azuma volcano (Japan) revealed by InSAR data
Authors: Himematsu Yuji , Ozawa Taku 
Published: March 2024

AbstractInflations at active volcanoes are indicators of overpressure in the subsurface, which is known to be a phenomenon that precedes eruptions. Volcanic overpressure is induced by the injection of magmatic fluids, accumulated magma, or heat supply from greater depths. Azuma volcano (Japan) has experienced several episodes of volcanic unrest with increases in seismicity at the depth of the hydrothermal system, implying a potential increase in phreatic eruptions. The time series of interferometric synthetic aperture radar data, associated with the unrest episodes occurring in 2014–2015 and 2018–2019, revealed spatiotemporal variations of inflation episodes, centered around Oana crater, the most active fumarole of Azuma volcano. The modeled best-fit geometry of the elongated pressure source for the local deformation has the same dip as the overlying topographic slope direction and angle around Oana crater, suggesting the existence of topography-correlated layered structures within the hydrothermal system. In contrast, the broader deformation associated with the 2014–2015 unrest was explained by the overpressure of a horizontal flat source at 360–1500 m below sea level, showing the similar depth of the top as the conductive low-resistivity or low-viscosity body suggested by previous studies. The unrest episodes were thus interpreted as resulting mainly from the supply of magmatic fluids, or the transfer of heat from greater depths. Our study helps in understanding the shallow structure of this volcanic system and contributes to evaluating the potential for forthcoming eruptions in Azuma volcano.
Graphical Abstract
Evaluation of dispensaries’ cannabis flowers for accuracy of labeling of cannabinoids content
Authors: Geweda Mona M. , Majumdar Chandrani G. , Moore Malorie N. , Elhendawy Mostafa A. , Radwan Mohamed M. , Chandra Suman , ElSohly Mahmoud A. 
Published: March 2024

Abstract
Background
Cannabis policies have changed drastically over the last few years with many states enacting medical cannabis laws, and some authorizing recreational use; all against federal laws. As a result, cannabis products are marketed in dispensaries in different forms, most abundantly as flowers intended for smoking and sometimes vaping. All samples used in this study were obtained directly from law enforcement. The sample collection process was facilitated and funded by the National Marijuana Initiative (NMI), part of the High-Intensity Drug Trafficking Area (HIDTA) program. This initial report focuses on cannabis flowers. Similar studies with other cannabis products will be the subject of a future report.

Methods
A total of 107 Δ9-THC cannabis flower samples were collected by law enforcement from adult commercial use cannabis dispensaries, located in three different states (Colorado, Oregon, and California) and analyzed in this study for cannabinoid concentration. Samples were analyzed by GC-FID following our previously published procedure.

Discussion
The label claims for total Δ9-THC content ranged from 12.04 to 58.20% w/w, while GC-FID results showed a concentration ranging from 12.95 to 36.55% w/w. Of the evaluated 107 products, only 32 samples have Δ9-THC content within ± 20% of the labeled content. However, the remaining 75 samples were found to be out of the ± 20% acceptance criteria. The degree of agreement for the tested samples using ± 20% tolerance with label claims was only 30%. The results of this study indicate that there is a need for more stringent regulations to ensure that product labeling is accurate, as 70% of the evaluated products did not meet the ± 20% acceptance criteria. This highlights the importance of healthcare professionals and patients being vigilant about the Δ9-THC content, as inaccurate labeling of cannabis products could potentially result in adverse health effects. Furthermore, there is a pressing need for more rigorous regulation of commercial cannabis products in the United States.
Cannabis and Cannabinoids in Adults With Cancer: ASCO Guideline
Authors: Braun Ilana M. , Bohlke Kari , Abrams Donald I. , Anderson Holly , Balneaves Lynda G. , Bar-Sela Gil , Bowles Daniel W. , Chai Peter R. , Damani Anuja , Gupta Arjun , Hallmeyer Sigrun , Subbiah Ishwaria M. , Twelves Chris , Wallace Mark S. , Roeland Eric J. 
Published: March 2024

PURPOSE To guide clinicians, adults with cancer, caregivers, researchers, and oncology institutions on the medical use of cannabis and cannabinoids, including synthetic cannabinoids and herbal cannabis derivatives; single, purified cannabinoids; combinations of cannabis ingredients; and full-spectrum cannabis. METHODS A systematic literature review identified systematic reviews, randomized controlled trials (RCTs), and cohort studies on the efficacy and safety of cannabis and cannabinoids when used by adults with cancer. Outcomes of interest included antineoplastic effects, cancer treatment toxicity, symptoms, and quality of life. PubMed and the Cochrane Library were searched from database inception to January 27, 2023. ASCO convened an Expert Panel to review the evidence and formulate recommendations. RESULTS The evidence base consisted of 13 systematic reviews and five additional primary studies (four RCTs and one cohort study). The certainty of evidence for most outcomes was low or very low. RECOMMENDATIONS Cannabis and/or cannabinoid access and use by adults with cancer has outpaced the science supporting their clinical use. This guideline provides strategies for open, nonjudgmental communication between clinicians and adults with cancer about the use of cannabis and/or cannabinoids. Clinicians should recommend against using cannabis or cannabinoids as a cancer-directed treatment unless within the context of a clinical trial. Cannabis and/or cannabinoids may improve refractory, chemotherapy-induced nausea and vomiting when added to guideline-concordant antiemetic regimens. Whether cannabis and/or cannabinoids can improve other supportive care outcomes remains uncertain. This guideline also highlights the critical need for more cannabis and/or cannabinoid research. Additional information is available at www.asco.org/supportive-care-guidelines .
Improving Diabetic Wound-Healing Outcomes With Topical Growth Factor Therapies
Authors: Wong Andrew Yew Wei , Hooi Natalie Ming Foong , Yeo Brian Sheng Yep , Sultana Rehena , Bee Yong Mong , Lee Ainsley Ryan Yan Bin , Tay Sook Muay 
Published: March 2024

Abstract

Context
Diabetes mellitus is associated with morbid complications such as diabetic foot ulcers (DFUs) that may lead to amputations or mortality if not managed adequately.

Objective
New adjunctive interventions to treat diabetic wounds include topical biologics and growth factors. This study aims to evaluate their efficacy in improving wound-healing outcomes and safety.

Methods
Comprehensive database searches of MEDLINE via PubMed, EMBASE, and Cochrane were performed from inception to December 2022. Three independent researchers selected the studies. Randomized controlled trials that compared the use of a topical biologic growth factor-containing regimen to other biologics or standard of care (SOC) were included. This review followed PRISMA guidelines. Risk of bias analysis was performed using the Jadad scale. Network meta-analysis was performed. Treatments were grouped into common nodes based on the type of biologic agent. Primary outcomes of interest were healing rate and time to wound closure. Secondary outcomes included wound infection, serious adverse events (AEs), and amputation rate.

Results
Human umbilical cord (HUC) was associated with the highest cure, followed by recombinant human epidermal growth factor (hEGF). A significantly greater reduction in the time to cure DFUs was seen in HUC, hEGF, and fibroblast growth factor (FGF). There was a significantly lower risk of AEs when platelet-rich plasma (PRP) was administered.

Conclusion
HUC, hEGF, and FGF are promising topical biologics with statistically significant primary outcomes compared to SOC, while PRP is effective in reducing ulcer-related AEs. HUC has been found to be the most effective in terms of cure rate and a reduction in time to cure.
Approach to the Patient With Bilateral Adrenal Masses
Authors: Vassiliadi Dimitra Argyro , Delivanis Danae Anastasia , Papalou Olga , Tsagarakis Stylianos 
Published: March 2024

Abstract
Bilateral adrenal masses, increasingly encountered in clinical practice, manifest across diverse contexts, including incidental discovery, malignancy staging, and targeted imaging after hormonal diagnosis of adrenal disorders. The spectrum encompasses various pathologies, such as cortical adenomas, macronodular adrenal disease, pheochromocytomas, myelolipomas, infiltrative disorders, and primary and secondary malignancies. Notably, not all masses in both adrenal glands necessarily share the same etiology, often exhibiting diverse causes. Recently, the European Society of Endocrinology and the European Network for the Study of Adrenal Tumors updated guidelines, introduced a 4-option schema based on imaging, aiding in targeted hormonal testing and management. This “Approach to the Patient” review delves into the latest advancements in imaging, biochemical, and genetic approaches for the diagnostic and management nuances of bilateral adrenal masses. It provides insights and a contemporary framework for navigating the complexities associated with this clinical entity.
Botiga i treball a domicili. Un exemple de protoindustrialització a Catalunya (Valls 1782-1800). El cas de Fidel Moragas Fortuny
Authors: Sanmarti Roset Carme , Sanmartí  Roset Montserrat 
Published: March 2024

Aquest article es proposa estudiar, des d'una perspectiva de gènere, el treball a domicili d'un conjunt de dones de Valls (Tarragona) en les dues darreres dpeades del segle XVIII, aprofundint en l'impacte de la seva feina tant a nivelk personal i famiiar com en el desenvolupament econòmic i social de l'entorn. Si be les transformacions experimentades per la societat catalana durant la protoindustrialització disposen d'un corpus bibliogràfic notable, i es continua estudiant, no existeixen estudis decas que analitzin les condicions socials i econòmiques de les dones que trebllaven a domicili. També tractarem la relació que aquestes dones mantenien amb la botiga que Moragas regentava en laqual venia almajori al detall una gran varietat de productes, entre els que destacaven els tèxtils. L'estudi mostra com la remuneració oercebuda per les treballadores garantia elpagament de les compres que feien a la botiga.