bluuebunny/crossref_metadata_2025_split huggingface dataset:
rhBMP-2 induces terminal differentiation of human bone marrow mesenchymal stromal cells only by synergizing with other signals
Authors: Kathami Neda , Moreno-Vicente Carolina , Martín Pablo , Vergara-Arce Jhonatan A. , Ruiz-Hernández Raquel , Gerovska Daniela , Aransay Ana M. , Araúzo-Bravo Marcos J. , Camarero-Espinosa Sandra , Abarrategi Ander 
Published: April 2024

Abstract
Background
Recombinant human bone morphogenetic protein 2 (rhBMP-2) and human bone marrow mesenchymal stromal cells (hBM-MSCs) have been thoroughly studied for research and translational bone regeneration purposes. rhBMP-2 induces bone formation in vivo, and hBM-MSCs are its target, bone-forming cells. In this article, we studied how rhBMP-2 drives the multilineage differentiation of hBM-MSCs both in vivo and in vitro.

Methods
rhBMP-2 and hBM-MSCs were tested in an in vivo subcutaneous implantation model to assess their ability to form mature bone and undergo multilineage differentiation. Then, the hBM-MSCs were treated in vitro with rhBMP-2 for short-term or long-term cell-culture periods, alone or in combination with osteogenic, adipogenic or chondrogenic media, aiming to determine the role of rhBMP-2 in these differentiation processes.

Results
The data indicate that hBM-MSCs respond to rhBMP-2 in the short term but fail to differentiate in long-term culture conditions; these cells overexpress the rhBMP-2 target genes DKK1, HEY-1 and SOST osteogenesis inhibitors. However, in combination with other differentiation signals, rhBMP-2 acts as a potentiator of multilineage differentiation, not only of osteogenesis but also of adipogenesis and chondrogenesis, both in vitro and in vivo.

Conclusions
Altogether, our data indicate that rhBMP-2 alone is unable to induce in vitro osteogenic terminal differentiation of hBM-MSCs, but synergizes with other signals to potentiate multiple differentiation phenotypes. Therefore, rhBMP-2 triggers on hBM-MSCs different specific phenotype differentiation depending on the signalling environment.
Mesenchymal stromal/stem cells promote intestinal epithelium regeneration after chemotherapy-induced damage
Authors: Yetkin-Arik B. , Jansen S. A. , Varderidou-Minasian S. , Westendorp B. , Skarp K.-P. , Altelaar M. , Lindemans C. A. , Lorenowicz M. J. 
Published: April 2024

Abstract
Background
Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for leukemia and a range of non-malignant disorders. The success of the therapy is hampered by occurrence of acute graft-versus-host disease (aGvHD); an inflammatory response damaging recipient organs, with gut, liver, and skin being the most susceptible. Intestinal GvHD injury is often a life-threatening complication in patients unresponsive to steroid treatment. Allogeneic mesenchymal stromal/stem cell (MSC) infusions are a promising potential treatment for steroid-resistant aGvHD. Data from our institution and others demonstrate rescue of approximately 40–50% of aGvHD patients with MSCs in Phase I, II studies and minor side effects. Although promising, better understanding of MSC mode of action and patient response to MSC-based therapy is essential to improve this lifesaving treatment.

Methods
Single cell human small intestine organoids were embedded in Matrigel, grown for 5 days and treated with busulfan for 48 h. Organoids damaged by treatment with busulfan or control organoids were co-cultured with 5000, 10,000, and 50,000 MSCs for 24 h, 48 h or 7 days and the analyses such as surface area determination, proliferation and apoptosis assessment, RNA sequencing and proteomics were performed.

Results
Here, we developed a 3D co-culture model of human small intestinal organoids and MSCs, which allows to study the regenerative effects of MSCs on intestinal epithelium in a more physiologically relevant setting than existing in vitro systems. Using this model we mimicked chemotherapy-mediated damage of the intestinal epithelium. The treatment with busulfan, the chemotherapeutic commonly used as conditioning regiment before the HSCT, affected pathways regulating epithelial to mesenchymal transition, proliferation, and apoptosis in small intestinal organoids, as shown by transcriptomic and proteomic analysis. The co-culture of busulfan-treated intestinal organoids with MSCs reversed the effects of busulfan on the transcriptome and proteome of intestinal epithelium, which we also confirmed by functional evaluation of proliferation and apoptosis.

Conclusions
Collectively, we demonstrate that our in vitro co-culture system is a new valuable tool to facilitate the investigation of the molecular mechanisms behind the therapeutic effects of MSCs on damaged intestinal epithelium. This could benefit further optimization of the use of MSCs in HSCT patients.
Radiosynthesis automation, non-human primate biodistribution and dosimetry of K+ channel tracer [11C]3MeO4AP
Authors: Zhou Yu-Peng , Wilks Moses Q. , Dhaynaut Maeva , Guehl Nicolas J. , Vesper Danielle R. , Moon Sung-Hyun , Rice Peter A. , El Fakhri Georges , Normandin Marc D. , Brugarolas Pedro 
Published: April 2024

Abstract
Background
4-Aminopyridine (4AP) is a medication for the symptomatic treatment of multiple sclerosis. Several 4AP-based PET tracers have been developed for imaging demyelination. In preclinical studies, [11C]3MeO4AP has shown promise due to its high brain permeability, high metabolic stability, high plasma availability, and high in vivo binding affinity. To prepare for the translation to human studies, we developed a cGMP-compatible automated radiosynthesis protocol and evaluated the whole-body biodistribution and radiation dosimetry of [11C]3MeO4AP in non-human primates (NHPs).

Methods
Automated radiosynthesis was carried out using a GE TRACERlab FX-C Pro synthesis module. One male and one female adult rhesus macaques were used in the study. A high-resolution CT from cranial vertex to knee was acquired. PET data were collected using a dynamic acquisition protocol with four bed positions and 13 passes over a total scan time of ~ 150 min. Based on the CT and PET images, volumes of interest (VOIs) were manually drawn for selected organs. Non-decay corrected time-activity curves (TACs) were extracted for each VOI. Radiation dosimetry and effective dose were calculated from the integrated TACs using OLINDA software.

Results
Fully automated radiosynthesis of [11C]3MeO4AP was achieved with 7.3 ± 1.2% (n = 4) of non-decay corrected radiochemical yield within 38 min of synthesis and purification time. [11C]3MeO4AP distributed quickly throughout the body and into the brain. The organs with highest dose were the kidneys. The average effective dose of [11C]3MeO4AP was 4.0 ± 0.6 μSv/MBq. No significant changes in vital signs were observed during the scan.

Conclusion
A cGMP-compatible automated radiosynthesis of [11C]3MeO4AP was developed. The whole-body biodistribution and radiation dosimetry of [11C]3MeO4AP was successfully evaluated in NHPs. [11C]3MeO4AP shows lower average effective dose than [18F]3F4AP and similar average effective dose as other carbon-11 tracers.
De-occlusion and recognition of frontal face images: a comparative study of multiple imputation methods
Authors: Mensah Joseph Agyapong , Nortey Ezekiel N. N. , Ocran Eric , Iddi Samuel , Asiedu Louis 
Published: April 2024

AbstractIncreasingly, automatic face recognition algorithms have become necessary with the development and extensive use of face recognition technology, particularly in the era of machine learning and artificial intelligence. However, the presence of unconstrained environmental conditions degrades the quality of acquired face images and may deteriorate the performance of many classical face recognition algorithms. Due to this backdrop, many researchers have given considerable attention to image restoration and enhancement mechanisms, but with minimal focus on occlusion-related and multiple-constrained problems. Although occlusion robust face recognition modules, via sparse representation have been explored, they require a large number of features to achieve correct computations and to maximize robustness to occlusions. Therefore, such an approach may become deficient in the presence of random occlusions of relatively moderate magnitude. This study assesses the robustness of Principal Component Analysis and Singular Value Decomposition using Discrete Wavelet Transformation for preprocessing and city block distance for classification (DWT-PCA/SVD-L1) face recognition module to image degradations due to random occlusions of varying magnitudes (10% and 20%) in test images acquired with varying expressions. Numerical evaluation of the performance of the DWT-PCA/SVD-L1 face recognition module showed that the use of the de-occluded faces for recognition enhanced significantly the performance of the study recognition module at each level (10% and 20%) of occlusion. The algorithm attained the highest recognition rate of 85.94% and 78.65% at 10% and 20% occlusions respectively, when the MICE de-occluded face images were used for recognition. With the exception of Entropy where MICE de-occluded face images attained the highest average value, the MICE and RegEM result in images of similar quality as measured by their Absolute mean brightness error (AMBE) and peak signal to noise ratio (PSNR). The study therefore recommends MICE as a suitable imputation mechanism for de-occlusion of face images acquired under varying expressions.
Microbial communities colonising plastics during transition from the wastewater treatment plant to marine waters
Authors: Tulloch Constance L. , Bargiela Rafael , Williams Gwion B. , Chernikova Tatyana N. , Cotterell Benjamin M. , Wellington Elizabeth M. H. , Christie-Oleza Joseph , Thomas David N. , Jones Davey L. , Golyshin Peter N. 
Published: April 2024

Abstract
Background
Plastics pollution and antimicrobial resistance (AMR) are two major environmental threats, but potential connections between plastic associated biofilms, the ‘plastisphere’, and dissemination of AMR genes are not well explored.

Results
We conducted mesocosm experiments tracking microbial community changes on plastic surfaces transitioning from wastewater effluent to marine environments over 16 weeks. Commonly used plastics, polypropylene (PP), high density polyethylene (HDPE), low density polyethylene (LDPE) and polyethylene terephthalate (PET) incubated in wastewater effluent, river water, estuarine water, and in the seawater for 16 weeks, were analysed via 16S rRNA gene amplicon and shotgun metagenome sequencing. Within one week, plastic-colonizing communities shifted from wastewater effluent-associated microorganisms to marine taxa, some members of which (e.g. Oleibacter-Thalassolituus and Sphingomonas spp., on PET, Alcanivoracaceae on PET and PP, or Oleiphilaceae, on all polymers), were selectively enriched from levels undetectable in the starting communities. Remarkably, microbial biofilms were also susceptible to parasitism, with Saprospiraceae feeding on biofilms at late colonisation stages (from week 6 onwards), while Bdellovibrionaceae were prominently present on HDPE from week 2 and LDPE from day 1. Relative AMR gene abundance declined over time, and plastics did not become enriched for key AMR genes after wastewater exposure.

Conclusion
Although some resistance genes occurred during the mesocosm transition on plastic substrata, those originated from the seawater organisms. Overall, plastic surfaces incubated in wastewater did not act as hotspots for AMR proliferation in simulated marine environments.
Extent, transparency and impact of industry funding for pelvic mesh research: a review of the literature
Authors: Coderre-Ball Angela , Phillips Susan P. 
Published: April 2024

Abstract
Background
Conflicts of interest inherent in industry funding can bias medical research methods, outcomes, reporting and clinical applications. This study explored the extent of funding provided to American physician researchers studying surgical mesh used to treat uterine prolapse or stress urinary incontinence, and whether that funding was declared by researchers or influenced the ethical integrity of resulting publications in peer reviewed journals.

Methods
Publications identified via a Pubmed search (2014–2021) of the terms mesh and pelvic organ prolapse or stress urinary incontinence and with at least one US physician author were reviewed. Using the CMS Open Payments database industry funding received by those MDs in the year before, of and after publication was recorded, as were each study’s declarations of funding and 14 quality measures.

Results
Fifty-three of the 56 studies reviewed had at least one American MD author who received industry funding in the year of, or one year before or after publication. For 47 articles this funding was not declared. Of 247 physician authors, 60% received > $100 while 13% received $100,000-$1,000,000 of which approximately 60% was undeclared. While 57% of the studies reviewed explicitly concluded that mesh was safe, only 39% of outcomes supported this. Neither the quality indicator of follow-up duration nor overall statements as to mesh safety varied with declaration status.

Conclusions
Journal editors’ guidelines re declaring conflicts of interest are not being followed. Financial involvement of industry in mesh research is extensive, often undeclared, and may shape the quality of, and conclusions drawn, resulting in overstated benefit and overuse of pelvic mesh in clinical practice.
The role of LncRNAs and CircRNAs in osteoporosis: a focus on osteogenesis and osteoclastogenesis signaling pathways
Authors: Ismail Suzan M. , Abd-Elmawla Mai A. , Shabayek Marwa I. , Darwish Hebatallah A. , El-Sawalhi Maha M. 
Published: April 2024

Abstract
Background
Osteoporosis is a crucial health concern interconnected with physical disabilities as well as financial burdens. It arises from an imbalance between osteoblasts and osteoclasts, provoking the reduction of bone mass and the disturbances in bone structure with high fracture risk. Considerable efforts were done to prevent and mitigate this public health issue. Nonetheless, further understanding of the etiopathology of osteoporosis and the underlying genetic and epigenetic pathways is required.

Main body
Emerging evidence indicates that noncoding RNAs, including long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), play crucial roles as epigenetic regulators in various pathological processes, including osteoporosis. LncRNAs are RNA transcripts with higher structural complexity that are developed owing to their secondary and tertiary structures, which allow them to create different binding sites for other biomolecules, such as DNA, RNA, and proteins. Another class of noncoding RNAs is circRNAs, which have a covalently closed loop structure without the 5′ cap and 3′ polyA tail and are formed by back-splicing of pre-mRNAs. Because of their closed structure, circRNAs are largely stable, resistant to RNA-degrading nucleases, and possess substantially longer circulatory half-lives than linear RNAs. Interestingly, both lncRNAs and circRNAs serve as competing endogenous RNAs by sponging multiple miRNA binding sites as well as interact with RNA-binding proteins (RBPs), thereby controlling the expression of their target genes. Several studies indicated that altered expression of these regulators could influence many biological processes in bone cells.

Conclusion
The current review provides current opinions on the role and the underlying mechanisms by which lncRNAs and circRNAs affect osteoblastic and osteoclastic activities. The deep understanding of these noncoding RNAs in osteoporosis offers distinctive avenues for innovative treatment strategies.
Comparison of Comorbidity Models Within a Population-Based Cohort of Older Adults With Non-Hodgkin Lymphoma
Authors: Gordon Max J. , Duan Zhigang , Zhao Hui , Nastoupil Loretta , Iyer Swaminathan , Ferrajoli Alessandra , Danilov Alexey V. , Giordano Sharon H. 
Published: April 2024

PURPOSE Compare the association of individual comorbidities, comorbidity indices, and survival in older adults with non-Hodgkin lymphoma (NHL), including in specific NHL subtypes. METHODS Data source was SEER-Medicare, a population-based registry of adults age 65 years and older with cancer. We included all incident cases of NHL diagnosed during 2008-2017 who met study inclusion criteria. Comorbidities were classified using the three-factor risk estimate scale (TRES), Charlson comorbidity index (CCI), and National Cancer Institute (NCI) comorbidity index categories and weights. Overall survival (OS) and lymphoma-specific survival, with death from other causes treated as a competing risk, were estimated using the Kaplan-Meier method from time of diagnosis. Multivariable Cox models were constructed, and Harrel C-statistics were used to compare comorbidity models. A two-sided P value of <.05 was considered significant. RESULTS A total of 40,486 patients with newly diagnosed NHL were included. Patients with aggressive NHL had higher rates of baseline comorbidity. Despite differences in baseline comorbidity between NHL subtypes, cardiovascular, pulmonary, diabetes, and renal comorbidities were frequent and consistently associated with OS in most NHL subtypes. These categories were used to construct a candidate comorbidity score, the non-Hodgkin lymphoma 5 (NHL-5). Comparing three validated comorbidity scores, TRES, CCI, NCI, and the novel NHL-5 score, we found similar associations with OS and lymphoma-specific survival, which was confirmed in sensitivity analyses by NHL subtypes. CONCLUSION The optimal measure of comorbidity in NHL is unknown. Here, we demonstrate that the three-category TRES and five-category NHL-5 scores perform as well as the 14-16 category CCI and NCI scores in terms of association with OS and lymphoma-specific survival. These simple scores could be more easily used in clinical practice without prognostic loss.
Phase Ib Study of Unesbulin (PTC596) Plus Dacarbazine for the Treatment of Locally Recurrent, Unresectable or Metastatic, Relapsed or Refractory Leiomyosarcoma
Authors: Van Tine Brian A. , Ingham Matthew A. , Attia Steven , Meyer Christian F. , Baird John D. , Brooks-Asplund Esther , D'Silva Dhiren , Kong Ronald , Mwatha Anthony , O'Keefe Kylie , Weetall Marla , Spiegel Robert , Schwartz Gary K. 
Published: April 2024

PURPOSE This multicenter, single-arm, open-label, phase Ib study was designed to determine the recommended phase II dose (RP2D) and to evaluate the safety and preliminary efficacy of unesbulin plus dacarbazine (DTIC) in patients with advanced leiomyosarcoma (LMS). PATIENTS AND METHODS Adult subjects with locally advanced, unresectable or metastatic, relapsed or refractory LMS were treated with escalating doses of unesbulin orally twice per week in combination with DTIC 1,000 mg/m2 intravenously (IV) once every 21 days. The time-to-event continual reassessment method was used to determine the RP2D on the basis of dose-limiting toxicities (DLTs) assessed during the first two 21-day treatment cycles. All explored doses of unesbulin (200 mg up to 400 mg) were in combination with DTIC. An expansion cohort was enrolled to evaluate the safety and efficacy of unesbulin at the RP2D. RESULTS Unesbulin 300 mg administered orally twice per week in combination with DTIC 1,000 mg/m2 IV once every 21 days was identified as the RP2D. On the basis of data from 27 subjects who were deemed DLT-evaluable, toxicity was higher in the unesbulin 400 mg group, with three of four subjects (75%) experiencing DLTs versus one of four subjects (25%) in the 200 mg group and three of 19 subjects (15.8%) in the 300 mg group. The most commonly reported DLTs and treatment-related grade 3 and 4 adverse events were thrombocytopenia and neutropenia. At the RP2D, seven subjects who were efficacy evaluable achieved partial response for an objective response rate of 24.1%. CONCLUSION Unesbulin 300 mg twice per week plus DTIC 1,000 mg/m2 once every 21 days was identified as the RP2D, demonstrating a favorable benefit-risk profile in a heavily pretreated population of adults with advanced LMS.
When Is Telemedicine Appropriate in the Management of Head and Neck Cancer? A Mixed-Methods Assessment Among Patients and Physicians
Authors: Hung Tony K.W. , Verdini Nicholas P. , Gilliland Jaime L. , Chimonas Susan , Cracchiolo Jennifer R. , Li Yuelin , Pfister David G. , Gillespie Erin F. 
Published: April 2024

PURPOSE Evidence suggests that oncology patients are satisfied with and sometimes prefer telemedicine compared with in-person visits; however, data are scarce on when telemedicine is appropriate for specific cancer populations. In this study, we aim to identify factors that influence patient experience and appropriateness of telemedicine use among a head and neck cancer (HNC) population. METHODS We performed a mixed-methods study at a multisite cancer center. First, we surveyed patients with HNC and analyzed factors that may influence their telemedicine experience using multivariate regression. We then conducted focus groups among HNC oncologists (n = 15) to evaluate their perception on appropriate use of telemedicine. RESULTS From January to December 2020, we collected 1,071 completed surveys (response rate 24%), of which 551 first unique surveys were analyzed. About half of all patients (56%) reported telemedicine as “same or better” compared with in-person visits, whereas the other half (44%) reported “not as good or unsure.” In multivariate analyses, patients with thyroid cancer were more likely to find telemedicine “same or better” (adjusted odds ratio, 2.08 [95% CI, 1.35 to 3.25]) compared with other HNC populations (mucosal/salivary HNC). Consistently, physician focus group noted that patients with thyroid cancer were particularly suited for telemedicine because of less emphasis on in-person examinations. Physicians also underscored factors that influence telemedicine use, including clinical suitability (treatment status, visit purpose, examination necessity), patient benefits (travel time, access), and barriers (technology, rapport-building). CONCLUSION Patient experience with telemedicine is diverse among the HNC population. Notably, patients with thyroid cancer had overall better experience and were identified to be more appropriate for telemedicine compared with other patients with HNC. Future research that optimizes patient experience and selection is needed to ensure successful integration of telemedicine into routine oncology practice.