bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patterns of treatment with everolimus exemestane in hormone receptor-positive HER2-negative metastatic breast cancer in the era of targeted therapy
Authors: Rozenblit Mariya , Mun Sophia , Soulos Pamela , Adelson Kerin , Pusztai Lajos , Mougalian Sarah 
Published: January 2021

AbstractBackgroundThere is currently no clinical trial data regarding the efficacy of everolimus exemestane (EE) following prior treatment with CDK4/6 inhibitors (CDK4/6i). This study assesses the use and efficacy of everolimus exemestane in patients with metastatic HR+ HER2− breast cancer previously treated with endocrine therapy (ET) or endocrine therapy + CDK4/6i.MethodsRetrospective analysis of electronic health record-derived data for HR+ HER2− metastatic breast cancer from 2012 to 2018. The proportion of patients receiving EE first-line, second-line, or third-line, and the median duration of EE prior to next line of treatment (TTNT) by line of therapy was calculated. OS for patients receiving EE first-line, second-line, or third-line, indexed to the date of first-line therapy initiation and stratified by prior treatment received, was calculated with Kaplan-Meier method with multivariable Cox proportional hazards regression analysis.ResultsSix hundred twenty-two patients received EE first-line (n = 104, 16.7%), second-line (n = 273, 43.9%) or third-line (n = 245, 39.4%). Median TTNT was 8.3 months, 5.5 months, and 4.8 months respectively. Median TTNT of EE second-line was longer following prior ET alone compared to prior ET + CDK4/6i (6.2 months (95% CI 5.2, 7.3) vs 4.3 months (95% CI 3.2, 5.7) respectively,p = 0.03). Similarly, EE third-line following ET alone vs ET + CDK4/6i in first- or second-line resulted in median TTNT 5.6 months (95% CI 4.4, 6.9) vs 4.1 months (95% CI 3.6, 6.1) respectively, although this was not statistically significant (p = 0.08). Median OS was longer for patients who received EE following prior ET + CDK4/6i. EE second-line following ET + CDK 4/6i vs ET alone resulted in median OS 37.7 months vs. 32.7 months (p = 0.449). EE third-line following ET + CDK4/6i vs prior ET alone resulted in median OS 59.2 months vs. 40.8 months (p < 0.010). This difference in OS was not statistically significant when indexed to the start of EE therapy.ConclusionThis study suggests that EE remains an effective treatment option after prior ET or ET + CDK4/6i use. Median TTNT of EE was longer for patients who received prior ET, whereas median OS was longer for patients who received prior ET + CDK4/6i. However, this improvement in OS was not statistically significant when indexed to the start of EE therapy suggesting that OS benefit is primarily driven by prior CDK4/6i use. EE remains an effective treatment option regardless of prior treatment option.
20-Hydroxyecdysone (20E) signaling as a promising target for the chemical control of malaria vectors
Authors: Ekoka Elodie , Maharaj Surina , Nardini Luisa , Dahan-Moss Yael , Koekemoer Lizette L. 
Published: January 2021

AbstractWith the rapid development and spread of resistance to insecticides among anopheline malaria vectors, the efficacy of current World Health Organization (WHO)-approved insecticides targeting these vectors is under threat. This has led to the development of novel interventions, including improved and enhanced insecticide formulations with new targets or synergists or with added sterilants and/or antimalarials, among others. To date, several studies in mosquitoes have revealed that the 20-hydroxyecdysone (20E) signaling pathway regulates both vector abundance and competence, two parameters that influence malaria transmission. Therefore, insecticides which target 20E signaling (e.g. methoxyfenozide and halofenozide) may be an asset for malaria vector control. While such insecticides are already commercially available for lepidopteran and coleopteran pests, they still need to be approved by the WHO for malaria vector control programs. Until recently, chemicals targeting 20E signaling were considered to be insect growth regulators, and their effect was mostly studied against immature mosquito stages. However, in the last few years, promising results have been obtained by applying methoxyfenozide or halofenozide (two compounds that boost 20E signaling) to Anopheles populations at different phases of their life-cycle. In addition, preliminary studies suggest that methoxyfenozide resistance is unstable, causing the insects substantial fitness costs, thereby potentially circumventing one of the biggest challenges faced by current vector control efforts. In this review, we first describe the 20E signaling pathway in mosquitoes and then summarize the mechanisms whereby 20E signaling regulates the physiological processes associated with vector competence and vector abundance. Finally, we discuss the potential of using chemicals targeting 20E signaling to control malaria vectors.
Graphical abstract
Global survey of miRNAs and tRNA-derived small RNAs from the human parasitic protist Trichomonas vaginalis
Authors: Wang Zhen-Sheng , Zhou Hong-Chang , Wei Chun-Yan , Wang Zhi-Hua , Hao Xiao , Zhang Lian-Hui , Li Jing-Zhong , Wang Zeng-Lei , Wang Heng 
Published: January 2021

Abstract
Background
Small non-coding RNAs play critical regulatory roles in post-transcription. However, their characteristics in Trichomonas vaginalis, the causative agent of human sexually transmitted trichomoniasis, still remain to be determined.

Methods
Small RNA transcriptomes from Trichomonas trophozoites were deep sequenced using the Illumina NextSeq 500 system and comprehensively analyzed to identify Trichomonas microRNAs (miRNAs) and transfer RNA (tRNA)-derived small RNAs (tsRNAs). The tsRNA candidates were confirmed by stem-loop quantitative reverse transcription-PCR, and motifs to guide the cleavage of tsRNAs were predicted using the GLAM2 algorithm.

Results
The miRNAs were found to be present in T. vaginalis but at an extremely low abundance (0.0046%). Three categories of endogenous Trichomonas tsRNAs were identified, namely 5′tritsRNAs, mid-tritsRNAs and 3′tritsRNAs, with the 5′tritsRNAs constituting the dominant category (67.63%) of tsRNAs. Interestingly, the cleavage site analysis verified both conventional classes of tRNA-derived fragments (tRFs) and tRNA-halves in tritsRNAs, indicating the expression of tRNA-halves in the non-stress condition. A total of 25 tritsRNAs were experimentally confirmed, accounting for 78.1% of all tested candidates. Three motifs were predicted to guide the production of tritsRNAs. The results prove the expression of tRFs and tRNA-halves in the T. vaginalis transcriptome.

Conclusions
This is the first report of genome-wide investigation of small RNAs, particularly tsRNAs and miRNAs, from Trichomonas parasites. Our findings demonstrate the expression profile of tsRNAs in T. vaginalis, while miRNA was barely detected. These results may promote further research aimed at gaining a better understanding of the evolution of small non-coding RNA in T. vaginalis and their functions in the pathogenesis of trichomoniasis.

Graphical Abstract
The survival and dispersal of Taenia eggs in the environment: what are the implications for transmission? A systematic review
Authors: Jansen Famke , Dorny Pierre , Gabriël Sarah , Dermauw Veronique , Johansen Maria Vang , Trevisan Chiara 
Published: January 2021

AbstractTaenia spp. are responsible for a substantial health and economic burden in affected populations. Knowledge of the fate of the eggs of Taenia spp. in the environment and of other factors facilitating the transmission of eggs to intermediate hosts is important for the control/elimination of infections caused by Taenia spp. The aim of this systematic review was to summarize current knowledge of the factors influencing the survival and dispersal of Taenia spp. eggs in the environment. Publications retrieved from international databases were systematically reviewed. Of the 1465 papers initially identified, data were ultimately extracted from 93 papers. The results of this systematic review indicate that survival is favoured at moderate temperatures (0–20 °C). Humidity seems to affect the survival of Taenia spp. eggs more than temperature. Under field circumstances, Taenia spp. eggs have been found to survive for up to 1 year. Taenia spp. eggs are commonly found on vegetables (0.9–30%) and in soil and water samples (0–43%), with their presence posing a risk to the consumer. Invertebrates may act as transport hosts, transferring the infection to an intermediate host, but the importance of this route of transmission is still open to question. Wastewater treatment systems are not capable of entirely eliminating Taenia spp. eggs. Access to surface water and the use of sewage sludge as fertilizer on pastures are important risk factors for bovine cysticercosis. Although information on the survival and spread of Taenia spp. eggs is available, in general the data retrieved and reviewed in this article were old, focused on very specific geographical regions and may not be relevant for other areas or not specific for different Taenia spp. Furthermore, it is unknown whether egg survival differs according to Taenia sp. Future studies are necessary to identify sustainable methods to identify and inactivate parasite eggs in the environment and reduce their spread.
Graphical Abstract
Meropenem-induced pancytopenia in a preterm neonate: a case report
Authors: Hussain Kashif , Salat Muhammad Sohail , Mohammad Naureen , Mughal Ambreen , Idrees Sidra , Iqbal Javaid , Ambreen Gul 
Published: January 2021

Abstract
Background
A post-marketing surveillance study has reported an association between meropenem use and the incidence of hematologic abnormalities, including leukopenia, thrombocytopenia, hemolysis, and neutropenia, but the precise incidence in neonates is unknown. Here, we report meropenem-induced pancytopenia in a preterm neonate.

Case presentation
A preterm newborn Pakistani received intravenous meropenem 40 mg/kg every 8 hours to treat Klebsiella pneumoniae in blood cultures and suspected meningitis. The baby developed severe thrombocytopenia, with a platelet count of 22 × 103 cells/mm3, low hemoglobin level of 9.7 g/dl, and low absolute neutrophil count (ANC) of 816 cells/mm3 on days 3, 14, and 17 of meropenem therapy, respectively. Based on the blood culture and institutional guidelines, meropenem treatment was continued with monitoring and supportive care for a total of 19 days. After discontinuation of meropenem, the baby was monitored continuously for hematological changes, and low counts persisted for 3 days. ANC improved to > 1500 cells/mm3 on the fourth day, and the platelet count reached > 150 × 103 cells/mm3 for the first time on the seventh day of meropenem discontinuation. All subsequent complete blood count (CBC) reports showed improving trends. The baby was discharged on the 48th day of life (DOL), with follow-up monitoring of CBC. The baby was kept on iron supplements, and hemoglobin level of 11.2 g/dl was observed on the 59th DOL.

Conclusion
Neonatal pancytopenia may lead to serious health complications; therefore, clinicians and pharmacists need to vigilantly monitor CBC in this vulnerable population, even when administering meropenem in septic doses for the recommended duration.
Adipose-derived cellular therapies prolong graft survival in an allogenic hind limb transplantation model
Authors: Chen Jingting , Wang Yinmin , Hu Haoyue , Xiong Yao , Wang Shoubao , Yang Jun 
Published: January 2021

AbstractBackgroundThe long-term survival after vascularized composite allotransplantation (VCA) is often limited by systemic rejection as well as the adverse effects of immunosuppressants. The stromal vascular fraction (SVF) can be expanded to produce adipose-derived stem cells (ADSC) which represents a combination of endothelial cells, preadipocytes, immune cells, and ADSC. It has been demonstrated that ADSC possess consistently reliable clinical results. However, literature is scarce regarding SVF in VCA. This study seeks to determine the impact of ex vivo allograft pretreatment in combination with SVF cells in the ability to promote composite tissue allotransplantation immunotolerance.MethodsA rat hind limb allotransplant model was used to investigate the influence of ex vivo pretreatment of SVF and ADSC on VCA survival. Intravascular cell-free saline, ADSC, or SVF was infused into the models with immunosuppressants. The histopathological examination and duration that the allografts went without displaying symptoms of rejection was documented. Peripheral T lymphocytes and Tregs were quantified with flow cytometry while allotissue expressions of CD31 were quantified with immunohistochemical staining (IHC). ELISA was used to detect vascular endothelial growth factor (VEGF)-A as well as anti- and pro-inflammatory cytokines.ResultsWe demonstrated that ex vivo treatment of allografts with SVF or ADSC prolonged allograft survival in contrast to medium control cohorts. There were also enhanced levels of immunomodulatory cytokines and increased VEGF-A and CD31 expression as well as reduced infiltration and proliferation of T lymphocytes along with raised Treg expressions.ConclusionThese studies demonstrated that adipose-derived cellular therapies prolong graft survival in an allogenic hind limb transplantation model and have the potential to establish immunotolerance.
In vivo interactome profiling by enzyme‐catalyzed proximity labeling
Authors: Xu Yangfan , Fan Xianqun , Hu Yang 
Published: January 2021

AbstractEnzyme-catalyzed proximity labeling (PL) combined with mass spectrometry (MS) has emerged as a revolutionary approach to reveal the protein-protein interaction networks, dissect complex biological processes, and characterize the subcellular proteome in a more physiological setting than before. The enzymatic tags are being upgraded to improve temporal and spatial resolution and obtain faster catalytic dynamics and higher catalytic efficiency. In vivo application of PL integrated with other state of the art techniques has recently been adapted in live animals and plants, allowing questions to be addressed that were previously inaccessible. It is timely to summarize the current state of PL-dependent interactome studies and their potential applications. We will focus on in vivo uses of newer versions of PL and highlight critical considerations for successful in vivo PL experiments that will provide novel insights into the protein interactome in the context of human diseases.
A traceability analysis system for model evaluation on land carbon dynamics: design and applications
Authors: Zhou Jian , Xia Jianyang , Wei Ning , Liu Yufu , Bian Chenyu , Bai Yuqi , Luo Yiqi 
Published: January 2021

AbstractBackgroundAn increasing number of ecological processes have been incorporated into Earth system models. However, model evaluations usually lag behind the fast development of models, leading to a pervasive simulation uncertainty in key ecological processes, especially the terrestrial carbon (C) cycle. Traceability analysis provides a theoretical basis for tracking and quantifying the structural uncertainty of simulated C storage in models. Thus, a new tool of model evaluation based on the traceability analysis is urgently needed to efficiently diagnose the sources of inter-model variations on the terrestrial C cycle in Earth system models.MethodsA new cloud-based model evaluation platform, i.e., the online traceability analysis system for model evaluation (TraceME v1.0), was established. The TraceME was applied to analyze the uncertainties of seven models from the Coupled Model Intercomparison Project (CMIP6).ResultsThe TraceME can effectively diagnose the key sources of different land C dynamics among CMIIP6 models. For example, the analyses based on TraceME showed that the estimation of global land C storage varied about 2.4 folds across the seven CMIP6 models. Among all models, IPSL-CM6A-LR simulated the lowest land C storage, which mainly resulted from its shortest baseline C residence time. Over the historical period of 1850–2014, gross primary productivity and baseline C residence time were the major uncertainty contributors to the inter-model variation in ecosystem C storage in most land grid cells.ConclusionTraceME can facilitate model evaluation by identifying sources of model uncertainty and provides a new tool for the next generation of model evaluation.
Investigations of the relics and altar materials relating to the apostles St James and St Philip at the Basilica dei Santi XII Apostoli in Rome
Authors: Rasmussen Kaare Lund , van der Plicht Johannes , La Nasa Jacopo , Ribechini Erika , Colombini Maria Perla , Delbey Thomas , Skytte Lilian , Schiavone Simone , Kjær Ulla , Grinder-Hansen Poul , Lanzillotta Lautaro Roig 
Published: January 2021

Abstract
Two types of materials were sampled as part of an investigation of the relics of the Holy Catholic Church of the Apostles St Philip and St James in the Basilica dei Santi Apostoli in Rome: bone- and mummy-materials and architectural samples. The analyses encompassed radiocarbon dating, thermoluminescence dating, gas and liquid chromatographic separation with mass spectrometric detection, X-Ray fluorescence, X-Ray diffraction, inductively coupled plasma mass spectrometry, Raman spectroscopy, and Fourier transform infrared spectroscopy. The results show that the samples were subjected to a number of conservational and exhibition-related treatments. The alleged femoral bone of St James was dated between AD 214 and 340 (2σ confidence), which shows that this cannot be the bone of St James. An encrustation found in a canal in the reliquary in the high altar construction showed the presence of heavily oxidized rapeseed oil, which was radiocarbon dated between AD 267 and 539 (2σ confidence), and a ceramic shard also found in the high altar construction was TL-dated to AD 314–746 (2σ confidence). The two latter dates are consistent with a translation of the relics following the erection of the church at the time of Pope Pelagius I in AD 556–561.
The (STEM)2 Network: a multi-institution, multidisciplinary approach to transforming undergraduate STEM education
Authors: Santangelo Jessica , Hobbie Lawrence , Lee Jacqueline , Pullin Michael , Villa-Cuesta Eugenia , Hyslop Alison 
Published: January 2021

AbstractBackgroundTransforming the culture of STEM higher education to be more inclusive and help more students reach STEM careers is challenging. Herein, we describe a new model for STEM higher education transformation, the Sustainable, Transformative Engagement across a Multi-Institution/Multidisciplinary STEM, (STEM)2, “STEM-squared”, Network. The Network embraces a pathways model, as opposed to a pipeline model, to STEM career entry. It is founded upon three strong theoretical frameworks: Communities of Transformation, systems design for organizational change, and emergent outcomes for the diffusion of innovations in STEM education. Currently composed of five institutions—three private 4-year universities and two public community colleges—the Network capitalizes on the close geographic proximity and shared student demographics to effect change across the classroom, disciplinary, institutional, and inter-institutional levels.ResultsThe (STEM)2Network has increased the extent to which participants feel empowered to be change agents for STEM higher education reform and has increased collaboration across disciplines and institutions. Participants were motivated to join the Network to improve STEM education, to improve the transfer student experience, to collaborate with colleagues across disciplines and institutions, and because they respected the leadership team. Participants continue to engage in the Network because of the collaborations created, opportunities for professional growth, opportunities to improve STEM education, and a sense that the Network is functioning as intended.ConclusionThe goal to increase the number and diversity of people entering STEM careers is predicated on transforming the STEM higher education system to embrace a pathways model to a STEM career. The (STEM)2Network is achieving this by empowering faculty to transform the system from the inside. While the systemic transformation of STEM higher education is challenging, the (STEM)2Network directly addresses those challenges by bridging disciplinary and institutional silos and leveraging the reward structure of the current system to support faculty as they work to transform this very system.
Financial development during COVID-19 pandemic: the role of coronavirus testing and functional labs
Authors: Anser Muhammad Khalid , Khan Muhammad Azhar , Zaman Khalid , Nassani Abdelmohsen A. , Askar Sameh E. , Abro Muhammad Moinuddin Qazi , Kabbani Ahmad 
Published: January 2021

AbstractThe outbreak of the SARS-CoV-2 virus in early 2020, known as COVID-19, spread to more than 200 countries and negatively affected the global economic output. Financial activities were primarily depressed, and investors were reluctant to start new financial investments while ongoing projects further declined due to the global lockdown to curb the disease. This study analyzes the money supply reaction to the COVID-19 pandemic using a cross-sectional panel of 115 countries. The study used robust least square regression and innovation accounting techniques to get sound parameter estimates. The results show that COVID-19 infected cases are the main contributing factor that obstructs financial activities and decrease money supply. In contrast, an increasing number of recovered cases and COVID-19 testing capabilities gave investors confidence to increase stock trade across countries. The overall forecast trend shows that COVID-19 infected cases and recovered cases followed the U-shaped trend, while COVID-19 critical cases and reported deaths showed a decreasing trend. Finally, the money supply and testing capacity show a positive trend over a period. The study concludes that financial development can be expanded by increasing the testing capacity and functional labs to identify suspected coronavirus cases globally.
First record of a southern elephant seal (Mirounga leonina) in Sri Lankan waters
Authors: de Vos Asha 
Published: January 2021

AbstractAn unusual sighting of a juvenile southern elephant seal (Mirounga leonina), outside its typical range, was recorded off the southern coast of Sri Lanka between 20th November and 20th December 2019. The individual, a male as confirmed by the presence of a prepuce, underwent a catastrophic moult during this 1 month period, following which no further observations were recorded and so it was assumed it returned to sea. This represents the first confirmed sighting of a southern elephant seal, and indeed a phocid, in Sri Lankan waters.