bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional Antagonism by CDK8 Inhibition Improves Therapeutic Efficacy of MEK Inhibitors
Authors: Malone Clare F. , Kim Minjee , Alexe Gabriela , Engel Kathleen , Forman Alexandra B. , Robichaud Amanda , Conway Amy Saur , Goodale Amy , Meyer Ashleigh , Khalid Delan , Thayakumar Allen , Hatcher John M. , Gray Nathanael S. , Piccioni Federica , Stegmaier Kimberly 
Published: November 2022

Abstract

Aberrant RAS/MAPK signaling is a common driver of oncogenesis that can be therapeutically targeted with clinically approved MEK inhibitors. Disease progression on single-agent MEK inhibitors is common, however, and combination therapies are typically required to achieve significant clinical benefit in advanced cancers. Here we focused on identifying MEK inhibitor-based combination therapies in neuroblastoma with mutations that activate the RAS/MAPK signaling pathway, which are rare at diagnosis but frequent in relapsed neuroblastoma. A genome-scale CRISPR-Cas9 functional genomic screen was deployed to identify genes that when knocked out sensitize RAS-mutant neuroblastoma to MEK inhibition. Loss of either CCNC or CDK8, two members of the mediator kinase module, sensitized neuroblastoma to MEK inhibition. Furthermore, small-molecule kinase inhibitors of CDK8 improved response to MEK inhibitors in vitro and in vivo in RAS-mutant neuroblastoma and other adult solid tumors. Transcriptional profiling revealed that loss of CDK8 or CCNC antagonized the transcriptional signature induced by MEK inhibition. When combined, loss of CDK8 or CCNC prevented the compensatory upregulation of progrowth gene expression induced by MEK inhibition. These findings propose a new therapeutic combination for RAS-mutant neuroblastoma and may have clinical relevance for other RAS-driven malignancies.

Significance:
Transcriptional adaptation to MEK inhibition is mediated by CDK8 and can be blocked by the addition of CDK8 inhibitors to improve response to MEK inhibitors in RAS-mutant neuroblastoma, a clinically challenging disease.
Oxaliplatin versus Irinotecan no câncer colorretal avançado
Authors: Prado Thaís Árabe do , Del Bel Giovanna Volpe , Levignali Milena Bongiorno , Resende Uanderson 
Published: November 2022

O câncer colorretal é uma neoplasia com alta prevalência e letalidade. A razão desse elevado número de mortes é a detecção da doença em estágios metastáticos, de difícil cura e que necessitam de terapia quimioterápica adjuvante ou paliativa. Na atualidade, o principal tratamento quimioterápico dessa neoplasia tem como base as drogas Oxaliplatina ou Irinotecano, isolados ou combinados com outros medicamentos. O objetivo desta revisão sistemática é avaliar se há superioridade do esquema quimioterápico com Irinotecano sobre o regime com Oxaliplatina. Foi realizada a análise de ensaios clínicos randomizados, fase II ou III, nas bases de dados eletrônicas Central e PubMed. Critérios de inclusão: ensaios clínicos randomizados comparando regimes à base de irinotecano ou oxaliplatina como tratamentos de primeira linha para câncer colorretal metastático. O desfecho primário analisado foi a superioridade entre os quimioterápicos sobre a sobrevida global. Os desfechos secundários incluíram sobrevida livre de progressão, taxa de resposta e efeitos colaterais. Registro na PROSPERO: CRD42019130339. Não houve diferença significativa nos 13 estudos sobre a sobrevida dos pacientes. Sobre os efeitos colaterais dos medicamentos, os regimes baseados em irinotecano foram associados a uma alta incidência de neutropenia e diarreia grave. Já os associados com oxaliplatin cursaram com alta incidência de neuropatia sensitiva. Não houve diferença estatisticamente significativa sobre a sobrevida global, sobrevivência livre de progressão e na taxa de resposta quando comparamos os pacientes que receberam oxaliplatina e irinotecano.
Orbitacolax iniistii sp. nov. (Copepoda, Cyclopoida, Bomolochidae) recovered from the blackspot razorfish Iniistius dea (Temminck & Schlegel, 1845) (Pisces, Labridae) in Japan
Authors: Izawa Kunihiko 
Published: November 2022

Abstract
Orbitacolax iniistii sp. nov. is described based on a single specimen of the female recovered from washing fluid of the blackspot razorfish Iniistius dea (Temminck & Schlegel, 1845) (Pisces, Labridae) in Japan.
Expression of the senescence-related gene FoxO in Daphnia pulex and its role in the regulation of reproductive transformation (Branchiopoda, Cladocera)
Authors: Zhang Shun , Zhou Xuan-Yu , Zhang Cheng , Zhao Chun-Pu , Li Wei , Wang Dan-Li , Xu Shan-Liang 
Published: November 2022

Abstract
The gene FoxO plays an important role in regulating individual growth and development, cell survival, and senescence, mainly through transcriptional regulation and the signal transduction pathway. In this study, the full-length cDNA sequence of the FoxO gene was cloned from Daphnia pulex. FoxO was silenced by RNA interference. The expression levels of the senescence-related genes FoxO, Akt, and Sir2 were analysed before and after interference by real-time polymerase chain reaction and Western blotting. Meanwhile, the production of an ephippium in D. pulex was evaluated before and after interference. The expression of FoxO and protein abundance decreased after interference. The number of ephippia produced in the Akt interference group was higher than in the two control groups, and the expressions of the senescence-related genes Akt and Sir2 decreased after interference. The results indicate that FoxO regulated senescence, primarily through the phosphorylation of Akt and acetylation of Sir2, thereby affecting the reproductive transformation of D. pulex.
The effect of ice trash fish, Leiognathus equula (Forsskål, 1775) (Percomorphi, Leiognathidae) and oyster, Crassostrea iredalei (Faustino, 1932) (Ostreida, Ostreidae) on the growth and mating of the mud crab, Scylla paramamosain Estampador, 1950 (Brachyura, Portunidae), cultured in a controlled tank
Authors: Gunarto Gunarto , Herlinah Herlinah , Muliani Muliani , Tampangallo Bunga Rante , Kamaruddin Kamaruddin 
Published: November 2022

Abstract
The aim of this study was to determine the most suitable kind of feed for the mud crab, Scylla paramamosain, to grow from juvenile to broodstock size and to monitor their monthly size and growth rate, as well as to (1) record them reaching maturity and (2) their subsequent mating frequency. For this research, a Complete Randomized Design was used with three treatments. Each treatment was carried out with 40 individuals. The crabs are usually grown in 90 m3 concrete tanks. The three feeds tested were: (A) trash fish, Leiognathus equula, (B) a combination of that ice trash fish and oyster meat from Crassostrea iredalei, and, (C) that same oyster meat only. The feed was always given at 3-10% of total body weight/day. Newly adult male crabs were selected for mating with a newly adult female crab. The male crabs fed treatments B and C grew faster than male crabs fed treatment A. While the female crabs fed treatment C grew significantly faster than female crabs fed treatment A (), but not significantly than the female crabs fed treatment B (). A total of 30 female crabs were followed in mating from July 2020 to January 2021, and the highest mating intensity was found from September to October 2020. The present study indicates that mud crabs grow fast when they are fed treatment C, i.e., oyster meat only.
Between Medicine and Gift
Authors: Liang Siran , Münster Daniel 
Published: November 2022

Abstract
Tibet’s wild fungus cordyceps (Ophiocordyceps sinensis), a prized commodity in metropolitan China, has been undergoing changes in the way it is traded and marketed in Tibet. Prized as a medicinal tonic and high-value gift, the parasitic fungus has traditionally been traded in its dried form. However, in recent years we have observed the emergence of trade in fresh cordyceps. This paper seeks to make sense of this change in the form of this commodity and its correlation to changing meanings of cordyceps in China. Based on ethnographic fieldwork in Tibet and textual analysis of online markets in China, this paper argues that this transformation is associated with China’s anticorruption campaigns, the rising importance of e-commerce infrastructures, and the biomedicalization of cordyceps through advancing biotechnologies. In addition, we argue that professional brokers play a key role in the emergence of the fresh cordyceps trade.
Contestations, Contradictions, and Co-optations of Naturopathy and Biomedicine
Authors: Bhardwaj Ruby 
Published: November 2022

Abstract
The introduction of naturopathy in India can be traced back to the colonial period when it was fielded in resistance to the growing prominence of biomedicine. Reporting the findings of an empirical study conducted in two naturopathy centers in Delhi, this article explores its contradictions, contestations, and co-optations with biomedicine. It argues that biomedicine conditions the proliferation of yoga and naturopathy through its shortcomings and excesses. Patient accounts reveal that the pursuit of yoga and naturopathic treatment is propelled by their dissatisfaction with biomedicine and perception of risk involved in the ingestion of drugs. Furthermore, the study explores how patients and practitioners negotiate through pluralistic settings, imposed by the adoption of biomedical diagnostics and nosology that contradict naturopathy’s episteme. The practice of naturopathy and yoga demonstrates therapeutic regimes severed from their ontological bearings, reducing them merely to adjunct therapies adapted to a biomedical episteme.
Philosophical Definitions: A Pragmatic Approach
Authors: Arroyo Gustavo 
Published: November 2022

Abstract
In this paper, I argue for a pragmatic theory of the motivations behind the practice of defining concepts in philosophy. The “correct” definition in philosophy is not, as is usually supposed, the definition that accurately describes some pre-philosophical meaning, but the definition which is useful for the achievement of certain theoretical goals. I consider different examples of definitional debates from the history of philosophy. The analysis of these examples also evidences why philosophers do not usually grant the incidence of pragmatic reason in their conceptual investigations. At the end of the paper, I provide some reasons that explain why the incidence of pragmatic reasons is inevitable.
The Place of Cities in the Evolution of International Humanitarian Law
Authors: Sossai Mirko 
Published: November 2022

Abstract
The increasing interest in the global dimension of cities and their engagement with international law has coincided with the emergence of a new wave of scholarship covering the main legal challenges related to urban warfare. In recent years, the devastating humanitarian consequences of war in cities have raised new questions regarding how relevant rules of international humanitarian law are interpreted and applied: cities are portrayed not only as the seat of political leadership or as cultural property but increasingly also as “populated areas” and an “interconnected infrastructure of essential services”. Urban fighting is uniquely characterized by the proximity of military objectives with civilians and civilian objects: the question of the use of explosive weapons against military objectives in populated areas reflects the need for further clarification with respect to the application of the relevant rules of international humanitarian law (IHL). Much debate has been devoted to the legal implications of the contemporary resurgence of sieges of cities. Given that sieges are not per se an explicitly prohibited method of warfare under IHL, a key topic has been the precise scope of the “starvation of civilians” as a method of combat, for the purposes of the prohibition under Article 54(1) of Additional Protocol I and customary law. It is worth considering to what extent the specific representation of what amounts to a city has been considered as a factor in the current debate.
Writing Women into the History of Philosophy: Contextualism Re-Examined
Authors: Kotevska Laura 
Published: November 2022

Abstract
Contextualism is an established approach in the history of philosophy. This paper explores the advantages and disadvantages of contextualism as it is used in the examination of philosophical works produced by women whose work has, until recent decades, been neglected by historians of philosophy. It examines how various options for practicing contextualist history of philosophy might help to explain a woman’s participation in philosophy or undermine her intellectual authority and obscure our understanding of her work. The paper concludes with three suggestions for writing and teaching work produced by women that are informed by the methodological considerations addressed in the paper in order to avoid some of the epistemically harmful outcomes that can emerge when placing a woman’s work in her patriarchal context.
Quantification of QLCS Tornadogenesis, Associated Characteristics, and Environments across a Large Sample
Authors: Goodnight James S. , Chehak Devin A. , Trapp Robert J. 
Published: November 2022

Abstract
The skillful anticipation of tornadoes produced by quasi-linear convective systems (QLCSs) is a well-known forecasting challenge. This study was motivated by the possibility that warning accuracy of QLCS tornadoes depends on the processes leading to tornadogenesis, namely, one that is dominated by an apparent release of horizontal shearing instability [shearing instability dominant (SID)] and one by a pre-tornadic mesocyclone [pre-tornadic mesocyclone dominant (PMD)] and its associated generative mechanisms. The manual classification of the genesis of 530 QLCS tornadoes as either SID or PMD was performed using heuristic, yet process-driven criteria based on single-Doppler radar (WSR-88D) data. This included 214, 213, and 103 tornadoes that occurred during 2019, 2017, and 2016, respectively. As a function of tornadogenesis process, 36% were classified as SID, and 60% were classified as PMD; the remaining 4% could not be classified. Approximately 30% of the SID cases were operationally warned prior to tornadogenesis, compared to 44% of the PMD cases. PMD tornadoes were also more common during the warm season and displayed a diurnal, midafternoon peak in frequency. Finally, SID cases were more likely to be associated with QLCS tornado outbreaks but tended to be slightly shorter lived. A complementary effort to investigate environmental characteristics of QLCS tornadogenesis revealed differences between SID and PMD cases. MLCAPE was relatively larger for warm-season SID cases, and 0–3-km SRH was relatively larger in warm-season PMD cases. Additionally, pre-tornadic frontogenesis was more prominent for cool-season SID cases, suggestive of a more significant role of the larger-scale meteorological forcing in vertical vorticity that fosters tornadogenesis through SID processes.
Association between serum uric acid level and systemic lupus erythematosus kidney outcome: An observational study in Southern Chinese population and a meta-analysis
Authors: Han Yipeng , Lu Xiaoxi , Xiao Shibai , Qin Jiayu , Zheng Lijuan , Feng Yi , Cai Yujie , Qiu Rong , Huang Qin , Yang Min 
Published: November 2022

Objective The study aimed to explore the effect of serum uric acid (SUA) level on the progression of kidney function in systemic lupus erythematosus (SLE) patients Methods A total of 123 biopsy-proven lupus nephritis (LN) patients were included in this retrospective observational study. Cox proportional hazard regression analyses as well as restricted cubic spline analyses were performed to identify predictors of renal outcome in LN patients. We also performed a systematic review and meta-analysis for SUA and overall kidney outcomes in SLE patients. Results Based on the laboratory tests at renal biopsy, 72 (58.5%) of the 123 patients had hyperuricemia. The median (IQR) follow-up duration was 3.67 years (1.79–6.63 years), and a total of 110 (89.4%) patients experienced progression of LN. Increased serum uric acid level, whether analyzed as continuous or categorical variable, was associated with higher risk of LN progression in Cox proportional hazard regression model (hazard ratio [HR]: 1.003, 95% confidence interval [CI]: 1.001–1.005; HR: 1.780, 95% CI: 1.201–2.639, respectively). This relationship maintained in women (HR: 1.947, 95% CI: 1.234–3.074) but not men (HR: 2.189, 95% CI: 0.802–5.977). The meta-analysis showed a similar result that both continuous and categorical SUA were positively associated with the risk of kidney function progression in LN (weighted mean difference [WMD]: 1.73, 95% CI: 0.97–2.49; odds ratio [OR]: 1.55, 95% CI: 1.20–2.01, respectively). Conclusions Our study found overall and especially in women that higher SUA in LN patients were associated with increased risk of renal progression. Meta-analysis yielded consistent results. Future studies are required to establish if uric acid can be used as a biomarker for risk assessment and/or as a novel therapeutic target in SLE.
Implementation of Acupuncture in Routine Oncology Care: A Comparison of Physicians’, Nurses’, Physiotherapists’ and Acupuncturists’ Practice and Beliefs
Authors: Efverman Anna 
Published: November 2022

Background: It is important to investigate beliefs in acupuncture in professionals because professionals’ expectations may affect treatment outcomes. Aim: To document the type, number, and education of professionals practicing acupuncture. Further, to compare beliefs about the effectiveness of acupuncture for common cancer related symptoms in the different types of professionals. Methods: This cross-sectional study employed a questionnaire on practice and beliefs regarding acupuncture effects for symptoms that commonly occur in patients treated within oncology care settings. The respondents (n = 555) consisted of oncology professionals that is, physicians (n = 133), nurses (n = 172), and physiotherapists (n = 117). Additional respondents consisted of acupuncturists (n = 133), working outside approved health care. Results: Of the respondents, acupuncture was practiced by 4% of the physicians, 6% of the nurses, 58% of the physiotherapists, and 90% of the acupuncturists. The professionals believed acupuncture to be effective for pain (of the physicians, nurses, physiotherapists, and acupuncturists, 94%, 98%, 89%, and 99% respectively believed in the effectiveness), chemotherapy-induced nausea (corresponding figures: 74%, 89%, 89%, and 93%), and vasomotor symptoms (corresponding figures: 71%, 81%, 80%, and 97%). The physicians believed acupuncture to be effective in a mean of 5 symptoms, nurses in 6 symptoms, physiotherapists in 6 symptoms, and acupuncturists in 10 symptoms ( P < .001). Conclusions: Since the professionals varied substantially regarding practice, education and beliefs in acupuncture, oncology clinics may consider delivering patient preferred acupuncture according to evidence-informed guidelines rather than on varying preferences among the professionals, since professionals’ treatment expectations may modify treatment outcomes.
Modeling optimal patient transport in a stroke network capable of remote telerobotic endovascular therapy
Authors: Beaman Charles , Holodinsky Jessalyn K , Goyal Mayank , Tateshima Satoshi , Hill Michael D , Saver Jeffrey L , Kamal Noreen 
Published: November 2022

Background Telerobotic endovascular therapy (EVT) has the potential to decrease time to treatment and expand existing networks of care to more rural populations. It is currently unclear how its implementation would impact existing stroke networks. Methods Conditional probability models were generated to predict the probability of excellent outcome for patients with suspected large vessel occlusion (LVO). A baseline stroke network was created for California using existing intravenous thrombolysis (IVT) centers and comprehensive stroke centers (CSCs) capable of IVT and EVT. Optimal transport decisions and catchment areas were generated for the baseline model and three hypothetical scenarios through conversion of IVT centers at various distances from a CSC into centers capable of telerobotic EVT [i.e., hospitals ≥15 and <50 miles from a CSC were converted (Scenario 1), ≥50 and <100 miles (Scenario 2), and ≥100 miles (Scenario 3)]. Procedural times and success rates were varied systematically. Results Telerobotic EVT centers decreased median travel time for LVO patients in all three scenarios. The estimated number of robotically treated LVOs per year in Scenarios 1, 2, and 3 were 2,172, 740, and 212, respectively. Scenario 1 (15–50 miles) was the most sensitive to robotic time delay and success rate, but all three scenarios were more sensitive to decreases in procedural success rate compared to time delay. Conclusions Telerobotic EVT has the potential to improve care for stroke patients outside of major urban centers. Compared to procedural time delays in robotic EVT, a decrease in procedural success rate would not be well tolerated.
Content reporting and effectiveness of therapeutic exercise in the management of massive rotator cuff tears: A systematic review with 490 patients
Authors: Fernández-Matías Rubén , García-Pérez Fernando , Requejo-Salinas Néstor , Gavín-González Carlos , Martínez-Martín Javier , García-Valencia Homero , Flórez-García Mariano Tomás 
Published: November 2022

Background Massive rotator cuff tears (MRCT) account for a substantial fraction of tears above the age of 60 years. However, there are no clear criteria for prescription parameters within therapeutic exercise treatments. The aim of this study was to evaluate the effects and characteristics of therapeutic exercise treatments in patients with MRCT. Methods A systematic search was conducted in MEDLINE/PubMed, Web of Science, SPORTDiscus, SciELO, Scopus and EMBASE from inception to August 2022. Studies were included if they evaluated the effects of exercise on patients with MRCT. The risk of bias was evaluated and the Consensus on Exercise Reporting Template (CERT) was also used. A narrative synthesis without meta-analysis was performed. Results One randomized controlled trial, two non-randomized studies, six non-controlled studies, one case series and four retrospective studies were included. They ranged from serious to moderate risk of bias. The CERT reflected a poor description of the exercise programmes. Studies showed a pattern of improvements in most patient-reported outcome measures (PROM) surpassing the MCID, and active elevation range of motion. Conclusions There is limited evidence that exercise and co-interventions are effective in the management of some patients with MRCT, based on a systematic review without meta-analysis. Future research should improve content reporting. Level of evidence IV.