bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene Expression Signature Correlates with Outcomes in Metastatic Renal Cell Carcinoma Patients Treated with Everolimus Alone or with a Vascular Disrupting Agent
Authors: Yang Eddy S. , Nassar Amin H. , Adib Elio , Jegede Opeyemi A. , Alaiwi Sarah Abou , Manna Deborah L. Della , Braun David A. , Zarei Mahsa , Du Heng , Pal Sumanta K. , Naik Gurudatta , Sonpavde Guru P. 
Published: June 2021

AbstractEverolimus monotherapy use for metastatic renal cell carcinoma (mRCC) has diminished due to recent approvals of immune checkpoint and VEGF inhibitors. We hypothesized that gene expression associated with everolimus benefit may provide rationale to select appropriate patients. To address this hypothesis, tumors from a phase I/II trial that compared everolimus alone or with BNC105P, a vascular disrupting agent, were profiled using Nanostring as a discovery cohort. A phase III trial (CheckMate 025) was used for validation. Clinical benefit (CB) was defined as response or stable disease for ≥6 months. A propensity score covariate adjustment was used, and model discrimination performance was assessed using the area under the ROC curve (AUC). In a discovery cohort of 82 patients, 35 (43%) were treated with everolimus alone and 47 (57%) received everolimus + BNC105P. Median PFS (mPFS) was 4.9 (95% CI, 2.8–6.2) months. A four-gene signature (ASXL1, DUSP6, ERCC2, and HSPA6) correlated with CB with everolimus ± BNC105P [AUC, 86.9% (95% CI, 79.2–94.7)]. This was validated in 130 patients from CheckMate 025 treated with everolimus [AUC, 60.2% (95% CI, 49.7–70.7)]. Among 43 patients (52.4%) with low expression of an 18-gene signature, everolimus + BNC105P was associated with significantly longer mPFS compared with everolimus alone (10.4 vs. 6.9 months; HR, 0.49; 95% CI, 0.24–1.002; P = 0.047). These signatures warrant further validation to select patients who may benefit from everolimus alone or with a vascular disrupting agent.
FTO (Fat-Mass and Obesity-Associated Protein) Participates in Hemorrhage-Induced Thalamic Pain by Stabilizing Toll-Like Receptor 4 Expression in Thalamic Neurons
Authors: Fu Ganglan , Du Shibin , Huang Tianfeng , Cao Minghui , Feng Xiaozhou , Wu Shaogen , Albik Sfian , Bekker Alex , Tao Yuan-Xiang 
Published: June 2021

Background and Purpose:

Hemorrhage-caused gene changes in the thalamus likely contribute to thalamic pain genesis. RNA N
6
-methyladenosine modification is an additional layer of gene regulation. Whether FTO (fat-mass and obesity-associated protein), an N
6
-methyladenosine demethylase, participates in hemorrhage-induced thalamic pain is unknown.

Methods:

Expression of
Fto
mRNA and protein was assessed in mouse thalamus after hemorrhage caused by microinjection of Coll IV (type IV collagenase) into unilateral thalamus. Effect of intraperitoneal administration of meclofenamic acid (a FTO inhibitor) or microinjection of adeno-associated virus 5 (AAV5) expressing Cre into the thalamus of
Fto
fl/fl
mice on the Coll IV microinjection–induced TLR4 (Toll-like receptor 4) upregulation and nociceptive hypersensitivity was examined. Effect of thalamic microinjection of AAV5 expressing
Fto
(AAV5-
Fto
) on basal thalamic TLR4 expression and nociceptive thresholds was also analyzed. Additionally, level of N
6
-methyladenosine in
Tlr4
mRNA and its binding to FTO or YTHDF2 (YTH N
6
-methyladenosine RNA binding protein 2) were observed.

Results:

FTO was detected in neuronal nuclei of thalamus. Level of FTO protein, but not mRNA, was time-dependently increased in the ipsilateral thalamus on days 1 to 14 after Coll IV microinjection. Intraperitoneal injection of meclofenamic acid or adeno-associated virus-5 expressing Cre microinjection into
Fto
fl/fl
mouse thalamus attenuated the Coll IV microinjection–induced TLR4 upregulation and tissue damage in the ipsilateral thalamus and development and maintenance of nociceptive hypersensitivities on the contralateral side. Thalamic microinjection of AAV5-
Fto
increased TLR4 expression and elicited hypersensitivities to mechanical, heat and cold stimuli. Mechanistically, Coll IV microinjection produced an increase in FTO binding to
Tlr4
mRNA, an FTO-dependent loss of N
6
-methyladenosine sites in
Tlr4
mRNA and a reduction in the binding of YTHDF2 to
Tlr4
mRNA in the ipsilateral thalamus.

Conclusions:
Our findings suggest that FTO participates in hemorrhage-induced thalamic pain by stabilizing TLR4 upregulation in thalamic neurons. FTO may be a potential target for the treatment of this disorder.
“A New Logic”: Bacon’s Novum Organum
Authors: Cassan Elodie 
Published: June 2021

Abstract
The purpose of this paper is to assess Bacon’s proclamation of the novelty of his Novum Organum. We argue that in the Novum Organum, Bacon reshapes the traditional representation of logic as providing tools for the building of philosophical discourse. For he refuses both an understanding of logic in terms of an ars disserendi, and an approach to philosophy in terms of a discourse of a certain type of necessity and universality. How can Bacon articulate a logic, that is, a set of rules with formal features, on the basis of a distrust of the paradigm of discourse? This seemingly paradoxical definition of logic follows from Bacon’s rejection of the conception of the scientific reasoning provided by the Organon. It also stems from his reworking of Aristotle’s semiotics, in an effort to deal with the gap between what reality consists in and what the mind perceives of it.
Inequality across Three Generations under Pressure from Sovietization Policies
Authors: Saar Ellu , Helemäe Jelena 
Published: June 2021

Abstract
This article explores the multigenerational impact of Sovietization policies on the reproduction of educational inequalities in Estonia. Estonia provides an opportunity to assess the multigenerational effect under conditions of regime changes after transitioning from the independent Estonian Republic to Soviet Estonia and thence to the newly independent post-Soviet Estonia. During Sovietization, a wide range of measures involving repressions and positive discrimination were applied to abruptly hinder intergenerational continuity. Analysis based on retrospective data from the Estonian Family and Fertility Survey 2004 indicates grandparents’ social positions are associated with grandchildren’s attainment of higher education. Their influence is only partially mediated through the parental generation. Overall, the Sovietization policies have not reduced either the two or three-generational reproduction of inequality. Moreover, these policies produced unintended consequences, facilitating the transmission of advantage in three generational perspectives. Our findings argue in favour of the importance of contextual sensitivity and a multigenerational perspective in research of social stratification.
“For I Say”: A Keeper at the Rabbinic Gates of Doubt
Authors: Baris Michael 
Published: June 2021

Abstract
The rabbinic idiom “for I say” (שאני אומר) has been construed philologically as a specific type of presumption, buttressed with first-person rhetoric. From the perspective of legal analysis, I contend that “for I say” and presumption are diametrically opposed decision-rules, employed consistently in tannaitic and amoraic literature. While presumptions are exclusionary rules, circumscribing doubt, “for I say” is an inclusionary rule, validating doubt. The versatility of the “for I say” rule testifies to its preliminary nature – while the outcome is determined by a robust set of primary decision rules. “For I say” should be read as: for I can say, legitimizing doubt and calling on primary rabbinic rules for treating cases of factual uncertainty, in contestable instances.
From the “Man of Jerusalem” to the Beit El Yeshiva: Late Nineteenth Century Rabbinic Leadership in the Jewish Community of Tripoli
Authors: Atia Ronel 
Published: June 2021

Abstract
This article details a polemic among the rabbinical leadership of the Jewish community of Tripoli, Libya, in the late nineteenth century. At stake was an initiative of the community’s spiritual leader, Rabbi Eliyahu Bechor Hazzan, to change the traditional educational system to include secular topics and foreign language. The communal rabbis who opposed the idea wrote the rabbinical leadership of Jerusalem, requesting support in overturning Rabbi Hazzan’s proposal. This study details the issues at stake in this aspect of the infiltration of modernism into Jewish communities in Muslim countries and presents the letter written to the rabbinic authorities of the land of Israel that led Rabbi Hazzan to abandon his initiative and, later, to resign from his leadership post.
Changes of Meaning in Biblical and Modern Given Names of the YIQTOL Noun Pattern
Authors: Yemini Bat-Zion 
Published: June 2021

Abstract
The biblical Hebrew tense system has two aspects: the perfective, indicating a completed action, and an imperfective aspect, denoting an action that has not yet ended. From the period of the rabbinic sages of the first centuries CE to today’s Modern Hebrew, an absolute tense system has been the norm, employing past, present, and future. This change in the system of tenses influenced the meaning of names created in the Qatal and Yiqtol patterns. The reason for the changed meanings is Modern Hebrew speakers’ lack of proficiency in the biblical system of tenses. To shed light on the language and culture of Modern Hebrew speakers, this article presents biblical and modern given names in the Yiqtol pattern and explains the changes in the modern names.
A Hundred Forms of Spirituality in the Least Religious Country in the World
Authors: Hiiemäe Reet 
Published: June 2021

Abstract
This paper is mainly based on interviews and observations that the author made during the process of writing a book about a hundred forms of religious and spiritual movements, teachings, and techniques in Estonia, thus being a reflection of trends and transformations of spiritual thought and practice in a country that has been repeatedly called the least religious country in Europe or even the whole world. Bringing some topical case analyses from this empirical material, the article will offer an amended interpretative framework for discussing features that are relevant in the research of Western contemporary spiritualities, for example multiple, situational, and fluctuating spiritual identities incongruent with the use of stable categories in religiosity statistics; children as important spiritual agents; mediatized liquidity and hybridity of spiritual thought being part of the ‘all-inclusive’ and ‘open-ended’ spiritual environment; and public conflicts and private symbioses of scientific, spiritual, and religious worldviews.
The Confession as Retrospective Narrative: A Genre for Ethnographically-Driven Theology
Authors: Whitmore Todd 
Published: June 2021

Abstract
The fieldwork experience often manifests itself to the researcher as a tangled cluster of thoughts and feelings that is difficult to write into accessible prose. However, pre-set narratives reduce the subjects of the fieldwork to being mere exemplifications of arguments worked out in advance. This article offers the confession as a kind of retrospective narrative that at once renders the field experience accessible to the reader and maintains the three-dimensional fullness of the lives of the fieldwork subjects. The author draws on his work among persons with opioid use disorders to display the possibilities.
Revealers, Skeptics, and Witnesses: Advancing a Witness Methodology in Ethnographic Theology and Ethics
Authors: Juskus Ryan 
Published: June 2021

Abstract
Drawing on original ethnographic fieldwork with a Christian environmental initiative in Appalachia and Alabama, this article argues that moral theologians should conceive of ethnography as witnessing witnesses to aid and multiply witnesses. An ethnographic ‘witness methodology’ is contrasted with two other approaches that the author calls revealer and skeptic methodologies. This witness methodology is developed primarily by analyzing a creation care organization’s practice of citizen science in places devastated by coal mining and coal burning. The author develops the concept of witness by reflecting on his role in helping the organization develop a slogan to describe their work and how this slogan encapsulates their citizen science practice. Though developed primarily in conversation with the author’s fieldwork, the proposed witness methodology is also supported through dialogue with Scripture, Christian ethics, and cultural anthropology.
Imagining a Sacramental Method: Divine Presence in the Lives of the Crucified Peoples
Authors: Theuring Ashley 
Published: June 2021

Abstract
This article argues that an ethnographic method informed by a sacramental worldview and guided by the ethical imperative of the preferential option for the poor can give theologians a fundamental tool to access revelation found in our everyday lives. This article begins with a case study investigating the presence of God in the midst of suffering among a community of domestic violence survivors. Then, this article argues that the Divine presence found through this case study can be theologically investigated through an ethnographic methodology informed by a sacramental worldview and the preferential option for the poor. Finally, to embody this proposed methodology and its radical potential, this article brings the narratives of the domestic violence survivors into critical dialogue with the Markan ‘Empty Tomb’ tradition, to uncover a renewed sense of God’s presence in the ‘Empty Tomb.’
The Mitridae (Gastropoda: Neogastropoda) of the Miocene Paratethys Sea
Authors: HARZHAUSER MATHIAS , LANDAU BERNARD 
Published: June 2021

The gastropod family Mitridae in the Miocene Paratethys Sea is revised. In total, 35 species in eight genera are reported. 75% of the species are so far known only from the Paratethys Sea. Biogeographic relations with the adjacent Proto-Mediterranean Sea are moderate and are mainly documented within Cancilla, but nearly absent in the other genera. A slight South-North trend in diversity is observed within the Paratethyan basins, with an outstandingly high diversity of 22 species in the Romanian Făget Basin, but only nine species in the Polish and Ukrainian parts of the Fore-Carpathian Basin. Fraudiziba nov. gen. and Wormsina nov. gen. are introduced as new genera. Twelve species are described as new: Episcomitra antibellardii nov. sp., Episcomitra leopoldiana nov. sp., Episcomitra pseudoincognita nov. sp., Episcomitra missile nov. sp., Episcomitra neubaueri nov. sp., Domiporta amoena nov. sp., Domiporta pulchra nov. sp., Domiporta turpis nov. sp., Nebularia soliphila nov. sp., Cancilla nanostriatula nov. sp., and Cancilla wagreichi nov. sp. Fraudiziba ottomanica nov. sp. is described as new species from the middle Miocene of the Karaman Basin in Turkey. Lectotypes are designated for M. austriaca Csepreghy-Meznerics, 1950, Mitra brusinai Hoernes & Auinger, 1880, M. cochlearella Mayer-Eymar, 1890, M. friedbergi Cossmann, 1912, Mitra hoernesi Mayer, 1864, Mitra perangulata Peyrot, 1928, M. praenigra Mayer-Eymar, 1890, and Mitra transsylvanica Hoernes & Auinger, 1880. Fraudiziba paratethyca nov. nom. is proposed as new name for Mitra austriaca Csepreghy-Meznerics 1950 [non Mayer-Eymar, 1898].
circVAPA promotes the proliferation, migration and invasion of oral cancer cells through the miR-132/HOXA7 axis
Authors: Chen Hao , Zhang Ye , Wu Kankui , Qiu Xiaoyong 
Published: June 2021

Objective To study the relationship between the circular RNA vesicle-associated membrane protein-associated protein A (circVAPA) and the pathogenesis of oral squamous cell carcinoma. Methods The expression of circVAPA was detected by RT-qPCR. In vitro loss-of-function experiments were performed in Cal-27 cells. The malignant phenotype of cells was evaluated by cell counting kit-8, clone formation and transwell assays. Luciferase reporter assays were used to assess the circVAPA/miR-132/homeobox A (HOXA) regulatory axis. Results circVAPA expression was significantly increased in oral cancer tissues and cells. The overall survival and progression-free survival of patients with oral cancer who exhibited high circVAPA expression were significantly shorter compared with those with low expression. circVAPA expression was closely related to tumor size, TNM stage and distant metastasis. circVAPA knockdown reduced the proliferation, invasion and migration of Cal-27 cells. MiR-132 was identified as a target of circVAPA in Cal-27 cells. Cotransfection with si-circVAPA and miR-132 inhibitor reversed the inhibitory effect of circVAPA knockdown on cell malignant phenotypes. HOXA7 was further identified as a downstream target of miR-132. Conclusion circVAPA is highly expressed in oral cancer, and its abnormal expression might affect the proliferation, invasion and migration of oral cancer cells by modulating the miR-132/HOXA7 signaling axis.
Measurement of Pharmacist-Physician Collaborative Care on Therapeutic Inertia in Patients With Type 2 Diabetes
Authors: Cowart Kevin , Emechebe Nnadozie , Pathak Rashmi , Abbruzese Lucas , Hann James , Lloyd Andie , Roetzheim Richard , Zgibor Janice , Updike Wendy H. 
Published: June 2021

Background Team-based care practice models have been shown to improve diabetes-related therapeutic inertia, yet the method and type of antidiabetic treatment intensification (TI) leading to improvements in glycemic control are not well understood. Objective To evaluate time to TI in a pharmacist-physician practice model (PPM) as compared with usual medical care (UMC), explore the method and type of antidiabetic TI, and evaluate achievement of hemoglobin A1C (A1C) goal among each cohort. Methods This was a retrospective cohort study conducted between January 1, 2017, and December 31, 2018. Median time to TI was calculated and compared between patients in the PPM and UMC groups using the log rank test. Descriptive statistics were used to evaluate the method and type of TI and A1C goal achievement. Results A total of 56 patients were included. The median (interquartile range) time to antidiabetic TI among the PPM cohort was 37.5 days (8, 216.5), as compared with 142 days (16, 465) in the UMC cohort ( P = 0.19). At 1 year post–index date, 25% of patients in the PPM cohort reached their A1C goal compared with 18.8% of patients in the UMC cohort. This effect was maintained in the subgroup (n = 49) of patients receiving TI (23.1% vs 17.8%). Conclusion and Relevance A shorter time to TI and improvement in A1C goal achievement was observed with pharmacist-physician care compared with UMC. These findings suggest that pharmacist-physician care may be one of several interventions necessary to overcome therapeutic inertia in diabetes care.
Return to Play After Open Calcaneoplasty for Insertional Achilles Tendinopathy With Haglund Deformity in Competitive Professional Athletes
Authors: Lee Kyung Tai , Hyuk Jegal , Kim Sung Jae 
Published: June 2021

Background: Surgical treatment of insertional Achilles tendinopathy with Haglund deformity in highly competitive professional athletes has not been previously investigated. Purpose: To assess clinical outcomes, including return to play (RTP), after surgical treatment of insertional Achilles tendinopathy in professional athletes. Study Design: Case-control study; Level of evidence, 3. Methods: This retrospective study included 20 professional athletes who were surgically treated for insertional Achilles tendinopathy and had at least 2 years of follow-up. An open longitudinal lateral approach was used for the operation, without violation of the Achilles tendon. Outcome evaluation included American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score, subjective patient satisfaction, mean time of return to competition (RTC), and rate of RTP. We defined RTC as return to an official match for at least 1 minute and RTP rate as the percentage of patients who were able to participate in at least 2 full seasons. A subgroup analysis was performed to compare the RTP and no-RTP groups. Results: The AOFAS score improved significantly from preoperatively to the final follow-up (from 65.1 to 88.4; P < .001), and 75% of the patients reported good to excellent satisfaction. The mean time of RTC was 7.45 months (range, 4-18 months), and the rate of RTP was 60%. The RTP group had a significantly lower mean body mass index than did the no-RTP group (22.03 vs 23.86, respectively; P = .005) and faster mean RTC (5.0 vs 11.1 months, respectively; P < .001). Conclusion: Open calcaneoplasty for surgical treatment of insertional Achilles tendinopathy with Haglund deformity in highly competitive professional athletes should be approached cautiously. Our patients had a 7.5-month recovery period before return to their first official match, and only 60% of the patients returned to their sports activity and participated in at least 2 full seasons. Lower body mass index and a faster RTC after surgery were related to longer functional maintenance.
Application of Digital Twin in Smart Battery Management Systems
Authors: Wang Wenwen , Wang Jun , Tian Jinpeng , Lu Jiahuan , Xiong Rui 
Published: June 2021

AbstractLithium-ion batteries have always been a focus of research on new energy vehicles, however, their internal reactions are complex, and problems such as battery aging and safety have not been fully understood. In view of the research and preliminary application of the digital twin in complex systems such as aerospace, we will have the opportunity to use the digital twin to solve the bottleneck of current battery research. Firstly, this paper arranges the development history, basic concepts and key technologies of the digital twin, and summarizes current research methods and challenges in battery modeling, state estimation, remaining useful life prediction, battery safety and control. Furthermore, based on digital twin we describe the solutions for battery digital modeling, real-time state estimation, dynamic charging control, dynamic thermal management, and dynamic equalization control in the intelligent battery management system. We also give development opportunities for digital twin in the battery field. Finally we summarize the development trends and challenges of smart battery management.
Self-Adaptive Control System for Additive Manufacturing Using Double Electrode Micro Plasma Arc Welding
Authors: Li Nan , Fan Ding , Huang Jiankang , Yu Shurong , Yuan Wen , Han Miaomiao 
Published: June 2021

AbstractWire arc additive manufacturing (WAAM) has been investigated to deposit large-scale metal parts due to its high deposition efficiency and low material cost. However, in the process of automatically manufacturing the high-quality metal parts by WAAM, several problems about the heat build-up, the deposit-path optimization, and the stability of the process parameters need to be well addressed. To overcome these issues, a new WAAM method based on the double electrode micro plasma arc welding (DE-MPAW) was designed. The circuit principles of different metal-transfer models in the DE-MPAW deposition process were analyzed theoretically. The effects between the parameters, wire feed rate and torch stand-off distance, in the process of WAAM were investigated experimentally. In addition, a real-time DE-MPAW control system was developed to optimize and stabilize the deposition process by self-adaptively changing the wire feed rate and torch stand-off distance. Finally, a series of tests were performed to evaluate the control system’s performance. The results show that the capability against interferences in the process of WAAM has been enhanced by this self-adaptive adjustment system. Further, the deposition paths about the metal part’s layer heights in WAAM are simplified. Finally, the appearance of the WAAM-deposited metal layers is also improved with the use of the control system.