bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase 2 trial for sequential treatment of high dose cabozantinib (CABO) or CABO plus nivolumab (NIVO) on/after progression on CABO monotherapy in advanced renal cell carcinoma (RCC): Seq-Cabo.
Authors: Qin Qian , Brugarolas James , Hammers Hans J. , Arafat Waddah , Courtney Kevin Dale , Wang Jue , Jiang Changchuan , Zhang Song , Cowey Charles Lance , Hutson Thomas E. , Zhang Tian 
Published: June 2024

TPS4609 Background: Efficacy outcomes for advanced RCC have improved with vascular endothelial growth factor receptor (VEGFR)-tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (IO), and CABO has become an established treatment for both front-line and refractory, advanced RCC. However, most patients develop resistance to CABO. With each subsequent line of therapy, efficacy and survival benefits also shorten and treatment options become limited. It is thus important to explore ways to maximize each line of therapy. Methods: Based on previous studies suggesting 1) dose-dependent effect of VEGFR-TKIs with feasibility/efficacy of CABO dose escalation to 80mg and 2) immune-modulatory effects of CABO, we have designed a two-cohort phase 2 trial to salvage CABO response, either by escalating the dose of CABO to 80mg oral (PO) daily (cohort 1) or by combining CABO 40mg PO daily with NIVO 480mg intravenous (IV) every 4 weeks (cohort 2), based on investigator choice. Subjects will be treated until progression or unacceptable toxicity. Main inclusion criteria include progressive advanced RCC after prior CABO monotherapy for at least 6 months, able to tolerate CABO 60mg PO daily (cohort 1) and 40mg PO daily (cohort 2), radiographically measurable disease, ECOG < 2, and adequate end-organ function. Main exclusion criteria include prior treatment with concurrent CABO/NIVO, uncontrolled co-morbidities, uncontrolled HIV, and concurrent malignancy (excepting completely excised skin cancers and organ-confined Gleason 6 prostate cancer). Primary endpoint is progression free survival (PFS) with key secondary endpoints including overall response rate, disease control rate, duration of response, and overall survival. The null hypothesis of median PFS 3 months will be tested against an alternative hypothesis of median PFS 6 months. Assuming a 2-sided significance level of 10% and 80% power, and estimating 10% drop out, 18 patients per cohort (36 patients total) will be enrolled.Pharmacokinetics, circulating biomarkers, and pre-/post-biopsies are planned for tissue-based analyses. The study is open for enrollment (NCT05931393). Clinical trial information: NCT05931393 .
A phase II study of lurbinectedin with or without avelumab in small cell carcinoma of the bladder (LASER).
Authors: Simon Nicholas I. , Chandran Elias , Niglio Scot Anthony , Kydd Andre Rashad , Atiq Saad Omar , Ley Lisa , Wang Tzu-fang , Boudjadi Salah , Smith Elizabeth , Akbulut Dilara , Steinberg Seth M. , Apolo Andrea B 
Published: June 2024

TPS4629 Background: Small cell carcinoma of the bladder (SCCB) is a rare, aggressive malignancy accounting for <1% of all bladder malignancies. Given its rarity, few prospective randomized trials have been completed in SCCB. Most therapeutic evidence comes from retrospective case series and due to its histologic similarity to small cell lung cancer (SCLC), current guidelines recommend bladder cancers with any component of small cell histology be treated similarly to SCLC. Lurbinectedin is a novel alkylating agent which recently received accelerated approval from the FDA as a second line treatment for SCLC after demonstrating an overall response rate (ORR) of 35.2% and median duration of response (DoR) of 5.3 months (Trigo et al., Lancet Oncol, 2020). Avelumab is an anti-PD-L1 antibody FDA approved as maintenance treatment for patients with locally advanced or metastatic urothelial cancer (UC) without progression on frontline chemotherapy. Case reports have demonstrated that second line options in SCLC, including immunotherapy, appear to have some efficacy in SCCB. The purpose of this study is to assess the efficacy of lurbinectedin, either alone or in combination with avelumab, in participants with SCCB or other high grade neuroendocrine tumors (HGNETs) of the urinary tract. Methods: LASER (NCT06228066) is a phase II, multisite, open label, nonrandomized study with two cohorts. Eligible patients must have pathologically confirmed SCCB or other HGNETs of the urinary tract. Patients with mixed histologies, with any component of neuroendocrine tumor, are eligible. Patients must have received or be ineligible/refused frontline platinum/etoposide therapy. Participants in Cohort 1 must have received prior immune checkpoint inhibitors (ICIs) or be ineligible for treatment with ICI. These patients will receive lurbinectedin 3.2mg/m2 IV every 21 days. Participants in Cohort 2 must be ICI naïve but eligible to receive them. These patients will receive lurbinectedin 3.2mg/m2 IV and avelumab 800mg IV every 21 days. The primary endpoint for both cohorts is ORR, with key secondary endpoints including clinical benefit rate, PFS, OS, and DoR. The study will be conducted using a Simon minimax two stage design to rule out an ORR of 5% in favor of an ORR of 25% or greater in each cohort. If 1 of the first 12 patients has a response accrual will continue up to 16 evaluable patients per cohort. Accrual ceiling will be set at 35 patients. Exploratory objectives include analyzing peripheral immune subsets, DNA and RNA sequencing of tumors, and measurement of ctDNA and CTCs. Clinical trial information: NCT06228066 .
SAVE: A prospective, single-arm, single-center clinical study of disitamab vedotin in combination with toripalimab in patients with advanced penile cancer that has progressed or is intolerant to cisplatin chemotherapy.
Authors: Yuan Fang 
Published: June 2024

TPS5107 Background: At present, penile cancer patients receiving chemotherapy with paclitaxel, ifosfamide and cisplatin or docetaxel, cisplatin and 5-fluorouracil have a lack of post-progression treatment, and some patients lose the opportunity for effective treatment due to inability to tolerate chemotherapy. Even though the epidermal growth factor receptor (EGFR) is ubiquitously expressed in penile squamous cell carcinoma, anti-EGFR-targeted drugs have not achieved significant survival benefit. Immune checkpoint inhibitors (ICIs) have achieved "de-tumor immune escape", and a small number of penile cancer cases have shown reactivity. However, only patients with high TMB, high PD-L1 expression, or MSI-H have benefited from ICIs. Antibody-drug conjugates (ADCs) have advanced rapidly in recent years, and HER2-targeted ADCs have shown significant efficacy in HER2-overexpressing urothelial carcinoma. HER2 ADC and ICI can simultaneously block HER2 and PD-1/PD-L1 signaling pathways, bridge PD-1-expressing T lymphocytes and HER2-expressing tumor cells, assist T cells to recognize and kill tumor cells, improve immunosuppression in the tumor microenvironment, and enhance the infiltration of immune cells into tumors. Recent cytology and animal studies have also shown that HER2-targeted ADCs exhibit significant anti-tumor activity in both HER2-positive and cisplatin-resistant penile cancers. Therefore, in order to explore the feasible and effective options for patients with advanced penile cancer who have progressed or are intolerant to cisplatin-based chemotherapy, a single-arm, single-center clinical study using Disitamab Vedotin combined with Toripalimab is proposed. Methods: About 20 patients with advanced penile cancer who have progressed or are intolerant to chemotherapy are planned to be enrolled with antibody-drug conjugates (Disitamab Vedotin for injection, 1 time/2 weeks, 2.0 mg/kg) and PD-1 (Toripalimab, 1 time/2 weeks, 3.0 mg/kg; or1 time/3 weeks, 240 mg/kg), regimen until the disease progresses or is intolerant. This study is expected to provide a basis for the treatment of advanced penile cancer using this regimen.
A randomized phase II study of ADT + abiraterone versus ADT + abiraterone + docetaxel in patients with low-volume metastatic hormone-sensitive prostate cancer.
Authors: Fenton Sarah Elizabeth , Kocherginsky Masha , VanderWeele David James , Hussain Maha H. A. 
Published: June 2024

TPS5121 Background: The PEACE-1 and ARASENS phase III trials showed benefit of “triplet” therapy in patients with metastatic hormone sensitive prostate cancer (mHSPC). Triplet therapy is defined as androgen deprivation therapy (ADT), docetaxel and an androgen receptor signaling inhibitor. Both trials showed improved outcomes in patients with a high volume of disease per CHAARTED criteria (≥ 4 bone lesions with ≥1 beyond the axial skeleton or visceral metastasis). The benefit was less clear in patients with low volumes of disease, this may be due to the use of docetaxel as the control arm in this patient population. In the CHAARTED study the benefit of docetaxel in addition to ADT was most pronounced in patients with high volume mHSPC, and the benefit was less certain in low volume disease. To address this uncertainty, we are conducting this phase II trial evaluating ADT/abiraterone versus ADT/abiraterone plus docetaxel in patients with low volume mHSPC. Methods: This is a multisite, randomized trial of ADT (physician’s choice) and abiraterone (1000mg daily + 5 mg prednisone) versus ADT, abiraterone and docetaxel (75 mg/m2 q3 weeks for 6 cycles). Patients may have started ADT up to 12 weeks prior to randomization. Key eligibility criteria include a tissue-confirmed diagnosis of prostate cancer (PCa) and evidence of metastatic disease on CT, MRI and/or bone scan that meets CHAARTED criteria for low volume disease. Recurrent PCa and exposure to ADT prior to the diagnosis of metastatic disease are allowed, as is concurrent treatment with radiation therapy. The primary objective is to assess and compare radiographic progression free survival (rPFS) between treatment arms. Power calculations assume the median rPFS of the control arm is 33 months (based on the LATITUDE trial) versus 55 months in the docetaxel arm (based on the PEACE-1 trial). A sample size of 120 patients will provide 80% power with a one-sided α = 0.10 Type I error rate based on the log rank test to detect a hazard ratio = 0.60. Assuming a 36-month accrual duration and an additional 3 years of follow up, a total of 70 events are expected to occur on this study. The study will enroll 150 patients (75 per arm) to obtain 120 evaluable patients (assuming a 20% attrition rate). Secondary endpoints include overall survival, PSA response rate, overall response rate, time to castration resistant PCa and time to initiation of subsequent anti-neoplastic therapy. Exploratory endpoints include quality of life assessments and rates of adverse events. Enrollment in this trial began in Dec 2023. It is open at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and other satellite sites affiliated with Northwestern University. Clinical trial information: NCT06060587 .
Psychosocial Stress Trajectories Are Associated With Puberty Timing: Findings From a 7-Year Cohort in Chongqing, China
Authors: Liu Shudan , Zhou Yangxue , Wu Di , Tian Yu , Luo Jie , Zhang Jie , Wang Wenhe , Yan Ge , Liu Qin 
Published: June 2024

Abstract

Context
Evidence for the associations between psychosocial stress PS related exposures and puberty timing are inconclusive. The PS of children has rarely been evaluated through repeated measurements.

Objective
To evaluate the associations between PS trajectories and pubertal outcomes of girls and boys in a Chinese cohort (2015-2022).

Methods
Pubertal outcomes of 732 girls and 688 boys were physically examined every 6 months. Stressful life events were repeatedly assessed 7 times. A group-based trajectory model was fitted for the optimum trajectories of total PS and PS from 5 sources. A Cox model adjusted for age, body mass index, and socioeconomic factors was used to evaluate the association.

Results
Compared with the “low, gradual decline” trajectory, the “moderate, gradual decline” trajectory of total PS was associated with late menarche (hazard ratio [HR] 0.816, 95% CI 0.677-0.983), late pubic hair development (HR 0.729, 95% CI 0.609-0.872), and late axillary hair development (HR 0.803, 95% CI 0.661-0.975) in girls. Girls following the “high, rise then decline” trajectory of PS from family life demonstrated delayed axillary hair development (HR 0.752, 95% CI 0.571-0.990). For boys, the “high, rise then decline” trajectory of PS from academic adaptation (HR 0.670, 95% CI 0.476-0.945) and life adaptation (HR 0.642, 95% CI 0.445-0.925) was associated with late axillary hair development. Boys in the “moderate, gradual decline” trajectory of PS from peer relationships was at risk of early testicular development (HR 1.353, 95% CI 1.108-1.653).

Conclusion
Chronic PS may be associated with delayed onset of several pubertal signs in both girls and boys. It may also accelerate testicular development of boys, indicating its varying impact on pubertal timing during early and later stages.
The Thrill of Becoming
Authors: Tian Xiaofei 
Published: June 2024

Abstract
What is the politics of form in the changing political climate? How does the writing of old-style poetry (jiuti shi) and new-style or modern vernacular poetry (xin shi) fare in digital times? As the internet, computers, smartphones, and Chinese internet poetry continue to evolve, how do these ongoing manifestations and technological transformations impact the landscape of poetry writing, and how do researchers answer these new challenges? This essay sketches the trajectory of change of modern old-style poetry and new-style poetry in response to the changing times and to each other, discusses how these changes embody larger cultural shifts, and addresses the role played by scholars and critics in the process. It argues that the gap between old-style poetry and new-style poetry is closing in interesting ways, and that scholarship on modern poetry is not about deciding the literary canon or predicting what comes next, but about constantly adjusting our understanding in the eternal process of becoming and realizing that the past is also changing owing to the changing perspective of the present.
Gaming Sinographs beyond the Ludic
Authors: O'Krent Michael 
Published: June 2024

Abstract
This article rethinks the notion of the Sinophone through digital technology by using the Taiwanese videogame Word Game (Wenzi youxi, Team9, 2022) as a case study. The digital Sinophone sees Chineseness as an act of positive identification claimed by engaging with digital artifacts; it defines a single mass audience coterminous with the Sinophone cultural sphere. Word Game constructs a two-dimensional space in which all objects are composed of sinographs, requiring the player to possess extensive knowledge of the construction of and relationship between sinographs according to Chinese grammatical and semiotic uses in order to progress in the game. Contrary to the internationalizing tendencies of the videogame market and the long history of tension between sinographic writing and the typographical technologies of technological modernity, the result is a uniquely Sinophone videogame. In Word Game, the logic of gameplay mechanics consists not of mathematical universals but culturally determined relationships between sinographs. The article concludes by examining the implications for the interdisciplinary study of videogames. Whereas contemporary videogame studies seeks to situate video gaming in broader cultural discourses, a culturalist view of videogames sees game mechanics as cocreators of culture rather than a mirror of culture.
Writing the Heart Sutra Online
Authors: Vermeeren Laura 
Published: June 2024

Abstract
Online calligraphic handwriting has taken on various creative forms: from WeChat handwriting communities to digital teaching apps and downloadable calligraphic fonts. This article proposes to consider online calligraphy practice a means to connect to an imagined past. Calligraphy, then, is employed for a haptic reconnecting with the past through movements of brush and wrist by restoring and reenacting an (imagined) classical Chinese culture on digital screens. This article focuses specifically on the affective modes of writing the Heart Sutra (Xin Jing 心經) in the online environment of the platform Kuaishou (快手). It analyzes how the affordances of the social media platform allow for various forms of affective engagement with the classicist text. This article suggests that the specific modalities underpinning Heart Sutra writings are informed by the nostalgic desire to perform a type of Chineseness. Instances of online sutra writings on Kuaishou further contest the widespread misconception that content uploaded on the specific platform is mostly subsumable under the cultural mode of tuwei 土味 or “vulgar content.”
Climate change consequences on the systemic heart of female Octopus maya: oxidative phosphorylation assessment and the antioxidant system
Authors: Meza-Buendia Ana Karen , Aparicio-Trejo Omar Emiliano , Díaz Fernando , Pedraza-Chaverri José , Álvarez-Delgado Carolina , Rosas Carlos 
Published: June 2024

ABSTRACT
There is evidence that indicates that temperature modulates the reproduction of the tropical species Octopus maya, through the over- or under-expression of many genes in the brain. If the oxygen supply to the brain depends on the circulatory system, how temperature affects different tissues will begin in the heart, responsible for pumping the oxygen to tissues. The present study examines the impact of heat stress on the mitochondrial function of the systemic heart of adult O. maya. The mitochondrial metabolism and antioxidant defense system were measured in the systemic heart tissue of female organisms acclimated to different temperatures (24, 26, and 30°C). The results show that acclimation temperature affects respiratory State 3 and State 4o (oligomycin-induced) with higher values observed in females acclimated at 26°C. The antioxidant defense system is also affected by acclimation temperature with significant differences observed in superoxide dismutase, glutathione S-transferase activities, and glutathione levels. The results suggest that high temperatures (30°C) could exert physical limitations on the circulatory system through the heart pumping, affecting nutrient and oxygen transport to other tissues, including the brain, which exerts control over the reproductive system. The role of the cardiovascular system in supporting aerobic metabolism in octopus females is discussed.
Re-assessment of the subcellular localization of Bazooka/Par-3 in Drosophila: no evidence for localization to the nucleus and the neuromuscular junction
Authors: Kim Soya , Shahab Jaffer , Vogelsang Elisabeth , Wodarz Andreas 
Published: June 2024

ABSTRACT
Bazooka/Par-3 (Baz) is an evolutionarily conserved scaffold protein that functions as a master regulator for the establishment and maintenance of cell polarity in many different cell types. In the vast majority of published research papers Baz has been reported to localize at the cell cortex and at intercellular junctions. However, there have also been several reports showing localization and function of Baz at additional subcellular sites, in particular the nuclear envelope and the neuromuscular junction. In this study we have re-assessed the localization of Baz to these subcellular sites in a systematic manner. We used antibodies raised in different host animals against different epitopes of Baz for confocal imaging of Drosophila tissues. We tested the specificity of these antisera by mosaic analysis with null mutant baz alleles and tissue-specific RNAi against baz. In addition, we used a GFP-tagged gene trap line for Baz and a bacterial artificial chromosome (BAC) expressing GFP-tagged Baz under control of its endogenous promoter in a baz mutant background to compare the subcellular localization of the GFP-Baz fusion proteins to the staining with anti-Baz antisera. Together, these experiments did not provide evidence for specific localization of Baz to the nucleus or the neuromuscular junction.
Clutter resilience via auditory stream segregation in echolocating greater mouse-eared bats
Authors: Pedersen Michael B. , Beedholm Kristian , Hubancheva Antoniya , Koseva Kaloyana , Uebel Astrid S. , Hochradel Klaus , Madsen Peter T. , Stidsholt Laura 
Published: June 2024

ABSTRACT
Bats use echolocation to navigate and hunt in darkness, and must in that process segregate target echoes from unwanted clutter echoes. Bats may do this by approaching a target at steep angles relative to the plane of the background, utilizing their directional transmission and receiving systems to minimize clutter from background objects, but it remains unknown how bats negotiate clutter that cannot be spatially avoided. Here, we tested the hypothesis that when movement no longer offers spatial release, echolocating bats mitigate clutter by calling at lower source levels and longer call intervals to ease auditory streaming. We trained five greater mouse-eared bats (Myotis myotis) to land on a spherical loudspeaker with two microphones attached. We used a phantom-echo setup, where the loudspeaker/target transmitted phantom clutter echoes by playing back the bats' own calls at time delays of 1, 3 and 5 ms with a virtual target strength 7 dB higher than the physical target. We show that the bats successfully landed on the target, irrespective of the clutter echo delays. Rather than decreasing their source levels, the bats used similar source level distributions in clutter and control trials. Similarly, the bats did not increase their call intervals, but instead used the same distribution of call intervals across control and clutter trials. These observations reject our hypothesis, leading us to conclude that bats display great resilience to clutter via short auditory integration times and acute auditory stream segregation rather than via biosonar adjustments.
Passive elasticity properties of Octopus rubescens arms
Authors: Halder Udit , Gribkova Ekaterina D. , Gillette Rhanor , Mehta Prashant G. 
Published: June 2024

ABSTRACT
In this report, passive elasticity properties of Octopus rubescens arm tissue are investigated using a multidisciplinary approach encompassing biomechanical experiments, computational modeling, and analyses. Tensile tests are conducted to obtain stress–strain relationships of the arm under axial stretch. Rheological tests are also performed to probe the dynamic shear response of the arm tissue. Based on these tests, comparisons against three different viscoelasticity models are reported.
Patients' behaviour after referral to a wound care clinic for diabetic foot ulcer care: a grounded theory study
Authors: Aagaard Thomas Vedste , Skou Søren T , Brorson Stig , Madsen Ulla Riis 
Published: June 2024

Objective: The aim of this study was to construct a grounded theory regarding patients' activity behaviour over time after referral to an outpatient clinic for diabetic foot ulcer (DFU) care. Method: A constructivist grounded theory approach was used. Data from observations of and interviews with participants were collected and analysed using the constant comparative method. Based on this, the grounded theory ‘Just a bump in the road’ was constructed. Results: The cohort included five participants who considered their ulcers as ‘Just a bump in the road’ in their lives, and four subcategories were embedded in this core category: ‘Restricting my freedom’; ‘Trusting or doubting the system’; ‘Feeling no pain or illness’; and ‘Receiving insufficient information’. Together, these categories describe the participants' behaviour and underlying concerns related to daily activities after referral to an outpatient clinic for the care of their DFU. Conclusion: The grounded theory ‘Just a bump in the road’ describes how participants with a DFU viewed their condition as merely a passing phase that would end with them regaining what they considered a normal life. Integrating these results into clinical practice could lead to improved care and a focus shift among health professionals from viewing patients as being defined by their wounds to seeing them as people who live with a wound.