bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trilaciclib use for prevention of hematological adverse events in chemotherapy: A meta-analysis of real-world studies and clinical trials.
Authors: Batra Nitya , Khosla Atulya Aman , Shrestha Abhigan Babu , Jaiswal Vikash , Alnabulsi Zaid , Kiryakoza Morgan , Chisti Mohammad Muhsin 
Published: July 2024

e24130 Background: Trilaciclib, a cyclin-dependent kinase (CDK)-4 and -6 inhibitor, is the only FDA-approved agent that preemptively protects hematopoietic stem cells from chemotherapy-induced myelosuppression (CIM) without compromising efficacy. It transiently arrests hematopoietic stem cells in the G1 phase, thus temporarily blocking progression through the cell cycle and protecting progenitor cells from cytotoxicity. It has been approved for use in extensive-stage small-cell lung cancer (SCLC). Limited real-world evidence of its efficacy exists owing to its recent approval. We sought to enhance our understanding and evaluate the preventive effect of trilaciclib through a combined meta-analysis of clinical trials and retrospective studies. Methods: A systematic literature search was performed on PubMed, Embase, Cochrane, and Scopus from inception until December 2023. Retrospective cohort studies and randomized-controlled trials with trilaciclib and non-trilaciclib arms were included. The primary outcomes of interest were CIM-related grade ≥3 hematological adverse events, and secondary outcomes included supportive care interventions to remedy CIM. Quantitative meta-analyses were conducted using the random-effects model on STATA v17. Results: The meta-analysis comprised seven studies, including four clinical trials and three real-world retrospective studies, including 6537 patients with extensive SCLC or locally recurrent or metastatic breast cancer. Chemotherapy regimens in SCLC patients included the combination of etoposide/platinum (E/P), E/P/PD-L1 inhibitors, or topotecan, and gemcitabine/carboplatin in patients with breast cancer. The mean age of the patients was 63.28 ± 5.31 years, and 49.21% were males. Administration of trilaciclib led to a reduction in the incidence of febrile neutropenia (2.41% vs. 7.56% OR = 0.35), severe neutropenia (21.76% vs. 41.91% OR = 0.57), anemia (18.02% vs. 32.41% OR = 0.51), and thrombocytopenia (20.06% vs. 31.25% OR = 0.62). Utilization of cytopenia-supportive therapies, including granulocyte colony-stimulating factor use (40.47% vs. 81.01% OR = 0.61) and RBC transfusions (16.66% vs. 18.25% OR = 0.59) were significantly lower in the trilaciclib cohort as compared to control. The overall response rate (mean difference = 1.09,95% CI = 0.74–1.60) and overall survival (OR = -0.02 95% CI = -0.95-0.92) were similar, and progression-free survival was noted to be longer in the trilaciclib group (mean difference = 1.75, 95% CI = 0.75-2.75). Conclusions: Trilaciclib use consistently demonstrated efficacy in reducing CIM, thus lowering cytopenia-related healthcare utilization without compromising treatment efficacy in trials and real-world settings. Its novel mechanism of action offers great promise, and further studies with larger sample sizes on various cancers will corroborate existing evidence.
A phase II randomized double-blind placebo-controlled study of fisetin to improve physical function in frail older breast cancer survivors (TROFFi).
Authors: Ji Jingran , Bae Marie , Wong Florence Lennie , Crespi Catherine M , Yee Lisa D , Sedrak Mina S. 
Published: July 2024

TPS1645 Background: Among postmenopausal breast cancer survivors treated with chemotherapy, one-third experience a persistent decline in physical function even 12 months after completing treatment. This decline has been associated with loss of independence, disability, and death. One mechanism that is thought to drive chemotherapy-related decline in physical function is cellular senescence, a state of terminal growth arrest. Chemotherapy increases the burden of senescent cells (Sncs), which develop a senescence-associated secretory phenotype (SASP) that over time leads to functional decline. Preclinical mouse studies have demonstrated that eliminating chemotherapy-induced Sncs in mice led to reductions in SASP and improved physical activity. In patients with stage I-III breast cancer treated with chemotherapy, expression of p16INK4a (p16), a known Snc marker, rapidly increased after chemotherapy and persisted over time. Higher levels of pretreatment p16 have also been associated with increased frailty in older breast cancer survivors. Novel senolytic agents have been developed to eliminate Sncs. Among existing senolytics, fisetin is a natural dietary supplement with a favorable safety profile and preclinical efficacy to reduce Snc burden and alleviate frailty in mice. There are multiple ongoing studies of this plant flavonoid in humans, but few are studying the effects of fisetin on chemotherapy-related functional decline in breast cancer survivors. Therefore, we hypothesize that targeting Sncs with fisetin after chemotherapy will improve physical function in frail older breast cancer survivors by reducing systemic Snc burden. Methods: This phase II randomized, placebo-controlled study will enroll 88 postmenopausal women with stage I-III breast cancer who experience physical functional decline after completing neo/adjuvant chemotherapy. Key eligibility criteria include being postmenopausal and within 12 months of completing neo/adjuvant chemotherapy at the time of enrollment. All participants must have evidence of physical functional decline, as measured by a 6-minute walk distance (6MWD) <400 meters, prior to enrollment. Participants will be randomized 1:1 to either placebo or oral fisetin (20mg/kg) on days 1-3 of 14-day cycles for a total of 4 cycles. The primary objective is to determine the effect of fisetin on physical function, as assessed by the change in 6MWD from baseline to end of treatment. Secondary objectives include studying the effect of fisetin on quality of life and additional measures of function including fatigue, cognition, and neuropathy. We will also determine the effect of fisetin on biomarkers of aging, including circulating markers of senescence, as well as the safety of and adherence to fisetin. Enrolment on this study began March 2023 and is currently ongoing. Clinical trial information: NCT05595499 .
Linking in with advice and supports for men impacted by metastatic cancer: The LIAM Mc trial (NCT05946993).
Authors: Gleeson Jack , Cahill Anita , Johnston Katie E , Corkery Stephanie , Medved Katarina , Cusack Anne Marie , Raigal Laia Aran , Hegarty Josephine , Connolly Roisin M. , Saab Mohamad M. , Bambury Richard Martin , Noonan Brendan 
Published: July 2024

TPS1646 Background: Multidisciplinary supportive care interventions are key to preventing and managing adverse effects of cancer and its treatment for patients, reducing symptom and psychological burdens and enhancing quality of life (QoL). However, the optimal composition of these interventions for men with genitourinary (GU) cancers is poorly understood. The LIAM Mc Trial is an enhanced supportive care programme, funded by the Irish Cancer Society and designed with the input of patient representatives who highlighted the unmet needs of cancer survivors. An important aspect of the trial is to demonstrate how to improve the survivorship supports and services for underserved communities of men who experience disparities in cancer incidence, prognosis, outcome and QoL, and have not traditionally been the focus of such initiatives. Methods: Using an embedded mixed-method process evaluation this prospective trial aims to assess the feasibility and impact of a holistic 12-week survivorship programme amongst men with advanced GU cancers at an Irish Cancer Centre. The programme involves twice-weekly sessions with input from a dedicated physiotherapist, dietitian, and nurse specialist, along with education sessions from medical social worker and psycho-oncology specialists, and programme oversight provided by medical oncologists. Outcomes are measured at three timepoints; pre-intervention, immediately post-intervention and at 6 months post intervention, and will include EORTC QoL; muscle strength; body composition through bioelectrical impedance analysis and ultrasound; diet quality; cancer related symptom control; cancer related fatigue scores; feasibility outcomes, qualitative interviews and a process evaluation. Any man with a locally advanced or metastatic GU cancer who has recently completed a course of treatment or is stable on active anti-cancer treatment is eligible for the programme. Over the two-year study period the sample size target is 72 participants. The primary endpoint of the study is to evaluate the feasibility of introducing an enhanced supportive care programme as part of routine management for male cancer patients with metastatic disease. Acceptability, satisfaction with the programme and QoL changes are key secondary endpoints. Barriers to participation are also a key outcome under investigation. The study was activated in May 2023 with the first participants enrolled in June 2023. To date 17 men have enrolled with accrual completion anticipated in June 2025. Clinical trial information: NCT05946993 .
A phase I/II open label study to assess safety and preliminary evidence of a therapeutic effect of azeliragon in patients refractory to first-line treatment of metastatic pancreatic cancer.
Authors: Hendifar Andrew Eugene , Marcus Stephen Garrett , Brenner Warren S. , Uemura Marc Isamu , Chung Ki Y. , Richards Donald A. , Bahary Nathan 
Published: July 2024

TPS4212 Background: Azeliragon is an orally administered small molecule, administered once daily, that inhibits RAGE interactions with its natural ligands, including HMGB1 and S100 proteins. Azeliragon was previously under development for Alzheimer’s disease and failed to show efficacy in phase 3 trials. Clinical safety data from these trials, with over 1500 individuals dosed for periods up to 18 months, indicated that azeliragon has a high level of safety and tolerability, virtually indistinguishable from placebo. RAGE, the receptor for advanced glycation end products, is highly expressed in pancreatic ductal adenocarcinoma (PDAC). RAGE interaction with its ligands, including S100 proteins and HMGB1 released from PDAC cells, promotes PDAC invasion, metastasis, and resistance to 5 FU and Gemcitabine. PDAC-secreted S100 proteins can also stimulate fibroblasts surrounding PDAC cells since RAGE is positively expressed in fibroblasts, promoting the desmoplastic response. RAGE has also been implicated in the muscle wasting associated with cancer and with aging, as well as in neuropathic pain, suggesting a potential supportive role in PDAC treatment. Methods: This is an open label study to determine the safety and preliminary evidence of a therapeutic effect of azeliragon in patients refractory to the standard of care treatment of metastatic pancreatic cancer. Azeliragon is administered at three dose levels in a rolling dose escalation strategy with 6 patients at each dose level: 5 mg/day (level 1), 10 mg/day (level 2) and 20 mg/day (level 3). These dose levels have an initial loading dose for 6 days at 15 mg daily, 15 mg twice a day and 30 mg twice a day, respectively. The primary objective is to determine the RP2D, defined as the dose for which <33% patients experience a dose limiting toxicity (DLT) within 28 days from initiation of dosing. Secondary endpoints include disease control, overall survival, changes in pain as determined by the Brief Pain Inventory, and changes in ECOG performance status, weight, and serum albumin. The study received regulatory approval and accrual started in June 2023. Clinical trial information: NCT05766748 .
EFFECT-neo: A phase 3 study of pembrolizumab plus chemotherapy versus chemotherapy as neoadjuvant therapy in patients with resectable locally advanced head and neck squamous cell carcinoma.
Authors: Zhang Yang , Guo Wei , Zhang Wenchao , Wang Zhenyu , Yu Kai , Li Li , Wang Yan , Huang Zhigang 
Published: July 2024

TPS6123 Background: There is still a huge need for treatment of operable locally advanced head and neck squamous cell carcinoma (LA HNSCC). Multiple phase 2 studies have shown that PD-1 combined with chemotherapy has good short-term efficacy, especially the pathological complete response (pCR) rate exceeds 30%, which is also considered to be an important factor in the survival benefit that neoadjuvant immune therapy may bring. The randomized, open-label, phase 3 EFFECT-neo study (NCT06102395) will evaluate efficacy and safety of pembrolizumab plus chemotherapy versus chemotherapy as neoadjuvant therapy in patients with resectable LA HNSCC. Methods: Patients with untreated LA HNSCC who met the inclusion criteria will be randomly assigned 1:1 to two treatment arms. Experimental group will be given 2 cycles of pembrolizumab (200mg d1, Q3W) + chemotherapy (perfer TPF regimens) . Control group will undergo 2 cycles of chemotherapy. Both two arms should finish imaging evaluation, and If the result is CR after neoadjuvant treatment, radiotherapy (RT) (60-70Gy) ± chemotherapy (investigator's choice) will be given as adjuvant treatment; if the result are PR or SD, surgery (within 2 weeks) will be performed, and then RT ± chemotherapy will be given. If the imaging evaluation is PD, patients will be received standard treatment. Enrolled patients must closely monitor the adverse reactions of chemotherapy and record the time, grade, treatment measures, outcomes, etc. All patients will be reviewed every 3 months for 1 year; after 1 year, they were reviewed every 6 months for 3 years; patient recurrence and survival data were recorded. Eligibility criteria will include age ≥18 years; untreated with immunotherapy, resectable, stage III/IVB HNSCC (AJCC Cancer Staging Manual, 8th edition); ECOG performance status 0-2; and the investigators believe that patients can safely receive pembrolizumab combined with chemotherapy in neoadjuvant chemotherapy. Randomization treatment will continue until disease progression, unacceptable toxicity, or decision to withdraw. Primary end points is pCR, defined as the absence of residual invasive squamous cell carcinoma within the primary tumor specimen on resection/needle biopsy (Patients with CR imaging results will undergo multi-point biopsy). Secondary end points include objective response rate, 1-year and 2-year event-free survival rates, 2-year overall survival rate, functional preservation rate, safety and Karnofsky performance status. Recruitment is ongoing and will continue until 272 patients are enrolled. Clinical trial information: NCT06102395 .
Proportional relations between the wave number and amplitude of spiral waves near Neimark-Sacker bifurcations
Authors: Xu Bin , Gao Jian , Shen Chuansheng 
Published: July 2024

Abstract
The spatiotemporal distribution patterns of interacting populations are broadly accepted as a pivotal factor in sustaining species diversity. Spiral waves represent common spatiotemporal patterns observed in ecosystems and biological systems, encompassing both continuous-time and discrete-time systems. The study of the dynamics and regulation of spiral waves in continuous-time systems, often observed in the vicinity of Hopf bifurcations, has been comprehensively examined. However, the dynamical characteristics and rules governing spiral waves near Hopf bifurcations in discrete-time systems, also named Neimark-Sacker bifurcations, are still not fully understood. Here, we investigate spiral waves in a discrete-time predator-pest model caused by a Neimark-Sacker bifurcation. Our results suggest a linear relationship between the amplitude and wave number of spiral waves near the Neimark-Sacker bifurcation. At last, we propose a model that can describe the behaviors of spiral waves in discrete-time systems near Neimark-Sacker bifurcations. Our findings illuminate the process of pattern formation in discrete-time systems, offering potential insights for forecasting and managing pest distribution.
From promoter motif to cardiac function: a single DPE motif affects transcription regulation and organ function in vivo
Authors: Sloutskin Anna , Itzhak Dekel , Vogler Georg , Pozeilov Hadar , Ideses Diana , Alter Hadar , Adato Orit , Shachar Hadar , Doniger Tirza , Shohat-Ophir Galit , Frasch Manfred , Bodmer Rolf , Duttke Sascha H. , Juven-Gershon Tamar 
Published: July 2024

ABSTRACT
Transcription initiates at the core promoter, which contains distinct core promoter elements. Here, we highlight the complexity of transcriptional regulation by outlining the effect of core promoter-dependent regulation on embryonic development and the proper function of an organism. We demonstrate in vivo the importance of the downstream core promoter element (DPE) in complex heart formation in Drosophila. Pioneering a novel approach using both CRISPR and nascent transcriptomics, we show the effects of mutating a single core promoter element within the natural context. Specifically, we targeted the downstream core promoter element (DPE) of the endogenous tin gene, encoding the Tinman transcription factor, a homologue of human NKX2-5 associated with congenital heart diseases. The 7 bp substitution mutation results in massive perturbation of the Tinman regulatory network that orchestrates dorsal musculature, which is manifested as physiological and anatomical changes in the cardiac system, impaired specific activity features, and significantly compromised viability of adult flies. Thus, a single motif can have a critical impact on embryogenesis and, in the case of DPE, functional heart formation.
A novel 3D imaging approach for quantification of GLUT4 levels across the intact myocardium
Authors: Geiser Angéline , Currie Susan , Al-Hasani Hadi , Chadt Alexandra , McConnell Gail , Gould Gwyn W. 
Published: July 2024

ABSTRACT
Cellular heterogeneity is a well-accepted feature of tissues, and both transcriptional and metabolic diversity have been revealed by numerous approaches, including optical imaging. However, the high magnification objective lenses needed for high-resolution imaging provides information from only small layers of tissue, which can result in poor cell statistics. There is therefore an unmet need for an imaging modality that can provide detailed molecular and cellular insight within intact tissue samples in 3D. Using GFP-tagged GLUT4 as proof of concept, we present here a novel optical mesoscopy approach that allows precise measurement of the spatial location of GLUT4 within specific anatomical structures across the myocardium in ultrathick sections (5 mm×5 mm×3 mm) of intact mouse heart. We reveal distinct GLUT4 distribution patterns across cardiac walls and highlight specific changes in GLUT4 expression levels in response to high fat diet-feeding, and we identify sex-dependent differences in expression patterns. This method is applicable to any target that can be labelled for light microscopy, and to other complex tissues when organ structure needs to be considered simultaneously with cellular detail.
Measurement of microclimates in a warming world: problems and solutions
Authors: Mitchell Duncan , Maloney Shane K. , Snelling Edward P. , Carvalho Fonsêca Vinícius de França , Fuller Andrea 
Published: July 2024

ABSTRACT
As the world warms, it will be tempting to relate the biological responses of terrestrial animals to air temperature. But air temperature typically plays a lesser role in the heat exchange of those animals than does radiant heat. Under radiant load, animals can gain heat even when body surface temperature exceeds air temperature. However, animals can buffer the impacts of radiant heat exposure: burrows and other refuges may block solar radiant heat fully, but trees and agricultural shelters provide only partial relief. For animals that can do so effectively, evaporative cooling will be used to dissipate body heat. Evaporative cooling is dependent directly on the water vapour pressure difference between the body surface and immediate surroundings, but only indirectly on relative humidity. High relative humidity at high air temperature implies a high water vapour pressure, but evaporation into air with 100% relative humidity is not impossible. Evaporation is enhanced by wind, but the wind speed reported by meteorological services is not that experienced by animals; instead, the wind, air temperature, humidity and radiation experienced is that of the animal's microclimate. In this Commentary, we discuss how microclimate should be quantified to ensure accurate assessment of an animal's thermal environment. We propose that the microclimate metric of dry heat load to which the biological responses of animals should be related is black-globe temperature measured on or near the animal, and not air temperature. Finally, when analysing those responses, the metric of humidity should be water vapour pressure, not relative humidity.
Implementasi Literasi Baca Tulis di Sekolah : Studi Kasus di SDN 39 Raba Bima
Authors: Fitri Nurmiatul , Haryadi Didit 
Published: July 2024

literasi baca tulis sangat diperlukan untuk mengembangkan komunikasi siswa. Adapun tujuan dari penelitian ini adalah untuk mengetahui Implementasi literasi baca tulis di SDN 39 Raba Bima yang dilihat dari aspek 1) Jumlah variasi bahan bacaan di sekolah 2) peminjaman bahan bacaan di perpustakaan 3) kegiatan sekolah yang berkaitan dengan literasi baca tulis 4) kebijakan kepala sekolah yang berkaitan dengan literasi baca tulis dan 5) Komunitas Baca di sekolah.
penelitian ini termasuk penelitian kuantitatif deskriptif. Pengambilan data menggunakan angket mendalam mengenai perkembangan literasi disekolah dan di bantu oleh wawancara dilakukan kepada beberapa pegiat literasi disekolah seperti kepala sekolah, kepala perpustakaan dan ibu pembimbing literasi ibu Y untuk mendukung data. Tehnik analisis data yang digunakan adalah deskriptif kuantitatif dengan menggunakan analisis deskriptif atau statistik deksriptif. Penarikan kesimpulan dilakukan dengan cara membandingkan hasil yang diperoleh dengan kategori nilai presentase menggunakan rumus likert skala 1 sampai 4.

Hasil Implementasi Literasi Baca Tulis SDN 39 Raba Bima masuk dalam kategori sangat baik dengan aspek 1) Jumlah variasi bahan bacaan di sekolah dengan presentase 83% dengan kategori sangat baik 2) peminjaman bahan bacaan di perpustakaan dengan presenatse 88 % dengan kategori sangat baik 3) kegiatan sekolah yang berkaitan dengan literasi baca tulis dengan presentase 84% dengan kategori sangat baik 4) kebijakan kepala sekolah yang berkaitan dengan literasi baca tulis dengan presentase 88% dengan kategori sangat baik dan 5) Komunitas Baca di sekolah dengan presentase 92% dengan kategori sangat baik. Secara garis besar Implementasi Literasi Baca Tulis SDN 39 Raba Bima sudah sangat baik akan tetapi masih harus meningkatkan kualitas implementasi literasi baca tulis dan harus dilakukan evaluasi literasi secara menyeluruh bukan saja hanya literasi baca tulis untuk mengetahui implementasi literasi secara keseluruhan.
The Existence of Muhammadiyah’s Islamic Education in Facing Generation Alpha and the Era Society 5.0
Authors: Rofingah Rofingah , Lailan Arqam Muhammad 
Published: July 2024

Generation Alpha and the era of society 5.0 are an obstacle for Muhammadiyah’s Islamic Education. Because everything is based on technology, all information is easy to get through digitally, which has positive and negative impacts. The negative effect is more dominant, so the progressivism of Muhammadiyah’s Islamic Education becomes necessary for education providers. The research aims to explore the existence of Muhammadiyah’s Islamic Education in facing the Alpha generation and the era of Society 5.0. In this study, the authors used a qualitative method of library research. Journals, articles, books, and other relevant information can support this article's data as a source.
The results showed that the existence of Muhammadiyah’s Islamic Education in the generation Alpha and the era Society 5.0 was pursued by innovating technology-based learning and lecture programs such as the eduMu, edutabMu, ISMUBAKU and SiberMu University and Trensains schools.