bluuebunny/crossref_metadata_2025 huggingface dataset:
ImmunoSarc II master trial (phase II of sunitinib and nivolumab): Results from the dedifferentiated chondrosarcoma (DDCS) cohort—A GEIS, ISG and UCL study.
Authors: Strauss Sandra J. , Hindi Nadia , Palmerini Emanuela , Martínez-Trufero Javier , Lopez-Pousa Antonio , Carrasco-Garcia Irene , Gonzalez-Billalabeitia Enrique , Moura David Silva , Ramos Rafael , Tirabosco Roberto , Gutierrez Antonio , Martin Broto Javier
Published: June 2024

11506

Background: Dedifferentiated chondrosarcoma (DDCS) is a rare aggressive CS subtype with a dismal prognosis and no standard of care systemic therapy. For those with advanced, metastatic disease, retrospective chemotherapy studies demonstrate short-term median progression-free survival (PFS) of around 3 to 5.5 months. Benefit from checkpoint and tyrosine kinase inhibitors has been reported, however clinical trial data is scarce, and endpoints are not well defined, thus benchmarking outcomes is challenging. The IMMUNOSARC I master-trial exploring sunitinib plus nivolumab in multiple sarcoma subtypes, detected potential activity in DDCS leading to a specific cohort within the phase II trial IMMUNOSARC II (NCT03277924). Methods: Patients (pts) with ECOG 0-1, centrally confirmed and progressive, measurable DDCS were eligible and treated with sunitinib 37.5 mg/d for 14 days (induction phase), followed by 25 mg/d, in combination with nivolumab 240 mg every 2 weeks until progressive disease (PD) or intolerance. Imaging assessments were performed every 8 weeks. Main endpoint was 6-m PFSR with one-arm survival design (type I error α 0.05, power 0.90, H0 40%, H1 70%) and a Brookmeyer-Crowley like test was assumed with at least 14 of 23 pts required without progression at 6 months. Results: Between December 2019 and October 2023, 24 pts with a median age of 60 years (38-76) were enrolled in 7 centres. Sixteen pts (66%), were male. Pts had received a median of 1 (0-2) prior lines of therapy. In total, 23 pts were evaluable with a median follow-up of 20.1 months (95%CI: 11.6-28.6). Median PFS, according to local site assessment, was 5.6 months (95%CI: 4.5-6.7); the 6m-PFSR was 10 of 23 pts (46%); (95%CI: 23-66) and median overall survival 10.3 months (95%CI: 6.7-13.9). In 19 pts with RECIST measurable response, 5 pts (26.3%) achieved a partial response; 10 (52.6%) stable disease and 4 (21.1%) PD. End-of-treatment reasons were PD in 21 pts (87%), toxicity 1 pt (4.2%) with two pts (8.4%) ongoing. For safety population, the most relevant study drug-related G3-4 toxicities were neutropenia (20.9%), anemia (16.7%), and increased ALT (12.5%). Conclusions: Sunitinib and nivolumab demonstrated encouraging activity in advanced DDCS that did not meet the primary endpoint, but compares favourably with previous analyses of cytotoxic and targeted therapy. The combination is worthy of further exploration in conjunction with reaching a consensus on clinically meaningful endpoints in this challenging population. Translational studies to identify potential predictive biomarkers are ongoing. Clinical trial information: NCT03277924 .
Phase II trial, multicenter, first line paclitaxel-avelumab treatment for inoperable angiosarcoma.
Authors: Kim Hye Ryeon , Kim Miso , Kim Jeong Eun , Kim Hyojeong , Kim Yu Jung , Kang Myoung Joo , Park Kwonoh , Bae Woo Kyun , Hong Jung Yong , Oh Sung Yong
Published: June 2024

11512

Background: Angiosarcomas are very rare tumors of vascular or lymphatic origin characterized by a clinical heterogeneity in terms of presentation and behavior. It can occur in any site of body but most commonly originate in the skin of head and neck and in breast area. Many patients could not receive surgical resection due to its location and/or rapid progression, even who had localized disease. Moreover, conventional cytotoxic chemotherapy has shown limited effect in angiosarcoma. Here, we conduct a prospective, phase II study to evaluate the efficacy and toxicities of paclitaxel plus avelumab as the first line therapy for unresectable angiosarcoma. Methods: Patients with unresectable locally advanced or metastatic angiosarcoma, who had not received systemic treatment, were enrolled. Paclitaxel (80 mg/m2) was intravenously infused on days 1, 8, and 15 of every 28-days cycle, and avelumab (10mg/kg) was intravenously infused biweekly. The treatment was continued until disease progression or unacceptable toxicity, or withdrawal of consent, whichever occurred first. The primary endpoint was the objective response rate (ORR), and the secondary endpoint was overall survival (OS), progression free survival (PFS), and safety profiles. Results: A total 32 patients (21 male, 11 female) were finally enrolled, and the median age was 63.5 (range, 27 to 82). The ORR was 50.0% (n = 16), including one complete response. Median OS and PFS were 14.5 (95% CI, 9.4 to 24.6) and 6.0 (95% CI, 5.4 to 9.5) months, respectively. Among patients who received at least one dose of treatment (n = 33), adverse events (AEs) of any grade were reported in 90.9% (n = 30), and severe AEs were in 12.1% (n = 4), including one death. The most common hematologic/non-hematologic AEs were neutropenia (n = 13, 39.4%) and pain (n = 12, 36.4%), respectively. Febrile neutropenia, neutropenia, and aspiration were reported in two patients (6.1%) each. Conclusions: Avelumab plus paclitaxel for patients with inoperable angiosarcoma, was effective and has tolerable safety profile. Additional translation studies and phase III studies are needed to clearly identify effectiveness and safety. Clinical trial information: NCT03512834 . [Table: see text]
Transcriptomic analysis of novel tumor suppressor gene fusions in bone sarcomas.
Authors: Grachev Dmitrii , Ivanov Danil , Kushnarev Vladimir , Yong Sheila T. , Kotlov Nikita , Chernyshov Konstantin , Bagaev Alexander , Fowler Nathan Hale , Conley Anthony Paul , Cote Gregory Michael , Chawla Sant P.
Published: June 2024

11523

Background: Despite the evolution of therapeutic strategies for sarcomas in the past four decades, survival in the metastatic setting remains poor. This underscores the urgent need to explore new diagnostic and treatment avenues to improve patient outcomes. Harnessing the capability of RNA sequencing (RNA-seq) to detect gene fusions de-novo, we analyzed treated bone sarcoma samples with the aim to uncover gene fusions and breakpoints that are potentially relevant as clinical biomarkers and treatment targets. Methods: We analyzed 83 formalin-fixed, paraffin-embedded tumor samples of treated bone sarcomas, including osteosarcomas, chondrosarcomas, chordomas, and Ewing sarcomas. These samples were subject to in-depth whole exome analysis and bulk RNA-seq. RNA-seq was employed to identify gene fusions, with STAR-fusion utilized for sequence calling. Quality control of all NGS samples was performed using FastQC, FastQ Screen, RSeQC, and MultiQC. Tumor purity was assessed via pathological and bioinformatics examination with the threshold set at 20%. Fusions involving tumor suppressor genes listed in the OncoKB database were investigated further. A comprehensive literature search on PubMed and Google Scholar as well as analysis of the FusionGDB and COSMIC databases were performed to verify candidates of novel gene fusions. We also compared our samples with those in the publicly available MSK sarcoma cohort and 11 osteosarcoma cell line datasets. Results: We detected 238 gene fusions in all samples analyzed. Among these fusions, 18 (16 previously unknown, 2 previously reported) involving known tumor suppressor genes were present in 14 samples (17%). Among the 16 previously unknown fusions, 8 were indicative of potential loss-of-function variants of tumor suppressors: TP53-NF1, TP53-CEMIP, CTNNBL1-RB1, PRPF40A-FBXW7, VAMP2-MSH3, and ETV6-ATM in osteosarcoma; BRD4-TP53 in unspecified bone sarcoma; and FBXW7-ZNF770 in Ewing sarcoma. Furthermore, we also uncovered a novel breakpoint combination in EWSR1-ETV4 in Ewing sarcoma that links exon 9 of EWSR1to exon 9 of ETV4. Conclusions: Our comprehensive transcriptomic analysis of treated sarcoma samples uncovered previously unknown gene fusions involving tumor suppressor genes and a unique breakpoint combination in an oncogene. These findings emphasize the crucial role of RNA-seq not only in advancing genomic research of sarcomas, but also in identifying potential biomarkers/targets and devising new treatment strategies for this rare cancer.
Personalized tumor-informed circulating tumor DNA analysis in monitoring recurrence following resection of high-risk stage II-III gastrointestinal stromal tumor.
Authors: Gao Zhidong , Cheng Baosen , Bao Yudi , Cui Peng , Du Haiwei , Fan Xuning , Peng Di , Yang Shuya , Wu Xin , Zhao Dongbing , Xing Zhaodong , Cao Feng , Zhang Wei , Li Bing , Li Chengcheng , Zhang Yuzi , Wang Guoqiang , Cai Shangli , Ye Yingjiang
Published: June 2024

11534

Background: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Radical resection is the standard treatment of localized GIST, yet the 5-year recurrence rate for high-risk GIST is more than 50%. It remains unclear whether detecting post-surgery molecular residual disease (MRD) via circulating tumor DNA (ctDNA) can predict the recurrence of high-risk locally advanced GIST. Methods: Patients with high-risk stage II-III GIST who underwent R0 surgery and following adjuvant imatinib/avapritinib were enrolled prospectively. Surgical tissue samples were collected. Blood samples were drawn pre-surgically, and at 7 days, 1 month, and every 3–6 months post-surgically. Tumor-derived variants were identified by whole-exon sequencing of the surgical tissues. Up to 50 highly ranked variants with a variant allele frequency 3.0% were selected for the personalized panel design, which was subsequently used to assess MRD status. Results: A total of 36 patients with a median age of 65 years were included in the current analysis (data cutoff on January 16, 2024). Most tumors (17/36, 47%) were located at the stomach or gastroesophageal junction, and 94.4% of patients (34/36) did not receive neoadjuvant treatment. The mean maximum diameter of tumors was 7.87 ± 2.87 cm. At present, 36 tissue samples, 34 pre- and 161 post-surgical blood samples were collected and analyzed. Tissue sample-based sequencing identified variants in KIT and PDGFRA in 31 (86%) and 4 (11%) patients, respectively. 98.4% (1003/1019) of tumor variants included in personalized panels were patient-specific. ctDNA was detected in 64.7% (22/34) of pre-surgical plasma samples. The ctDNA-positive rate at baseline was associated with tumor mutation burden (p < 0.05), rather than tumor size (p = 0.6). Landmark analysis at 1 week post-surgery showed that 12.1% of patients were positive for ctDNA. Up to now, 4 patients were identified with tumor recurrence based on imaging results. Among these patients, 3 patients (3/4) exhibited ctDNA positivity preceding radiological recurrence. Notably, a 71-year-old patient was ctDNA-positive at 1 week post-surgery. Longitudinal analysis revealed that his ctDNA became negative after adjuvant treatment but turned positive at 9 months post-surgery, with a lead time of 2 months prior to his radiological recurrence. Additionally, a patient tested positive for ctDNA at 3 months post-surgery but had negative imaging results. Follow-up visits are ongoing for this patient. Conclusions: The present study suggests that personalized tumor-informed ctDNA has the potential to inform recurrence in high-risk stage II-III GIST patients. Clinical enrollment is still ongoing.
Phase IB/II trial of durvalumab plus doxorubicin combination in patients with advanced soft-tissue sarcoma.
Authors: Cho Hee Jin , Sim Nam Suk , Shin Su-Jin , Yun Kum-Hee , Lee Young Han , Jun Hyun Jung , Rha Sun Young , Kim Hyo Song
Published: June 2024

11552

Background: We conducted an open-label, phase IB/II study to determine the activity and safety of the standard-of-care, doxorubicin in combined with the anti-PD-L1 immune checkpoint inhibitor, durvalumab, in patients with anthracycline-naïve soft tissue sarcoma (STS) and identified patients who would likely benefit from combination treatment. Methods: In this trial (NCT03798106), we enrolled patients with metastatic and/or recurrent STS had not received anthracycline chemotherapy and PD-L1/PD-1 inhibitor. Phase IB assessed the safety and tolerability of doxorubicin [level 1 (75mg/m2) and level -1 (60 mg/m2)] in combination with durvalumab 1500 mg once every 3 weeks until documented disease progression or unacceptable toxicity. Phase II assessed the efficacy, with the primary endpoint to detect a difference in objective response between 5% and 20%. Results: No DLTs were observed during the phase IB (n=3), therefore recommended phase II dose was defined at doses of 75/m2 doxorubicin and proceed the phase II part. Of 41 evaluable patients, 1 (2.4%) achieved complete response, 12 (29.3%) achieved confirmed partial response, yielding an objective response rate of 31.7%. The median progression free survival was 8.2 months (95% CI, 7.3-9.0) and median overall survival was 24.1 months (95% CI, 7.6-40.3). Treatment-related adverse events of grade 3 or 4 occurred in neutropenia (n = 23, 53.4%), thrombocytopenia (n=6, 13.9%), and anemia (n=5, 11.6%). The prespecified genomic analysis with targeted and transcriptomic sequencing will be available at the meeting. Conclusions: Durvalumab combined with doxorubicin demonstrated promising efficacy in an unselected STS cohort, with a manageable toxicity profile. Clinical trial information: NCT03798106 .
Safety and toxicity evaluation of the combination of selinexor with atezolizumab in patients with soft tissue sarcomas.
Authors: Ahmed Jibran , O'Sullivan Coyne Geraldine Helen , Moore Nancy , Foster Jared C. , Gore Steven , Chen Helen X. , Juwara Lamin , Johnson Barry C. , Doroshow James H. , Chen Alice P.
Published: June 2024

11557

Background: The U.S. Food and Drug Administration (FDA) recently approved the anti-PD-L1 antibody atezolizumab for alveolar soft part sarcoma (ASPS). Selinexor, a selective XPO1 inhibitor, demonstrated cytotoxic activity in ASPS-KY and ASPS-1 cell lines of ASPS and other sarcoma cell lines; it has been approved as a part of regimens to treat multiple myeloma and diffuse large B-cell lymphoma. Preliminary clinical data demonstrate acceptable safety profiles in patients with melanoma who received selinexor in combination with an anti-PD-1 antibody. Methods: We designed a randomized phase 2 study to evaluate atezolizumab with or without selinexor in adult patients with ASPS that included a safety run-in (SR) open to patients with soft tissue sarcoma (NCT05333458). Prior immune checkpoint inhibitor therapy was not allowed. During the SR, patients received selinexor (60 mg PO) on days 1, 8, and 15 of the 28-day cycle and atezolizumab (1200 mg flat dose IV) on day 8 at the Developmental Therapeutics Clinic. Protocol-defined treatment-related adverse events (TRAEs) occurring during cycle 1 would either expand accrual to the SR or close the study. Safety data were evaluated by the principal investigator and NCI CTEP (National Cancer Institute Cancer Therapy Evaluation Program). Results: Six patients were enrolled in the SR and were evaluated weekly during the first cycle of study treatment. All patients were female with a median age of 47 years (range: 22-71 years). Diagnoses included sclerosing epithelioid fibrosarcoma (n=2), dedifferentiated liposarcoma (n=1), metastatic leiomyosarcoma (n=1), metastatic angiosarcoma (n=1), and ASPS (n=1). No patients were removed from the SR due to AEs. Two patients experienced grade 3 TRAEs, including one instance each of neutropenia and lymphopenia (Table). Beyond cycle 1, there was 1 occurrence of grade 3 lymphopenia. No grade 4 or 5 AEs have occurred during the SR. Fatigue and nausea were the most prevalent TRAEs, but only one patient experienced grade 2 nausea; all other occurrences of nausea and fatigue were at grade 1. Conclusions: The safety run-in completed without any occurrences of protocol-defined treatment-related toxicity during cycle 1. The treatment was well tolerated. Based on these data, the randomized part of this study began accruing patients with ASPS across the ETCTN (Experimental Therapeutics Clinical Trials Network). Clinical trial information: NCT05333458 . [Table: see text]
Efficacy and safety of lurbinectedin (LUR) with irinotecan (IRI) in a phase 2 expansion cohort of patients (Pts) with synovial sarcoma (SS).
Authors: Cote Gregory Michael , Martin Broto Javier , Chawla Sant P. , Bockorny Bruno , Falcon Gonzalez Alejandro , López Pousa Antonio , Paz-Ares Luis G. , Verret Benjamin , Martinez Sara , Extremera Sonia , Cullell-Young Martin , Fudio Salvador , Kahatt Carmen Maria , Zeaiter Ali Hassan , Le Cesne Axel
Published: June 2024

11560

Background: LUR has shown activity in several solid malignancies. Preclinical studies found synergism for LUR combined with IRI (Galmarini C. Cancer Res 2013; 73: Abst 5499). The phase 1b/2 study PM1183-A-014-15 (NCT02611024) evaluated the LUR/IRI combination in pretreated pts with advanced solid tumors. The recommended dose was defined at LUR 2.0 mg/m2 on Day (D) 1 + IRI 75 mg/m2 on D1, D8 q3wk with primary G-CSF prophylaxis. After observing 3 partial responses in SS pts during the phase 1b part, a phase 2 expansion cohort was implemented to explore this activity further. Methods: This cohort included pts with SS progressing after up to 2 prior cytotoxic-containing lines for advanced disease. The primary endpoint was overall response rate (ORR) per independent review committee (IRC)/investigator. Results: Thirty pts were enrolled and treated. Baseline characteristics were median age 41 y (range, 19-73), 57% males, 53% ECOG PS=1. Primary tumor location was mostly in the extremities (53%). Most common tumor metastatic sites at study entry were lung (83%), pleura (37%) and lymph nodes (23%). 60% had at least one lesion >50mm. The median number of prior lines was 2 (range, 1-5), and the median number of prior chemotherapy lines for advanced disease was 1 (range, 0-3). The median time from diagnosis was 32 mo (range, 2-160 mo). The best response to first-line therapy was stable disease in 50% of pts and progressive disease in 8%. Efficacy results are summarized (Table). Most common G3/4 events/abnormalities were neutropenia (60%), anemia (27%), thrombocytopenia (17%), diarrhea (10%), fatigue (10%) and febrile neutropenia (10%). 20% had treatment-related SAEs. No treatment-related discontinuations or deaths occurred. No evidence of drug-drug interaction was observed in the PK analysis. Conclusions: The LUR/IRI combination showed activity in pretreated SS with manageable toxicity. These results reinforce the rationale for assessing the activity of LUR combined with IRI in SS and other tumor types. Clinical trial information: NCT02611024 .[Table: see text]
Predictors of cardiotoxicity in patients with early breast cancer treated with doxorubicin and/or trastuzumab: Implications of race/ethnicity and insurance status.
Authors: Jahangier Shahzaad Khadeem , Qamar Rubina
Published: June 2024

12021

Background: Approximately 4.1 million women in the US are living with breast cancer1. Cardiac dysfunction is a significant adverse effect of commonly used breast cancer therapies like doxorubicin (D) and trastuzumab (T). The cardiotoxicity (CTox) associated with these agents manifests as a reduction in left ventricular ejection fraction (LVEF) with or without signs and symptoms of heart failure. Purpose: Identify high-risk populations susceptible to developing CTox, with a focus on identifying individuals who could potentially benefit from the early initiation of empiric cardioprotective therapies. Methods: We investigated the relationship of race/ethnicity, insurance status, treatment regimen and comorbidities including hypertension (HTN), hyperlipidemia (HLD), diabetes mellitus (DM), tobacco use, BMI, age, and radiation therapy on the development of CTox from D and/or T. A total of 133 newly diagnosed stage I-III invasive breast cancer patients were enrolled in a prospective clinical trial (2013-2017) and received standard of care D and/or T based systemic therapy. Echocardiogram data was collected every 6 months for two years and then based on clinical need for a total of six years. CTox was defined as a >10% drop in LVEF, and/or LVEF <50%. Results: Our study included a population of 133 patients comprising Black (22%), White (77%), and Hispanic (1.5%) individuals. Among these patients, 32 developed CTox (Black 41%, White 19%, Hispanic 50%). Of all patients, 29% had State insurance while 71% had Private insurance. Prevalence rates for comorbidities were as follows: HTN (41%), HLD (32%), DM (13%), and tobacco use (36%). In a univariate logistic regression model, race/ethnicity, HTN, insurance status, and tobacco use were most strongly associated with Ctox. When controlling for tobacco use and HTN, race/ethnicity was not significantly associated with Ctox. However, direct comparisons of levels of race/ethnicity showed that Black patients were more likely to develop Ctox when compared to White patients (OR 2.60, 95% CI = 1.01-6.65, P = 0.045). HTN patients were also more likely to develop Ctox, when controlling for ethnicity and tobacco use (OR 2.62, 95% CI = 1.10-6.43, P = 0.031). In a separate multivariate analysis, we examined insurance as a surrogate for socioeconomic status. State insurance was associated with an increased risk of developing CTox when controlling for race/ethnicity and HTN (OR 3.73, 95% CI = 1.47-9.58, P = 0.006). Furthermore, in all models, HLD, DM, BMI, age, and radiation field were not found to be significantly associated with increased CTox. Conclusions: In our well characterized population of patients with stage I-III breast cancer, who were prospectively followed and received standard of care systemic therapy, we observed an association between insurance status with increased risk of CTox from treatment regimen.
Using natural language processing to qualitatively assess goals of care conversations for patients with cancer.
Authors: Greene Melissa , Broadwater Gloria , Niedzwiecki Donna , LeBlanc Thomas William , Ma Jessica , Casarett David J. , Davidson Brittany Anne
Published: June 2024

12035

Background: The importance of goals of care (GOC) discussions during end-of-life (EOL) care is well known. Institutions are increasingly tracking the frequency and timing of GOC documentation, but qualitative assessments of this content on a large scale have been limited given the person-power required and constraints of electronic health systems. Our aim is to use natural language processing to qualitatively assess the content of GOC documentation and associations with EOL care in patients who died with cancer. Methods: This is a retrospective review of patients with solid or hematologic malignancies who died between 2018-2022 with documented GOC notes in the last 12 months of life at a single academic National Cancer Institute-designated cancer center. Eight GOC components were identified based on prior literature: current understanding of patient’s illness, information preferences, disclosure of prognosis, goals, fears, acceptable function, trade-offs, and family involvement. GOC notes were extracted from the electronic health record and text annotation software Clinical Regex was utilized to search for the aggregate presence of these GOC components. Associations between these 8 components and receipt of aggressive EOL care (chemotherapy within 14 days of death, no hospice care, or hospice admission ≤3 days of death) were evaluated. Results: 2,031 patients met inclusion criteria. The most common disease sites were gynecologic (22.6%), gastrointestinal (20.3%), and thoracic (16.7%). The most common GOC components addressed were family involvement (75.0%), patient goals (72.0%), acceptable function, and decision making & information preferences (both 65.8%). Only 5.4% had all 8 components addressed in documentation the last 12 months of life. More comprehensive GOC notes were associated with lower rates of aggressive EOL care; 73.2% received aggressive EOL when 0/8 components were documented, compared to 56.8% and 50.3% when 6 or 7 components were discussed, respectively. In multivariate logistic regression, GOC components documented (≤6 vs ≥7), primary tumor site, and inpatient palliative care referral were independent predictors of aggressive EOL care (p-values <0.0001). Conclusions: GOC conversation documentation is largely not comprehensive. Increasingly comprehensive documentation is associated with a lower likelihood of receiving aggressive EOL care, suggesting opportunities to improve both the quality and documentation of GOC conversations may impact the EOL care for patients with cancer. Opportunities for increasing outpatient palliative care referrals may also improve the quality of the EOL experience for patients.[Table: see text]
Chemotherapy-induced peripheral neuropathy research: A National Institute of Health (NIH) grant portfolio analysis.
Authors: Altshuler Rachel D. , Minasian Lori M. , Schweppe Catherine , Kadan-Lottick Nina S.
Published: June 2024

12064

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, debilitating cancer treatment-related toxicity associated with considerable discomfort, functional loss, and impaired quality of life both acutely and long-term. Unfortunately, limited prevention and treatment options for CIPN currently exist. In this portfolio analysis, we sought to describe the landscape of CIPN research and identify gaps and opportunities to meet the needs of patients with CIPN. Methods: Using the NIH Query View Report system to search all NIH-funded competitive grants awarded between fiscal years 2014-2023, we identified 660 grants containing text pertaining to CIPN in the Abstract or Specific Aims. Grants were then manually reviewed and 480 were excluded as not specifically addressing CIPN. We categorized the final 180 grants as preclinical, clinical, or preclinical/clinical, followed by ascertainment of preclinical model, clinical population, CIPN assessment techniques, and/or clinical trial design, as applicable. Results: Of the 180 grants, 119 were preclinical, 51 clinical, and 10 with both preclinical and clinical components. The larger number of CIPN grants (n=27) were awarded in fiscal year 2022 vs. the lowest number (n=10) in 2014. Among the preclinical grants, 89% of grants utilized rodent models of CIPN, of which 19% proposed tumor-bearing models. A large majority of preclinical grants investigated paclitaxel (71%), followed by oxaliplatin (23%); none proposed studies of newer immune therapies. Among clinical grants, 41% (n=21) were interventional trials, 38% were prospective observational studies, and 15% retrospective studies. Clinical grants most frequently focused on breast cancer patients (41%), followed by unspecified cancer diagnoses (33%) and colorectal cancer (18%). For age of eligibility, 11% included patients younger than 18 years, while a higher proportion included 18-39 (82%), 40-64 (88%), and ≥65 (89%). The 21 interventional study grants investigated behavioral interventions (44%), pharmacological agents (28%), and devices (28%). Conclusions: The number of CIPN grants awarded annually by NIH have generally increased since fiscal year 2014, indicating increased investment by NIH. However, multiple gaps and opportunities remain. At the preclinical level, in addition to current rodent models and the narrow range of treatment exposures, novel strategies to mimic human CIPN conditions may improve translatability. Clinical studies are needed in younger patients that can be impacted by CIPN long-term. Also, there are important gaps in the CIPN-associated cancer diagnoses and therapy exposures (including novel agents) in current studies. Addressing the highlighted gaps may identify avenues to study additional interventions that achieve the highest impact in the populations that most need them.
Exploring “good days” in advanced cancer: Activities, behaviors, and quality of life.
Authors: Lazris David , Cheng Svea , Bartel Christianna , Durica Krina , Fedor Jennifer , Chen Leeann , Schenker Yael , Low Carissa A.
Published: June 2024

12074

Background: Advancements in cancer treatments have contributed to people living longer with Stage IV cancer. People living with advanced cancer face significant and unique psychological challenges related to dynamic treatment schedules, fluctuating physical symptoms, and uncertainty regarding prognosis. Understanding what constitutes a “good day” may help patients, their family members, and clinicians to recognize and prioritize factors that improve quality of life. The goal of this project was to understand activities and behaviors that characterize a “good day” among people living with advanced cancer. Methods: We enrolled 20 patients with advanced cancer (M 63 years old, range 41-75; 65% female; 65% white and 35% black; mean 1.5 years since Stage IV diagnosis [range 9 days to 7.5 years]). Participants completed semi-structured interviews and two weeks of nightly diaries, using a 1-5 rating scale (1 = very bad, 5 = very good) to rate their daily quality of life and document various activities and experiences. We conducted t-tests to determine differences in “goodness” on days with and without different experiences along with a Pearson correlation between each patients’ mean goodness rating and Patient-Reported Outcomes Measurement Information System (PROMIS) scores. Results: Interviews revealed themes of "good days," including emphasizing control, normalcy, positive impact, and presence. Loss of control, uncertainty, disruptive symptoms, negative healthcare experiences, and unmet goals were more common on “bad days.” Nightly diaries revealed significant correlations between active engagement in social, hobby, club, religious, cooking, reading, and meditation activities and reporting a good day (all p values < .05). Mean diary goodness ratings correlated positively with Ability to Participate in Social Roles/Activities (r(19) = .54, p = .016) and inversely with Anxiety (r(19) =-.63, p = .004) and Depression (r(19) = -.53, p = .020) and was marginally inversely correlated with Fatigue (r(19) = -.44, p = .059) and Pain Interference (r(19) = -.46, p = .050). No significant correlations were observed with Physical Function (r(19) = .15, p = .544), Cognitive Function (r(19) = .36, p = .134), and Sleep Disturbance (r(19) = -.26, p = .286). Conclusions: Preliminary findings suggest that days on which individuals with advanced cancer are able to engage in activities that give them a sense of normalcy, control, self-identity, and connection to others are better than days without these activities. This is further supported by the positive correlation between goodness ratings and the ability to participate in social roles and activities. Understanding the individual’s values, perceived social roles, and priorities may help care teams support people with advanced cancer to optimize their quality of life and functioning and navigate treatment decisions.
Racial and ethnic differences in patient-reported provider communication among patients with cancer.
Authors: Swami Nishwant , Patel Tej A. , Dee Edward Christopher Christopher , Thom Bridgette , Chino Fumiko
Published: June 2024

12102

Background: Patient-provider communication is essential for improving patient experience and understanding. Given significant care coordination in cancer treatment, effective communication is crucial to ensure timely care, optimal patient outcomes, and shared decision making. Improved patient-provider communication also provides opportunities to promote equitable cancer care. We used national survey data to assess racial/ethnic differences in perceptions of provider communication among patients with cancer. Methods: 2011-2021 biannual data from the US Medical Expenditure Panel Survey was used to select cancer survivors aged ≥18. Primary outcomes included how often patients reported their providers (1) treated them with respect, (2) listened carefully, (3) explained things in a way they understood, and (4) spent enough time. Survey-adjusted percentages with chi-square tests characterized differences in patient-reported communication by racial/ethnic group. Multivariable ordinal logistic regression (MVA) models adjusting for survey year, insurance status, income level, geography, sex, and age generated adjusted odds ratios (aORs) with 95% CI to examine associations of race/ethnicity and provider communication. Results: 5,085 patients representing 10,950,670 survivors met inclusion criteria. American Indian (AI) survivors reported the lowest rates of effective provider communication across all four domains (55%: always listened, 42%: always spent enough time, 58%: always showed respect, and 50%: always explained; p<.001), while non-Hispanic Black (NHB) patients reported the highest rates of effective communication in listening (72%), explaining (70%), respect (74%), and spending enough time (63%; p<.001). On MVA, NHB, non-Hispanic Asian (NHA), and Hispanic (HSP) patients were more likely to report feeling listened to (NHB: OR 1.54 95% CI 1.19-1.98; NHA: OR 1.87 95% CI 1.14-3.05; HSP: OR 1.39 95% CI 1.06-1.83) when compared to non-Hispanic White (NHW) patients. NHB and HSP patients reported feeling more respected (NHB: OR 1.40 95% CI 1.109-1.81; HSP: OR 1.39 95% CI 1.04-1.86) when compared to NHW patients. NHB patients were more likely to report that doctors explained well (OR: 1.31 95% CI 1.02-1.67). Conclusions: This national analysis finds that cancer survivors from historically (and presently) marginalized groups – including Black, Asian, and Hispanic patients - were more likely to perceive effective provider communication when compared to non-Hispanic White patients. Considering known disparities in cancer care access and outcomes, these results may reflect differing patient expectations of effective provider communication or the positive results of concerted efforts to improve provider communication to marginalized groups. Univariate analysis also revealed less effective communication for AI patients, suggesting potential unmet needs.
Investigating the mediating role of mental adjustment in the relationship between perceived stress and quality of life in patients with cancer.
Authors: Onyedibe Maria-Chidi Christiana , Chidebe Runcie C. W.
Published: June 2024

12106

Background: Cancer patients undergo a multifaceted journey fraught with substantial psychological distress and coping hurdles, profoundly influencing their overall well-being. The intricate nexus between perceived stress and diminished Health-Related Quality of Life (HRQoL) in this population has garnered significant attention. However, the pivotal role played by mental adjustment to cancer (MAC) as a potential mediator in this intricate relationship remains inadequately explored. Given the paramount importance of understanding the psychological dynamics inherent to cancer care, our study sought to delve into the mediating influence exerted by MAC on the association between perceived stress and HRQoL among individuals grappling with cancer. Methods: The study enrolled 214 cancer patients (74 male, 140 female, mean age = 50.57, SD= 13.07) from a University Teaching Hospital in South-West Nigeria. Participants completed assessments utilizing the Impact of Event Scale, Mental Adjustment to Cancer, and Health-Related Quality of Life (measured by the Functional Assessment of Cancer Therapy–General). The study utilized a cross-sectional design, and data analysis was performed using mediation analysis with PROCESS procedures in SPSS. Results: Results indicated that perceived stress was associated with lower HRQoL (β = -.71, p < .001, CI, -1.02, -.39). Among the five dimensions of MAC, three sub-dimensions: helplessness (β = -.49, p < .05, CI, -.95, -.02), anxious occupation (β = -1.45, p < .05, CI, -1.92, -.96) and cognitive avoidance (β = 1.43, p < .001, CI, .61 – 2.25) were significantly associated with HRQoL. Mediation analysis showed that only two dimensions—helplessness and anxious preoccupation —mediated the relationship between cancer-related stress and HRQoL. The indirect effect for both helplessness (β = -.14, SE = .069, CI -.24, -.01) and anxious preoccupation (β = -.31, SE = .09, CI -.51, -.15) were significant. The findings indicate that stress related to cancer may lead to elevated levels of helplessness and anxious preoccupation, subsequently contributing to a decrease in Health-Related Quality of Life (HRQoL). Conclusions: This study provides valuable insights into the intricate relationship between perceived stress, mental adjustment to cancer, and HRQoL, offering implications for targeted interventions aimed at enhancing the well-being of individuals grappling with the challenges of cancer diagnosis and treatment. By tailoring interventions to address these nuanced dynamics, healthcare providers can foster improved overall well-being and adaptive capacities in individuals navigating the complexities of cancer care. Key words: Cancer patients, mental adjustment to cancer, perceived stress, health-related quality of life
Defective FGFR1 Signaling Disrupts Glucose Regulation: Evidence From Humans With FGFR1 Mutations
Authors: Stamou Maria I , Chiu Crystal J , Jadhav Shreya V , Lopes Vanessa Ferreira , Salnikov Kathryn B , Plummer Lacey , Lippincott Margaret F , Lee Hang , Seminara Stephanie B , Balasubramanian Ravikumar
Published: June 2024

Context

Activation of fibroblast growth factor receptor 1 (FGFR1) signaling improves the metabolic health of animals and humans, while inactivation leads to diabetes in mice. Direct human genetic evidence for the role of FGFR1 signaling in human metabolic health has not been fully established.

Objective

We hypothesized that individuals with naturally occurring FGFR1 variants (“experiments of nature”) will display glucose dysregulation.

Methods

Participants with rare FGFR1 variants and noncarrier controls. Using a recall-by-genotype approach, we examined the β-cell function and insulin sensitivity of 9 individuals with rare FGFR1 deleterious variants compared to 27 noncarrier controls, during a frequently sampled intravenous glucose tolerance test at the Reproductive Endocrine Unit and the Harvard Center for Reproductive Medicine, Massachusetts General Hospital. FGFR1-mutation carriers displayed higher β-cell function in the face of lower insulin sensitivity compared to controls.

Conclusion

These findings suggest that impaired FGFR1 signaling may contribute to an early insulin resistance phase of diabetes pathogenesis and support the candidacy of the FGFR1 signaling pathway as a therapeutic target for improving the human metabolic health.
Το 2D animation ως μοντέλο οπτικοποίησης και μετάδοσης της πληροφορίας και η σύγχρονη γραφιστική στην ανάδειξη αρχαιολογικών ευρημάτων, χώρων και επιστημονικών κειμένων
Authors: Σκουρλής Στυλιανός
Published: June 2024

Ο στόχος αυτής της διατριβής είναι να εξετάσει και να αξιοποιήσει τη σύγχρονη γραφιστική και το 2D animation σε συνδυασμό με σύγχρονες τεχνολογίες, με σκοπό να αναδείξει και να προωθήσει αρχαιολογικά ευρήματα, χώρους και επιστημονικά κείμενα. Το 2D animation, ως μέσο ενημέρωσης και προσέλκυσης, διαθέτει δυνατότητες που δείχνουν τον δρόμο για τη δημιουργία νέων εμπειριών κατά την επίσκεψη μουσείων και αρχαιολογικών χώρων. Το αντικείμενο της διατριβής είναι η διερεύνηση της χρήσης πολυμεσικού υλικού ως μέσο για τη βελτίωση της επίσκεψης σε ένα μουσείο ή αρχαιολογικό χώρο, με στόχο τη δημιουργία συνθηκών που θα επιτρέπουν τη μετατροπή της σε μια εμπειρία επίσκεψης.Επικεντρώνει την προσοχή σε τρεις κύριους τομείς έρευνας - Γραφιστική, Κινούμενο Σχέδιο, και 3D scanning - καθώς και την εφαρμογή τους σε πολυμεσικές εφαρμογές, η παρούσα έρευνα διατυπώνει βασικά ερωτήματα με στόχο την ανάδειξη και βελτίωση της κατανόησης των εκθεμάτων και επίσκεψης των αρχαιολογιών χώρων. Στον τομέα της γραφιστικής, πραγματοποιείται έρευνα σχετικά με τα υφιστάμενα έντυπα, επικεντρώνοντας ταυτόχρονα στις βελτιώσεις που προτάθηκαν και υλοποιήθηκαν από τον ερευνητή. Στον τομέα του 2D animation, πραγματοποιείται έρευνα πάνω σε παλαιότερες ταινίες. Έχει δοκιμαστεί η δημιουργία animation με βάση εικονογραφήσεις από αγγεία του Εθνικού Αρχαιολογικού Μουσείου. Στη συνέχεια, αναλύονται τα αποτελέσματα και η επίδραση τους σε κοινό και τους αρχαιολόγους. Χρησιμοποιώντας τρισδιάστατα μοντέλα, προσπαθούμε να αναπαραστήσουμε, να δημιουργήσουμε πολυμεσικές εφαρμογές και να χρησιμοποιήσουμε την τρισδιάστατη εκτύπωση για την προβολή και ανάδειξη των ευρημάτων. Η έννοια της ψηφιακής ανάπλασης-αναδημιουργίας αρχαιολογικών ευρημάτων, ανέδειξε τον εαυτό της ως την πιο κατάλληλη μέθοδο πειραματισμού για τους καλλιτεχνικούς και γραφιστικούς στόχους της διατριβής αυτής. Αυτή η προσέγγιση έδωσε τη δυνατότητα για τη δημιουργία νέων εκδοχών και ερμηνειών των αρχαίων ευρημάτων, συνδυάζοντας την τεχνολογία με την αισθητική και την ιστορία, προσφέροντας έτσι ένα νέο ερευνητικό και δημιουργικό πεδίο μελέτης. Η έρευνα χρησιμοποίησε και ποσοτικές και ποιοτικές μεθόδους. Πέραν αυτών, πραγματοποιήθηκε πειραματισμός σε θεωρητικές και πρακτικές τεχνικές για την παραγωγή κυρίως οπτικού υλικού. Στην ποσοτική έρευνα, χρησιμοποιήθηκαν ερωτηματολόγια προς εργαζομένους και επισκέπτες, Έλληνες και αλλοδαπούς. Η ποιοτική έρευνα περιλάμβανε συνεντεύξεις.
The genome sequence of the Plain Longtail butterfly, Spicauda simplicius (Stoll, 1807)
Authors: Ribeiro Pedro , Matos-Maraví Pável , Linke Daniel , Meier Joana ,   Wellcome Sanger Institute Tree of Life Management, Samples and Laboratory team,   Wellcome Sanger Institute Scientific Operations: Sequencing Operations,   Wellcome Sanger Institute Tree of Life Core Informatics team,   Tree of Life Core Informatics collective
Published: June 2024

We present a genome assembly from an individual female Spicauda simplicius (the Plain Longtail butterfly; Arthropoda; Insecta; Lepidoptera; Hesperiidae). The genome sequence is 610.1 megabases in span. Most of the assembly is scaffolded into 32 chromosomal pseudomolecules, including the Z and W sex chromosomes. The mitochondrial genome has also been assembled and is 15.54 kilobases in length. Gene annotation of this assembly on Ensembl identified 18,506 protein coding genes.
The effects of different starch levels on the physical quality of high-oil extruded fish feed
Authors: Demir Soker Pınar , Kop Aysun , Korkut Ali Yıldırım
Published: June 2024

In this study, the effects of different starch levels (5%, 8% and 11%) on the physical properties of extruded fish feeds with high oil content (22%) were investigated. For this purpose, 3 types of extruded trout feed with different starch levels (S5, S8 and S11) were produced. Physical (moisture, feed diameter, bulk density and pellet durability) and chemical (lipid, starch, water absorption index, water solubility index and water stability) analyses of these feeds were performed in 3 repetitions on the samples taken from the extruder outlet, lubrication outlet and sieve outlet. An increase in the amount of starch in the feed caused an increase in feed diameter and durability of the pellets, while a decrease in bulk density was observed. According to the results of the chemical analysis, it was seen that the increase in the starch ratio had no effect on the crude oil and water solubility index values, the best water absorption index value was in the S8 feed, and the water stability values decreased from S5 to S11.
Investigation of microalgae isolated from different water resources of Türkiye for their biotechnological utilization
Authors: Polat Eyüp , Taştan Burcu Ertit
Published: June 2024

Microalgae are among the important microorganisms for a sustainable world as a source of renewable energy. In this study, three new microalgae were isolated from different regions of Türkiye and identified by molecular techniques. First isolate was Chlorella sorokiniana Shihira and Krauss, 1965 which was isolated from Dim River, second was Pseudochloris wilhelmii Somogyi et al., 2013 from Tokat and the third was Tetradesmus obliquus (Turpin) Wynne and Hallan, 2016 from Tunca River. The maximum biomass of C. sorokiniana was 1.02 g/L, 1.86 g/L for P. wilhelmii and 0.80 g/L for T. obliquus. The chlorophyll (a+b) concentrations were 0.146, 0.278 and 0.181 µg/mL for C. sorokiniana, P. wilhelmii and T. obliquus, respectively. The biotechnological utilization capacities of new isolates were revealed with the support of literature.
Adherence to Physical Activity Guidelines in the Behavioral Management of Type 2 Diabetes
Authors: Czapska Mirella , Babkiewicz-Jahn Kamila , Matuszewska Justyna , Pakaszewski Wojciech , Wojcik Alicja
Published: June 2024

Introduction and purpose
Diabetes comprises a group of metabolic disorders characterized by persistent hyperglycemia. This elevated blood glucose level arises from impaired insulin secretion and/or action. In type 2 diabetes, modifiable risk factors include an unhealthy diet, sedentary lifestyle, and obesity. Given the reversibility of these factors, lifestyle interventions, particularly those promoting physical activity, are deemed beneficial.
To evaluate the adherence to type 2 diabetes management guidelines, focusing on the incorporation of physical activity as a critical aspect of behavioral treatment for diabetes.
.
Materials and methods. Author's survey covering patients' knowledge about their disease, needs and expectations regarding education. The questionnaire examines the physical activity of patients newly diagnosed and already treated for type 2 diabetes.
Results The most performed exercise among patients was moderate-intensity activities such as walking or Nordic walking. These activities were more frequently intensified compared to others. Patients engaging in these forms of exercise did so more frequently and consistently than those participating in other types of physical activity. Additional activities included running and cycling, predominantly among the younger patient cohort. Patients who derived enjoyment from physical exercise demonstrated a higher likelihood of regular and willing participation.
Conclusions. Patients exhibited reluctance to engage in physical exercise and typically did not regard it as a crucial component of their treatment regimen. The exercise they performed was generally of low intensity, and few patients increased their physical activity following their diagnosis. A significant number of respondents lacked understanding of the role of exercise in the management of their condition and its effect on blood glucose levels.
Chronotypy a obraz snu utrwalony we frazematyce gwarowej
Authors: Bolęba-Bocheńska Katarzyna
Published: June 2024

The aim of the article is to discuss the linguistic image of chronotypes in Polish dialectal phrases. In the research material, following Wojciech Chlebda, it was assumed that phrases are multi-word phrases reproduced in specific speech situations. The research material consists of units taken from dialectal dictionaries, collections of dialectal and national proverbs, and in a small part also units obtained from indigenous people. The first part of the work explains the basic concepts: chronotype, phrase, linguistic image of the world and cognitive definition. The next one analyzed the material. It was divided into the following categories, which are folk beliefs regarding sleep and the times of getting up and waking up: Like a day, like a dream, Dreams should not be believed, Sleep is the brother of death, Sleep is a waste of time, During sleep we have no control over ourselves, A person should work from the morning. The conclusions stated that the reproduction of phrases becomes a intergenerational message and may have a negative impact on the behavior of individuals.