bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and characteristics of patients with incidental cardiac uptake on bone scintigraphy
Authors: Son Jihee , Han Yeon-Hee , Lee Sun Hwa 
Published: August 2024

Abstract
Background
Bone scintigraphy is emerging as a confirmatory diagnostic tool for transthyretin cardiac amyloidosis (ATTR-CA). This study aimed to investigate the frequency and clinical characteristics of patients with incidental cardiac uptake and incidental ATTR-CA on bone scintigraphy.

Methods
All bone scintigraphic studies performed at a tertiary teaching hospital between 2011 and 2022 were reviewed retrospectively. Patients who underwent bone scintigraphy to confirm ATTR-CA were excluded. Patients with cardiac uptake of grade 2 or 3 were included and divided into two groups: possible ATTR-CA group and noncardiac amyloidosis (non-CA) group.

Results
Of the 61,432 bone scintigraphic studies performed on 32,245 patients, 23 (0.07%) had grade 2 or 3 cardiac uptake. Nine of 23 patients (39.1%) were assigned to the non-CA group because they showed cardiac uptake from definite other causes or focal uptake that did not match CA. The remaining 14 patients (60.9%) were classified as the possible ATTR-CA group, and five patients were referred to cardiologists and finally diagnosed with ATTR-CA. Two patients were treated with tafamidis. Patients in the ATTR-CA group were significantly older and had a less frequent history of end-stage renal disease than those in the non-CA group. Other characteristics were comparable in both groups.

Conclusions
Although incidental ATTR-CA in patients undergoing bone scintigraphy for noncardiac reasons is uncommon, if cardiac uptake is observed in elderly patients without metastatic calcification associated with end-stage renal disease, further diagnostic work-up for ATTR-CA as a cause of undiagnosed heart failure should be considered.
A randomized, double-blind controlled trial of medicinal cannabis vs placebo for symptom management in patients with advanced cancer receiving palliative care.
Authors: Hardy Janet Rea , Greer Ristan , Gurgenci Taylan , Kearney Alison , Ladwa Rahul , Huggett Georgie , Good Phillip 
Published: August 2024

12020 Background: Medicinal cannabis remains very popular amongst cancer patients. In our previous study (JCO 2023; 41(7):1444-1452), cannabidiol (CBD) did not improve symptom management above that provided by standard palliative care alone. This study utilized the same design to test whether the addition of tetrahydrocannabinol(THC) to CBD resulted in improved symptom control. Methods: Patients with advanced cancer and a total symptom distress score (TSDS) of ≥10/90 as measured by the Edmonton Symptom Assessment Scale (ESAS) who were receiving palliative care were randomised to a 10mg/ml THC:10mg/ml CBD combination oil (MC) or matched placebo. The dose was escalated according to tolerance and perceived efficacy from 2.5 to 30mg/day over 14 days and continued at that dose to day 28. The primary outcome was the change in TSDS from baseline at day 14. Secondary outcomes included change in individual symptoms, patient-selected dose, global impression of change, anxiety/depression, opioid use, quality of life and toxicity. Results: Of the 144 randomized from Sept 2019 to July 2023 (72 to MC, 72 to placebo), 56 and 65 participants reached the primary analysis point at 14 days, and 33 and 50 to day 28. The most common cancers were breast, lung and gynecological. Most participants were of reasonable performance status (AKPS 70%) and were taking opioids at baseline. Mean baseline TSDS scores were 37.6/90 (MC) and 36.5/90 (placebo). Mean TSDS scores fell over time with no difference between arms at day 14 (-6.3 (SD 12.3) MC and -6.98 (SD 12.6), p = 0.76) or day 28 (-9.24 (SD 15.3) and 8.42 (SD 13.6), p = 0.8). Adjusted for baseline, there was a significant improvement in pain score from baseline in favor of MC (-1.41 (2.15) vs -0.46 (2.82), p = 0.04) and in overall wellbeing in favor of placebo (-0.48 (2.78) and -1.29 (2.74), p = 0.02) at day 14. The median (range) patient selected dose of oil at day 14 was 1.5ml (0.5-3.0) (equivalent to a dose of 15mgTHC/15mg CBD) and 3.0ml (0.5-3.0) for placebo. Side-effects were generally mild. More participants on MC reported confusion (26/69 and 12/72, p = 0.005), feeling high (21/69 and 10/72, p = 0.02) and an exaggerated sense of well-being (10/69 and 2/72, p = 0.01) as worse than baseline. Those on MC reported an improved global impression of change over time but this lost significance when considering those who exited early. Conclusions: Although showing no advantage over placebo with respect to improving total symptom distress, a 1:1 THC:CBD medicinal cannabis oil resulted in a statistically significant improvement in cancer-related pain at the expense of increased psychomimetic toxicity. Trial registration: ACTRN 12619000037101. Sponsor: Australian Government Medical Research Future Fund. Clinical trial information: ACTRN12619000037101.
Phase II study of neoadjuvant ipilimumab and nivolumab in combination with paclitaxel following anthracycline-based chemotherapy in patients with treatment resistant stage III triple negative breast cancer (TNBC): BCT1702—Survival results.
Authors: Loi Sherene , Francis Prudence A. , Zdenkowski Nicholas , Gebski Val , Fox Stephen B. , White Michelle , Kiely Belinda Emma , Hui Rina , Redfern Andrew David , Calvert Raewyn , Rennie Lauren , Badger Heath , Boyle Frances M. ,   Breast Cancer Trials - Australia and New Zealand
Published: August 2024

608 Background: We examined the efficacy and safety of neoadjuvant ipilimumab and nivolumab combined with paclitaxel following suboptimal response to anthracycline-based chemotherapy in patients with early-stage TNBC. Methods: This single arm phase 2 study enrolled 34 patients at 8 sites. Patients had stage 3 TNBC, after 4 cycles of anthracycline-based therapy, with ≥15mm of tumor remaining or ≥10mm of tumor with ≥1 positive lymph node. A suboptimal response at baseline was defined as <50% reduction in tumor volume after anthracycline-based therapy. Patients received neoadjuvant ipilimumab 1mg/kg IV 6 weekly for 2 doses and nivolumab 240mg every 2 weeks for 6 doses, with weekly paclitaxel at 80mg/m2 for 12 weeks, followed by surgery. Nivolumab (480mg 4-weekly) continued post operatively for a further 9 months. Primary endpoint was pathological complete response (pCR: ypT0/is, ypN0) in breast and axilla, with secondary endpoints pCR in the suboptimal responders, pCR in PD-L1 positive (≥1% by SP142) or TIL% high (≥30%), event-free (EFS) and overall survival (OS). Results: Between December 2018 and April 2020, 34 patients were enrolled, 33 were evaluable for the primary endpoint. Median age was 46.6yrs. At diagnosis, 97% patients were clinical stage III, 24/34 (70.5%) were clinically node positive, 9/31 (27%) were PD-L1 positive and 6/30 (20%) were TILs% high. At study entry (after anthracycline-based chemo), the median tumor size by ultrasound was 28mm (12-62). The pCR rate was 24.2% (95% CI, 11.09-42.26) in all evaluable, 44.4% [4/9] in PD-L1+ and 9.5% [2/21] in PD-L1- patients. In suboptimal responders, the pCR rate was 25% (95% CI,8.6-49.1) (3/16). At a median follow up of 36.6 months, 9 patients have died. The KM estimates for EFS and OS at 12 months were 96.8% and 93.7%, at 24 months were 84.4% and 84.4% and at 36 months 61.2% and 71.9%, respectively. Patients who achieved a pCR had numerically better EFS (HR 3.61 (0.47-28.2, p=0.2) and OS (HR 2.6 (0.33-21.08); p=0.34). Patients with PD-L1+ tumors vs PD-L1- had a 3-year EFS of 100% vs 52% (p=0.01) and 100% vs 67% OS (p=0.05). Results were similarly favorable for TIL high vs low. Conclusions: The addition of ipilimumab and nivolumab to neoadjuvant chemotherapy resulted in 100% survival for high-risk patients with PD-L1+ and/or TIL% high tumors. Combination CTLA4 and PD-1 targeting agents should be further investigated in Stage 3 TNBC patients. Translational research is ongoing. Clinical trial information: ACTRN12617000651381. [Table: see text]
Efficacy, safety, and predictive biomarkers of dalpiciclib combined with letrozole, pertuzumab and trastuzumab as neoadjuvant therapy in HR+/HER2+ breast cancer: A phase II study.
Authors: Liang Xinrui , Wu Jing , Zhang Ningning , Zeng Xiaohua 
Published: August 2024

e12621 Background: HR+/HER2+ breast cancer is a unique subtype of breast cancer. Between ER and HER2 crosstalk pathways may affect the sensitivity to both HER2-targeted and endocrine therapy in patients with HR+/HER2+ breast cancer. Current therapies for HER2-positive breast cancer have demonstrated limited efficacy in patients with HR+/HER2+ breast cancer. This Phase II trial aimed to assess the efficacy and safety of a neoadjuvant regimen combining trastuzumab, pertuzumab, dalpiciclib (a cyclin dependent kinase 4/6 inhibitor) and letrozole in patients with HR+/HER2+ breast cancer, alongside the exploration of efficacy biomarkers. Methods: Patients were administered six 28-day cycles of dalpiciclib (150 mg once daily on days 1-21) and letrozole (2.5 mg once daily), plus six 21-day cycles of trastuzumab (8 mg/kg loading dose followed by 6 mg/kg maintenance dose on day 1), pertuzumab (840mg loading dose followed by 420mg maintenance dose on day 1), prior to surgery. The primary endpoint was total pathological complete response (tpCR, ypT0/is, ypN0) rate. Secondary endpoints were objective response rate (ORR), breast pathological complete response (bpCR; ypT0/is) rate, change in Ki-67 level from baseline to one cycle of treatment and to surgery, and safety. For biomarkers analysis, next-generation sequencing was performed on pre-treatment tissue and circulating tumor DNA (ctDNA) at various time points before surgery. Results: A total of 14 patients who completed the neoadjuvant treatment and surgery between July 12, 2022 and August 12, 2023 were enrolled. A 50.0% (7 out of 14) tpCR and bpCR rate was observed, with an ORR of 92.9%. Significant reductions in Ki-67 levels were noted after both one ( P<0.05) and six cycles of neoadjuvant therapy ( P<0.05). Grade 4 neutropenia was reported in one case, with no fatalities. The most common grade 3 adverse events were neutropenia (10 [71.4%]) and leukopenia (8 [57.1%]). NGS identified frequent mutations in TP53 (84.6%), PIK3CA (53.8%), and ARID1A (30.8%). Cell cycle pathway gene alterations correlated with a higher pCR rate (80% vs 25%, P=0.103). Eight (61.5%) patients had positive ctDNA at baseline, and ctDNA positivity decreased significantly post-neoadjuvant treatment ( P<0.05). Patients with positive ctDNA at baseline without clearance post-treatment exhibited a trend towards a lower pCR rate. Conclusions: This combination neoadjuvant regimen of dalpiciclib, letrozole, pertuzumab and trastuzumab demonstrated promising pathological responses and manageable safety in patients with HR+/HER2+ breast cancer. The predictive value of genetic alterations and ctDNA status for treatment efficacy warrants further investigation. Clinical trial information: ChiCTR2200062114.
Pyrotinib plus taxanes or vinorelbine for human epidermal growth factor receptor 2-positive metastatic breast cancer: A prospective study.
Authors: Xiong Weili , Zhang Lili , Yuan Yuan , Gu Quan , Hu Sainan , Huang Jiayuan , Dong Min , Feng Jifeng 
Published: August 2024

e13004 Background: Pyrotinib in combination with capecitabine is recommended as the second-line treatment for human epidermal growth factor 2 (HER2)-positive metastatic breast cancer (MBC) in China. The efficacy and safety of pyrotinib combined with non-capecitabine chemotherapy regimens remain unclear. Thus, we conducted this study to evaluate the efficacy and safety of pyrotinib combined with taxanes or vinorelbine in HER2-positive MBC. Methods: Patients with HER2-positive MBC were included to receive pyrotinib combined with taxanes or vinorelbine in Jiangsu Cancer Hospital. Patients received pyrotinib 400mg orally once daily plus taxanes (docetaxel 75-100 mg/m2 on day1, or nab-paclitaxel 125 mg/m2 on days 1 and 8, paclitaxel 80 mg/m2 on days 1 and 8, every 3 week) or vinorelbine 25 mg/m2 on days 1 and 8, every 3 weeks. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), overall survival (OS) and safety. Results: Between Nov 20, 2018, and Jan 11, 2023, a total of 101 patients were assigned to pyrotinib plus taxanes group (n=83) and pyrotinib plus vinorelbine group (n=18). The median number of pyrotinib therapy lines was 2 (IQR 1-7), the first line accounted for 23.8%, the second line, and third line and above was 34.6%, 41.6%, respectively. As of May 24, 2023, the median PFS in the total was 11.5 months (95% confidence interval [CI], 8.8-15.7). The median PFS was significantly longer in the pyrotinib plus taxanes group than in the pyrotinib plus vinorelbine group, with median PFS being 12.2 months (95% CI, 9.2-18.6) and 8.4 months (95% CI, 5.5-13.7) (HR=2.2 [95% CI, 1.2-3.9]; P=0.005), respectively. The median PFS in the first-line, second-line, and third-line and above treatment was 28.6 (95% CI, 10.6-NA), 12.2 (95% CI, 8.5-16.3), and 8.3 months (95% CI, 6.3-14.5), respectively. The most common grade 3 or 4 adverse events were diarrhea (22.8%), leukopenia (19.5%), and neutropenia (18.2%). Conclusions: The median PFS of pyrotinib plus taxanes or vinorelbine, especially taxanes, was not inferior even superior to that of pyrotinib combined capecitabine. No increase treatment-related side effects was reported. Thus, the combination of pyrotinib and taxanes or vinorelbine regimen can be an option for HER2-positive MBC. Clinical trial information: ChiCTR2000041217.
The efficacy and safety of neoadjuvant sintilimab combined with chemotherapy in resectable locally advanced lymph node-positive esophageal squamous cell carcinoma: A real world study.
Authors: Ye Peng , Rusidanmu Aizemaiti , Lin Shuang , Zhou Kun , Wu Xuhui , Huang Bin , Wu Gongzhi , Peng Congxiong , Peng Xuyang , Ding Jianyang , Huang Mingjiang , Yu Huanming , Zhi Shengxu 
Published: August 2024

e16091 Background: Many phase III clinical trials (Keynote 590, Orient 15, etc) have all proved the role of immunotherapy combined with chemotherapy in the treatment of esophageal squamous cell carcinoma. This study was designed to evaluate the efficacy and safety of immunotherapy and chemotherapy as neoadjuvant therapy for resectable locally advanced lymph node-positive esophageal squamous cell carcinoma. Methods: This is a multicenter, 2-cohort (IO+CT group & CRT group), real world study. In IO+CT group, patients(pts) will receive sintilimab 200 mg once on day 1, albumin-bound paclitaxel 260g/m2 from day 1 to 4, carboplatin 80mg/m2 on day 1, every 21 days(Q3W) for 2 cycles. Key eligibility criteria included resectable, locally advanced lymph node-positive esophageal squamous cell carcinoma conformed by histology, and aged ≥18 years old with ECOG PS 0-1. The primary endpoint was pathologic complete response (pCR) rate. The secondary endpoints were event free survival (EFS), objective response rate (ORR), overall survival (OS) and safety. Results: From 7/2022 to 9/2023, 30 pts were enrolled in IO+CT group. In IO+CT group, among 30 pts who underwent surgery, 9 (30%) achieved pCR. 93.3% pts (28/30) achieved R0 resection. In 20 evaluable pts, 3(15%) achieved complete response (CR), 15(75%) achieved partial response (PR), 2(10%) achieved stable disease (SD). ORR and DCR were 90.0% (18/20) and 100.0% (20/20), respectively. There were no grade ≥2 treatment-related adverse events (TRAEs) appeared. The most common grade 1 TRAEs was fatigue (13.3%). Conclusions: In the real world, sintilimab plus chemotherapy used as neoadjuvant therapy in resectable locally advanced lymph node-positive esophageal squamous cell carcinoma could be effective and manageable toxicity. Clinical trial information: ChiCTR2200058565.
A phase IIA clinical trial to evaluate a reversible Bruton’s tyrosine kinase inhibitor (BTKi) HBW-3220 capsules in patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL).
Authors: Lee Ning , Li Yingfu , Mao Yong , Liu Guanfeng , Li Jiang , Liu Qingchun 
Published: August 2024

e19042 Background: This clinical study is to evaluate HBW-3220, a novel BTKi with an improved in vitro profile than the existing non-covalent drugs pirtobrutinib (approved) and nemtabrutinib (Phase III). HBW-3220 shows superior inhibition against BTK wild-type and several common mutants, such as C481S, C481R, T474I, T316A, and L528W (enriched in pirtobrutinib resistance), and hematopoietic cell kinase (HCK, a key contributor to BTKi resistance due to kinase-defective BTK). Methods: This phase IIA clinical study is conducted in R/R B-NHL patients who had received two or more prior lines of treatment. The dose escalation study adopts accelerated titration and a "3+3" design, with a daily single dose of 15, 30, 60, 90, 120, or 150 mg. During the dose escalation phase, the sponsor and investigators determine whether to expand the cohort of the previous dose based on the existing data. Adverse events (AEs) are assigned according to NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Response assessment is based on iwCLL 2018 guidelines for chronic lymphocytic leukemia (CLL), IWWM-7 consensus for Waldenstrom macroglobulinemia (WM), and Lugano 2014 guidelines for all other lymphomas, including small lymphocytic lymphoma (SLL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), and follicular lymphoma (FL). Results: 29 patients have been enrolled, and the dose escalation study has been completed. No dose-limiting toxicity (DLT) occurred in any patient, implicating good tolerability. Adverse events (AEs), similar to other BTKis, were mostly Grade 1 or 2, including fever (36%), diarrhea (32%), headache (18%), anemia (39%), infectious pneumonia (18%), decreased neutrophils count (39%), decreased platelet count (29%), increased alanine aminotransferase (21%), etc. Drug-related Grade 3 AEs included decreased neutrophil count (n=3, 11%), increased lymphocyte count (n=2, 7%), and infectious pneumonia (n=2, 7%). 23 patients underwent at least 1 response assessment. The overall response rate (ORR) in CLL/SLL (all with prior irreversible BTKi treatment, and 4 of them with additional BCL2 inhibitor treatment), MZL, MCL, and DLBCL patients were 83% (5/6), 50% (2/4), 40% (2/5) and 33% (1/3), respectively. Among the ORR, 90% (9/10) were in the 90 mg and above dose group, regardless of previous BTKi treatment history or mutation status of p53 and BTK. After oral administration, the drug exposures showed dose-dependent increases. The time to maximum plasma concentration (Tmax) was 2 hours, and the elimination half-life (T1/2) was 19 hours. Conclusions: The current data show that HBW-3220 is well tolerated with no DLT occurred at daily doses up to 150 mg, displaying most promising efficacy in patients with CLL/SLL, MZL, and MCL. Clinical trial information: ChiCTR2200062537.
Knowledge Production in the “Arab-Majority” World and Unlearning in the Field
Authors: Kassem Ali 
Published: August 2024

Abstract
This paper presents and autoethnographically analyzes three key sites in which the author—a Lebanese “Arabo-Muslim man”—failed to interpellate the lifeworlds of Lebanese “Arabo-Muslim” female participants during a research project in Lebanon: the public-private divide, gender, and the autonomous subject. Specifically, the article identifies key forces that produce this failure, including education, presence in the Westernized university, Westernized secularization, social class, family background, and urbanity, all situated within the larger structures of modernity/coloniality. Doing this, the article grates against the assumption that researchers who share a “race,” citizenship, language, or ethnicity and who are “from” the Arab region are de facto well placed to pursue decolonial knowledge production alongside the region and its dwellers. The article consequently posits the possibility of unlearning and relearning—disrupting this failure—through immersive embodied listening fieldwork within the material space of the Arab world, undoing the formation of an alienated, fractured, Westernized self. Moving beyond the cognitive and theoretical to the material, experiential, and embodied, the article accordingly underlines reflexive listening fieldwork's potential as a generative site (among others) from which alternative knowledges of/with/on the global South(s) can emerge.
The potency of yellow pigment extract from the marine bacterium Pseudomonas oryzihabitans SAB E-3 as an antioxidant agent
Authors: PUTRI DELFIANI ANGGIAS , ASTUTI RIKA INDRI , WAHYUDI ARIS TRI 
Published: August 2024

Abstract. Putri DA, Astuti RI, Wahyudi AT. 2024. The potency of yellow pigment extract from the marine bacterium Pseudomonas oryzihabitans SAB E-3 as an antioxidant agent. Biodiversitas 25: 2565-2575. Metabolic processes in cells can produce byproducts in the form of Reactive Oxygen Species (ROS). Excessive amounts of ROS are one of the causes of oxidative stress. Antioxidants are known to act as free radical-scavenging compounds. Pigment-producing bacteria associated with sponges have been widely reported to have antioxidant compounds. In this study, the marine bacterium Pseudomonas oryzihabitans SAB E-3 produced intracellular yellow pigments with potential antioxidant activity. Therefore, this study aimed to assess the in vitro antioxidant and mitochondrial activity at the cellular level and identify chemical compounds. The intracellular pigments produced by P. oryzihabitans SAB E-3 were extracted using methanol, acetone, chloroform, and ethyl acetate. The methanol pigment extract contained the highest number of phenolic and flavonoid compounds, which may have contributed to its antioxidant activity. Furthermore, the active fraction obtained from the bioautographic TLC and harvested using preparative TLC had stronger antioxidant activity against DPPH radicals (75.71 µg/mL) than the crude pigment extract. However, the ABTS radical-reducing activity was lower (226.59 µg/mL) than the crude pigment extract. The maximum wavelength of the pigment extract was 453 nm, indicating the presence of carotenoids. In addition, the lowest concentration of the crude pigment extract (50 µg/mL) and selected active fractions (18.75 µg/mL) increased yeast Schizosaccharomyces pombe ARC039 tolerance to oxidative stress and induced mitochondrial activity. Active fraction one extract analyzed using LC-MS/MS contained piceatannol, resveratrol, isorhapontigenin, isoliquiritigenin, liquiritin, and 2-Omethylisohemigossylic acid lactone, which may contribute to its antioxidant activity. Therefore, the yellow pigment extract and the active fraction produced by P. oryzihabitans SAB E-3 are potential candidates for natural antioxidant sources.
Hepatitis E virus in the Kathmandu Valley: Insights from a representative longitudinal serosurvey
Authors: Katuwal Nishan , Thapa Melina , Shrestha Sony , Vaidya Krista , Bogoch Isaac I. , Shrestha Rajeev , Andrews Jason R. , Tamrakar Dipesh , Aiemjoy Kristen 
Published: August 2024

Background
Hepatitis-E virus (HEV), an etiologic agent of acute inflammatory liver disease, is a significant cause of morbidity and mortality in South Asia. HEV is considered endemic in Nepal; but data on population-level infection transmission is sparse.

Methods
We conducted a longitudinal serosurvey in central Nepal to assess HEV exposure. At each visit, capillary blood samples were collected and analyzed for the presence of anti-HEV IgG antibodies. The study took place between February 2019 and April 2021, with up to 4 visits per participant approximately 6 months apart.

Results
We collected 2513 samples from 923 participants aged 0–25 years, finding a seroprevalence of 4.8% and a seroincidence rate of 10.9 per 1000 person-years. Young adults and individuals consuming surface water faced the highest incidence of infection. Geospatial analysis identified potential HEV clusters, suggesting a need for targeted interventions.

Significance
Our findings demonstrate that HEV is endemic in Nepal and that the risk of infection increases with age.