bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Phase 1, randomized, double-blind, placebo-controlled, single- and multiple-dose escalation study to evaluate the safety and pharmacokinetics/pharmacodynamics of PF-06835375, a C-X-C chemokine receptor type 5 directed antibody, in patients with systemic lupus erythematosus or rheumatoid arthritis
Authors: Cohen Stanley , Beebe Jean S. , Chindalore Vishala , Guan Shunjie , Hassan-Zahraee Mina , Saxena Madhurima , Xi Li , Hyde Craig , Koride Sarita , Levin Robert , Lubaczewski Shannon , Salganik Mikhail , Sloan Abigail , Stevens Erin , Peeva Elena , Vincent Michael S. , Martin David A. , Chu Myron 
Published: June 2024

Abstract
Background
The objective of this study was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of PF‑06835375, a potent selective afucosyl immunoglobulin G1 antibody targeting C-X-C chemokine receptor type 5 (CXCR5) that potentially depletes B cells, follicular T helper (Tfh) cells, and circulating Tfh-like (cTfh) cells, in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).

Methods
This first-in-human, multicenter, double-blind, sponsor-open, placebo-controlled Phase 1 study recruited patients aged 18–70 years with SLE or RA. In Part A, patients received single doses of intravenous PF-06835375 (dose range: 0.03–6 mg) or placebo in six sequential single ascending dose (SAD) cohorts. In Part B, patients received repeat doses of subcutaneous PF-06835375 (dose range: 0.3–10 mg) or placebo on Days 1 and 29 in five multiple ascending dose (MAD) cohorts. Tetanus/Diphtheria (Td) and Meningococcal B (MenB/Trumenba™) vaccines were administered at Day 4 (Td and MenB) and Week 8 (MenB only) to assess PF-06835375 functional effects. Endpoints included treatment-emergent adverse events (TEAEs), pharmacokinetic parameters, pharmacodynamic effects on B and cTfh cells, and biomarker counts, vaccine response, and exploratory differential gene expression analysis. Safety, pharmacokinetic, and pharmacodynamic endpoints are summarized descriptively. The change from baseline of B and Tfh cell-specific genes over time was calculated using a prespecified mixed-effects model, with a false discovery rate < 0.05 considered statistically significant.

Results
In total, 73 patients were treated (SAD cohorts: SLE, n = 17; RA, n = 14; MAD cohorts: SLE, n = 22; RA, n = 20). Mean age was 53.3 years. Sixty-two (84.9%) patients experienced TEAEs (placebo n = 17; PF-06835375 n = 45); most were mild or moderate. Three (9.7%) patients experienced serious adverse events. Mean t1/2 ranged from 3.4–121.4 h (SAD cohorts) and 162.0–234.0 h (MAD cohorts, Day 29). B and cTfh cell counts generally showed dose-dependent reductions across cohorts (range of mean maximum depletion: 67.3–99.3%/62.4–98.7% [SAD] and 91.1–99.6%/89.5–98.1% [MAD], respectively). B cell-related genes and pathways were significantly downregulated in patients treated with PF-06835375.

Conclusions
These data support further development of PF-06835375 to assess the clinical potential for B and Tfh cell depletion as a treatment for autoimmune diseases.

Trial registration
ClinicalTrials.gov identifier: NCT03334851.
Public support and willingness to pay for a carbon tax in Hungary: can revenue recycling make a difference?
Authors: Muth Daniel , Weiner Csaba , Lakócai Csaba 
Published: June 2024

Abstract
Background
To curb human-made carbon-dioxide emissions, the European Union will introduce carbon pricing for buildings and transport in 2027. Central and East European (CEE) countries are pressured to embark on ambitious decarbonization pathways leading to carbon-neutral economies by 2050. This paper is the first to investigate the public acceptance of and the willingness to pay (WTP) for a carbon tax in a CEE country, Hungary. It analyzes the support-increasing effects of five revenue-recycling mechanisms (tax cuts, green spending, support for poor households, funding for health care and education, and debt reduction), a wider range than covered in previous studies. A national face-to-face survey of 3013 adults on public attitudes to climate change, conducted in summer 2022, is the main method of data collection. This is combined with secondary analysis of related statistics and documentary analysis of relevant materials.

Results
The results show low public acceptance, with only a modest increase from 20.3% to 27.3% due to revenue recycling. This is accompanied by low WTP values and WTP increases. All these are lower than those found in Western surveys. A novel empirical result is the relative popularity of public health care and education in revenue recycling, though differences in revenue-recycling preferences are apparent between those who accept a carbon tax even without a redistribution mechanism and those who are willing to pay only if redistribution is included. Green spending also performed relatively well, while supporting the poor fared less well, albeit with relatively high WTP values. Reducing taxes and public debt were the least likely to instigate carbon-tax acceptance.

Conclusions
The results highlight the importance of carefully assessing the distributional impact of implementing carbon pricing mechanisms and thoroughly integrating social considerations into climate policy. Based on this, as well as the analysis of the social conditions and political economy of climate policy development in Hungary, policies—such as a gradually increasing carbon tax, social cushioning, legal earmarking of carbon-tax revenues, and policy bundling—are proposed to make carbon pricing socially tolerable and politically acceptable. The findings and conclusions might also be relevant for other parts of the CEE region.
Inactivation of KDM6A promotes the progression of colorectal cancer by enhancing the glycolysis
Authors: Zhang Dexiang , Zhao Xiaohong , Gao Yu , Wang Meixing , Xiao Mi , Zhu Kaihua , Niu Wei , Dai Yuedi 
Published: June 2024

AbstractKDM6A (lysine demethylase 6A) has been reported to undergo inactivating mutations in colorectal cancer, but its function in the progression of colorectal cancer has not been evaluated using animal models of colorectal cancer. In this study, we found that knocking out KDM6A expression in mouse intestinal epithelium increased the length of villus and crypt, promoting the development of AOM (azoxymethane)/DSS (dextran sulfate sodium salt)-induced colorectal cancer. On the other hand, knocking down KDM6A expression promoted the growth of colorectal cancer cells. In molecular mechanism studies, we found that KDM6A interacts with HIF-1α; knocking down KDM6A promotes the binding of HIF-1α to the LDHA promoter, thereby promoting LDHA expression and lactate production, enhancing glycolysis. Knocking down LDHA reversed the malignant phenotype caused by KDM6A expression loss. In summary, this study using animal models revealed that KDM6A loss promotes the progression of colorectal cancer through reprogramming the metabolism of the colorectal cancer cells, suggesting that restoring the function of KDM6A is likely to be one of the strategies for colorectal cancer treatment.
Novel therapeutic activities of dragon blood from palm tree Daemonorops draco for the treatment of chronic diabetic wounds
Authors: Chen Hong-Chi , You Ren-In , Lin Fang-Mei , Lin Guan-Ling , Ho Tsung-Jung , Chen Hao-Ping 
Published: June 2024

Abstract
Background
The clinical efficacy of Jinchuang Ointment, a traditional Chinese medicine (TCM), in treating chronic non-healing diabetic wounds has been demonstrated over the past decades. Both in vitro and in vivo angiogenic activities have been reported for its herbal ingredients, including dragon blood from the palm tree Daemonorops draco and catechu from Uncaria gambir Roxb. Additionally, crude extracts of dragon blood have exhibited hypoglycemic effects not only in animal studies but also in cell-based in vitro assays.

Results
Our findings indicate that crude dragon blood extract promotes the differentiation of myoblasts into myotubes. Partially purified fractions of dragon blood crude extract significantly enhance the expression of muscle cell differentiation-related genes such as myoG, myoD, and myoHC. Our results also demonstrate that crude extracts of dragon blood can inhibit platelet-derived growth factor-induced PAI-1 expression in primary rat vascular smooth muscle cells, thereby favoring changes in hemostasis towards fibrinolysis. Consistent with previous reports, reduced expression of plasminogen activator inhibitor 1 (PAI-1) accelerates wound healing. However, further separation resulted in a significant loss of both activities, indicating the involvement of more than one compound in these processes. Stem cells play a crucial role in muscle injury repair. Neither dragon blood nor catechu alone stimulated the proliferation of human telomerase reverse transcriptase (hTERT)-immortalized and umbilical cord mesenchymal stem cells. Interestingly, the proliferation of both types of stem cells was observed when crude extracts of dragon blood and catechu were present together in the stem cell growth medium.

Conclusions
Dragon blood from D. draco offers multifaceted therapeutic benefits for treating chronic nonhealing diabetic wounds from various perspectives. Most drugs in Western medicine consist of small molecules with defined ingredients. However, this is not the case in TCM, as the activities of dragon blood reported in this study. Surprisingly, the activities documented here align with descriptions in ancient Chinese medical texts dating back to A.D. 1625.
Does consensus contour improve robustness and accuracy in 18F-FDG PET radiomic features?
Authors: Zhuang Mingzan , Li Xianru , Qiu Zhifen , Guan Jitian 
Published: June 2024

Abstract
Purpose
The purpose of our study is to validate the robustness and accuracy of consensus contour in 2-deoxy-2-[$$^{18}$$

18

F]fluoro-D-glucose ($$^{18}$$

18

F-FDG) PET radiomic features.

Methods
225 nasopharyngeal carcinoma (NPC) and 13 extended cardio-torso (XCAT) simulated data were enrolled. All segmentation were performed with four segmentation methods under two different initial masks, respectively. Consensus contour (ConSeg) was then developed using the majority vote rule. 107 radiomic features were extracted by Pyradiomics based on segmentation and the intraclass correlation coefficient (ICC) was calculated for each feature between masks or among segmentation, respectively. In XCAT ICC between segmentation and simulated ground truth were also calculated to access the accuracy.

Results
ICC varied with the dataset, segmentation method, initial mask and feature type. ConSeg presented higher ICC for radiomic features in robustness tests and similar ICC in accuracy tests, compared with the average of four segmentation results. Higher ICC were also generally observed in irregular initial masks compared with rectangular masks in both robustness and accuracy tests. Furthermore, 19 features (17.76%) had ICC ≥ 0.75 in both robustness and accuracy tests for any of the segmentation methods or initial masks. The dataset was observed to have a large impact on the correlation relationships between radiomic features, but not the segmentation method or initial mask.

Conclusions
The consensus contour combined with irregular initial mask could improve the robustness and accuracy in radiomic analysis to some extent. The correlation relationships between radiomic features and feature clusters largely depended on the dataset, but not segmentation method or initial mask.
Knowledge mobilization between the food industry and public health nutrition scientists: findings from a case study
Authors: Le Bouthillier Marie , Veilleux Sophie , Loignon Jeanne , Turcotte Mylène , Trudel Laurélie , Provencher Véronique 
Published: June 2024

Abstract
Background
Improving the nutritional quality of the food supply increases access to nutritious foods, which improves dietary habits and population health. Yet, knowledge mobilization initiatives between public health nutrition researchers and food industries are often not adequately considered and understood. This study explored what elements related to this specific context need to be recognized so that researchers can better mobilize nutrition science knowledge with the food industry to promote the nutritional improvement of food products.

Method
A case study qualitative approach was selected to answer the research question, using semi-structured interviews as the data collection technique. Québec baking industry actors were shown a mock-up of an online mobilization platform sharing the results of the Food Quality Observatory that describes the nutritional quality of breads offered in Québec, Canada. They were asked to think aloud as they explored the web platform and were interviewed. Two coders analyzed the data using an inductive approach and thematic content analysis, starting with individual open coding, and then put forward their analyses and drafted the final themes.

Results
The final data consisted of 10 semi-structured interviews conducted between October 2019 and August 2020. Four main themes were identified: the industry’s context, the knowledge mobilization initiative, the product-related matters stemming from the information shared and the motivation within the industry. Within each theme, sub-themes were highlighted and related to the industries’ motivation to improve their products’ nutritional quality. This study also specified key considerations for changes to the sodium and fiber content in bread.

Conclusion
Other steps beyond using simple language and a website format could be taken to better mobilize scientific knowledge with food industries, such as providing more consumer information, using an integrated knowledge mobilization approach that includes a consideration of ethics, working with communication professionals, collaborating with food science experts, and providing resources to act on shared information. Legislation such as the front-of-pack regulations could accelerate the pace of collaboration between researchers and industry. Overall, establishing a prior relationship with industries could help gain a better understanding of the themes highlighted in this study. Future research could build on this case study to provide more insights and solidify these findings.

Classification codes
Public Health, Public Private, Policy Making, Research Institutions, Use of Knowledge.
Remitting seronegative symmetrical synovitis with pitting edema syndrome: case report of an atypical presentation of a rare syndrome and literature review
Authors: Schulz Nils , Müller-Ladner Ulf , Lange Uwe , Klemm Philipp 
Published: June 2024

Abstract
Background
Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare syndrome. The following case shows an atypical course of the disease with successful treatment. In addition, the accompanied review highlights current findings in the pathogenesis and treatment. Clinicians should be aware of the differential diagnosis of RS3PE syndrome.

Case presentation
A 67-year-old female patient with recurrent, asymmetric, and painful swelling of both hands with pitting edema, predominantly affecting the dorsal right hand, presented at our in-patient clinic. Over the years of her disease, first diagnosed as rheumatoid arthritis and then psoriatic arthritis, prednisolone treatment had the most favorable effects over various disease-modifying antirheumatic drugs.
Subsequent diagnostic evaluation confirmed RS3PE syndrome, a rare inflammatory disorder primarily affecting the elderly population. Manifesting as symmetrical joint inflammation of small joints with pitting edema, RS3PE syndrome typically onsets suddenly and may be accompanied by systemic symptoms like fever, fatigue, and weight loss. Although the precise etiology remains enigmatic, both the innate and the adaptive immune system seem to play a pathogenic role. Treatment is conventionally based on prednisolone, which effectively mitigates symptoms.
Ultimately, RS3PE was diagnosed in the context of psoriatic arthritis without dermatological or nail involvement. Given the unusual presentation marked by female gender, asymmetry, and prolonged and extensive disease with various prior treatments and in the context of psoriatic arthritis, a tumor necrosis factor alpha inhibitor was initiated in addition to low-dose prednisolone resulting in clinical remission for the first time.

Conclusions
In conclusion, the aforementioned atypical manifestation highlights the significance of including RS3PE syndrome as a potential differential diagnosis, particularly in instances where specific diagnostic criteria for rheumatoid arthritis, polymyalgia rheumatica, or psoriatic arthritis are absent. RS3PE responds well to the administration of prednisolone. In refractory cases, a therapeutic trial with tumor necrosis factor alpha inhibitors can be conducted.
Implementation of Universal Pan-Cancer Germline Genetic Testing in an Arab Population: The Jordanian Exploratory Cancer Genetics Study
Authors: Abdel-Razeq Hikmat , Sharaf Baha' , Bani Hani Hira , Abu Hijlih Ramiz , Alkyam Mais , Al-Azzam Khansa , Elemian Shatha , Tbakhi Abdelghani , Al-Atary Areej , Ellsworth Rachel E. , Russell Emily M. , Esplin Edward D. , Horani Malek , Zeidan Zeidan , Alzibdeh Abdulla , Heald Brandie , Nielsen Sarah M. , Nussbaum Robert L. 
Published: June 2024

PURPOSE Germline genetic testing (GGT) significantly affects cancer care. While universal testing has been studied in Western societies, less is known about adoption elsewhere. MATERIALS AND METHODS In this study, 3,319 unselected, pan-cancer Jordanian patients diagnosed between April 2021 and September 2022 received GGT. Pathogenic germline variant (PGV) frequency among patients who were in-criteria (IC) or out-of-criteria (OOC; 2020 National Comprehensive Cancer Network criteria) and changes in clinical management in response to GGT results were evaluated. Statistical analysis was performed using two-tailed Fisher's exact test with significance level P < .05. RESULTS The cohort was predominantly female (69.9%), with a mean age of 53.7 years at testing, and 53.1% were IC. While patients who were IC were more likely than patients who were OOC to have a PGV (15.8% v 9.6%; P < .0001), 149 (34.8%) patients with PGVs were OOC. Clinical management recommendations in response to GGT, including changes to treatment and/or follow-up, were made for 57.3% (161 of 281) of patients with high- or moderate-risk PGVs, including 26.1% (42 of 161) of patients who were OOC. CONCLUSION Universal GGT of patients with newly diagnosed cancer was successfully implemented in Jordan and led to identification of actionable PGVs that would have been missed with guidelines-based testing.
Trastuzumab deruxtecan in patients with breast cancer with brain metastases: The DE-REAL study.
Authors: Botticelli Andrea , Fabi Alessandra , Rossi Alessandro , Caputo Roberta , Pisegna Simona , Pantano Francesco , D'Auria Giuliana , Carbognin Luisa , Fedele Palma , Fabbri Agnese , Vernieri Claudio , Palleschi Michela , Ferretti Gianluigi , Paris Ida , Di Monte Elena , Pavese Francesco , Garrone Ornella , Giannarelli Diana , De Laurentiis Michelino , Scambia Giovanni 
Published: June 2024

1032 Background: Almost 30-50% of patients with human epidermal growth factor (HER2)-positive breast cancer (BC) will develop brain metastases (BMs) in their treatment journey. Despite impressive results achieved for extracranial disease, the central nervous system (CNS) compartment remains highly challenging, and local approaches must now be associated with a prompt and adequate systemic intervention. Trastuzumab deruxtecan (T-Dxd) obtained impressive results both in heavily pretreated patients previously received TDM-1 and in the comparative DESTINY BREAST03 phase III trial. However, patients with active CNS involvement were traditionally excluded from clinical trials and BM-related outcomes are not often included among study endpoints. Moreover, a real-world evidence focused on intracranial activity for patients with BMs treated with T-Dxd is still lacking. In an effort to add further information on the clinical activity and safety of T-Dxd in both naïve and previously treated patients with BMs, we performed a sub-analysis of an Italian large retrospective database, the DE-REAL study. Methods: We reviewed a database of 143 patients with HER2-positive BC from 11 Italian Oncological Units, and obtained a total of 39 patients with CNS involvement treated in various lines setting with T-Dxd between April 2021 and October 2022. Results: Overall intracranial response rate (icRR) was 59% (43.5-74.4), with an imPFS of 14.1 months (9.3-18.9). Intracranial disease control rate (icDCR) was 94.9% (87.9-100.0), duration of response (icDoR) was 11.9 months (10.1-13.7), and clinical benefit rate (icCBr) at 6 and 12 months were 69.2% and 59%, respectively. IntracranialOS was not reached, with an overall rate of 76.6% of patients alive at 12 months. When comparing intracranial responders (CR/PR/SD) to non-responders (PD), median PFS was 15.5 months (13.7-17.3) vs 7.9 months (6.4-9.5), p<0.001. Toxicities were in line with what previously reported in larger registered clinical trials. Conclusions: Our real-world analysis indicated a clinically meaningful intracranial activity of T-Dxd in patients with HER2-positive BC and BMs, and supports its use for both patients with treated/stable and untreated/active lesions.
Multiple alternative splicing of HER2 transcripts and exon skipping with potential consequences on function and antibody-based therapy.
Authors: Albitar Maher , Zhang Hong , Charifa Ahmad , Ip Andrew , Agersborg Sally , Mohtashamian Arash , Graham Deena Mary Atieh , McNamara Donna M. , Waintraub Stanley E. , Gutierrez Martin , Pecora Andrew L , Goy Andre 
Published: June 2024

1033 Background: Multiple studies have demonstrated that ERBB2 (HER2) exon 16 skipping is associated with resistance to antibody-based therapy. However, ERBB2 gene contains 30 exons with potential for alternative splicing involving all exons. With the increasing utilization of antibody-drug conjugates (ADC) in treating patients, it is important to evaluate the various ERBB2 isoforms that are expressed in various tumors. Toward this goal we evaluated the various splicing forms and exons skipping in domains II and III that are involved in dimerization and binding to pertuzumab, and in domain IV, which is a juxtamembrane domain and involved in trastuzumab binding. Methods: RNA was extracted from 3170 FFPE tissue from various types of tumors including breast, ovary, endometrium, lung, colon, stomach, esophagus, and others. RNA was sequenced using a hybrid capture-targeted panel. Data analysis is focused on ERBB2 gene. Results: Of the 3170 tested solid tumor samples, 824 (26%) showed high expression meeting the criteria for gene amplification and “low-HER2”. Of these cases, 199 (24%) samples showed exon skipping in domains II and III ranging from exons 6 to 14. Skipping in domain IV was detected in 236 cases (29%) involving exons from 13 to 29. However, 107 samples of the 824 (13%) showed skipping of exons in both domains II/III and domain IV. The most common exon skipping were in exons 6 to 7 and in exon 16. Most of the cases with exon 16 skipping (1.5% of total) also showed skipping in exons 6 and 7. Conclusions: Alternative splicing and exon skipping in HER2 transcripts is common and involves critical functional domains of the protein. The percentage of skipped transcripts is low. However, since these isoforms have deficiency in critical domains for membrane anchoring and for dimerization, the biological effects might be more significant than that expected from percentage of abnormal protein. Further studies are needed to correlate exon skipping with efficacy and outcome of antibody-based therapy. [Table: see text]