bluuebunny/crossref_metadata_2025_split huggingface dataset:
General practitioners and palliative care practices: a better knowledge of specific services is still needed
Authors: Niaré Daouda , Robert Guillaume , Rocquevieille Auriane , De Geyer Loïc , Frin Maguy , Pennec Sophie , Hanslik Thomas , Blanchon Thierry , Rossignol Louise , Morel Vincent 
Published: July 2024

Abstract
Background
France allows deep sedation for pain relief, but not for euthanasia. In anticipation of an increase in home-based palliative care, the role of general practitioners is central to the design of outpatient palliative care services. This study aimed to describe the knowledge, attitudes, and practices of general practitioners in mainland France regarding palliative and end of life care.

Methods
This was a national descriptive cross-sectional study within the Sentinelles network. Self-report questionnaires were distributed to general practitioners between November 2020 and November 2021. A descriptive analysis was carried out.

Results
Out of the 123 participating general practitioners, 84% had received academic training in palliative care (n = 104). While a significant majority (69%) expressed comfort in pain management, only a quarter (25%) declared that they were competent at indicating deep and continuous sedation for pain relief. Awareness of outpatient palliative care facilities close to their place of practice such as hospitalization at home was over 97% (n = 117/120). Awareness of hospital facilities, including identified palliative care beds on hospital wards and palliative care units, was lower (75% (n = 59/79) and 86% (n = 86/100), respectively).

Conclusions
Our results suggest that French general practitioners are reasonably aware of palliative care resources available. However, there is room for improvement, particularly in understanding hospital-based facilities. Furthermore, a quarter of the general practitioners expressed discomfort with deep and continuous sedation for pain relief, highlighting the need for increased training in this specific aspect of palliative and end of life care.
Empagliflozin protects against heart failure with preserved ejection fraction partly by inhibiting the senescence-associated STAT1–STING axis
Authors: Shi Ying , Zhao Lili , Wang Jing , Liu Xiankun , Bai Yiming , Cong Hongliang , Li Ximing 
Published: July 2024

AbstractHeart failure with preserved ejection fraction (HFpEF) is a mortal clinical syndrome without effective therapies. Empagliflozin (EMPA) improves cardiovascular outcomes in HFpEF patients, but the underlying mechanism remains elusive. Here, mice were fed a high-fat diet (HFD) supplemented with L-NAME for 12 weeks and subsequently intraperitoneally injected with EMPA for another 4 weeks. A 4D-DIA proteomic assay was performed to detect protein changes in the failing hearts. We identified 310 differentially expressed proteins (DEPs) (ctrl vs. HFpEF group) and 173 DEPs (HFpEF vs. EMPA group). The regulation of immune system processes was enriched in all groups and the interferon response genes (STAT1, Ifit1, Ifi35 and Ifi47) were upregulated in HFpEF mice but downregulated after EMPA administration. In addition, EMPA treatment suppressed the increase in the levels of aging markers (p16 and p21) in HFpEF hearts. Further bioinformatics analysis verified STAT1 as the hub transcription factor during pathological changes in HFpEF mice. We next treated H9C2 cells with IFN-γ, a primary agonist of STAT1 phosphorylation, to investigate whether EMPA plays a beneficial role by blocking STAT1 activation. Our results showed that IFN-γ treatment caused cardiomyocyte senescence and STAT1 activation, which were inhibited by EMPA administration. Notably, STAT1 inhibition significantly reduced cellular senescence possibly by regulating STING expression. Our findings revealed that EMPA mitigates cardiac inflammation and aging in HFpEF mice by inhibiting STAT1 activation. The STAT1–STING axis may act as a pivotal mechanism in the pathogenesis of HFpEF, especially under inflammatory and aging conditions.
Graphical abstract
The schematic figure depicts a mechanism model of the STAT1–STING axis in HFpEF (this figure was drawn using FigDraw software).
Nur77 improves ovarian function in reproductive aging mice by activating mitophagy and inhibiting apoptosis
Authors: Yao Ying , Wang Bin , Yu Kaihua , Song Ji , Wang Liyan , Zhang Xuehong , Li Yulan 
Published: July 2024

AbstractReproductive aging not only affects the fertility and physical and mental health of women but also accelerates the aging process of other organs. There is an urgent need newfor novel mechanisms, targets, and drugs to break the vicious cycle of mitochondrial dysfunction, redox imbalance, and germ cell apoptosis associated with ovarian aging. Autophagy, recognized as a longevity mechanism, has recently become a focal point in anti-aging research. Although mitophagy is a type of autophagy, its role and regulatory mechanisms in ovarian aging, particularly in age-related ovarian function decline, remain unclear. Nerve growth factor inducible gene B (Nur77) is an early response gene that can be stimulated by oxidative stress, DNA damage, metabolism, and inflammation. Recent evidence recommends that decreased expression of Nur77 is associated with age-related myocardial fibrosis, renal dysfunction, and Parkinson's disease; however, its association with ovarian aging has not been studied yet. We herein identified Nur77 as a regulator of germ cell senescence, apoptosis, and mitophagy and found that overexpression of Nur77 can activate mitophagy, improve oxidative stress, reduce apoptosis, and ultimately enhance ovarian reserve in aged mice ovaries. Furthermore, we discovered an association between Nur77 and the AKT pathway through String and molecular docking analyses. Experimental confirmation revealed that the AKT/mTOR signaling pathway is involved in the regulation of Nur77 in ovarian function. In conclusion, our results suggest Nur77 as a promising target for preventing and treating ovarian function decline related to reproductive aging.
Application of peripheral blood routine parameters in the diagnosis of influenza and Mycoplasma pneumoniae
Authors: Chen Jingrou , Wang Yang , Hong Mengzhi , Wu Jiahao , Zhang Zongjun , Li Runzhao , Ding Tangdan , Xu Hongxu , Zhang Xiaoli , Chen Peisong 
Published: July 2024

Abstract
Objectives
Influenza and Mycoplasma pneumoniae infections often present concurrent and overlapping symptoms in clinical manifestations, making it crucial to accurately differentiate between the two in clinical practice. Therefore, this study aims to explore the potential of using peripheral blood routine parameters to effectively distinguish between influenza and Mycoplasma pneumoniae infections.

Methods
This study selected 209 influenza patients (IV group) and 214 Mycoplasma pneumoniae patients (MP group) from September 2023 to January 2024 at Nansha Division, the First Affiliated Hospital of Sun Yat-sen University. We conducted a routine blood-related index test on all research subjects to develop a diagnostic model. For normally distributed parameters, we used the T-test, and for non-normally distributed parameters, we used the Wilcoxon test.

Results
Based on an area under the curve (AUC) threshold of ≥ 0.7, we selected indices such as Lym# (lymphocyte count), Eos# (eosinophil percentage), Mon% (monocyte percentage), PLT (platelet count), HFC# (high fluorescent cell count), and PLR (platelet to lymphocyte ratio) to construct the model. Based on these indicators, we constructed a diagnostic algorithm named IV@MP using the random forest method.

Conclusions
The diagnostic algorithm demonstrated excellent diagnostic performance and was validated in a new population, with an AUC of 0.845. In addition, we developed a web tool to facilitate the diagnosis of influenza and Mycoplasma pneumoniae infections. The results of this study provide an effective tool for clinical practice, enabling physicians to accurately diagnose and differentiate between influenza and Mycoplasma pneumoniae infection, thereby offering patients more precise treatment plans.
The myelin water imaging transcriptome: myelin water fraction regionally varies with oligodendrocyte-specific gene expression
Authors: Lee Jaimie J. , Scheuren Paulina S. , Liu Hanwen , Loke Ryan W. J. , Laule Cornelia , Loucks Catrina M. , Kramer John L.K. 
Published: July 2024

AbstractIdentifying sensitive and specific measures that can quantify myelin are instrumental in characterizing microstructural changes in neurological conditions. Neuroimaging transcriptomics is emerging as a valuable technique in this regard, offering insights into the molecular basis of promising candidates for myelin quantification, such as myelin water fraction (MWF). We aimed to demonstrate the utility of neuroimaging transcriptomics by validating MWF as a myelin measure. We utilized data from a normative MWF brain atlas, comprised of 50 healthy subjects (mean age = 25 years, range = 17–42 years) scanned at 3 Tesla. Magnetic resonance imaging data included myelin water imaging to extract MWF and T1 anatomical scans for image registration and segmentation. We investigated the inter-regional distributions of gene expression data from the Allen Human Brain Atlas in conjunction with inter-regional MWF distribution patterns. Pearson correlations were used to identify genes with expression profiles mirroring MWF. The Single Cell Type Atlas from the Human Protein Atlas was leveraged to classify genes into gene sets with high cell type specificity, and a control gene set with low cell type specificity. Then, we compared the Pearson correlation coefficients for each gene set to determine if cell type-specific gene expression signatures correlate with MWF. Pearson correlation coefficients between MWF and gene expression for oligodendrocytes and adipocytes were significantly higher than for the control gene set, whereas correlations between MWF and inhibitory/excitatory neurons were significantly lower. Our approach in integrating transcriptomics with neuroimaging measures supports an emerging technique for understanding and validating MRI-derived markers such as MWF.
Exploring the influence of leadership styles on psychological well-being and satisfaction of Pilates classes clients
Authors: Kim Youngmi , Chae Soowon , Sim Insuk , Kim Buom 
Published: July 2024

Abstract
Background
The recent trend of increased indoor activities has significantly influenced daily life, enhancing the popularity of exercises like Pilates. This study explores how Pilates instructors’ leadership styles affect class satisfaction and psychological well-being, addressing the research gap concerning the specific impact of leadership within the context of Pilates classes.

Methods
The study surveyed 388 participants from 39 Pilates studios across South Korea, utilizing a questionnaire to assess leadership styles (transformational, transactional, and servant leadership), class satisfaction, and psychological well-being. Using statistical analyses, leadership styles were assessed for their correlation with class satisfaction and psychological well-being.

Results
Findings revealed that transformational and transactional leadership styles were positively correlated with class satisfaction and psychological well-being. Specifically, transformational leadership significantly enhanced educational satisfaction and personal growth, while transactional leadership most strongly influenced social satisfaction and the sense of purpose in life. Servant leadership was notably effective in improving physical class satisfaction. The study also highlighted the critical role of class satisfaction in promoting psychological well-being among participants.

Conclusion
This research underscores the importance of leadership styles in enhancing the Pilates class experience, suggesting that instructors’ leadership approaches can significantly impact participants’ satisfaction and psychological well-being. The study advocates developing training programs that equip Pilates instructors with the skills to adopt effective leadership styles, fostering a more positive and fulfilling class environment.
A phase 1 clinical trial of DB-020 intratympanic injections administered prior to high-dose cisplatin chemotherapy to reduce ototoxicity.
Authors: Panizza Benedict J. , O'Leary Stephen John , Hart Christopher David , Diwakarla Chandra Sai , Barnett Catherine , Lapuerta Pablo , Lee John , Raines Shane , Quigley Tera , Wolff Heather M , Keilty John , Ladwa Rahul , Porceddu Sandro V , McGrath Margaret , Seetharamu Nagashree , Fua Tsien , Rischin Danny 
Published: July 2024

6100 Background: Hearing loss (HL) as a result of cisplatin (CP) chemotherapy is common. DB-020 is a formulation of sodium thiosulfate for intratympanic (IT) injection being developed to reduce CP ototoxicity. This phase 1 study was designed to evaluate safety and tolerability of repeated IT injections of DB-020 and compare CP-induced hearing changes with DB-020 vs placebo. Methods: Patients scheduled for at least three cycles of CP and cumulative exposure of ≥280 mg/m2 were randomized to blinded, bilateral, IT injection with DB-020 (12% or 25%) in one ear and placebo in the other ear, once every 3 or 4 weeks, ≤3 hours before receiving CP. Patients naïve to CP with moderate or severe HL at baseline were excluded. Ototoxicity was defined by American Speech-Language-Hearing criteria: ≥20 dB threshold increase at any one test frequency, or ≥10 dB threshold increase in any two adjacent frequencies, or loss of response at three consecutive frequencies where responses were previously obtained. Severe ototoxicity was defined as ≥20 dB threshold increase in any two adjacent frequencies. Pre-specified analyses evaluated safety, ototoxicity (with McNemar’s test using the last observation carried forward), and average threshold shifts (from air conduction audiometry, analyzed with a mixed model with repeated measures). This is the final analysis of the data set following the interim analysis presented in 2023. Results: Twenty-two patients were randomized with a mean age of 55 years (86% male; 100% white). Pre-DB-020 treatment, mean cumulative CP dose was 255 mg/m2, and 95% had head and neck cancers; 5% had lung cancer. Twenty patients had both baseline and follow-up audiometry, and 18/20 had baseline audiograms within 5 dB of the median threshold for age-matched controls. Free CP systemic levels (overall mean cumulative CP dose was 254.7 mg/m2) were similar to reference values. Acute or temporary ear pain (18/22 patients, 82%), and tinnitus (11/22 patients, 50%) were common. Ear pain was more common in DB-020 treated ears, and tinnitus in placebo treated ears. No persistent tympanic perforations, no serious adverse events in the ear and labyrinth disorders category, and no deaths were reported. Ototoxicity was significantly more common and severe in placebo treated ears. Conclusions: In this initial clinical trial experience, there was no significant safety signal, and DB-020 IT injections showed a meaningful reduction in CP-induced ototoxicity. Clinical trial information: NCT04262336 . [Table: see text]
Clinical outcomes of NOTCH pathway-activated adenoid cystic carcinoma with and without co-occurrent TP53 mutation.
Authors: Haider Syeda Malaika , Haigh Joseph Edward , Patel Karan , Rack Samuel , Spurgeon Laura , Betts Guy , Harrington Kevin Joseph , Metcalf Robert 
Published: July 2024

6101 Background: Adenoid cystic carcinoma (ACC) is a salivary cancer with a variable disease course. Inoperable locally advanced, recurrent or metastatic ACC (LA-R/M-ACC) are its commonest manifestations. The disease course is typically indolent with patients remaining on surveillance for many years before initiating relatively ineffective systemic therapies. A sub-group of patients experience rapid disease progression and surveillance is not indicated. NOTCH gain-of-function mutation (NOTCHgof) is well characterised, defining a genomic sub-group with shorter survival times. However, there remains a need to identify additional prognostic biomarkers to inform the clinical management of these patients. TP53 mutation (TP53mt) has been proposed as a prognostic biomarker warranting further evaluation. Methods: Clinical-genomic data from 349 ACC patients with LA-R/M-ACC were included. 198 patients provided written informed consent to an ethically approved study, and a further 151 were identified through cBioPortal (MetTropsim, Cell, 2021). ACC tumour samples were evaluated by next-generation sequencing (NGS) for the presence of NOTCHgof and TP53mt. Kaplan-Meier analysis was performed, and p values calculated with the log-rank test, to calculate overall survival (OS) from inoperable LA or R/M disease for patients with either NOTCHgof alone, TP53mt alone or both NOTCHgof/TP53mt combined. Results: ACC tumours harboured NOTCHgof in 14.0% (49/349) and TP53mt in 13.8% (48/349) of cases, respectively. Co-occurrence of TP53mt was identified in 16% of ACC tumours with NOTCHgof (8/49), being in 2.3 % of all LA-R/M-ACC cases. Median OS from inoperable LA-R/M disease was significantly reduced for patients with co-occurrent NOTCHgof/TP53mt (n=8, 10.0 mo; 95% CI 8–12), followed by NOTCHgof/TP53wt (n=41, 15.2 mo; 95% CI 8–22), NOTCHwt/TP53wt (n=262, 58.6 mo; 95% CI 52–65) and NOTCHwt/TP53mt (n=40, 69 mo; 95% CI 13–125) (p=<0.001). TP53 alterations were available for functional classification in 33 patients and were classed as loss-of-function point mutations in 81.8% or truncating frameshift mutations in 18.2%. Truncating TP53mt were mutually exclusive with NOTCHgof. Although the smaller number in this group limits statistical power, patients with truncating TP53mt had shorter OS from recurrence (15.9 mo; 95% CI 0-39) compared with other TP53mt (51.0 mo; 95% CI 0-108; p=0.41). Conclusions: A subgroup of LA-R/M ACC patients with co-occurrent TP53mt and NOTCHgof were identified with significantly shorter OS from recurrence than either NOTCHgof or TP53mt alone. Truncating TP53mt may have greater prognostic value than other TP53mt in NOTCHwt ACC. This study provides further evidence of the potential prognostic utility of some TP53 mutations in ACC and highlights groups of patients with aggressive disease who are potentially suitable for inclusion in therapeutic research programmes.
Pyrotinib in HER2-altered advanced salivary gland carcinomas: Analysis of two cohorts from an exploratory study.
Authors: Dou Shengjin , Zhang Lin , Jiang Wen , Ye Lulu , Li Rongrong , Zhu Guopei 
Published: July 2024

6108 Background: The HER2 altered in a subset of salivary gland cancers (SGCs). Pyrotinib is an oral irreversible pan-HER receptor tyrosine kinase inhibitor targeting HER1, HER2, and HER4. In this study, we assessed the efficacy and safety of pyrotinib in patients with HER2-amplified/overexpressed/mutated advanced SGCs, including recurrent/metastatic(R/M) and locally advanced (LA) patients with high-risk of recurrence. Methods: R/M and high-risk LA SGCs with HER2-alteration were enrolled. Pyrotinib (400 mg) was given orally once daily. In LA cohort, pyrotinib were given as adjuvant therapy after standard surgery and postoperative radiation. Results: Between August 2019 and August 2023, 18 patients were enrolled (10 in R/M cohort and 8 in LA cohort). In R/M cohort, the median age was 58.5 years, and all patients were grade III. The ORR was 90%, including 2 CRs, 7 PRs and 1PD; median DOR was 5.7 months (range: 3.1-13.7) and median PFS was 7.6 months (range: 2.7-16.8). In LA cohort, the median age was 59.0 years, and all patients but one were grade III. All patients but one had T4 disease; 5 patients had N3 and 2 had N2b disease; 5 patients had ENE and 5 patients had positive margin. With a median follow up 21.3 months, only 3 patients experienced recurrence, and one patient died due to non-tumor reasons. The estimated 2-years PFS and 2-years OS were 75% and 100%. The most common adverse event was diarrhea, which occurred in 11/18 (61.1%) patients and 3/18 (16.7%) were grade III. Conclusions: Pyrotinib showed promising antitumor activity in recurrent/metastatic HER2-altered SGCs, and had a potential to prolong survival outcome as adjuvant treatment in LA patients setting, which needs further randomized studies. Clinical trial information: NCT05087706 .
Phase II trial of regorafenib in metastatic medullary thyroid carcinoma (MTC) and radioactive iodine refractory differentiated thyroid carcinoma (RAIR DTC).
Authors: Sehgal Kartik , Shi Ruichao , Pappa Theodora , Min Judy K , Oakley Liam B , ONeill Anne , Dennis Michael J. , Deshpande Hari Anant , Haddad Robert I. , Lorch Jochen H. 
Published: July 2024

6109 Background: Multi-kinase inhibitors show activity in both MTC & RAIR DTC. However, therapeutic options are limited after disease becomes refractory to one or two lines of standard of care therapies. We report here results of an investigator-initiated phase II clinical trial evaluating regorafenib in this population (NCT02657551). Methods: Patients with MTC (disease progression within 6-12 months, mo, prior to study registration) and RAIR DTC (progression within 12 mo) were enrolled regardless of prior lines of therapy. Regorafenib (each cycle 3 weeks ON/1 week OFF) was started at 80 mg daily, with planned escalation after 1 & 2 weeks to 120 mg daily & 160 mg daily, respectively, in absence of significant treatment-related adverse events (TRAEs). The highest tolerated dose was continued from cycle 2 onwards until progression. The primary endpoints were proportion progression-free at 10 months in MTC & overall response rate (ORR) by RECIST v1.1 in RAIR DTC. Simon two-stage design was utilized; MTC: <2 in 8 progression-free in first stage stops for futility, stage 2: enroll 13, >6/21 provides 81% power for proportion >20%; DTC: <3 in 9 in response in first stage stops for futility; stage 2: enroll 11, >7/20 provides 81% power for ORR >25%. Results: 17 patients (8 MTC, 9 DTC) were enrolled between April 2016 and October 2022. Among MTC, median (range) age was 54.7y (48.1, 62.8), 25% female. Among DTC, median age (range) was 62.8y (44.3, 75.8), 55.6% female. In MTC group, the proportion progression-free at 10 months was 12.5% (95% CI 0.3%, 52.7%) & did not meet the criteria to continue into 2nd stage. ORR in MTC group was 12.5% (95% CI 0.3%, 52.7%). In DTC group, ORR was 11.1% (95% CI 0.3%, 48.2%), & did not meet the criteria to continue into 2nd stage. No patients were receiving treatment at cutoff. Patients with MTC and DTC with objective responses (1 each) had received one (vandetanib) & no prior systemic therapy, respectively. The most common reason for discontinuation was disease progression in MTC (4, 50%) & DTC (5, 55.6%). Grade 3-4 TRAEs were observed in 8/17 (47.1%), most frequent were diarrhea, hypophosphatemia, & hypertension (each grade 3: 2, 11.7%). There were no treatment-related deaths. Median progression-free survival (PFS) in MTC & DTC were 5.3 (95% CI 3.6, 20.1) & 11.0 (95% CI 1.2, 24.0) mo, respectively. Median overall survival (OS) in MTC & DTC were 16.1 (95% CI 5.2, NA) and 20.1 (95% CI 1.6, NA) mo, respectively. Conclusions: Regorafenib clinical trial did not reach its primary endpoints in MTC and DTC. Analyses are planned to investigate impact of prior VEGFR inhibitor exposure, biomarkers and resistance mechanisms. Clinical trial information: NCT02657551 . [Table: see text]