bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dalpiciclib in combination with letrozole/anastrozole or fulvestrant in HR-positive and HER2-negative advanced breast cancer: results from a phase Ib study
Authors: Zhang Qingyuan , Zhang Pin , Yan Min , Yan Xi , Wang Xian , Gu Yuanting , Qu Xiujuan , Li Shaorong , Xu Guoying , Zhu Xiaoyu , Xu Binghe 
Published: September 2024

Background: Dalpiciclib is a novel cyclin-dependent kinase 4/6 inhibitor which showed tolerability and preliminary efficacy as monotherapy for pretreated advanced breast cancer (BC). Objectives: To further assess dalpiciclib with endocrine therapy (ET) in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative BC. Design: A multicenter, open-label, phase Ib trial. Methods: Patients with locally recurrent or metastatic BC were enrolled in five cohorts. Patients without prior treatment for advanced disease (cohorts 1–2) were given dalpiciclib (125 or 150 mg) plus letrozole/anastrozole; patients who progressed after ET (cohorts 3–5) were given dalpiciclib (125, 150, or 175 mg) plus fulvestrant. Dalpiciclib was administered orally once daily in 3-weeks-on/1-week off schedule. The primary endpoint was safety. Results: A total of 58 patients received dalpiciclib with letrozole/anastrozole and 46 received dalpiciclib with fulvestrant. No maximum tolerated dose of dalpiciclib was reached with letrozole/anastrozole or fulvestrant. Across all cohorts, 86.7%–93.8% of patients had a grade ⩾3 adverse event, with the most common being neutropenia (grade 3, 40.0% for dalpiciclib 175 mg and 61.8%–87.5% for lower doses; grade 4, 46.7% and 4.2%–20.6%, respectively) and leukopenia (grade 3, 80.0% for 175 mg and 33.3%–54.2% for lower doses; grade 4, 0% for all doses). At tested dose levels, steady-state areas under the concentration curve and peak concentration of dalpiciclib increased with dose when combined with letrozole/anastrozole and fulvestrant. Dalpiciclib at 150 mg was associated with a numerically higher objective response rate in both patients untreated for advanced disease (67.6%; 95% confidence interval (CI) 49.5–82.6) and patients progressing after ET (53.3%; 95% CI 26.6–78.7); as of July 30, 2022, the median progression-free survival with dalpiciclib 150 mg was 24.1 months (95% CI 16.9–46.0) with letrozole/anastrozole and 16.7 months (95% CI 1.9–24.1) with fulvestrant. Conclusion: Dalpiciclib plus letrozole/anastrozole or fulvestrant showed an acceptable safety profile. The recommended phase III dose of dalpiciclib was 150 mg. Trial registration: ClinicalTrials.gov identifier: NCT03481998.
Nontuberculous mycobacterial pulmonary disease presenting as bronchiolitis pattern on CT without cavity or bronchiectasis
Authors: Yoon Sung Hyun , Kim Hyung-Jun , Kim Jihang , Kim Junghoon , Lee Jae Ho 
Published: September 2024

Abstract
Background
This study aimed to investigate the radiological changes in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) having bronchiolitis patterns on computed tomography (CT).

Methods
We retrospectively reviewed the final diagnosis and radiologic changes of patients suspected of having NTM-PD without cavity or bronchiectasis on CT image, between January 1, 2005 and March 31, 2021. NTM-PD was diagnosed based on the American Thoracic Society and Infectious Diseases Society of America criteria. The initial and final CT findings (bronchiectasis, cellular bronchiolitis, cavity formation, nodules, and consolidation) were compared between patients diagnosed with and without NTM-PD.

Results
This study included 96 patients and 515 CT images. The median CT follow-up duration was 1510.5 (interquartile range: 862.2–3005) days. NTM-PD was recognized in 43 patients. The clinical variables were not significantly different between patients with and without NTM-PD, except for underlying chronic airway disease (P < 0.001). Nodule and consolidation were more frequently observed on the initial CT scans of patients with NTM-PD compared with those without (P < 0.05). On the final follow-up CT scan, bronchiectasis (P < 0.001), cavity (P < 0.05), nodule (P < 0.05), and consolidation (P < 0.05) were more frequently observed in patients with NTM-PD. Among the 43 patients with NTM-PD, 30 showed a radiological progression on CT, with bronchiectasis (n = 22) being the most common finding. The incidence of bronchiectasis increased over time.

Conclusion
The bronchiolitis pattern on CT images of patients with NTM-PD showed frequent radiological progression during the follow-up period.
The effect of nebulized N-acetylcysteine on the phlegm of chronic obstructive pulmonary disease: the NEWEST study
Authors: Rhee Chin Kook , Lim Seong Yong , Lee Won-Yeon , Jung Ji Ye , Park Yong Bum , Lee Chang Youl , Hwang Yong Il , Song Jin Woo , Choi Won-Il , Yoo Kwang Ha , Kim Ki Uk , Kim Yu-Il , Kim Tae-Hyung , Park Seong Ju , Shin Kyeong-Cheol , Um Soo-Jung , Yoon Hyoung Kyu , Lee Ho Sung , Kim Deog Kyeom , Leem Ah Young ,   on Behalf of the Korean Pulmonary Rehabilitation Study Group
Published: September 2024

Abstract
Background
Phlegm is prevalent symptom in patients with chronic obstructive pulmonary disease (COPD). Few studies have investigated the effectiveness of N-acetylcysteine (NAC) nebulizer therapy in COPD patients. We evaluated the effect of nebulized NAC on the improvement of phlegm symptom in COPD patients.

Methods
This was a 12-week, prospective, single-arm, open-label, phase IV multi-center trial (NCT05102305, Registration Date: 20-October-2021). We enrolled patients aged ≥ 40 years with post bronchodilator forced expiratory volume in one second/forced vital capacity (FEV1/FVC) < 0.7 and COPD assessment test (CAT) phlegm score ≥ 2; the patients were current or ex-smoker with smoking pack-years ≥ 10. The primary endpoint was to determine the change in CAT phlegm score at 12 weeks compared to the baseline. Patients were assessed at baseline, 4, 8, and 12 weeks of treatment using the CAT score.

Results
In total, 100 COPD patients were enrolled from 10 hospitals. The mean age of the patients was 71.42 ± 8.20 years, with 19.78% being current-smokers and 80.22% being ex-smokers. The mean smoking pack-years was 40.32 ± 35.18. The mean FVC, FEV1, and FEV1/FVC were 3.94 L (75.44%), 2.22 L (58.50%), and 0.53, respectively. The CAT phlegm score at baseline was 3.47 ± 1.06, whereas after 12 weeks of nebulized NAC it significantly decreased to 2.62 ± 1.30 (p < 0.01). More than half (53.5%) of the patients expressed satisfaction with the effects of nebulized NAC therapy. Adverse events occurred in 8 (8.0%) patients. Notably, no serious adverse drug reactions were reported.

Conclusion
In this study, we have established the effectiveness and safety of nebulized NAC over 12 weeks.
“… I carry their stories home …”: experiences of nurses and midwives caring for perinatal adolescent mothers in primary health care settings in Rwanda
Authors: Nkurunziza Aimable , Smye Victoria L. , Jackson Kimberley T. , Wathen C. Nadine , Cechetto David F. , Tryphonopoulos Panagiota , Gishoma Darius , Muhayimana Alice 
Published: September 2024

Abstract
Introduction
Adolescent mothers require trauma- and violence-informed care during the perinatal period due to trauma histories and ongoing violence as a result of pregnancy. Nurses and midwives play a critical role in caring for adolescent mothers in primary healthcare settings in Rwanda in the perinatal period.

Purpose
To explore the experiences of nurses and midwives working with adolescent mothers in selected primary healthcare settings in Rwanda to inform the delivery of trauma- and violence- informed care.

Methods
This study utilized an interpretive description qualitative approach and was conducted in eight primary healthcare settings in Rwanda. Twelve nurses and midwives working in perinatal services and four heads of health centers participated in in-depth individual interviews. Data were analyzed thematically.

Results
The analysis revealed four main themes and 11 (sub-themes): (a) relational practice (being creative and flexible, “lending them our ears”); (b) individual challenges of providing care to adolescent mothers (lack of knowledge to provide care related to gender-based violence, and gendered experience); (c) factors contributing to workarounds (inflexible guidelines, lack of protocol and procedures, lack of nurses’ and midwives’ in service training, and the physical structure of the perinatal environment); and (d) vicarious trauma (living the feelings, “I carry their stories home,” and hypervigilance in parenting).

Conclusion
Nurses and midwives find caring for adolescent mothers challenging due to their unique needs. These needs require them to be creative, adaptable, and attentive listeners to better understand their challenges. These practitioners face difficulties such as insufficient specific knowledge related to, for example, gender-based violence, inflexible guidelines, and a lack of protocols and training. Additionally, in the perinatal environment attention to the needs of practitioners in those settings is often lacking, and many nurses and midwives report experiencing vicarious trauma. Consequently, there is a pressing need for guidelines and protocols specifically tailored for the care of adolescent mothers. Ongoing trauma- and violence- informed care training and professional education should be provided to enhance the ability of nurses and midwives to care for adolescent mothers and prevent re-traumatization and mitigate vicarious trauma effectively.
Building a learning health care community in rural and remote areas: a systematic review
Authors: Asghari Shabnam , Bent Jennifer , Modir Ali , MacDonald Alison , Farrell Alison , Bethune Cheri , Graham Wendy 
Published: September 2024

Abstract
Background
A Learning Health Care Community (LHCC) is a framework to enhance health care through mutual accountability between the health care system and the community. LHCC components include infrastructure for health-related data capture, care improvement targets, a supportive policy environment, and community engagement. The LHCC involves health care providers, researchers, decision-makers, and community members who work to identify health care needs and address them with evidence-based solutions. The objective of this study was to summarize the barriers and enablers to building an LHCC in rural areas.

Methods
A systematic review was conducted by searching electronic databases. Eligibility criteria was determined by the research team. Published literature on LHCCs in rural areas was systematically collected and organized. Screening was completed independently by two authors. Detailed information about rural health care, activities, and barriers and enablers to building an LHCC in rural areas was extracted. Qualitative analysis was used to identify core themes.

Results
Among 8169 identified articles, 25 were eligible. LHCCs aimed to increase collaboration and co-learning between community members and health care providers, integrate community feedback in health care services, and to share information. Main barriers included obtaining adequate funding and participant recruitment. Enablers included meaningful engagement of stakeholders and stakeholder collaboration.

Conclusions
The LHCC is built on a foundation of meaningful use of health data and empowers health care practitioners and community members in informed decision-making. By reducing the gap between knowledge generation and its application to practice, the LHCC has the potential to transform health care delivery in rural areas.
Evaluation of a digital patient education programme in patients with coronary artery disease, a survey-based study
Authors: Sandberg Anna , Ravn-Fischer Annica , Johnsson Annika , Lachonius Maria , Bäck Maria 
Published: September 2024

Abstract
Introduction
Patient education programmes focusing on risk factor modification and lifestyle changes are well established as part of cardiac rehabilitation in patients with coronary artery disease (CAD). As participation rates are low, digital patient education programmes (DPE) are interesting alternatives to increase access. Understanding patients’ perceptions of DPE are important in terms of successful implementation in clinical practice but are not well known. Therefore, the aim of this study was to assess patients’ perceptions of using a DPE in terms of end-user acceptance and usability, perceived significance for lifestyle changes and secondary preventive goal fulfilment in patients with CAD.

Methods
This was a cross-sectional survey-based study. The survey was distributed to all 1625 patients with acute coronary syndrome or chronic CAD with revascularisation, who were registered users of the DPE between 2020 and 2022 as part of cardiac rehabilitation. The survey contained 64 questions about e.g., acceptance and usability, perceived significance for making lifestyle changes and secondary preventive goal fulfilment. Patients who had never logged in to the DPE received questions about their reasons for not logging in. Data were analysed descriptively.

Results
A total of 366 patients (mean age: 69.1 ± 11.3 years, 20% female) completed the survey and among those 207 patients (57%) had used the DPE. Patients reported that the DPE was simple to use (80%) and improved access to healthcare (67–75%). A total of 69% of the patients were generally satisfied with the DPE, > 60% reported that the DPE increased their knowledge about secondary preventive treatment goals and approximately 60% reported having a healthy lifestyle today. On the other hand, 35% of the patients would have preferred a hospital-based education programme. Among the 159 patients (43%) who had never used the DPE, the most reported reason was a perceived need for more information about how to use the DPE (52%).

Conclusions
This study shows an overall high level of patient acceptance and usability of the DPE, which supports its continued development and long-term role in cardiac rehabilitation in patients with CAD. Future studies should assess associations between participation in the DPE and clinical outcomes, such as secondary preventive goal fulfilment and hospitalisation.
The mTOR pathway controls phosphorylation of BRAF at T401
Authors: Christen Daniel , Lauinger Manuel , Brunner Melanie , Dengjel Jörn , Brummer Tilman 
Published: September 2024

AbstractBRAF serves as a gatekeeper of the RAS/RAF/MEK/ERK pathway, which plays a crucial role in homeostasis. Since aberrant signalling of this axis contributes to cancer and other diseases, it is tightly regulated by crosstalk with the PI3K/AKT/mTOR pathway and ERK mediated feedback loops. For example, ERK limits BRAF signalling through phosphorylation of multiple residues. One of these, T401, is widely considered as an ERK substrate following acute pathway activation by growth factors. Here, we demonstrate that prominent T401 phosphorylation (pT401) of endogenous BRAF is already observed in the absence of acute stimulation in various cell lines of murine and human origin. Importantly, the BRAF/RAF1 inhibitor naporafenib, the MEK inhibitor trametinib and the ERK inhibitor ulixertinib failed to reduce pT401 levels in these settings, supporting an alternative ERK-independent pathway to T401 phosphorylation. In contrast, the mTOR inhibitor torin1 and the dual-specific PI3K/mTOR inhibitor dactolisib significantly suppressed pT401 levels in all investigated cell types, in both a time and concentration dependent manner. Conversely, genetic mTOR pathway activation by oncogenic RHEB (Q64L) and mTOR (S2215Y and R2505P) mutants substantially increased pT401, an effect that was reverted by dactolisib and torin1 but not by trametinib. We also show that shRNAmir mediated depletion of the mTORC1 complex subunit Raptor significantly enhanced the suppression of T401 phosphorylation by a low torin1 dose, while knockdown of the mTORC2 complex subunit Rictor was less effective. Using mass spectrometry, we provide further evidence that torin1 suppresses the phosphorylation of T401, S405 and S409 but not of other important regulatory phosphorylation sites such as S446, S729 and S750. In summary, our data identify the mTOR axis and its inhibitors of (pre)clinical relevance as novel modulators of BRAF phosphorylation at T401.
Persistence of two coronaviruses and efficacy of steam vapor disinfection on two types of carpet
Authors: Huang Jinge , Fraser Angela , Jiang Xiuping 
Published: September 2024

Abstract
Background
Coronaviruses, a group of highly transmissible and potentially pathogenic viruses, can be transmitted indirectly to humans via fomites. To date, no study has investigated their persistence on carpet fibers. Establishing persistence is essential before testing the efficacy of a disinfectant.

Methods
The persistence of BCoV and HCoV OC43 on polyethylene terephthalate (PET) and nylon carpet was first determined using infectivity and RT-qPCR assays. Then, the disinfectant efficacy of steam vapor was evaluated against both coronaviruses on nylon carpet.

Results
Immediately after inoculation of carpet coupons, 32.50% of BCoV and 3.87% of HCoV OC43 were recovered from PET carpet, compared to 34.86% of BCoV and 24.37% of HCoV OC43 recovered from nylon carpet. After incubation at room temperature for 1 h, BCoV and HCoV OC43 showed a 3.6 and > 2.8 log10 TCID50 reduction on PET carpet, and a 0.6 and 1.8 log10 TCID50 reduction on nylon carpet. Based on first-order decay kinetics, the whole gRNA of BCoV and HCoV OC43 were stable with k values of 1.19 and 0.67 h− 1 on PET carpet and 0.86 and 0.27 h− 1 on nylon carpet, respectively. A 15-s steam vapor treatment achieved a > 3.0 log10 TCID50 reduction of BCoV and > 3.2 log10 TCID50 reduction of HCoV OC43 on nylon carpet.

Conclusion
BCoV was more resistant to desiccation on both carpet types than HCoV OC43. Both viruses lost infectivity quicker on PET carpet than on nylon carpet. Steam vapor inactivated both coronaviruses on nylon carpet within 15 s.
Electroacupuncture reduces inflammatory damage following cerebral ischemia–reperfusion by enhancing ABCA1-mediated efferocytosis in M2 microglia
Authors: Liao Yu-sha , Zhang Tie-chun , Tang Yu-qi , Yu Pei , Liu Ya-ning , Yuan Jing , Zhao Ling 
Published: September 2024

AbstractIschemic stroke (IS) is a severe cerebrovascular disease with high disability and mortality rates, where the inflammatory response is crucial to its progression and prognosis. Efferocytosis, the prompt removal of dead cells, can reduce excessive inflammation after IS injury. While electroacupuncture (EA) has been shown to decrease inflammation post-ischemia/reperfusion (I/R), its link to efferocytosis is unclear. Our research identified ATP-binding cassette transporter A1 (Abca1) as a key regulator of the engulfment process of efferocytosis after IS by analyzing public datasets and validating findings in a mouse model, revealing its close ties to IS progression. We demonstrated that EA can reduce neuronal cell death and excessive inflammation caused by I/R. Furthermore, EA treatment increased Abca1 expression, prevented microglia activation, promoted M2 microglia polarization, and enhanced their ability to phagocytose injured neurons in I/R mice. This suggests that EA's modulation of efferocytosis could be a potential mechanism for reducing cerebral I/R injury, making regulators of efferocytosis steps a promising therapeutic target for EA benefits.
Felodipine attenuates neuroinflammatory responses and tau hyperphosphorylation through JNK/P38 signaling in tau-overexpressing AD mice
Authors: Hwang Jeong-Woo , Kim Jeongha , Park Jin-Hee , Nam Jinhan , Jang Ji-Yeong , Jo Aran , Lee Hyun-ju , Hoe Hyang-Sook 
Published: September 2024

AbstractWe previously demonstrated that felodipine, an L-type calcium channel blocker, inhibits LPS-mediated neuroinflammatory responses in BV2 microglial cells and wild-type mice. However, the effects of felodipine on tau pathology, a hallmark of Alzheimer's disease (AD), have not been explored yet. Therefore, in the present study, we determined whether felodipine affects neuroinflammation and tau hyperphosphorylation in 3-month-old P301S transgenic mice (PS19), an early phase AD mice model for tauopathy. Felodipine administration decreased tauopathy-mediated microglial activation and NLRP3 expression in PS19 mice but had no effect on tauopathy-associated astrogliosis. In addition, felodipine treatment significantly reduced tau hyperphosphorylation at S202/Thr205 and Thr212/Ser214 residues via inhibiting JNK/P38 signaling in PS19 mice. Collectively, our results suggest that felodipine significantly ameliorates tau hyper-phosphorylation and tauopathy-associated neuroinflammatory responses in AD mice model for tauopathy and could be a novel therapeutic agent for AD.
Running-induced neurogenesis reduces CA1 perineuronal net density without substantial temporal delay
Authors: Terstege Dylan J. , Goonetilleke Duneesha , Barha Cindy K. , Epp Jonathan R. 
Published: September 2024

AbstractAerobic exercise has many effects on brain function, particularly at the hippocampus. Exercise has been shown to increase the rate of adult neurogenesis within the dentate gyrus and decrease the density of perineuronal nets in area CA1. The relationship between the rate of neurogenesis and the density of perineuronal nets in CA1 is robust; however, these studies only ever examined these effects across longer time scales, with running manipulations of 4 weeks or longer. With such long periods of manipulation, the precise temporal nature of the relationship between running-induced neurogenesis and reduced perineuronal net density in CA1 is unknown. Here, we provided male and female mice with home cage access to running wheels for 0, 1, 2, or 4 weeks and quantified hippocampal neurogenesis and CA1 perineuronal net density. In doing so, we observed a 2-week delay period prior to the increase in neurogenesis, which coincided with the same delay prior to decreased CA1 perineuronal net density. These results highlight the closely linked temporal relationship between running-induced neurogenesis and decreased perineuronal net expression in CA1.
Sex- and gender-based medicine in pediatric nutrition
Authors: Tagi Veronica Maria , Fiore Giulia , Tricella Chiara , Eletti Francesca , Visioli Alessandro , Bona Federica , Zuccotti Gianvincenzo , Corsello Antonio , Verduci Elvira 
Published: September 2024

AbstractConsistent evidence increasingly highlights the significance of integrating sex and gender medicine to ensure a precision approach according to individual patient needs. Gender discrepancies emerge across various areas, even from pediatric age. The importance of recognizing these differences in pediatric nutrition is critical for the development of targeted nutritional strategies and interventions, particularly in cases of associated pathologies, including obesity, metabolic-associated fatty liver disease, eating disorders, and inflammatory bowel disease. The review highlights the biological and sociocultural factors that contribute to different nutritional needs and health outcomes in male and female children. By examining current evidence, we underscore the necessity for precision medicine approaches in pediatric care that consider these sex- and gender-based differences. Moreover, differences in dietary requirements and dietary patterns between males and females are evident, underscoring the need for precise nutrition strategies for a more accurate management of children and adolescents. This approach is essential for improving clinical outcomes and promoting equitable healthcare practices. This review aims to provide an overview of nutrition-related medical conditions exhibiting sex- and gender-specific discrepancies, which might lead to distinct outcomes requiring unique management and prevention strategies. Future research and public health initiatives should address these differences in designing effective lifestyle education programs and nutrition interventions targeting both children and adolescents.