bluuebunny/crossref_metadata_2025 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.
Increasing Access to Undesignated Asthma Medication in Illinois
Authors: Boston Rebecca , Sachs Haley
Published: September 2024

Asthma is common among the pediatric population. Exacerbations of this chronic condition can lead to emergency department visits and hospitalizations, resulting in time away from school. Children spend the majority of their day at school, where they may need access to quick relief medication to treat respiratory distress. Students’ personal asthma medication is not always available in school. School nurses in Illinois collected data and undertook a quality improvement project to increase the number of schools in North Suburban Cook County with undesignated asthma medication. A toolkit was created and shared, helping to remediate barriers associated with obtaining undesignated asthma medication. With access to undesignated asthma medication, school nurses ensure students with asthma receive prompt treatment and coordination of care.
Multilingual media repertoires of young people in the migration society: A plea for a language and culture-aware approach to media education
Authors: Bozdağ Çiğdem , Karakasoğlu Yasemin
Published: September 2024

Digital media provide easy access to media content in multiple languages from local, national, and transnational contexts. This accessibility of diverse content enables young people in the migration society to develop multilingual and transnational media repertoires: they have the option to continuously and strategically navigate between different platforms, between different contexts and multiple languages. In this paper, we discuss how multilingualism and transnationalism can be used as key concepts for understanding the cross-media practices of young people and their participation in the migration society. Based on focus groups with young people living in a culturally diverse and socio-economically disadvantaged neighborhood of Bremen, Germany, we discuss how and why young people choose specific media content in a specific language in their daily media practices. Our discussion of the findings then focuses on the question of how media education in the migration society can take the multilingual and transnational media repertoires into account and benefit from it.
Beyond Burnout: Nurses’ Perspectives on Chronic Suffering During and After the COVID-19 Pandemic
Authors: Powell Melissa A. , Oyesanya Tolu O. , Scott Susan D. , Allen Deborah H. , Walton AnnMarie
Published: September 2024

Nurses around the globe have been impacted psychologically and emotionally during and after the COVID-19 pandemic. The purpose of this study was to describe nurses’ perspectives on the concepts of compassion fatigue, second victimhood, burnout, and moral injury. Eight nurses were interviewed either individually or in groups of two. Data were analyzed using conventional content analysis. The following themes were identified: waves of compassion fatigue, traumatization within second victimhood, never the same after chronic burnout, moral injury: nurses couldn’t do their best, and connections across concepts. Results showed nurses were most familiar with burnout and compassion fatigue, which remain chronic struggles. Second victimhood and moral injury were more distinct experiences related to traumatic or morally distressing events and likely contributed to experiencing burnout or compassion fatigue. Nurses’ suffering heightened during the COVID-19 pandemic and remains prominent three years later. Future research and interventions are urgently needed globally to reduce workplace stressors and promote nurse well-being.
Simmering Storm in the East China Sea: Shifting Dynamics in the Great Power Rivalries of East Asia
Authors: Mason Ra , Park Soul
Published: September 2024

The East China Sea (ECS) is one of the region’s most significant and oft-times under-addressed potential flashpoints. In this article we take a holistic approach and reexamine the recent actions of East Asia’s two most significant powers, China and Japan, in relation to this important body of maritime space, as well as those of the United States (US), as the incumbent regional hegemon. Specifically, we examine the efficacy of each. This highlights a dynamism in Chinese actions, as well as elucidating how the US and Japan have come to adopt policies that are of dubious efficacy as a means of alleviating or nullifying the escalation of unwanted tensions across the ECS. In so doing, we draw upon two key concepts, immobilism and confirmation bias, that help us to understand why the US and Japan are failing to achieve their assumed objectives of regional stability and the maintenance of the status quo. Ultimately, we argue that a combination of immobilism and confirmation bias in American and Japanese foreign policy, in response to the greater dynamism and adaptability of regional great powers such as China, has led to latent changes in the status quo that risk undermining stability across the ECS.
Designing Omni-Channel Retailing to Align Financial Performance with Strategy
Authors: Chopra Sunil
Published: September 2024

Sunil Chopra describes how looking at combinations of product and channel through the lens of return on invested capital (ROIC) allows retailers to design omni-channel portfolios that align their products, service offerings, and pricing. By using each channel to improve invested capital turns or broaden profit margin, these portfolios increase the company’s value.
Service Industrialization, Convergence, and Digital Transformation – II
Authors: Karmarkar Uday
Published: September 2024

Digital technologies are changing the structure of information intensive services through a process of industrialization. The effects are specific to each service category including transactional, functional, content-based, and knowledge-based services. Consumer consumption behavior and physical services are also affected.
THE ROAD TO FAILURE IS PAVED WITH GOOD DISCOUNTS: HOW PREMATURE DISCOUNTS HURT ENTREPRENEURS ON KICKSTARTER
Authors: Schulze Christian , Blaseg Daniel
Published: September 2024

Christian Schulze and Daniel Blaseg show why entrepreneurs seeking customer attention should stay away from price discounts.
The Wonderland model of toxic creativity in leadership: When the “never again” impossible becomes not only possible but actual
Authors: Sternberg Robert J. , Soleimani Dashtaki Arezoo , Power Séamus A.
Published: September 2024

We suggest that toxic creative leaders succeed by creating a fantastic future in a fantasy world that we call “Wonderland.” They make what was thought to be impossible, not only possible but actual. The game is similar to board games that bring one of the players playing them to some wonderful destination at the end of the game. The future they create, however, is an illusion, designed to appeal to people who feel under-appreciated, disempowered, victimized, deprived of material or other resources, or in need of a radical change that will empower them. The creatively toxic leaders are usually underestimated and their overwhelming skills at acquiring and maintaining power are viewed as malleable for other powerful people’s purposes. Ultimately, the toxic creative leaders take over and end up manipulating rather than being manipulated by those who had sought to use the leaders for their own ends. We discuss some of the ways that can be used to combat toxic creative leaders so that what should have been “never again” stays that way—in the realm of impossibility.
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

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

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

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

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

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

BRAF 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

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

Ischemic 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

We 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

Aerobic 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

Consistent 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.
Analysis of ductal carcinoma in situ by self-reported race reveals molecular differences related to outcome
Authors: Strand Siri H. , Houlahan Kathleen E. , Branch Vernal , Lynch Thomas , Rivero-Guitiérrez Belén , Harmon Bryan , Couch Fergus , Gallagher Kristalyn , Kilgore Mark , Wei Shi , DeMichele Angela , King Tari , McAuliffe Priscilla , Curtis Christina , Owzar Kouros , Marks Jeffrey R. , Colditz Graham A. , Hwang E. Shelley , West Robert B.
Published: September 2024

Background

Ductal carcinoma in situ (DCIS) is a non-obligate precursor to invasive breast cancer (IBC). Studies have indicated differences in DCIS outcome based on race or ethnicity, but molecular differences have not been investigated.

Methods

We examined the molecular profile of DCIS by self-reported race (SRR) and outcome groups in Black (n = 99) and White (n = 191) women in a large DCIS case-control cohort study with longitudinal follow up.

Results

Gene expression and pathway analyses suggested that different genes and pathways are involved in diagnosis and ipsilateral breast outcome (DCIS or IBC) after DCIS treatment in White versus Black women. We identified differences in ER and HER2 expression, tumor microenvironment composition, and copy number variations by SRR and outcome groups.

Conclusions

Our results suggest that different molecular mechanisms drive initiation and subsequent ipsilateral breast events in Black versus White women.
Robust mosquito species identification from diverse body and wing images using deep learning
Authors: Nolte Kristopher , Sauer Felix Gregor , Baumbach Jan , Kollmannsberger Philip , Lins Christian , Lühken Renke
Published: September 2024

Mosquito-borne diseases are a major global health threat. Traditional morphological or molecular methods for identifying mosquito species often require specialized expertise or expensive laboratory equipment. The use of convolutional neural networks (CNNs) to identify mosquito species based on images may offer a promising alternative, but their practical implementation often remains limited. This study explores the applicability of CNNs in classifying mosquito species. It compares the efficacy of body and wing depictions across three image collection methods: a smartphone, macro-lens attached to a smartphone and a professional stereomicroscope. The study included 796 specimens of four morphologically similar Aedes species, Aedes aegypti, Ae. albopictus, Ae. koreicus and Ae. japonicus japonicus. The findings of this study indicate that CNN models demonstrate superior performance in wing-based classification 87.6% (95% CI: 84.2–91.0) compared to body-based classification 78.9% (95% CI: 77.7–80.0). Nevertheless, there are notable limitations of CNNs as they perform reliably across multiple devices only when trained specifically on those devices, resulting in an average decline of mean accuracy by 14%, even with extensive image augmentation. Additionally, we also estimate the required training data volume for effective classification, noting a reduced requirement for wing-based classification compared to body-based methods. Our study underscores the viability of both body and wing classification methods for mosquito species identification while emphasizing the need to address practical constraints in developing accessible classification systems.

Graphical abstract
Heterogeneous response of estimated insulin sensitivity indices to metformin in young individuals with type 1 diabetes and different phenotypes
Authors: Ramaldes Luana A. L. , dos Santos Sarah S. , Dualib Patricia M. , de Sa Joao R. , Dib Sérgio A.
Published: September 2024

Aims

This study aimed to investigate whether the response to adding metformin to insulin in young adults with type 1 diabetes (T1D) differs according to weight phenotype and insulin sensitivity index.

Methods

A prospective pilot study was conducted over 26 weeks in which insulin plus metformin (2 g/day) was administered to 35 individuals, ranging from normal weight (NW) to overweight (OW) to obese (OB) T1D individuals, to correlate insulin sensitivity indices and other clinical variables.

Results

At the end of the follow-up period, all groups showed an increase in the eGDR (NW: 7.37 vs 8.16, p = 0.002; OW: 7.28 vs 8.24, p < 0.001; OB: 6.33 vs 7.52 p < 0.001). KITT and SEARCH SCORE improved only in the OB group (2.15 vs 3.14, p < 0.001 and 5.26 vs 5.72, p = 0.007, respectively). Furthermore, HbA1c and BMI were significantly greater in the OB group (− 0.62%, p < 0.001; − 1.12 kg/m2, p = 0.031, respectively). Regression analysis revealed that the serum levels of triglycerides and uric acid were significantly (0.059, p = 0.013; 0.076, p = 0.001) associated with insulin sensitivity indices.

Conclusions

The study showed that eGDR improved independently of basal weight after metformin treatment. However, the KITT and SEARCH indices improved only in the obese group. Triglycerides and uric acid are associated with insulin sensitivity indices. These results highlight the heterogeneity of the mechanisms underlying insulin resistance and its response to metformin in individuals with T1D.
Postharvest food loss reduction and agriculture policy framework in Tanzania: status and way forward
Authors: Rutta Evodius Waziri
Published: September 2024

In 2014, Tanzania became a signatory of the African Union Postharvest Loss Management Strategy (AU-PHLMS) under the Malabo Declaration, a policy framework of the African Union aimed at reducing the continent's postharvest food losses by 50 percent by 2025. Though Tanzania has several agriculture development policies, very little research exists on to what extent the postharvest food loss agenda is reflected and integrated into Tanzania's agriculture policy framework, making it difficult to assess Tanzania's commitment and progress made to realize these ambitious targets in 2025. Using a scoping review method, this study reviews agriculture-food security policies and programs enacted by the government of Tanzania from the 1990s to 2022. Findings reveal that despite high postharvest food losses, policies, and agriculture development programs in favor of increasing food production remain the central focus of the government, while interventions to eliminate food loss and waste have not been prioritized. Results also show that with nearly half of the food produced not reaching consumers, Tanzania's ambitions to be food secure may only be realized if policy measures to increase crop productivity go hand in hand with preventing postharvest food losses. The study calls for full policy integration of postharvest management programs and more investment in farmer-focused interventions to reduce food loss and waste in Tanzania.
Prevalence and correlations of schistosomiasis mansoni and schistosomiasis haematobium among humans and intermediate snail hosts: a systematic review and meta-analysis
Authors: Wang Xin-Yao , Li Qin , Li Yin-Long , Guo Su-Ying , Li Shi-Zhu , Zhou Xiao-Nong , Guo Jia-Gang , Bergquist Robert , Juma Saleh , Zhang Jian-Feng , Yang Kun , Xu Jing
Published: September 2024

Background

The control of schistosomiasis is particularly difficult in sub-Saharan Africa, which currently harbours 95% of this disease. The target population for preventive chemotherapy (PC) is expanded to all age group at risk of infection, thus increasing the demands of praziquantel (PZQ) tablets according to the new released guideline by World Health Organization. Due to the gap between available PZQ for PC and requirements, alternative approaches to assess endemicity of schistosomiasis in a community, are urgently needed for more quick and precise methods. We aimed to find out to which degree the infection status of snails can be used to guide chemotherapy against schistosomiasis.

Methods

We searched literature published from January 1991 to December 2022, that reported on the prevalence rates of Schistosoma mansoni, S. haematobium in the intermediate snails Biomphalaria spp. and Bulinus spp., respectively, and in humans. A random effect model for meta-analyses was used to calculate the pooled prevalence estimate (PPE), with heterogeneity assessed using I-squared statistic (I2), with correlation and regression analysis for the exploration of the relationship between human S. mansoni and S. haematobium infections and that in their specific intermediate hosts.

Results

Forty-seven publications comprising 59 field investigations were included. The pooled PPE of schistosomiasis, schistosomiasis mansoni and schistosomiasis haematobium in humans were 27.5% [95% confidence interval (CI): 24.0–31.1%], 25.6% (95% CI: 19.9–31.3%), and 28.8% (95% CI: 23.4–34.3%), respectively. The snails showed an overall infection rate of 8.6% (95% CI: 7.7–9.4%), with 12.1% (95% CI: 9.9–14.2%) in the Biomphalaria spp. snails and 6.9% (95% CI: 5.7–8.1%) in the Bulinus spp. snails. The correlation coefficient was 0.3 (95% CI: 0.01–0.5%, P < 0.05) indicating that the two variables, i.e. all intermediate host snails on the one hand and the human host on the other, were positively correlated.

Conclusions

The prevalence rate of S. mansoni and S. haematobium is still high in endemic areas. Given the significant, positive correlation between the prevalence of schistosomes in humans and the intermediate snail hosts, more attention should be paid to programme integration of snail surveillance in future.

Graphical Abstract
Is high-intensity conflict escalation inevitable in the future? A two-level game analysis on the causes of US-Iran risky rivalry
Authors: Wang Yaohui , Wang Richard Xuetao , Zhang Jiajia
Published: September 2024

In recent years, there appears to be a growing consensus among policymakers in both the East and the West, that the decades of global peace after the Cold War has now come to an end, and that the world is facing mounting security risks to the future of humanity. Among those challenges, the ongoing U.S.-Iran conflict poses particularly significant risks to regional and global security, and is closely related to many other contemporary international crises involving European states and their allies, particularly the Russo-Ukrainian War, the nuclear proliferation in Europe, and the military disputes between the Iran-backed Houthis and EU forces. But why has the U.S.-Iran relationship deteriorated so dramatically over the past years, and what are the future risks its presents to the international community? While extensive scholarly works have been conducted to examine the ideological, historical, and geopolitical variables that fuel this observed escalating antagonism, no study to date has formal-modelled the complex interactions between Tehran and Washington into a two-level game. Utilizing an infinitely-repeated game theory approach, this research presents a comprehensive analytical framework that explains how interrelated political factors at both the international and the domestic level jointly shape the dynamic of this bilateral relationship. We contend that the domestic rally effect created by risk-oriented diplomacy, incompatible ideological stances and political values, the increasing polarization within U.S. Congress, and the mounting rivalry between Israel and the Iran-led Axis of Resistance convince policymakers from both sides that their utilities can be maximized in a non-cooperative game. Based on our models, it can be forecasted that there is hardly any chance Washington and Tehran will concede to the other’s security demands in the foreseeable future. Thus, the risks of high-intensity conflict escalation due to miscalculation will continue to upsurge in the future.
The effect of technology-based service characteristics on relationship quality in metaverse exercise services: a questionnaire survey of bicycle simulator users in Korea
Authors: Kim Dong-Kyu , Lee So-Eun , Park Sung-Un , Choi Chulhwan
Published: September 2024

Background

As non-face-to-face contact has become a daily routine owing to the development of science and technology and impact of the coronavirus disease (COVID-19) pandemic, online technology-based services (TBSSs) have been expanding. Consequently, in virtual metaverse exercise spaces, the number of participants using TBSS is increasing. This study aimed to examine the effects of TBSS characteristics on the quality of the relationship between service providers and users of metaverse exercise services.

Methods

The participants were metaverse exercise service users in Korea, who were selected through purposive sampling (n = 254, 194 men, 61 women). A questionnaire survey was conducted to measure the participants’ TBSS characteristics (enjoyment, stability, usefulness, ease of use, and reliability) and relationship quality (satisfaction, trust, and commitment). We analyzed the frequency, validity, reliability, and descriptive statistics of the collected data. Moreover, correlation and multivariate multiple regression analyses were conducted.

Results

Enjoyment, stability, usefulness, and reliability of TBSS had positive effects on satisfaction; however, ease of use did not have a significant effect. In addition, enjoyment, usefulness, ease of use, and reliability of TBSS had positive effects on trust; however, stability did not have a significant effect. Furthermore, enjoyment and reliability of TBSS had positive effects on commitment; however, usefulness, ease of use, and stability had no significant effects.

Conclusions

This study provides metaverse exercise service providers with management strategies for attracting and retaining members. The results of this study could help develop effective TBSS and aid metaverse service companies facing a fiercely competitive environment.
The efficiency of detecting seabird behaviour from movement patterns: the effect of sampling frequency on inferring movement metrics in Procellariiformes
Authors: Schoombie Stefan , Wilson Rory P. , Ropert-Coudert Yan , Dilley Ben J. , Ryan Peter G.
Published: September 2024

Background

Recent technological advances have resulted in low-cost GPS loggers that are small enough to be used on a range of seabirds, producing accurate location estimates (± 5 m) at sampling intervals as low as 1 s. However, tradeoffs between battery life and sampling frequency result in studies using GPS loggers on flying seabirds yielding locational data at a wide range of sampling intervals. Metrics derived from these data are known to be scale-sensitive, but quantification of these errors is rarely available. Very frequent sampling, coupled with limited movement, can result in measurement error, overestimating movement, but a much more pervasive problem results from sampling at long intervals, which grossly underestimates path lengths.

Methods

We use fine-scale (1 Hz) GPS data from a range of albatrosses and petrels to study the effect of sampling interval on metrics derived from the data. The GPS paths were sub-sampled at increasing intervals to show the effect on path length (i.e. ground speed), turning angles, total distance travelled, as well as inferred behavioural states.

Results

We show that distances (and per implication ground speeds) are overestimated (4% on average, but up to 20%) at the shortest sampling intervals (1–5 s) and underestimated at longer intervals. The latter bias is greater for more sinuous flights (underestimated by on average 40% when sampling > 1-min intervals) as opposed to straight flight (11%). Although sample sizes were modest, the effect of the bias seemingly varied with species, where species with more sinuous flight modes had larger bias. Sampling intervals also played a large role when inferring behavioural states from path length and turning angles.

Conclusions

Location estimates from low-cost GPS loggers are appropriate to study the large-scale movements of seabirds when using coarse sampling intervals, but actual flight distances are underestimated. When inferring behavioural states from path lengths and turning angles, moderate sampling intervals (10–30 min) may provide more stable models, but the accuracy of the inferred behavioural states will depend on the time period associated with specific behaviours. Sampling rates have to be considered when comparing behaviours derived using varying sampling intervals and the use of bias-informed analyses are encouraged.