bluuebunny/crossref_metadata_2025 huggingface dataset:
Lactoferrin and lysozyme to promote nutritional, clinical and enteric recovery: a protocol for a factorial, blinded, placebo-controlled randomised trial among children with diarrhoea and malnutrition (the Boresha Afya trial)
Authors: Tiwari Ruchi , Tickell Kirkby D , Yoshioka Emily , Otieno Joyce , Shah Adeel , Richardson Barbra A , Keter Lucia , Okello Maureen , Nyabinda Churchil , Trehan Indi , McGrath Christine J , Means Arianna Rubin , Houpt Eric R , Liu Jie , Platts-Mills James A , Njunge James M , Rwigi Doreen , Diakhate Mareme M , Nyaoke Julius , Ochola Eric , John-Stewart Grace , Walson Judd L , Pavlinac Patricia B , Singa Benson O
Published: August 2024

Introduction

Children with moderate or severe wasting are at particularly high risk of recurrent or persistent diarrhoea, nutritional deterioration and death following a diarrhoeal episode. Lactoferrin and lysozyme are nutritional supplements that may reduce the risk of recurrent diarrhoeal episodes and accelerate nutritional recovery by treating or preventing underlying enteric infections and/or improving enteric function.

Methods and analysis

In this factorial, blinded, placebo-controlled randomised trial, we aim to determine the efficacy of lactoferrin and lysozyme supplementation in decreasing diarrhoea incidence and improving nutritional recovery in Kenyan children convalescing from comorbid diarrhoea and wasting. Six hundred children aged 6–24 months with mid-upper arm circumference <12.5 cm who are returning home after an outpatient visit or inpatient hospital stay for diarrhoea will be enrolled. Children will be randomised to 16 weeks of lactoferrin, lysozyme, a combination of the two, or placebo and followed for 24 weeks, with biweekly home visits by community health workers and clinic visits at 4, 10, 16 and 24 weeks. The primary analysis will compare the incidence of moderate-to-severe diarrhoea and time to nutritional recovery between each intervention arm and placebo. The trial will also test whether these interventions reduce enteric pathogen carriage, decrease enteric permeability and/or increase haemoglobin concentration in enrolled children. Finally, we will evaluate the acceptability, adherence and cost-effectiveness of lactoferrin and/or lysozyme.

Ethics and dissemination

The trial has been approved by the institutional review boards of the Kenya Medical Research Institute, the University of Washington, the Kenyan Pharmacy and Poisons Board, and the Kenyan National Commission on Science, Technology and Innovation. The results of this trial will be shared with local and international stakeholders and published in peer-reviewed journals, and the key findings will be presented at relevant conferences.

Trial registration number

NCT05519254, PACTR202108480098476.
Impact of the Korea Early Childhood Home-visiting Intervention (KECHI) on child health and development and maternal health: a randomised controlled trial protocol
Authors: Khang Young-Ho , Kim Yu-Mi , Kim Joo Hyun , Yu Jungok , Oh Rora , June Kyung Ja , Cho Sung-Hyun , Lee Ji Yun , Cho Hong-Jun
Published: August 2024

Introduction

Randomised controlled trials (RCTs) of early childhood home-visiting interventions led by nurses have been conducted mainly in Western countries, whereas such trials have been limited in non-Western cultures, including Asia. In South Korea, a national nurse home visit programme (Korea Early Childhood Home-visiting Intervention (KECHI)) was developed in 2020 and launched throughout the country. We designed a pragmatic RCT to evaluate the effectiveness of KECHI on child health and development and maternal health.

Methods and analysis

Eligible participants will be pregnant women at <37 weeks of gestation with risk factor scores of 2 or over, who are sufficiently fluent in Korean to read and answer the questionnaire written in Korean and live in districts where the KECHI services are available. Eight hundred participants will be recruited from the general community and through the District Public Health Centres. The participants will be randomised 1:1 to KECHI plus usual care or usual care. KECHI encompasses 25–29 home visits, group activities and community service linkage. Participants will complete assessments at baseline (<37 weeks gestation), 6 weeks, 6 months, 12 months, 18 months and 24 months post partum. The six primary outcomes will be (1) home environment (assessed by Infant/Toddler Home Observation for Measurement of the Environment), (2) emergency department visits due to injuries, (3) child development (assessed using Korean Bayley Scales of Infant and Toddler Development-III), (4) breastfeeding duration, (5) maternal self-rated health and (6) community service linkage.

Ethics and dissemination

This trial has received full ethical approval from the Institutional Review Board of the Seoul National University Hospital. Written consent will be obtained from the participants. The results will be reported at conferences, disseminated through peer-reviewed publications and used by the Korean government to expand the KECHI services.

Trial registration number

NCT04749888.
Impact of the COVID-19 pandemic on self-paid vaccination intentions for children: a cross-sectional study in China
Authors: Wang Shuo , Xu Junfang , Zhu Jiming
Published: August 2024

Objectives

While it is widely accepted that COVID-19 has disrupted routine vaccination globally, the long-term impact of COVID-19 on parental vaccination intentions is uncertain. This study aims to estimate whether COVID-19 impacted parental intentions for self-paid vaccines, and provides suggestions for local vaccination policy and intervention strategies accordingly.

Methods

A questionnaire-based cross-sectional survey was conducted among 2212 caregivers in Zhejiang province between 22 March and 30 June 2023. The following information was collected: sociodemographic characteristics, self-paid vaccination related intentions and behaviours, and vaccine hesitancy measured by the Vaccine Hesitancy Scale. Multiple multinomial logistic regression models were used to analyse the factors influencing the change in vaccination intentions.

Results

In total, 19.32% (n=390) of respondents increased their intention to immunise their children with self-paid vaccines after the COVID-19 epidemic, 9.16% (n=185) decreased their intention, and 71.52% (n=1444) of respondents indicated that the COVID-19 epidemic did not affect their intention. The major reason for increased intentions was ‘Vaccines are effective in preventing diseases’ (83.89%) and for decreased intentions was ‘Worried about the side effects of vaccines’ (65.95%). A higher hesitancy degree (OR=2.208, p=0.0001), reduced trust in vaccines after COVID-19 (OR=16.650, p<0.0001), doctors’ recommendation of Expanded Programme on Immunization vaccines (OR=2.180, p=0.0076), and non-perfect satisfaction with vaccine information (all OR>1, all p<0.05) were considered to be drivers of decreased intention.

Conclusion

Although the intentions of self-paid vaccinations were not largely influenced, nearly 30% of caregivers’ vaccination intentions changed after the COVID-19 pandemic and most of them increased their intentions. In addition, vaccination history of self-paid vaccines, vaccine information, vaccine trust and doctors’ recommendations were the active factors for self-paid vaccination. Therefore, education on the knowledge of self-paid vaccines for caregivers should be implemented to increase their vaccination intentions and decrease the threat of infectious diseases to children’s health.
Keep your friends close, and your enemies closer: structural properties of negative relationships on Twitter
Authors: Tacchi Jack , Boldrini Chiara , Passarella Andrea , Conti Marco
Published: August 2024

The Ego Network Model (ENM) is a model for the structural organisation of relationships, rooted in evolutionary anthropology, that is found ubiquitously in social contexts. It takes the perspective of a single user (Ego) and organises their contacts (Alters) into a series of (typically 5) concentric circles of decreasing intimacy and increasing size. Alters are sorted based on their tie strength to the Ego, however, this is difficult to measure directly. Traditionally, the interaction frequency has been used as a proxy but this misses the qualitative aspects of connections, such as signs (i.e. polarity), which have been shown to provide extremely useful information. However, the sign of an online social relationship is usually an implicit piece of information, which needs to be estimated by interaction data from Online Social Networks (OSNs), making sign prediction in OSNs a research challenge in and of itself. This work aims to bring the ENM into the signed networks domain by investigating the interplay of signed connections with the ENM. This paper delivers 2 main contributions. Firstly, a new and data-efficient method of signing relationships between individuals using sentiment analysis and, secondly, we provide an in-depth look at the properties of Signed Ego Networks (SENs), using 9 Twitter datasets of various categories of users. We find that negative connections are generally over-represented in the active part of the Ego Networks, suggesting that Twitter greatly over-emphasises negative relationships with respect to “offline” social networks. Further, users who use social networks for professional reasons have an even greater share of negative connections. Despite this, we also found weak signs that less negative users tend to allocate more cognitive effort to individual relationships and thus have smaller ego networks on average. All in all, even though structurally ENMs are known to be similar in both offline and online social networks, our results indicate that relationships on Twitter tend to nurture more negativity than offline contexts.
A SUPS formulation for simulating unsteady natural/mixed heat convection phenomena in square cavities under intense magnetic forces
Authors: Cengizci Süleyman
Published: August 2024

This paper presents stabilized finite element simulations of unsteady natural and mixed heat convection phenomena occurring in square enclosures. It is assumed that the enclosures are subject to intense uniform magnetic fields applied perpendicular to the vertical walls. It is well known that the classical Galerkin finite element method (GFEM) is prone to yielding nonphysical oscillations when simulating convection-dominated flows. Therefore, in order to handle such flows occurring at high Hartmann ($$0 \le {\rm Ha} \le 100$$

0
≤
Ha
≤
100

) and Rayleigh ($$10^{3} \le {\rm Ra} \le 10^{8}$$

10
3

≤
Ra
≤

10
8

) numbers, the stabilization of the GFEM is accomplished with the streamline-upwind/Petrov–Galerkin and pressure-stabilizing/Petrov–Galerkin formulations. Temporal discretizations are performed with the backward Euler formula. At each time step, the nonlinear systems are linearized with the Newton–Raphson (N–R) method, and the linearized systems are solved directly using the sparse lower–upper decomposition. The incompressible flow solvers are developed in-house, run in parallel within the FEniCS ecosystem, and tested on a comprehensive set of numerical experiments with various thermal boundary conditions. Numerical simulations and comparisons reveal that the proposed formulation performs quite well at high Hartmann and Rayleigh numbers without exhibiting any significant localized or globally spread numerical instabilities. Moreover, it achieves this by using uniform meshes and only linear elements, making the formulation much more computationally efficient. Mesh convergence analyses are also performed to demonstrate the reliability of the numerical results obtained.
East Siberian Sea Composite Tectono-Sedimentary Element, Siberian Arctic
Authors: Drachev Sergey S. , Ershova Victoria B. , Myklebust Reidun , Rekant Pavel V.
Published: August 2024

The East Siberian Sea Composite Tectono-Sedimentary Element (ESS CTSE) occupies most of the central and southern parts of the East Siberian Sea (ESS) and extends onshore into the Chukchi Peninsula. The first multichannel seismic reflection data, acquired in this region in 1989 and 1991 revealed its structural complexity and the presence of a deep sedimentary depocentre in its central part. In the 2010s, the first long-offset seismic data provided a much better understanding of the geology of this remote segment of the Arctic shelf. It includes a large extensional basin that started to form in the Albian (?)-Cenomanian, postdating the Barremian-Aptian Chukotkan orogeny and formation of the New Siberian-Chukchi Fold-and-Thrust Belt (FTB). The latter experienced extensional collapse and developed into the tectonic basement that underlies the CTSE over its entire extent. The ESS CTSE is mainly composed of Upper Cretaceous-Holocene siliciclastic sedimentary strata with a total thickness up to 14 km. This succession has not been drilled deep enough to test its hydrocarbon potential since the beginning of exploration around 2013. However, the strata contain abundant terrestrial organic matter and are considered as potential source rocks sufficient for generating gas accumulations.
Statin therapy improves locomotor muscle microvascular reactivity in patients with heart failure with preserved ejection fraction
Authors: Iacovelli Jarred J. , Alpenglow Jeremy K. , Ratchford Stephen M. , Craig Jesse C. , Simmons Jonah M. , Zhao Jia , Reese Van , Bunsawat Kanokwan , Ma Christy L. , Ryan John J. , Wray D. Walter
Published: August 2024

Peripheral microvascular dysfunction has been documented in patients with heart failure with preserved ejection fraction (HFpEF), which may be related to elevated levels of inflammation and oxidative stress. Unfortunately, few strategies have been identified to effectively ameliorate this disease-related derangement. Thus, using a parallel, double-blind, placebo-controlled design, this study evaluated the efficacy of 30-day atorvastatin administration (10mg QD) on lower limb microvascular reactivity, functional capacity, and biomarkers of inflammation and oxidative stress in patients with HFpEF (Statin: n=8, 76±6 yr; Placebo: n=8, 68±9 yr). The passive limb movement (PLM)-induced hyperemic response and 6-Minute Walk Test (6MWT) distance were evaluated to assess ambulatory muscle microvascular function and functional capacity, respectively. Circulating biomarkers were also measured to assess the contribution of changes in inflammation and redox balance to these outcomes. The total hyperemic response to PLM, assessed as leg blood flow area under-the-curve (LBFAUC), increased following the statin intervention (pre: 60 ± 68 mL; post: 164 ± 90 mL; P < 0.01), whereas these variables were unchanged in the placebo group ( P=0.99). There were no significant differences in 6MWT distance following statin or placebo intervention. Malondialdehyde (MDA), a marker of lipid peroxidation, was significantly reduced following the statin intervention (pre: 0.68 ± 0.10; post: 0.51 ± 0.11; P < 0.01), while other circulating biomarkers were unchanged. Together, these data provide new evidence for the efficacy of low-dose statin administration to improve locomotor muscle microvascular reactivity in patients with HFpEF, which may be due, in part, to a diminution in oxidative stress.
Toxicity Evaluation of a Polyphenolic Extract from Flourensia cernua DC through Artemia Lethality Assay, Hemolytic Activity, and Acute Oral Test
Authors: Aguirre-García Yulma Lizbeth , Castillo-Manzanares Ainara , Palomo-Ligas Lissethe , Ascacio-Valdés Juan Alberto , Campos-Múzquiz Lizeth Guadalupe , Esparza-González Sandra Cecilia , Rodríguez-Herrera Raúl , Nery-Flores Sendar Daniel
Published: August 2024

Flourensia cernua DC, commonly known as hojasen or tarbush, is a medicinal plant used in arid regions due to its therapeutic properties, especially in the treatment of gastrointestinal disorders. This study aimed to assess the toxicity of a polyphenolic extract obtained from F. cernua. This research involved both in vitro (hemolytic and brine shrimp assay) and in vivo tests (acute oral toxicity) to determine the safety profile of this extract. The extract was obtained through a novel ultrasound‐microwave extraction and purified by ion‐exchange chromatography. Analysis of the polyphenolic extract revealed a rich composition of flavonoids and hydroxycinnamic acids, mainly apigenin glycosides. In toxicity tests, the polyphenols did not exhibit toxicity towards Artemia salina at a concentration of 1 mg/ml. Furthermore, incubation at 500 μg/ml for 4 hours showed a slight toxic effect on erythrocytes. In the acute oral toxicity test in mice, doses of 300 mg/kg and 2000 mg/kg did not result in animal mortality, indicating that the LD50 exceeds 2000 mg/kg. However, the higher dose induced signs of toxicity, including lethargy, drowsiness, piloerection, and a significant decrease in weight during the initial two days postadministration of the polyphenolic extract. In addition, histological analysis suggested potential kidney damage at the 2000 mg/kg dose. According to OECD guidelines, while the extract can be classified as category 5 (low acute toxicity) due to the absence of mortality at 2000 mg/kg, the observed signs of toxicity should be considered in the overall risk assessment. These findings highlight the potential of F. cernua in pharmaceutical and nutraceutical applications due to its high polyphenolic content. However, further investigations are necessary to explore the specific effects of the compounds present in the extract. In addition, continuous evaluation of its long‐term toxicity is essential to fully understand the extract’s safety profile and efficacy.
Locoregional Lymph Node Metastasis from Clinically Occult Breast Cancer: Prognostic Significance of Mastectomy
Authors: Nærum Andreas Werner , Holm-Rasmussen Emil Villiam , Vejborg Ilse , Knoop Ann Søegaard , Lænkholm Anne-Vibeke , Kroman Niels , Tvedskov Tove Filtenborg
Published: August 2024

Background and Purpose. Occult breast cancer (OBC) is a rare condition. Due to the small number of patients in previous studies, the benefits of treatment with mastectomy are still discussed. This study aims to determine the clinicopathological characteristics, treatment, and prognosis of OBC presenting with locoregional lymph node metastasis (LNM). Materials and Methods. This study included patients registered in the national Danish Breast Cancer Group (DBCG) database between 2001 and 2015, with locoregional LNM as well as a bilateral negative mammography, ultrasonography, and physical examination of the breasts. Overall survival (OS) and invasive disease‐free survival (IDFS) were compared by treatment groups, ALND + RT (axillary lymph node dissection and radiotherapy) or ALND + MAST ± RT (axillary lymph node dissection, mastectomy with or without radiotherapy). Results. In total, 56 patients were included in the study, of which 37 were treated by ALND + RT, 16 by ALND + MAST ± RT, and the remaining three patients receiving different treatments. The median follow‐up for the 53 OBC patients sorted by treatment group was 12.2 years (interquartile range: 10.1 years; 15.3 years). There was no significant difference in OS or IDFS between the treatment groups, except for a subgroup of 46 (out of 53) patients without verified in situ lesions before treatment, where ALND + RT treatment showed an improved OS (log‐rank p = 0.05). Conclusion. Treating OBC patients with ALND and radiotherapy resulted in a similar outcome as treatment with ALND and mastectomy. This supports omission of mastectomy in favor of radiotherapy of the breast in these patients.
Path Tracking Control of Fixed‐Wing Unmanned Aerial Vehicle Based on Modified Supertwisting Algorithm
Authors: Zhao Chenbo , Guo Luji , Yan Qichen , Chang Zhe , Chen Pengyun
Published: August 2024

This paper focuses on the issues of low path tracking precision and weak disturbance rejection capability in fixed‐wing unmanned aerial vehicle (UAV). This study designs a path tracking controller that combines the radial basis function (RBF) neural network and the supertwisting sliding mode control (STSMC) algorithm. The theoretical stability of the proposed controller is proved by using the Lyapunov theory. The research begins by establishing the motion model of the fixed‐wing UAV. The designed controller, integrating the RBF neural network and STSMC, is implemented to enable the UAV to focus on accurately tracking the desired path. The RBF neural network is utilized to estimate and compensate for external disturbances within the model. Validation of the proposed approach is conducted through semiphysical simulation experiments, demonstrating that the designed control method can effectively enhance anti‐interference ability and suppress chattering.
Current Challenges in the Development of Platelet‐Rich Plasma‐Based Therapies
Authors: Mercader-Ruiz Jon , Beitia Maider , Delgado Diego , Sánchez Pello , Porras Begoña , Gimeno Irene , González Sergio , Benito-Lopez Fernando , Basabe-Desmonts Lourdes , Sánchez Mikel
Published: August 2024

Nowadays, biological therapies are booming and more of these formulations are coming to the market. Platelet‐rich plasma, or PRP, is one of the most widely used biological therapies due to its ease of obtention and autologous character. Most of the techniques to obtain PRP are focusing on new processes and methods of optimization. However, not enough consideration is being given to modify the molecular components of PRP to generate more effective formulations with the aim of improving PRP treatments. Therefore, this review covers different novel PRP‐obtaining methods that attempt to modify the molecular composition of the plasma.
Low Sidelobe Slot Array Antenna Radiating Monopulse Patterns Based on Groove‐Transform‐Ridge Gap Waveguide
Authors: Li Liang , Gao Hongwei , Zhang Binchao , Jin Cheng
Published: August 2024

In this paper, a W‐band unequal power divider is proposed on the basis of groove‐to‐ridge gap waveguide, and it is employed to design a low sidelobe level (SLL) slot array antenna with monopulse radiation patterns. The proposed unequal power divider is capable of realizing large power ratio and small phase difference. In light of this property, three different unequal power dividers with various output power ratios and phase balance are proposed for designing a low SLL array antenna. Furthermore, a compare network with planar Magic‐Tee is designed for realizing the monopulse radiation patterns. Then, a 32 × 32 antenna array consisting of five unconnected layers is designed, fabricated, and measured. The measured results indicate that the relative impedance bandwidth of the antenna is about 5.5%. In addition, the realized gain of the sum pattern at 84 GHz is 35.4 dBi, while the null of the difference pattern is less than 38 dB. Furthermore, the SLL of the antenna array is more than −25 dB on both the E‐ and H‐planes within the operating band.
Epigenetic and Oncogenic Inhibitors Cooperatively Drive Differentiation and Kill KRAS-Mutant Colorectal Cancers
Authors: Loi Patrick , Schade Amy E. , Rodriguez Carrie L. , Krishnan Anjana , Perurena Naiara , Nguyen Van T.M. , Xu Yilin , Watanabe Marina , Davis Rachel A. , Gardner Alycia , Pilla Natalie F. , Mattioli Kaia , Popow Olesja , Gunduz Nuray , Lannagan Tamsin R.M. , Fitzgerald Samantha , Sicinska Ewa T. , Lin Jia-Ren , Tan William , Brais Lauren K. , Haigis Kevin M. , Giannakis Marios , Ng Kimmie , Santagata Sandro , Helin Kristian , Sansom Owen J. , Cichowski Karen
Published: August 2024

Current treatments for KRAS-mutant colorectal cancers are often limited by cellular plasticity and rewiring responses. Here we describe a promising therapeutic strategy that simultaneously targets epigenetic and oncogenic signals. Specifically, we show that inhibitors of histone methyltransferase, EZH2, synergize with various rat sarcoma virus (RAS) pathway inhibitors and promote dramatic tumor regression in vivo. Together these agents cooperatively suppress Wingless and Int-1 (WNT)-driven transcription and drive colorectal cancers into a more differentiated cell state by inducing the Groucho/transducin-like enhancer corepressor, TLE4, along with a network of WNT pathway inhibitors and intestinal differentiation proteins. However, these agents also induce the proapoptotic protein BCL2 modifying factor (BMF), which subsequently kills these more differentiated cells. Accordingly, cell death can be prevented by activating β-catenin, by blocking differentiation, or by ablating BMF expression. Collectively, these studies reveal a new therapeutic approach for treating KRAS-mutant colorectal cancers and illustrate a critical convergence of EZH2 and RAS on oncogenic WNT signals, intestinal differentiation, and apoptosis.

Significance:

Combined EZH2 and RAS pathway inhibitors kill KRAS-mutant colorectal cancer cells and promote durable tumor regression in vivo. These agents function by cooperatively suppressing the WNT pathway, driving differentiation, and epigenetically reprogramming cells to permit the induction of apoptotic signals, which then kill these more differentiated tumor cells.
Supplementary Fig. 7 from Tumor Vessel Normalization via PFKFB3 Inhibition Alleviates Hypoxia and Increases Tumor Necrosis in Rectal Cancer upon Radiotherapy
Authors: Edelmann Marcus , Fan Shuang , De Oliveira Tiago , Goldhardt Tina , Sartorius Dorothée , Midelashvili Teona , Conrads Karly , Paul Niels B. , Beißbarth Tim , Fleischer Johannes R. , Blume Moritz L. , Bohnenberger Hanibal , Josipovic Natasa , Papantonis Argyris , Linnebacher Michael , Dröge Leif H. , Ghadimi Michael , Rieken Stefan , Conradi Lena-Christin
Published: August 2024

Supplementary Fig. 7
Supplementary Fig. 6 from Tumor Vessel Normalization via PFKFB3 Inhibition Alleviates Hypoxia and Increases Tumor Necrosis in Rectal Cancer upon Radiotherapy
Authors: Edelmann Marcus , Fan Shuang , De Oliveira Tiago , Goldhardt Tina , Sartorius Dorothée , Midelashvili Teona , Conrads Karly , Paul Niels B. , Beißbarth Tim , Fleischer Johannes R. , Blume Moritz L. , Bohnenberger Hanibal , Josipovic Natasa , Papantonis Argyris , Linnebacher Michael , Dröge Leif H. , Ghadimi Michael , Rieken Stefan , Conradi Lena-Christin
Published: August 2024

Supplementary Fig. 6
Table S3 from p53R172H and p53R245W Hotspot Mutations Drive Distinct Transcriptomes in Mouse Mammary Tumors Through a Convergent Transcriptional Mediator
Authors: McDaniel Joy M. , Morrissey Rhiannon L. , Dibra Denada , Patel Lalit R. , Xiong Shunbin , Zhang Yun , Chau Gilda P. , Su Xiaoping , Qi Yuan , El-Naggar Adel K. , Lozano Guillermina
Published: August 2024

Summary of Hallmarks enriched in MaPR245W/- mammary tumors compared to MaP-/- mammary tumors.
Supplementary Fig. 3 from Tumor Vessel Normalization via PFKFB3 Inhibition Alleviates Hypoxia and Increases Tumor Necrosis in Rectal Cancer upon Radiotherapy
Authors: Edelmann Marcus , Fan Shuang , De Oliveira Tiago , Goldhardt Tina , Sartorius Dorothée , Midelashvili Teona , Conrads Karly , Paul Niels B. , Beißbarth Tim , Fleischer Johannes R. , Blume Moritz L. , Bohnenberger Hanibal , Josipovic Natasa , Papantonis Argyris , Linnebacher Michael , Dröge Leif H. , Ghadimi Michael , Rieken Stefan , Conradi Lena-Christin
Published: August 2024

Supplementary Fig. 3
Figure 2 from p53R172H and p53R245W Hotspot Mutations Drive Distinct Transcriptomes in Mouse Mammary Tumors Through a Convergent Transcriptional Mediator
Authors: McDaniel Joy M. , Morrissey Rhiannon L. , Dibra Denada , Patel Lalit R. , Xiong Shunbin , Zhang Yun , Chau Gilda P. , Su Xiaoping , Qi Yuan , El-Naggar Adel K. , Lozano Guillermina
Published: August 2024

Metastasis in MaP mice. A, Metastasis incidence in MaP mice. B, Histology and immunofluorescence staining of TdTomato in a primary breast tumor and matched lung metastasis from a MaPR172H/− mouse, YZ2. C, Histology and immunofluorescence staining of TdTomato in a primary breast tumor and matched lung metastasis from a MaPR245W/− mouse, JM1233. H&E, hematoxylin and eosin; IF, immunofluorescence.
Effect of Long-Snake Moxibustion on Gut Microbiota of Patients with Ankylosing Spondylitis
Authors: Yu Xijing , Jin Mengyu , Huang Hui , Qiu Fenfen , Geng Lele , Guo Rong , Zhu Xiaoyan , Hu Xiuwu
Published: August 2024

Objective: The objectively was to study the effect of long-snake moxibustion intervention on gut microbiota of patients with ankylosing spondylitis (AS) by 16S rDNA sequencing technology. Methods: Thirty AS patients and 30 healthy volunteers were recruited and treated with long-snake moxibustion once a week for 12 weeks. AS patients were divided into pretreatment and posttreatment groups. VAS, BASDAI, and BASFI scores of AS patients before and after treatment were collected. 16S rDNA high-throughput sequencing technology was used to analyze the characteristics and differences of gut microbiota in AS patients before and after treatment and in healthy volunteers. Results: VAS, BASDAI, and BASFI scores of AS patients after long-snake moxibustion treatment were lower than those of pretreatment group (p < 0.05). The results of gut microbiota alpha diversity showed that Ace and Chao1 index of the posttreatment group were higher than those of the health group (p < 0.05), but there was no statistical significance in Ace and Chao1 index between the pretreatment group and the posttreatment group (p > 0.05). Beta diversity analysis showed that mild classification aggregation occurred between the health group and the pretreatment group but did not reach a significant level, and there was no significant difference between the pretreatment group and the posttreatment group. The results of species abundance showed that, at the phylum level, compared with the health group, the relative abundance of Firmicutes and Proteobacteria decreased in the pretreatment group, while the relative abundance of Bacteroidetes and Actinobacteria increased. Compared with the pretreatment group, the relative abundance of Firmicutes increased and the relative abundance of Actinobacteria decreased in the posttreatment group, but there were no statistically significant differences in the above changes (p > 0.05). At the genus level, compared with the health group, the relative abundances of Subdoligranulum in the pretreatment group were increased (p < 0.05), while the relative abundances of Bifidobacterium and Streptococcus were decreased (p < 0.05). Compared with the pretreatment group, the relative abundance of Romboutsia in the posttreatment group was increased (p < 0.05). Conclusion: Long-snake moxibustion can obviously improve the clinical symptoms of AS patients. The possible mechanism of action is related to regulating the abundance of gut microbiota, increasing beneficial bacteria, and restoring the homeostasis of gut microorganisms.
The Impact of Statistical Thinking on Operational Performance and Managerial Decision-Making in Private Dental Service Organizations in the Southern Region of Saudi Arabia: An Empirical Investigation
Authors: Alshehri Abdulrahman , Lichy Jessica Victoria
Published: August 2024

Introduction: The literature has extensively addressed statistical thinking (STk) as a set of principles and concepts implemented within organizations to adopt a statistical perspective. This approach is frequently linked to the application of continuous improvement programs (CIPs), such as Six Sigma and Lean Six Sigma. This study examines whether implementing STk principles positively correlates with operational performance (OP) within private dental services organizations operating in the CIP framework. Methods: This empirical study investigated a sample of 34 organizations from the private sector. Structural equation modeling, specifically partial least squares, was used for data analysis. Results: Statistical significance for the outer model loadings was demonstrated. Mediating variables positively affect the constructs’ explanatory power, even when statistical techniques (STes) do not show direct associations. The model exhibited a significant degree of explanatory power. Further, it effectively captured the association among STes, OP, and decision-making (DM). In the multigroup analysis, only STes did not exhibit a statistically significant difference compared with the other components. Conclusion: The results provide evidence that CIPs are beneficial for applying STk principles and have a favorable effect on both OP and DM. This highlights the significance of CIPs, such as Six Sigma, Lean Six Sigma, and Total Quality Management, in a managerial context. This highlights the need to establish mechanisms that facilitate the dissemination and application of STk principles and STes to improve OP and DM in the dental services sector.
Acute Sympathetic Blockade Improves Insulin‐Mediated Microvascular Blood Flow in the Forearm of Adult Human Subjects With Obesity
Authors: Smith Emily C. , Patel Jay N. , Wahba Amr , Cluckey Andrew , Celedonio Jorge , Park JinWoo , Hannah LaToya , Lonce Suzanna , Shibao Cyndya A. , Paranjape Sachin Y. , Diedrich Andre , McGuinness Owen , Wasserman David H. , Biaggioni Italo , Gamboa Alfredo
Published: August 2024

Background

Obesity is associated with resistance to the metabolic (glucose uptake) and vascular (nitric‐oxide mediated dilation and microvascular recruitment) actions of insulin. These vascular effects contribute to insulin sensitivity by increasing tissue delivery of glucose. Studies by us and others suggest that sympathetic activation contributes to insulin resistance to glucose uptake. Here we tested the hypothesis that sympathetic activation contributes to impaired insulin‐mediated vasodilation in adult subjects with obesity.

Methods and Results

In a randomized crossover study, we used a euglycemic hyperinsulinemic clamp in 12 subjects with obesity to induce forearm arterial vasodilation (forearm blood flow) and microvascular recruitment (contrast‐enhanced ultrasonography) during an intrabrachial infusion of saline (control) or phentolamine (sympathetic blockade). Insulin increased forearm blood flow on both study days (from 2.21±1.22 to 4.89±4.21 mL/100 mL per min,
P
=0.003 and from 2.42±0.89 to 7.19±3.35 mL/100 mL per min,
P
=0.002 for the intact and blocked day, respectively). Sympathetic blockade with phentolamine resulted in a significantly greater increase in microvascular flow velocity (∆microvascular flow velocity: 0.23±0.65 versus 2.51±3.01 arbitrary intensity units (AIU/s) for saline and phentolamine respectively,
P
=0.005), microvascular blood volume (∆microvascular blood volume: 1.69±2.45 versus 3.76±2.93 AIU, respectively,
P
=0.05), and microvascular blood flow (∆microvascular blood flow: 0.28±0.653 versus 2.51±3.01 AIU
2
/s, respectively,
P
=0.0161). To evaluate if this effect was not due to nonspecific vasodilation, we replicated the study in 6 subjects with obesity comparing intrabrachial infusion of phentolamine to sodium nitroprusside. At doses that produced similar increases in forearm blood flow, insulin‐induced changes in microvascular flow velocity were greater during phentolamine than sodium nitroprusside (%microvascular flow velocity=58% versus 29%, respectively,
P
=0.031).

Conclusions

We conclude that sympathetic activation impairs insulin‐mediated microvascular recruitment in adult subjects with obesity.
Safety of Antiplatelet Therapy in Noncardioembolic Ischemic Stroke With Thrombocytopenia: The CASE II Study
Authors: Xu Dongjuan , Zhou Huan , Zhang Tingxia , Gong Weiwei , Zhong Jieming , Yu Han , Chen Fujian , Zhong Wansi , Yan Shenqiang , Lou Min ,   the CASE II investigators
Published: August 2024

Background

There is scant evidence regarding the safety of antiplatelet therapy in acute ischemic stroke (AIS) patients with thrombocytopenia. Our study aims to address this concern by examining AIS patients with thrombocytopenia from a large database in real‐world settings.

Methods and Results

We included patients with AIS with a platelet count <100×10
9
/L who had complete records of antiplatelet drug use. Those requiring anticoagulation or having contraindications to antiplatelet therapy were excluded. Short‐term safety outcomes were in‐hospital bleeding events, while the long‐term safety outcome was 1‐year all‐cause mortality. A good clinical outcome was defined as functional independence, indicated by a modified Rankin Scale score of 0 to 2 at discharge. Propensity score matched analyses were used. We screened 169 423 patients with AIS from 90 stroke centers in the CASE II register, ultimately enrolling 2808 noncardioembolic patients with thrombocytopenia. In the propensity score matched analyses, no significant difference was observed between the antiplatelet and nonantiplatelet groups in terms of intracranial hemorrhage (odds ratio=0.855 [95% CI, 0.284–5.478];
P
=0.160) or gastrointestinal bleeding (odds ratio=2.034 [95% CI, 0.755–5.478];
P
=0.160). Antiplatelet therapy was associated with improved functional outcomes at discharge (odds ratio=1.405 [95% CI, 1.028–1.920];
P
=0.033), and showed a trend towards reducing 1‐year mortality (odds ratio=0.395 [95% CI, 0.152–1.031];
P
=0.058).

Conclusions

The use of antiplatelet therapy lessened as platelet count decreased in patients with AIS with thrombocytopenia. However, our findings suggest that antiplatelet medications remain safe and effective for this population.
Impact of Chronic Kidney Disease on the Processes of Care and Long‐Term Mortality of Non–ST‐Segment–Elevation Myocardial Infarction: A Nationwide Cohort Study and Long‐Term Follow‐Up
Authors: Weight Nicholas , Moledina Saadiq , Ullah Mohsin , Wijeysundera Harindra C. , Davies Simon , Chew Nicholas W. S. , Lawson Claire , Khan Safi U. , Gale Chris P. , Rashid Muhammad , Mamas Mamas A.
Published: August 2024

Background

A growing population of patients with chronic kidney disease (CKD) presents with non–ST‐segment–elevation myocardial infarction, although little is known about their longer‐term mortality.

Methods and Results

Using the MINAP (Myocardial Ischaemia National Audit Project) registry, linked to Office for National Statistics mortality data, we analyzed 363 559 UK patients with non–ST‐segment–elevation myocardial infarction, with or without CKD. Cox regression models were fitted, adjusting for baseline demographics. Compared with patients without CKD, patients with CKD were less frequently prescribed P2Y12 inhibitors (89% versus 86%,
P
<0.001) less likely to undergo invasive angiography (67% versus 41%,
P
<0.001) or percutaneous coronary intervention (41% versus 25%,
P
<0.001), and were less often referred to cardiac rehabilitation (80% versus 66%,
P
<0.001). Following non–ST‐segment–elevation myocardial infarction, patients with CKD had higher risk of 30‐day (adjusted hazard ratio [HR], 1.24 [95% CI, 1.20–1.29], 1‐year 1.47 [95% CI, 1.44–1.51]) and 5‐year mortality 1.55 (95% CI, 1.53–1.58) than patients without CKD (all
P
<0.001). Risk of mortality over the entire study period was highest in CKD Stage 5 (HR, 2.98 [95% CI, 2.87–3.10]), even after excluding mortality ≤30 days (HR, 3.03 [95% CI, 2.90–3.17]) (
P
<0.001). There was no significant difference in proportion of deaths attributable to cardiovascular disease at 30 days (CKD; 76% versus no CKD; 76%), or 1 ‐year (CKD; 62% versus no CKD; 62%).

Conclusions

Patients with CKD were significantly less likely to receive invasive investigation or undergo percutaneous coronary intervention and had significantly higher risk of short‐ and longer‐term mortality. Risk of mortality increased with reducing CKD stage. Cardiovascular disease was the main cause of mortality in patients with CKD, but at comparable rates to the general population with non–ST‐segment–elevation myocardial infarction.
Physician‐Reported Facilitators and Barriers for Side Effect Management of Heart Failure Medications
Authors: Mangal Sabrina , Hyder Maryam , Mancini John , Zarzuela Kate , McDonald William , Safford Monika , Lachs Mark , Goyal Parag
Published: August 2024

Background

Physician underprescribing and patient nonadherence are major barriers to the benefits of guideline‐directed medical therapy. An important contributor to both underprescribing and patient nonadherence is concern about medication‐related side effects. Yet, there are few to no data on approaches used by physicians to: (1) elicit medication‐related side effects, (2) attribute these side effects to specific medications, and (3) take appropriate action.

Methods and Results

The authors conducted semistructured interviews with physicians to identify facilitators and barriers to each critical step of heart failure medication management: elicitation of side effects, attribution of side effects to a medication, and action in response to attributed side effects. Interviews were transcribed and coded using directed content analysis. For elicitation of potential side effects, limited patient communication and family discordance in reporting were key barriers, whereas guiding questions, measurement, and open channels of communication were key facilitators. For attribution of side effects, confounding from other medications, limited time for clinical encounters, and nonspecific symptoms were key barriers, whereas time‐limited medication discontinuation trials and medication rechallenges were key facilitators. For taking action, challenges with weighing risks and benefits and physician fear about causing harm or interfering with other clinicians were barriers, whereas patient‐physician communication and the results of a medication discontinuation trials and medication rechallenge were facilitators.

Conclusions

This study generated key facilitators and barriers to 3 key aspects of heart failure medication management related to side effects that should drive future work to improve heart failure medication management.
Treatment Adherence Rates and Long‐Term Mortality in a Quaternary Multidisciplinary Heart Team: An Observational Cohort
Authors: McNamara David A. , Akram Mahrukh F. , Burgess Andrea L. , Stickland DeeAnn , VanOosterhout Stacie M. , Parker Jessica L. , Madder Ryan D. , Wohns David , Willekes Charles L. , McNamara Richard F.
Published: August 2024

Background

A multidisciplinary heart team (HT) approach to patients with complex coronary artery disease has a class IB recommendation, yet there are limited data on adherence to HT treatment recommendations and long‐term clinical follow‐up. The objective of this study was to assess adherence rates to HT recommendations and assess long‐term mortality rates among patients with complex CAD.

Methods and Results

Six hundred eighty‐four sequential HT cases for complex coronary artery disease from January 2015 to May 2017 were reviewed. After excluding cases with significant comorbid valve disease, baseline characteristics were compared based on HT treatment recommendations: optimal medical therapy, percutaneous coronary intervention, and coronary artery bypass grafting. Adherence rates were manually extracted, and 5‐year mortality rates were obtained from the Michigan Death Registry. Seventy‐two percent of 405 included patients were men (mean age 66±11 years), with high rates of medical comorbidities. Estimated surgical risk scores were lowest in the coronary artery bypass grafting group. Optimal medical therapy was recommended in 138 patients (34%), percutaneous coronary intervention in 95 (23%), and coronary artery bypass grafting in 172 (42%). Adherence to HT recommendations across groups was high (96%) and did not differ between treatment groups. Over 5 years of follow‐up, there were 119 deaths, resulting in a cumulative mortality rate of 29%.

Conclusions

In the largest HT cohort in the United States to date, high rates of adherence to HT recommendations were observed among high‐risk patients with coronary artery disease. High rates of adherence to HT recommendations were observed irrespective of treatment group recommendation, suggesting that HT recommendations were individualized and acceptable to both patients and physicians alike.
Cardiovascular Risks in People With Narcolepsy: Expert Panel Consensus Recommendations
Authors: Kwon Younghoon , Gami Apoor S. , Javaheri Shahrokh , Pressman Gregg S. , Scammell Thomas E. , Surkin Lee A. , Zee Phyllis C.
Published: August 2024

Background

Observational and retrospective studies suggest that people with narcolepsy may have an increased prevalence of cardiovascular and cardiometabolic comorbidities and may be at greater risk for future cardiovascular events. An expert consensus panel was formed to establish agreement on the risk of hypertension and cardiovascular/cardiometabolic disease in people with narcolepsy and to develop strategies to mitigate these risks.

Methods and Results

Experts in sleep medicine and cardiology were selected to participate in the panel. After reviewing the relevant literature, the experts identified key elements, drafted recommendation statements, and developed discussion points to provide supporting evidence for the recommendations. The draft and final recommendations were rated on a scale from 0 (not at all agree) to 4 (very much agree). All experts had an agreement rating of 4.0 for all 14 revised recommendation statements for patients with narcolepsy. These statements comprised 3 themes: (1) recognize the risk of hypertension and cardiovascular/cardiometabolic disease, (2) reduce the risk of hypertension and cardiovascular/cardiometabolic disease, and (3) reduce sodium intake to lower the risk of hypertension and cardiovascular disease.

Conclusions

These consensus recommendations are intended to increase awareness of potential cardiovascular/cardiometabolic risks in patients with narcolepsy for all clinicians. Early monitoring for, and prevention of, cardiovascular risks in this population are of great importance, especially as narcolepsy usually develops in adolescents and young adults, who will be exposed to adverse effects of the disease for decades. Prospective systematic studies are needed to determine association and causation of narcolepsy with cardiovascular/cardiometabolic disorders.
LifeCourse Socioeconomic Position and Ideal Cardiovascular Health in Hispanic/Latino Adults of the Hispanic Community Health Study/Study of Latinos
Authors: Filigrana Paola , Moon Jee‐Young , Gallo Linda C. , Fernández‐Rhodes Lindsay , Perreira Krista M. , Daviglus Martha L. , Thyagarajan Bharat , Garcia‐Bedoya Olga L. , Cai Jianwen , Xue Xiaonan , Kaplan Robert C. , Suglia Shakira , Isasi Carmen R.
Published: August 2024

Background

The Hispanic/Latino population experiences socioeconomic disadvantages across the lifespan. Yet, little is known about the role of these disadvantages in cardiovascular health (CVH). We assessed the association of lifecourse socioeconomic position (SEP) with ideal CVH and change in Hispanic/Latino adults.

Methods and Results

We used longitudinal data from the HCHS/SOL (Hispanic Community Health Study/Study of Latinos). Childhood SEP was determined using parental educational attainment. Adult SEP was determined through an index combining participants' education, occupation, income, and assets at baseline. We classified participants into 4 socioeconomic mobility categories (eg, stable low or high SEP, upward or downward mobility). Using the 4 health factors of the American Heart Association “Life's Essential 8,” we built a score of ideal CVH at baseline and the 6‐year follow‐up. Linear mixed‐effects models using inverse probability weighting were fitted to assess the main associations. Higher childhood SEP was associated with higher ideal CVH at baseline (β for high school versus high school versus <high school, 3.76 [95% CI, 1.99–5.52]). Middle (β for middle versus low SEP, 3.57 [95% CI, 1.65–5.49]) and high adult SEP (β for high versus low SEP, 5.05 [95% CI, 2.55–7.55]) were also associated with higher ideal CVH. Socioeconomic mobility was also associated with higher ideal CVH. No life‐course SEP exposure was associated with the change in ideal CVH over a 6‐year period.

Conclusions

Although high childhood and adult SEP and socioeconomic mobility were associated with higher levels of ideal CVH, they were not associated with change in ideal‐CVH.