bluuebunny/crossref_metadata_2025 huggingface dataset:
The interplay between IGF-1R signaling and Hippo-YAP in breast cancer stem cells
Authors: Chan Yu-Tzu , Lin Ruey-Jen , Wang Ya-Hui , Hung Tsai-Hsien , Huang Yenlin , Yu John , Yu Jyh-Cherng , Yu Alice L.
Published: April 2023

Background

Both IGF-1R/PI3K/AKT/mTOR and Hippo pathways are crucial for breast cancer stem cells (BCSCs). However, their interplay remains unclear.

Methods

Four triple negative breast cancer cell lines derived from CSC of two patient-derived xenografts (PDXs), AS-B145, AS-B145-1R, AS-B244, and AS-B244-1R, were used to elucidate the role of YAP in BCSCs. YAP silenced BCSCs were analyzed by cell proliferation, aldehyde dehydrogenase (ALDH) activity, mammosphere formation, and tumorigenesis. The effects of modulating IGF-1R and IGF-1 on YAP expression and localization were evaluated. The clinical correlation of YAP and IGF-1R signaling with the overall survival (OS) of 7830 breast cancer patients was analyzed by KM plotter.

Results

Knockdown of YAP abates the viability and stemness of BCSCs in vitro and tumorigenicity in vivo. Depletion of IGF-1R by shRNA or specific inhibitor decreases YAP expression. In contrast, IGF-1 addition upregulates YAP and enhances its nuclear localization. YAP overexpression increased the mRNA level of IGF-1, but not IGF-1R. Data mining of clinical breast cancer specimens revealed that basal-like breast cancer patients with higher level of IGF-1 and YAP exhibit significantly shorter OS.

Conclusions

YAP contributes to stemness features of breast cancer in vitro and in vivo. The expression and localization of YAP was regulated by IGF-1R and YAP expression in turns upregulates IGF-1, but not IGF-1R. Clinically, higher level of YAP and IGF-1 significantly correlated with shorter OS in basal-like breast cancer. Taken together, these findings suggest the clinical relevance of interplay between YAP and IGF-1/IGF-1R pathway in sustaining the properties of BCSCs.
Decidual derived exosomal miR-99a-5p targets Ppp2r5a to inhibit trophoblast invasion in response to CeO2NPs exposure
Authors: Zhong Hangtian , Geng Yanqing , Gao Rufei , Chen Jun , Chen Zhuxiu , Mu Xinyi , Zhang Yan , Chen Xuemei , He Junlin
Published: April 2023

Background

The biological effects of cerium dioxide nanoparticles (CeO2NPs), a novel material in the biomedical field, have attracted widespread attention. Our previous study confirmed that exposure to CeO2NPs during pregnancy led to abnormal trophoblast invasion during early placental development, thereby impairing placental development. The potential mechanisms may be related to low-quality decidualization triggered by CeO2NPs exposure, such as an imbalance in trophoblast invasion regulators secreted by decidual cells. However, the intermediate link mediating the “dialogue” between decidual cells and trophoblasts during this process remains unclear. As an important connection between cells, exosomes participate in the “dialogue” between endometrial cells and trophoblasts. Exosomes transfer bioactive microRNA into target cells, which can target and regulate the level of mRNA in target cells.

Results

Here, we constructed a mice primary uterine stromal cell-induced decidualization model in vitro, and detected the effect of CeO2NPs exposure on the expression of decidual-derived exosomal miRNAs by high-throughput sequencing. Bioinformatics analysis and dual-luciferase reporter assays were performed to identify target genes of the screened key miRNAs in regulating trophoblast invasion. Finally, the role of the screened miRNAs and their target genes in regulating trophoblast (HTR-8/SVneo cells) invasion was confirmed. The results showed that CeO2NPs exposure inhibited trophoblast invasion by promoting miR-99a-5p expression in decidual-derived exosomes, and Ppp2r5a is a potential target gene for miR-99a-5p to inhibit trophoblast invasion.

Conclusions

This study revealed the molecular mechanism by which CeO2NPs exposure inhibits trophoblast invasion from the perspective of decidual derived exosomal miRNAs. These results will provide an experimental basis for screening potential therapeutic targets for the negative biological effects of CeO2NPs exposure and new ideas for studying the mechanism of damage to trophoblast cells at the decidual-foetal interface by harmful environmental or occupational factors.
Role and research progress of hematological markers in laryngeal squamous cell carcinoma
Authors: Qi Hui
Published: April 2023

Laryngeal cancer is one of the most common malignant tumors of the head and neck, accounting for about 20%. Due to its high disability rate, the diagnosis and treatment of laryngeal cancer have always been the focus and difficulty of head and neck surgery. The outcome of cancer is affected not only by tumor-related factors but also by host-related factors, especially systemic inflammation, this is usually reflected by a variety of hematological markers. Studies have confirmed that there is a significant correlation between hematological markers and the occurrence, development, and prognosis of laryngeal squamous cell carcinoma (LSCC), and has a certain value in auxiliary diagnosis and prognosis prediction of LSCC. We reviewed various hematological markers related to LSCC aim to summarize the role and research progress of hematological markers in LSCC.
Huge left atrial myxoma: about 2 cases resected in the Democratic Republic of Congo
Authors: Nzomvuama Alphonse Ndonga N’sungu , Mutuale Cédric Nyombo , Kongo Roger Minga , Mbanzulu Irène Nsolani , Nsiala Joseph Makunza
Published: April 2023

Background

Myxoma is the most common cardiac tumor, found in 75–80% of cases in the left atrium. It can grow quietly and therefore reach a large size before being symptomatic. Poor availability of echocardiography also contributes to delayed diagnosis. In Sub-Saharan African countries, myxoma diagnosis can be missed for many patients. Myxoma resection surgery, although technically simple, is not always possible, because of the lack of cardiac surgery development. The aim of this report is to describe the first two consecutive resection cases of huge left-atrial myxoma performed in Kinshasa, Democratic Republic of Congo (DRC) and to discuss the specificities of this surgery in this low-resource context.

Case presentation

Two patients, 54 and 48 years old, were diagnosed with giant myxoma of the left atrium in the management of progressive dyspnea The first patient's transthoracic echocardiography revealed a pedunculated atrial mass (37 × 48 mm) on the interatrial septum, passing through the mitral valve. For the second patient, the mass (64 × 26 mm) was attached to the roof of the left atrium and protruded into the mitral valve, with significant mitro-tricuspid regurgitation The first patient underwent a simple resection of the myxoma. For the second patient, it was associated to a mitro-tricuspid annuloplasty. The postoperative course was simple for the first patient, but the second patient developed a biventricular failure requiring vasoactive drugs. Both patients were discharged alive from the hospital on postoperative days 10 and 12, respectively. They are regularly followed up and are doing well 2 years after surgery.

Discussion and conclusion

Surgical resection is the only effective treatment of myxoma. Our first results are encouraging The poor availability of the echocardiography is a challenge in the diagnosis of myxoma. The development of cardiac surgery in DRC and ongoing country-level efforts to address diagnostic challenges for these often silent tumors will allow us to expect more resections to be performed locally and larger series published.
Leveraging the glymphatic and meningeal lymphatic systems as therapeutic strategies in Alzheimer’s disease: an updated overview of nonpharmacological therapies
Authors: Formolo Douglas A. , Yu Jiasui , Lin Kangguang , Tsang Hector W. H. , Ou Haining , Kranz Georg S. , Yau Suk-Yu
Published: April 2023

Understanding and treating Alzheimer’s disease (AD) has been a remarkable challenge for both scientists and physicians. Although the amyloid-beta and tau protein hypothesis have largely explained the key pathological features of the disease, the mechanisms by which such proteins accumulate and lead to disease progression are still unknown. Such lack of understanding disrupts the development of disease-modifying interventions, leaving a therapeutic gap that remains unsolved. Nonetheless, the recent discoveries of the glymphatic pathway and the meningeal lymphatic system as key components driving central solute clearance revealed another mechanism underlying AD pathogenesis. In this regard, this narrative review integrates the glymphatic and meningeal lymphatic systems as essential components involved in AD pathogenesis. Moreover, it discusses the emerging evidence suggesting that nutritional supplementation, non-invasive brain stimulation, and traditional Chinese medicine can improve the pathophysiology of the disease by increasing glymphatic and/or meningeal lymphatic function. Given that physical exercise is a well-regarded preventive and pro-cognitive intervention for dementia, we summarize the evidence suggesting the glymphatic system as a mediating mechanism of the physical exercise therapeutic effects in AD. Targeting these central solute clearance systems holds the promise of more effective treatment strategies.
Practical assessment of risk of VILI from ventilating power: a conceptual model
Authors: Marini John J. , Thornton Lauren T. , Rocco Patricia R. M. , Gattinoni Luciano , Crooke Philip S.
Published: April 2023

At the bedside, assessing the risk of ventilator-induced lung injury (VILI) requires parameters readily measured by the clinician. For this purpose, driving pressure (DP) and end-inspiratory static ‘plateau’ pressure ($$P_{s}$$

P
s

) of the tidal cycle are unquestionably useful but lack key information relating to associated volume changes and cumulative strain. ‘Mechanical power’, a clinical term which incorporates all dissipated (‘non-elastic’) and conserved (‘elastic’) energy components of inflation, has drawn considerable interest as a comprehensive ‘umbrella’ variable that accounts for the influence of ventilating frequency per minute as well as the energy cost per tidal cycle. Yet, like the raw values of DP and $$P_{s}$$

P
s

, the absolute levels of energy and power by themselves may not carry sufficiently precise information to guide safe ventilatory practice. In previous work we introduced the concept of ‘damaging energy per cycle’. Here we describe how—if only in concept—the bedside clinician might gauge the theoretical hazard of delivered energy using easily observed static circuit pressures ($$P_{s}$$

P
s

and positive end expiratory pressure) and an estimate of the maximally tolerated (threshold) non-dissipated (‘elastic’) airway pressure that reflects the pressure component applied to the alveolar tissues. Because its core inputs are already in use and familiar in daily practice, the simplified mathematical model we propose here for damaging energy and power may promote deeper comprehension of the key factors in play to improve lung protective ventilation.
pycoMeth: a toolbox for differential methylation testing from Nanopore methylation calls
Authors: Snajder Rene , Leger Adrien , Stegle Oliver , Bonder Marc Jan
Published: April 2023

We presentpycoMeth, a toolbox to store, manage and analyze DNA methylation calls from long-read sequencing data obtained using the Oxford Nanopore Technologies sequencing platform. Building on a novel, rapid-access, read-level and reference-anchored methylation storage formatMetH5, we propose efficient algorithms for haplotype aware, multi-sample consensus segmentation and differential methylation testing. We show thatMetH5is more efficient than existing solutions for storing Oxford Nanopore Technologies methylation calls, and carry out benchmarking forpycoMethsegmentation and differential methylation testing, demonstrating increased performance and sensitivity compared to existing solutions designed for short-read methylation data.
Glucagon-like peptide-1 analogues: a new way to quit smoking? (SKIP)—a structured summary of a study protocol for a randomized controlled study
Authors: Lengsfeld Sophia , Burkard Thilo , Meienberg Andrea , Jeanloz Nica , Coynel David , Vogt Deborah R. , Hemkens Lars G. , Speich Benjamin , Zanchi Davide , Erlanger Tobias E. , Christ-Crain Mirjam , Winzeler Bettina
Published: April 2023

Background

Cigarette smoking is the leading preventable cause of premature death. Despite dedicated programmes, quit rates remain low due to barriers such as nicotine withdrawal syndrome or post-cessation weight gain. Glucagon-like peptide-1 (GLP-1) analogues reduce energy intake and body weight and seem to modulate addictive behaviour. These GLP-1 properties are of major interest in the context of smoking cessation. The aim of this study is to evaluate the GLP-1 analogue dulaglutide as a new therapy for smoking cessation.

Methods

This is a placebo-controlled, double-blind, parallel group, superiority, single-centre randomized study including 255 patients. The intervention consists of a 12-week dulaglutide treatment phase with 1.5 mg once weekly or placebo subcutaneously, in addition to standard of care (behavioural counselling and pharmacotherapy with varenicline). A 40-week non-treatment phase follows. The primary outcome is the point prevalence abstinence rate at week 12. Smoking status is self-reported and biochemically confirmed by end-expiratory exhaled carbon monoxide measurement. Further endpoints include post-cessational weight gain, nicotine craving analysis, glucose homeostasis and long-term nicotine abstinence.

Two separate substudies assess behavioural, functional and structural changes by functional magnetic resonance imaging and measures of energy metabolism (i.e. resting energy expenditure, body composition).

Discussion

Combining behavioural counselling and medical therapy, e.g. with varenicline, improves abstinence rates and is considered the standard of care. We expect a further increase in quit rates by adding a second component of medical therapy and assume a dual effect of dulaglutide treatment (blunting nicotine withdrawal symptoms and reducing post-cessational weight gain). This project is of high relevance as it explores novel treatment options aimed at preventing the disastrous consequences of nicotine consumption and obesity.

Trial registration

ClinicalTrials.gov NCT03204396. Registered on June 26, 2017.
CD33 as a leukocyte-associated marker expressed on human spermatozoa
Authors: Sereshki Nasrin , Rafiee Mitra , Alipour Razieh , Rahimyan Kourosh , Wilkinson David
Published: April 2023

Objective

Sialic acid-binding immunoglobulin-type lectins (Siglecs) are commonly present on immune cells and often mediate cell-to-cell interactions and signaling. Studies have shown the presence of Siglecs 1, 2, 5, 6, 10 and 14 on human spermatozoa. To the best of our knowledge, the expression of CD33 on spermatozoa has not yet been studied. Semen samples were collected from 25 healthy men with normal semen status. CD33 expression on purified spermatozoa was evaluated by flow cytometry methods.

Results

The results demonstrate the expression of CD33 on the surface of purified spermatozoa. The mean (± SD) of MFI (mean fluorescence intensity) was 12.85 (± 1.33) and the mean percentage of spermatozoa that express CD33 was 73.75 (± 3.75). Results were obtained showing that spermatozoa express CD33 (or Siglec-3) on their surface. The physiological role of these molecules on spermatozoa remains to be determined. It is recommended that further research be undertaken regarding the role of Siglecs (such as CD33) on spermatozoa apoptosis.
Higher performance for women than men in MRI-based Alzheimer’s disease detection
Authors: Klingenberg Malte , Stark Didem , Eitel Fabian , Budding Céline , Habes Mohamad , Ritter Kerstin ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: April 2023

Introduction

Although machine learning classifiers have been frequently used to detect Alzheimer’s disease (AD) based on structural brain MRI data, potential bias with respect to sex and age has not yet been addressed. Here, we examine a state-of-the-art AD classifier for potential sex and age bias even in the case of balanced training data.

Methods

Based on an age- and sex-balanced cohort of 432 subjects (306 healthy controls, 126 subjects with AD) extracted from the ADNI data base, we trained a convolutional neural network to detect AD in MRI brain scans and performed ten different random training-validation-test splits to increase robustness of the results. Classifier decisions for single subjects were explained using layer-wise relevance propagation.

Results

The classifier performed significantly better for women (balanced accuracy$$87.58\pm 1.14\%$$87.58±1.14%) than for men ($$79.05\pm 1.27\%$$79.05±1.27%). No significant differences were found in clinical AD scores, ruling out a disparity in disease severity as a cause for the performance difference. Analysis of the explanations revealed a larger variance in regional brain areas for male subjects compared to female subjects.

Discussion

The identified sex differences cannot be attributed to an imbalanced training dataset and therefore point to the importance of examining and reporting classifier performance across population subgroups to increase transparency and algorithmic fairness. Collecting more data especially among underrepresented subgroups and balancing the dataset are important but do not always guarantee a fair outcome.
Long term longitudinal follow-up of an AD-HIES cohort: the impact of early diagnosis and enrollment to IPINet centers on the natural history of Job’s syndrome
Authors: Carrabba Maria , Dellepiane Rosa Maria , Cortesi Manuela , Baselli Lucia Augusta , Soresina Annarosa , Cirillo Emilia , Giardino Giuliana , Conti Francesca , Dotta Laura , Finocchi Andrea , Cancrini Caterina , Milito Cinzia , Pacillo Lucia , Cinicola Bianca Laura , Cossu Fausto , Consolini Rita , Montin Davide , Quinti Isabella , Pession Andrea , Fabio Giovanna , Pignata Claudio , Pietrogrande Maria Cristina , Badolato Raffaele
Published: April 2023

Job’s syndrome, or autosomal dominant hyperimmunoglobulin E syndrome (AD-HIES, STAT3-Dominant Negative), is a rare inborn error of immunity (IEI) with multi-organ involvement and long-life post-infective damage. Longitudinal registries are of primary importance in improving our knowledge of the natural history and management of these rare disorders. This study aimed to describe the natural history of 30 Italian patients with AD-HIES recorded in the Italian network for primary immunodeficiency (IPINet) registry. This study shows the incidence of manifestations present at the time of diagnosis versus those that arose during follow up at a referral center for IEI. The mean time of diagnostic delay was 13.7 years, while the age of disease onset was < 12 months in 66.7% of patients. Respiratory complications, namely bronchiectasis and pneumatoceles, were present at diagnosis in 46.7% and 43.3% of patients, respectively. Antimicrobial prophylaxis resulted in a decrease in the incidence of pneumonia from 76.7% to 46.7%. At the time of diagnosis, skin involvement was present in 93.3% of the patients, including eczema (80.8%) and abscesses (66.7%). At the time of follow-up, under therapy, the prevalence of complications decreased: eczema and skin abscesses reduced to 63.3% and 56.7%, respectively. Antifungal prophylaxis decreased the incidence of mucocutaneous candidiasis from 70% to 56.7%. During the SARS-CoV-2 pandemic, seven patients developed COVID-19. Survival analyses showed that 27 out of 30 patients survived, while three patients died at ages of 28, 39, and 46 years as a consequence of lung bleeding, lymphoma, and sepsis, respectively. Analysis of a cumulative follow-up period of 278.7 patient-years showed that early diagnosis, adequate management at expertise centers for IEI, prophylactic antibiotics, and antifungal therapy improve outcomes and can positively influence the life expectancy of patients.
DQN-based resource allocation for NOMA-MEC-aided multi-source data stream
Authors: Ling Jing , Xia Junjuan , Zhu Fusheng , Gao Chongzhi , Lai Shiwei , Balasubramanian Venki
Published: April 2023

This paper investigates a non-orthogonal multiple access (NOMA)-aided mobile edge computing (MEC) network with multiple sources and one computing access point (CAP), in which NOMA technology is applied to transmit multi-source data streams to CAP for computing. To measure the performance of the considered NOMA-aided MEC network, we first design the system cost as a linear weighting function of energy consumption and delay under the NOMA-aided MEC network. Moreover, we propose a deep Q network (DQN)-based offloading strategy to minimize the system cost by jointly optimizing the offloading ratio and transmission power allocation. Finally, we design experiments to demonstrate the effectiveness of the proposed strategy. Specifically, the designed strategy can decrease the system cost by about 15% compared with local computing when the number of sources is 5.
Study on Hermite-Hadamard-type inequalities using a new generalized fractional integral operator
Authors: Ni Jinbo , Chen Gang , Dong Hudie
Published: April 2023

In this study, a new definition of the fractional integral operator is first proposed, which generalizes some well-known fractional integral operators. Then, by using this newly generalized fractional integral operator, we proved several new Hermite-Hadamard-type inequalities for convex functions. Finally, we provided some corollaries to show that the current results extend and enrich the previous results in the literature.
Positive continuous solutions for some semilinear elliptic problems in the half space
Authors: Alsaedi Ramzi , Ghanmi Abdeljabbar , Zeddini Noureddine
Published: April 2023

The aim of this article is twofold. The first goal is to give a new characterization of the Kato class of functions $K^{\infty}({\mathbb{R}}_{+}^{d})$

K
∞

(

R
+
d

)
that was defined in (Bachar et al. 2002:41, 2002) for $d=2$
d
=
2
and in (Bachar and Mâagli 9(2):153–192, 2005) for $d\geq 3$
d
≥
3
and adapted to study some nonlinear elliptic problems in the half space. The second goal is to prove the existence of positive continuous weak solutions, having the global behavior of the associated homogeneous problem, for sufficiently small values of the nonnegative constants λ and μ to the following system: $\Delta u=\lambda f(x,u,v)$
Δ
u
=
λ
f
(
x
,
u
,
v
)
, $\Delta v=\mu g(x,u,v)$
Δ
v
=
μ
g
(
x
,
u
,
v
)
in ${\mathbb{R}}_{+}^{d}$

R
+
d

, $\lim _{x\rightarrow (\xi ,0)}u(x)=a_{1}\phi _{1}(\xi )$

lim

x
→
(
ξ
,
0
)

u
(
x
)
=

a
1

ϕ
1

(
ξ
)
, $\lim _{x\rightarrow (\xi ,0)}v(x)=a_{2}\phi _{2}(\xi )$

lim

x
→
(
ξ
,
0
)

v
(
x
)
=

a
2

ϕ
2

(
ξ
)
for all $\xi \in {\mathbb{R}}^{d-1}$
ξ
∈

R

d
−
1

, $\lim _{x_{d} \rightarrow \infty}\frac{u(x)}{x_{d}}=b_{1}$

lim

x
d

→
∞

u
(
x
)

x
d

=

b
1

, $\lim _{x_{d} \rightarrow \infty}\frac{v(x)}{x_{d}}=b_{2}$

lim

x
d

→
∞

v
(
x
)

x
d

=

b
2

, where $\phi _{1}$

ϕ
1

and $\phi _{2}$

ϕ
2

are nontrivial nonnegative continuous functions on $\partial {\mathbb{R}}_{+}^{d}= {\mathbb{R}}^{d-1}\times \{0\}$
∂

R
+
d

=

R

d
−
1

×
{
0
}
, $a_{1}, a_{2}, b_{1}, b_{2}$

a
1

,

a
2

,

b
1

,

b
2

are nonnegative constants such that $(a_{1}+b_{1})(a_{2}+b_{2})>0$
(

a
1

+

b
1

)
(

a
2

+

b
2

)
>
0
. The functions f and g are nonnegative and belong to a class of functions containing in particular all functions of the type $f(x,u,v)=p(x) u^{\alpha}g_{1}(v)$
f
(
x
,
u
,
v
)
=
p
(
x
)

u
α

g
1

(
v
)
and $g(x,u,v)=q(x)g_{2}(u)v^{\beta}$
g
(
x
,
u
,
v
)
=
q
(
x
)

g
2

(
u
)

v
β

with $\alpha \geq 1$
α
≥
1
, $\beta \geq 1$
β
≥
1
, $g_{1}$

g
1

, $g_{2}$

g
2

are continuous on $[0,\infty )$
[
0
,
∞
)
, and $p,q$
p
,
q
are nonnegative functions in $K^{\infty}({\mathbb{R}}_{+}^{d})$

K
∞

(

R
+
d

)
.
Exploring the eating disorder curricula of accredited university dietetic programs in Australia and New Zealand
Authors: Parker Elizabeth Kumiko , Ashley Mellisa Anne , Harris Deanne Maree , Stefoska-Needham Anita
Published: April 2023

Background

Dietitians are viewed as integral members of the multidisciplinary treatment team for people with eating disorders (EDs). However, low levels of perceived confidence, competence, and willingness to practice in this clinical area, have been reported by dietitians and student dietitians. As the extent of ED-specific knowledge and skills-based training within tertiary accredited dietetic programs is currently unknown, this research aimed to: (1) obtain insights into the current ED-specific knowledge base and training content of dietetic curricula in both Australian and New Zealand universities; (2) understand the perspectives of course convenors regarding the role of dietitians in ED treatment and their employment opportunities; and (3) identify gaps and opportunities for improving university programs and the dietetic workforce.

Methods

Course convenors (or their nominated representative) of Australian and New Zealand accredited dietetic programs were invited to participate in a semi-structured virtual interview. A purpose-built question guide was developed to explore the inclusion and/or integration of ED-specific content into the curricula, and the perspectives of course convenors toward the role of dietitians in the treatment of EDs, and their employment opportunities. The interviews were audio recorded, transcribed verbatim, and analysed qualitatively using inductive thematic analysis.

Results

Thirteen participants who represented 14 universities and 19 individual accredited dietetic programs, were interviewed, with some participants representing more than one university. Three dominant themes emerged: (1) varying ED-specific content and training in dietetic programs; (2) unclear dietitian's role in the treatment of EDs, and (3) contrasting views regarding ED clinical practice and employment.

Conclusions

ED-specific content was embedded within all the dietetic programs investigated in this study. However, this content was generally limited to an introductory level, with notable variations found between the depth of content and the type of training provided. Risk-mitigation skill development, such as screening for EDs, and early identification of symptoms, also varied between programs. Therefore, it is recommended that ED-specific skill development and knowledge is enhanced within Australian and New Zealand university programs, to support effective, safe, and timely care for people with EDs. This research has implications for current and future university dietetic program development and the broader dietetic workforce.
Remifentanil but not sufentanil induces cardioprotection in human ischemic heart muscle in vitro
Authors: Kunecki Marcin , Oleksy Tomasz , Martynów Jan , Zygmunt Michalina , Deja Marek , Kargul Tomasz , Biernat Jolanta , Podolec Piotr , Gołba Krzysztof S. , Płazak Wojciech
Published: April 2023

Background

Previous studies on animal models have suggested that δ-opioid receptor (OR) signaling is the primary pathway responsible for opioids' cardioprotective effect. We hypothesize that the μ-OR's activation protects the human heart muscle.

Methods

We performed the experiments on muscular trabeculae obtained from the right atrial appendages of 104 consecutive patients subjected to coronary artery bypass surgery. Two trabeculae from each patient were studied simultaneously and exposed to 60 min of hypoxia with subsequent 60 min of reoxygenation. Remifentanil (5 μM or 50 μM) or sufentanil (40 μM or 400 μM) was used from the time of reoxygenation. Trabeculae contractility was assessed as the maximal amplitude of the contraction at baseline, after 60 min of hypoxia, during reoxygenation, and after norepinephrine application.

Results

During reperfusion, the application of remifentanil improved cardiomyocytes' function as compared to the control group (time from reperfusion: 15 min: 39.8% vs. 21.7%, p = 0.01; 30 min: 41.4% vs. 21.8%, p = 0.01; 60 min: 42.7% vs. 26.9%, p = 0.04; after norepinephrine: 64.7% vs. 43.2%, p = 0.03). The application of sufentanil did not influence cardiomyocyte function as can be seen when comparing the results of the experimental and control group.

Conclusions

Remifentanil, but not sufentanil, induces a cardioprotective effect on human right atria muscle in in vitro conditions, manifested as the increased amplitude of their contraction during reperfusion after 60 min of ischemia.
Experimental study on convective heat transfer of an open-loop borehole heat exchanger
Authors: Bu Xianbiao , Jiang Kunqing , Li Huashan , Ma Feng , Wang Lingbao
Published: April 2023

Open-loop borehole heat exchanger (OBHE) is a single well geothermal heat exchanger with an open-loop structure that can realize the geothermal energy extraction without mining the geothermal water. In this paper, a sandbox experiment is designed to simulate the convective heat transfer process in the reservoir area of OBHE. The mechanism of convective heat transfer in the reservoir area is studied, and the key factors that affect the convection heat transfer intensity are analyzed. The results show that the convection heat transfer of OBHE in the reservoir area is affected by both the driving effect of fluid flow inside the screen tube and the buoyancy effect. In the forward flow mode, the two effects have the opposite direction. While in the backward mode, the two effects have the same direction. The backward flow mode is more conducive to convective heat transfer. In addition, many factors influencing significantly the convective heat transfer of OBHE include inlet temperature, inlet flow rate, reservoir temperature, fluid flow direction and inner tube diameter.
Identification of qBK2.1, a novel QTL controlling rice resistance against Fusarium fujikuroi
Authors: Chen Szu-Yu , Lai Ming-Hsin , Chu Yi-Ling , Wu Dong-Hong , Tung Chih-Wei , Chen Yue-Jie , Chung Chia-Lin
Published: April 2023

Background

Bakanae disease caused by Fusarium fujikuroi is an increasing threat to rice production. The infected plants show symptoms such as elongation, slenderness, chlorosis, a large leaf angle, and even death. Bakanae disease is traditionally managed by seed treatment. However, fungicide-resistant F. fujikuroi isolates have emerged in several Asian areas, including Taiwan. This study aimed to identify new bakanae resistance quantitative trait loci (QTLs) and provide molecular markers to assist future breeding.

Results

A population of F2:9 recombinant inbred lines (RILs) was derived from the cross between an elite japonica Taiwanese cultivar ‘Taikeng 16 (TK16)’ and an indica variety ‘Budda’. ‘Budda’ was found highly resistant to all 24 representative isolates of the F. fujikuroi population in Taiwan. For the RIL population, 6,492 polymorphic single nucleotide polymorphisms (SNPs) spanning the rice genome were obtained by genotyping-by-sequencing (GBS) technique, and the disease severity index (DSI) was evaluated by inoculation with a highly virulent F. fujikuroi isolate Ff266. Trait-marker association analysis of 166 RILs identified two QTLs in ‘Budda’. qBK2.1 (21.97–30.15 Mb) is a novel and first bakanae resistance QTL identified on chromosome 2. qBK1.8 (5.24–8.66 Mb) partially overlaps with the previously reported qBK1.3 (4.65–8.41 Mb) on chromosome 1. The log of odds (LOD) scores of qBK1.8 and qBK2.1 were 4.75 and 6.13, accounting for 4.9% and 8.1% of the total phenotypic variation, respectively. 64 RILs carrying both qBK1.8 and qBK2.1 showed lower DSI (7%) than the lines carrying only qBK1.8 (15%), only qBK2.1 (13%), or none of the two QTLs (21%). For the future application of identified QTLs, 11 KBioscience competitive allele-specific PCR (KASP) markers and 3 insertion-deletion (InDel) markers were developed.

Conclusions

Compared to other important rice diseases, knowledge of bakanae resistance has been insufficient, which limited the development and deployment of resistant cultivars. The discovery of qBK2.1 has provided a new source of bakanae resistance. The resistant RILs inheriting good plant type, good taste, and high yield characteristics from ‘TK16’ can be used as good resistance donors. Our newly developed markers targeting qBK2.1 and qBK1.8 can also serve as an important basis for future fine-mapping and resistance breeding.
First non-invasive magnetic phrenic nerve and diaphragm stimulation in anaesthetized patients: a proof-of-concept study
Authors: Panelli Alessandro , Bartels Hermann Georges , Krause Sven , Verfuß Michael André , Grimm Aline Michèle , Carbon Niklas Martin , Grunow Julius J. , Stutzer Diego , Niederhauser Thomas , Brochard Laurent , Weber-Carstens Steffen , Schaller Stefan J.
Published: April 2023

Background

Mechanical ventilation has side effects such as ventilator-induced diaphragm dysfunction, resulting in prolonged intensive care unit length of stays. Artificially evoked diaphragmatic muscle contraction may potentially maintain diaphragmatic muscle function and thereby ameliorate or counteract ventilator-induced diaphragm dysfunction. We hypothesized that bilateral non-invasive electromagnetic phrenic nerve stimulation (NEPNS) results in adequate diaphragm contractions and consecutively in effective tidal volumes.

Results

This single-centre proof-of-concept study was performed in five patients who were 30 [IQR 21–33] years old, 60% (n = 3) females and undergoing elective surgery with general anaesthesia. Following anaesthesia and reversal of muscle relaxation, patients received bilateral NEPNS with different magnetic field intensities (10%, 20%, 30%, 40%); the stimulation was performed bilaterally with dual coils (connected to one standard clinical magnetic stimulator), specifically designed for bilateral non-invasive electromagnetic nerve stimulation. The stimulator with a maximal output of 2400 Volt, 160 Joule, pulse length 160 µs at 100% intensity was limited to 50% intensity, i.e. each single coil had a maximal output of 0.55 Tesla and 1200 Volt. There was a linear relationship between dosage (magnetic field intensity) and effect (tidal volume, primary endpoint, p < 0.001). Mean tidal volume was 0.00, 1.81 ± 0.99, 4.55 ± 2.23 and 7.43 ± 3.06 ml/kg ideal body weight applying 10%, 20%, 30% and 40% stimulation intensity, respectively. Mean time to find an initial adequate stimulation point was 89 (range 15–441) seconds.

Conclusions

Bilateral non-invasive electromagnetic phrenic nerve stimulation generated a tidal volume of 3–6 ml/kg ideal body weight due to diaphragmatic contraction in lung-healthy anaesthetized patients. Further perspectives in critically ill patients should include assessment of clinical outcomes to confirm whether diaphragm contraction through non-invasive electromagnetic phrenic nerve stimulation potentially ameliorates or prevents diaphragm atrophy.
The MATE trial: a multicentre, mixed-methodology, pilot, randomised controlled trial in neovascular age-related macular degeneration
Authors: Airody Archana , Baseler Heidi A. , Seymour Julie , Allgar Victoria , Mukherjee Rajarshi , Downey Louise , Dhar-Munshi Sushma , Mahmood Sajjad , Balaskas Konstantinos , Empeslidis Theo , Hanson Rachel L. W. , Dorey Tracey , Szczerbicki Tom , Sivaprasad Sobha , Gale Richard P.
Published: April 2023

Background/objectives

In healthcare research investigating complex interventions, gaps in understanding of processes can be filled by using qualitative methods alongside a quantitative approach. The aim of this mixed-methods pilot trial was to provide feasibility evidence comparing two treatment regimens for neovascular age-related macular degeneration (nAMD) to inform a future large-scale randomised controlled trial (RCT).

Subjects/methods

Forty-four treatment-naïve nAMD patients were followed over 24 months and randomised to one of two treatment regimens: standard care (SC) or treat and extend (T&E). The primary objective evaluated feasibility of the MATE trial via evaluations of screening logs for recruitment rates, nonparticipation and screen fails, whilst qualitative in-depth interviews with key study staff evaluated the recruitment phase and running of the trial. The secondary objective assessed changes in visual acuity and central retinal thickness (CRT) between the two treatment arms.

Results

The overall recruitment rate was 3.07 participants per month with a 40.8% non-participation rate, 18.51% screen-failure rate and 15% withdrawal/non-completion rate. Key themes in the recruitment phase included human factors, protocol-related issues, recruitment processes and challenges. Both treatment regimens showed a trend towards a visual acuity gain at month 12 which was not maintained at month 24, whilst CRT reduced similarly in both regimens over the same time period. These were achieved with one less treatment following a T&E regimen.

Conclusion

This mixed-methodology, pilot RCT achieved its pre-defined recruitment, nonparticipation and screen failure rates, thus deeming it a success. With some minor protocol amendments, progression to a large-scale RCT will be achievable.
Updates in the perioperative management of postpartum hemorrhage
Authors: Samir Ghada M.
Published: April 2023

Background

Postpartum hemorrhage (PPH) is the leading cause of maternal death all over the world. It could be primary or secondary with uterine atony being the cause in 80% of cases.

Main body

For anticipated PPH, special antenatal preparation for abnormal placentation, inherited coagulation disorders, and Jehovah’s Witnesses must be done. Optimal surgical management of placenta accreta is done by scheduling delivery in an appropriate surgical facility, by insertion of prophylactic embolization catheters in the uterine or internal iliac arteries, and by rapid diagnosis of PPH. The obstetric shock index (SI) is highly specific for PPH. Optimal anesthetic management is done by oxygen supply, using warming devices, ensuring wide bore intravenous (IV) access with adequate volume replacement, and blood product preparation. The non-pneumatic anti-shock garment (NASG) could be used as first-aid compression device. Permissive resuscitation, uterotonic administration, tranexamic acid, recombinant active factor seven (VIIa), and lyophilized fibrinogen concentrate are beneficial. Hemostatic reanimation to correct coagulopathy and cell saver auto-transfusion are applied. For unanticipated PPH, guidelines and regular skill training reduce the incidence of severe PPH.

Conclusions

Anticipated PPH requires antenatal preparation, optimal anesthetic management with the implementation of permissive resuscitation, hemostatic reanimation, and optimal surgical management.
Pelvic venous congestion syndrome: female venous congestive syndromes and endovascular treatment options
Authors: Kashef Elika , Evans Elizabeth , Patel Neeral , Agrawal Deepsha , Hemingway Anne P
Published: April 2023

Pelvic venous congestion syndrome (PVCS) is a common, but underdiagnosed, cause of chronic pelvic pain (CPP) in women.

PVCS occurs usually, but not exclusively, in multiparous women. It is characterized by chronic pelvic pain of more than six months duration with no evidence of inflammatory disease.

The patients present to general practitioners, gynaecologists, vascular specialists, pain specialists, gastroenterologists and psychiatrists. Pain of variable intensity occurs at any time but is worse in the pre-menstrual period, and is exacerbated by walking, standing, and fatigue. Post coital ache, dysmenorrhea, dyspareunia, bladder irritability and rectal discomfort are also common. Under-diagnosis of this condition can lead to anxiety and depression.

A multidisciplinary approach in the investigation and management of these women is vital.

Non-invasive imaging (US, CT, MRI) are essential in the diagnosis and exclusion of other conditions that cause CPP as well in the definitive diagnosis of PVCS. Trans-catheter venography remains the gold standard modality for the definitive diagnosis and is undertaken as an immediate precursor to ovarian vein embolization (OVE). Conservative, medical and surgical management strategies have been reported but have been superseded by OVE, which has a reported technical success rates of 96–100%, low complication rates and long-term symptomatic relief in between 70–90% of cases.

The condition, described in this paper as PVCS, is referred to by a wide variety of other terms in the literature, a cause of confusion.

There is a significant body of literature describing the syndrome and the excellent outcomes following OVE however the lack of prospective, multicentre randomized controlled trials for both investigation and management of PVCS is a significant barrier to the complete acceptance of both the existence, investigation and management of the condition.
Left atrial appendage morphofunctional indices could be predictive of arrhythmia recurrence post-atrial fibrillation ablation: a meta-analysis
Authors: Papathanasiou Konstantinos A. , Vrachatis Dimitrios A. , Kazantzis Dimitrios , Kossyvakis Charalampos , Giotaki Sotiria G. , Deftereos Gerasimos , Raisakis Konstantinos , Kaoukis Andreas , Avramides Dimitrios , Lambadiari Vaia , Siasos Gerasimos , Deftereos Spyridon
Published: April 2023

Background

Left atrium changes are implicated in atrial fibrillation (AF) substrate and are predictive of AF outcomes. Left atrial appendage (LAA) is an integral component of left atrial structure and could be affected by atrial cardiomyopathy. We aimed to elucidate the association between LAA indices and late arrhythmia recurrence after atrial fibrillation catheter ablation (AFCA).

Methods

The MEDLINE database, ClinicalTrials.gov, medRxiv and Cochrane Library were searched for studies evaluating LAA and late arrhythmia recurrence in patients undergoing AFCA. Data were pooled by meta-analysis using a random-effects model. The primary endpoint was pre-ablation difference in LAA anatomic or functional indices.

Results

A total of 34 studies were found eligible and five LAA indices were analyzed. LAA ejection fraction and LAA emptying velocity were significantly lower in patients with AF recurrence post-ablation [SMD = − 0.66; 95% CI (− 1.01, − 0.32) and SMD = − 0.56; 95% CI (− 0.73, − 0.40) respectively] as compared to arrhythmia free controls. LAA volume and LAA orifice area were significantly higher in patients with AF recurrence post-ablation (SMD = 0.51; 95% CI 0.35–0.67, and SMD = 0.35; 95% CI 0.20–0.49, respectively) as compared to arrhythmia free controls. LAA morphology was not predictive of AF recurrence post-ablation (chicken wing morphology; OR 1.27; 95% CI 0.79–2.02). Moderate statistical heterogeneity and small case–control studies are the main limitations of our meta-analysis.

Conclusions

Our findings suggest that LAA ejection fraction, LAA emptying velocity, LAA orifice area and LAA volume differ between patients suffering from arrhythmia recurrence post-ablation and arrhythmia free counterparts, while LAA morphology is not predictive of AF recurrence.
Effect of intranasal oxytocin combination therapy with applied behavior analysis on social impairments in pediatric’s children with autism spectrum disorder
Authors: Karbasi Afsaneh , Shafiezadegan Isfahani Safie , Maracy Mohammad R. , Sabzghabaee Ali Mohammad
Published: April 2023

Background

The use of oxytocin as a therapy to treat social deficiencies in autism spectrum disorders (ASD) is gaining popularity. This study aimed to determine oxytocin nasal spray’s effect in combination with applied behavior analysis (ABA) method in improving social impairments in pediatrics with ASD.

Results

Our study’s main findings have revealed that intervention with INT-OXT compared to NS effectively reduced the ASD index and stereotyped behaviors on the GARS-2 scale (p < 0.05), in addition to teacher and parent’s SDQ mean score (p < 0.001). Also, during the follow-up time, the intervention with INT-OXT in ASD index, stereotyped behaviors, communication, social interaction, and parent and teacher mean SDQ scores were statically significant (p < 0.001).

Conclusions

In pediatrics with autism aged between 4 and 17 years, a 6-week course of INT-OXT combination therapy with ABA improved GARS-2 and teacher and parent SDQ scores compared to NS.
Prognostic significance of chest CT severity score in mortality prediction of COVID-19 patients, a machine learning study
Authors: Zakariaee Seyed Salman , Abdi Aza Ismail , Naderi Negar , Babashahi Mashallah
Published: April 2023

Background

The high mortality rate of COVID-19 makes it necessary to seek early identification of high-risk patients with poor prognoses. Although the association between CT-SS and mortality of COVID-19 patients was reported, its prognosis significance in combination with other prognostic parameters was not evaluated yet.

Methods

This retrospective single-center study reviewed a total of 6854 suspected patients referred to Imam Khomeini hospital, Ilam city, west of Iran, from February 9, 2020 to December 20, 2020. The prognostic performances of k-Nearest Neighbors (kNN), Multilayer Perceptron (MLP), Support Vector Machine (SVM), and J48 decision tree algorithms were evaluated based on the most important and relevant predictors. The metrics derived from the confusion matrix were used to determine the performance of the ML models.

Results

After applying exclusion criteria, 815 hospitalized cases were entered into the study. Of these, 447(54.85%) were male and the mean (± SD) age of participants was 57.22(± 16.76) years. The results showed that the performances of the ML algorithms were improved when they are fed by the dataset with CT-SS data. The kNN model with an accuracy of 94.1%, sensitivity of 100. 0%, precision of 89.5%, specificity of 88.3%, and AUC around 97.2% had the best performance among the other three ML techniques.

Conclusions

The integration of CT-SS data with demographics, risk factors, clinical manifestations, and laboratory parameters improved the prognostic performances of the ML algorithms. An ML model with a comprehensive collection of predictors could identify high-risk patients more efficiently and lead to the optimal use of hospital resources.
Transcatheter versus surgical closure of ventricular septal defect: a comparative study
Authors: Singab Hamdy , Elshahat Mohamed Khairat , Taha Ahmed Samy , Ali Yasmin Abdelrazek , El-Emam Ahmed Meawad , Gamal Mohamed Ahmed
Published: April 2023

Background

In many countries, surgical closure of ventricular septal defects remains the recommended approach of ventricular septal defect closure. The aim of this study is to compare the safety, efficacy, and clinical effects of surgical versus transcatheter closure of a ventricular septal defect.

Methods

We conducted a comparative randomized study on patients undergoing ventricular septal defect closure. Patients were allocated to undergo either surgical (group I) or catheter (group II) ventricular septal defect closure.

Results

Seventy-two patients were included. Operation success was achieved in 100% of the surgical group versus 33 of 36 patients of the percutaneous group (91.6%) (p value 0.076). There was no significant difference regarding the residual ventricular septal defect. The postoperative echo in group I revealed severe tricuspid regurgitation in one patient (2.7%), and one patient needed a permanent pacemaker. On the other hand, in group II, during the procedure, one patient had severe tricuspid regurge (2.7%). There was a significant difference in the postoperative data favoring group II over group I regarding ventilation duration, intensive care unit stay, total hospital stay, and blood transfusion (P value < 0.001 each).

Conclusion

Both transcatheter device closure and surgical repair are effective treatments. In contrast, the psychological profile of the transcatheter device was superior to the surgical repair, especially in terms of avoiding sternotomy scar, blood loss and transfusion, and hospital stay. On the other hand, transcatheter intervention is limited only to the anatomically suitable ventricular septal defects, in addition, surgical backup is a must in case of complicated transcatheter closure, which gives the upper hand to surgery to be the recommended approach for most of the ventricular septal defects.

Clinical registration number

NCT05306483 registered 04/05/2022 (retrospectively registered) at ClinicalTrials.gov PRS.

Graphical Abstract