bluuebunny/crossref_metadata_2025 huggingface dataset:
Retroviral PBS-segment sequence and structure: Orchestrating early and late replication events
Authors: Heng Xiao , Herrera Amanda Paz , Song Zhenwei , Boris-Lawrie Kathleen
Published: June 2024

An essential regulatory hub for retroviral replication events, the 5’ untranslated region (UTR) encodes an ensemble of cis-acting replication elements that overlap in a logical manner to carry out divergent RNA activities in cells and in virions. The primer binding site (PBS) and primer activation sequence initiate the reverse transcription process in virions, yet overlap with structural elements that regulate expression of the complex viral proteome. PBS-segment also encompasses the attachment site for Integrase to cut and paste the 3’ long terminal repeat into the host chromosome to form the provirus and purine residues necessary to execute the precise stoichiometry of genome-length transcripts and spliced viral RNAs. Recent genetic mapping, cofactor affinity experiments, NMR and SAXS have elucidated that the HIV-1 PBS-segment folds into a three-way junction structure. The three-way junction structure is recognized by the host’s nuclear RNA helicase A/DHX9 (RHA). RHA tethers host trimethyl guanosine synthase 1 to the Rev/Rev responsive element (RRE)-containing RNAs for m7-guanosine Cap hyper methylation that bolsters virion infectivity significantly. The HIV-1 trimethylated (TMG) Cap licenses specialized translation of virion proteins under conditions that repress translation of the regulatory proteins. Clearly host-adaption and RNA shapeshifting comprise the fundamental basis for PBS-segment orchestrating both reverse transcription of virion RNA and the nuclear modification of m7G-Cap for biphasic translation of the complex viral proteome. These recent observations, which have exposed even greater complexity of retroviral RNA biology than previously established, are the impetus for this article. Basic research to fully comprehend the marriage of PBS-segment structures and host RNA binding proteins that carry out retroviral early and late replication events is likely to expose an immutable virus-specific therapeutic target to attenuate retrovirus proliferation.

Graphical abstract
Mitotic kinases are emerging therapeutic targets against metastatic breast cancer
Authors: Aquino-Acevedo Alexandra N. , Orengo-Orengo Joel A. , Cruz-Robles Melanie E. , Saavedra Harold I.
Published: June 2024

This review aims to outline mitotic kinase inhibitors’ roles as potential therapeutic targets and assess their suitability as a stand-alone clinical therapy or in combination with standard treatments for advanced-stage solid tumors, including triple-negative breast cancer (TNBC). Breast cancer poses a significant global health risk, with TNBC standing out as the most aggressive subtype. Comprehending the role of mitosis is crucial for understanding how TNBC advances from a solid tumor to metastasis. Chemotherapy is the primary treatment used to treat TNBC. Some types of chemotherapeutic agents target cells in mitosis, thus highlighting the need to comprehend the molecular mechanisms governing mitosis in cancer. This understanding is essential for devising targeted therapies to disrupt these mitotic processes, prevent or treat metastasis, and improve patient outcomes. Mitotic kinases like Aurora kinase A, Aurora Kinase B, never in mitosis gene A-related kinase 2, Threonine-Tyrosine kinase, and Polo-kinase 1 significantly impact cell cycle progression by contributing to chromosome separation and centrosome homeostasis. When these kinases go awry, they can trigger chromosome instability, increase cell proliferation, and activate different molecular pathways that culminate in a transition from epithelial to mesenchymal cells. Ongoing clinical trials investigate various mitotic kinase inhibitors as potential biological treatments against advanced solid tumors. While clinical trials against mitotic kinases have shown some promise in the clinic, more investigation is necessary, since they induce severe adverse effects, particularly affecting the hematopoietic system.
Increased thyroid stimulating hormone (TSH) as a possible risk factor for atherosclerosis in subclinical hypothyroidism
Authors: Alomair Basil Mohammed , Al-Kuraishy Hayder M. , Al-Gareeb Ali I. , Alshammari Majed Ayed , Alexiou Athanasios , Papadakis Marios , Saad Hebatallah M. , Batiha Gaber El-Saber
Published: June 2024

Primary hypothyroidism (PHT) is associated with an increased risk for the development of atherosclerosis (AS) and other cardiovascular disorders. PHT induces atherosclerosis (AS) through the induction of endothelial dysfunction, and insulin resistance (IR). PHT promotes vasoconstriction and the development of hypertension. However, patients with subclinical PHT with normal thyroid hormones (THs) are also at risk for cardiovascular complications. In subclinical PHT, increasing thyroid stimulating hormone (TSH) levels could be one of the causative factors intricate in the progression of cardiovascular complications including AS. Nevertheless, the mechanistic role of PHT in AS has not been fully clarified in relation to increased TSH. Therefore, in this review, we discuss the association between increased TSH and AS, and how increased TSH may be involved in the pathogenesis of AS. In addition, we also discuss how L-thyroxine treatment affects the development of AS.
Tumor promoting effect of PDLIM2 downregulation involves mitochondrial ROS, oncometabolite accumulations and HIF-1α activation
Authors: Yang Jing-Xing , Chuang Yu-Chen , Tseng Jen-Chih , Liu Yi-Ling , Lai Chao-Yang , Lee Alan Yueh-Luen , Huang Chi-Ying F. , Hong Yi-Ren , Chuang Tsung-Hsien
Published: June 2024

Background

Cancer is characterized by dysregulated cellular metabolism. Thus, understanding the mechanisms underlying these metabolic alterations is important for developing targeted therapies. In this study, we investigated the pro-tumoral effect of PDZ and LIM domain 2 (PDLIM2) downregulation in lung cancer growth and its association with the accumulation of mitochondrial ROS, oncometabolites and the activation of hypoxia-inducible factor-1 (HIF-1) α in the process.

Methods

Databases and human cancer tissue samples were analyzed to investigate the roles of PDLIM2 and HIF-1α in cancer growth. DNA microarray and gene ontology enrichment analyses were performed to determine the cellular functions of PDLIM2. Seahorse assay, flow cytometric analysis, and confocal microscopic analysis were employed to study mitochondrial functions. Oncometabolites were analyzed using liquid chromatography–mass spectrometry (LC–MS). A Lewis lung carcinoma (LLC) mouse model was established to assess the in vivo function of PDLIM2 and HIF-1α.

Results

The expression of PDLIM2 was downregulated in lung cancer, and this downregulation correlated with poor prognosis in patients. PDLIM2 highly regulated genes associated with mitochondrial functions. Mechanistically, PDLIM2 downregulation resulted in NF-κB activation, impaired expression of tricarboxylic acid (TCA) cycle genes particularly the succinate dehydrogenase (SDH) genes, and mitochondrial dysfunction. This disturbance contributed to the accumulation of succinate and other oncometabolites, as well as the buildup of mitochondrial reactive oxygen species (mtROS), leading to the activation of hypoxia-inducible factor 1α (HIF-1α). Furthermore, the expression of HIF-1α was increased in all stages of lung cancer. The expression of PDLIM2 and HIF-1α was reversely correlated in lung cancer patients. In the animal study, the orally administered HIF-1α inhibitor, PX-478, significantly reduces PDLIM2 knockdown-promoted tumor growth.

Conclusion

These findings shed light on the complex action of PDLIM2 on mitochondria and HIF-1α activities in lung cancer, emphasizing the role of HIF-1α in the tumor-promoting effect of PDLIM2 downregulation. Additionally, they provide new insights into a strategy for precise targeted treatment by suggesting that HIF-1α inhibitors may serve as therapy for lung cancer patients with PDLIM2 downregulation.
Mycoplasma pneumoniae pneumonia-associated thromboembolism with plastic bronchitis: a series of five case reports and literature review
Authors: Jin Peng , Han Chunjiao , Guo Wei , Xu Yongsheng
Published: June 2024

Background

Mycoplasma pneumoniae pneumonia is a common respiratory infection among children. However, the occurrence of thromboembolism with plastic bronchitis in association with Mycoplasma pneumoniae pneumonia is extremely rare. This case series presents five cases of children with Mycoplasma pneumoniae pneumonia who developed thromboembolism and plastic bronchitis. The clinical presentation, diagnostic approach, and management strategies are discussed.

Methods

A retrospective analysis was conducted on medical records from a pediatric hospital. Patient demographics, clinical features, laboratory findings, imaging results, treatment modalities, and outcomes were collected.

Results

The patients in our case series presented with varying degrees of respiratory distress, cough, and fever. Imaging studies revealed evidence of thromboembolism based on pulmonary artery occlusion. Bronchial casts were observed by bronchoscopy. Laboratory tests demonstrated elevated D-dimer levels and fibrinogen degradation products. All patients received a combination of low molecular weight heparin anticoagulation and supportive care.

Conclusion

Thromboembolism with plastic bronchitis associated with Mycoplasma pneumoniae pneumonia is a rare but potentially serious complication in children. Prompt recognition and management are crucial for improving patient outcomes. This case series highlights the diverse clinical presentations, diagnostic challenges, and treatment strategies for this unique clinical entity. Further research is needed to better understand the pathogenesis and optimal management of this condition.
Beyond benchmarking and towards predictive models of dataset-specific single-cell RNA-seq pipeline performance
Authors: Fang Cindy , Selega Alina , Campbell Kieran R.
Published: June 2024

Background

The advent of single-cell RNA-sequencing (scRNA-seq) has driven significant computational methods development for all steps in the scRNA-seq data analysis pipeline, including filtering, normalization, and clustering. The large number of methods and their resulting parameter combinations has created a combinatorial set of possible pipelines to analyze scRNA-seq data, which leads to the obvious question: which is best? Several benchmarking studies compare methods but frequently find variable performance depending on dataset and pipeline characteristics. Alternatively, the large number of scRNA-seq datasets along with advances in supervised machine learning raise a tantalizing possibility: could the optimal pipeline be predicted for a given dataset?

Results

Here, we begin to answer this question by applying 288 scRNA-seq analysis pipelines to 86 datasets and quantifying pipeline success via a range of measures evaluating cluster purity and biological plausibility. We build supervised machine learning models to predict pipeline success given a range of dataset and pipeline characteristics. We find that prediction performance is significantly better than random and that in many cases pipelines predicted to perform well provide clustering outputs similar to expert-annotated cell type labels. We identify characteristics of datasets that correlate with strong prediction performance that could guide when such prediction models may be useful.

Conclusions

Supervised machine learning models have utility for recommending analysis pipelines and therefore the potential to alleviate the burden of choosing from the near-infinite number of possibilities. Different aspects of datasets influence the predictive performance of such models which will further guide users.
SCANPatient: study protocol for a multi-centre, batched, stepped wedge, comparative effectiveness, randomised clinical trial of synoptic reporting of computerised tomography (CT) scans assessing cancers of the pancreas
Authors: Li Lin , Kasza Jessica , Recasens Ariadna , Ioannou Liane , Greenhill Elysia , Merrett Neil , Cavallucci David , Ellis Samantha , Madgwick Helen , Ko Hyun Soo , Chantrill Lorraine , Loveday Benjamin , Nikfarjam Mehrdad , Croagh Daniel , Yang Jessica , Dwyer Andrew , Zalcberg John , Pilgrim Charles ,   SCANPatient Authorship Group
Published: June 2024

Background

Complete surgical removal of pancreatic ductal adenocarcinoma (PDAC) is central to all curative treatment approaches for this aggressive disease, yet this is only possible in patients technically amenable to resection. Hence, an accurate assessment of whether patients are suitable for surgery is of paramount importance. The SCANPatient trial aims to test whether implementing a structured synoptic radiological report results in increased institutional accuracy in defining surgical resectability of non-metastatic PDAC.

Methods

SCANPatient is a batched, stepped wedge, comparative effectiveness, cluster randomised clinical trial. The trial will be conducted at 33 Australian hospitals all of which hold regular multi-disciplinary team meetings (MDMs) to discuss newly diagnosed patients with PDAC. Each site is required to manage a minimum of 20 patients per year (across all stages). Hospitals will be randomised to begin synoptic reporting within a batched, stepped wedge design. Initially all hospitals will continue to use their current reporting method; within each batch, after each 6-month period, a randomly selected group of hospitals will commence using the synoptic reports, until all hospitals are using synoptic reporting. Each hospital will provide data from patients who (i) are aged 18 or older; (ii) have suspected PDAC and have an abdominal CT scan, and (iii) are presented at a participating MDM. Non-metastatic patients will be documented as one of the following categories: (1) locally advanced and surgically unresectable; (2) borderline resectable; or (3) anatomically clearly resectable (Note: Metastatic disease is treated as a separate category). Data collection will last for 36 months in each batch, and a total of 2400 patients will be included.

Discussion

Better classifying patients with non-metastatic PDAC as having tumours that are either clearly resectable, borderline or locally advanced and unresectable may improve patient outcomes by optimising care and treatment planning. The borderline resectable group are a small but important cohort in whom surgery with curative intent may be considered; however, inconsistencies with definitions and an understanding of resectability status means these patients are often incorrectly classified and hence overlooked for curative options.

Trial registration

The SCANPatient trial was registered on 17th May 2023 in the Australian New Zealand Clinical Trials Registry (ANZCTR) (ACTRN12623000508673).
Hepatic myelopathy neurological complication of chronic liver disease: two case reports
Authors: Mhiri Mariem , Ben Abdelwahed Mehdi , Dhiflaoui Mohamed Amine , Ben Dhia Rihab , Gouta Narjes , Jemni Imen , Baklouti Raoua , Zakhama Mejda , Gueddiche Arwa , Loghmari Mohamed Hichem , Ben Chaabene Nabil , Safer Leila , Frih-Ayed Mahbouba
Published: June 2024

Background

Hepatic myelopathy is a very rare neurological complication of chronic liver disease. Patients habitually present with progressive pure motor spastic paraparesis. This neurological dysfunction is almost always due to cirrhosis and portocaval shunt, either surgical or spontaneous.

Cases report

We report two cases of a 57-year-old man and a 37-year-old woman with progressive spastic paraparesis linked to cirrhosis and portal hypertension. The two patients are of Tunisian origin (north Africa). Magnetic resonance imaging of the spinal cord of two patients was normal, while brain magnetic resonance imaging showed a T2 hypersignals of the pallidums. These signs, in favor of hepatic encephalopathy in the two patients with cirrhosis with isolated progressive spastic paraparesis without bladder or sensory disorders, help to retain the diagnosis of hepatic myelopathy.

Conclusion

Hepatic myelopathy is a severe and debilitating neurological complication of chronic liver disease. The pathogenesis is misunderstood and seems to be multifactorial, including the selective neurotoxic role both of ammonia and other pathogenic neurotoxins. Usually a pathological brain magnetic resonance imaging showing a hepatic encephalopathy was documented, contrasting with a normal spinal cord magnetic resonance imaging that contributed to diagnosis of hepatic myelopathy. Conservative therapies such as ammonia-lowering measures, diet supplementation, antispastic drugs, and endovascular shunt occlusion show little benefit in improving disease symptoms. Liver transplantation performed at early stage can prevent disease progression and could probably allow for recovery.
Highly compact UWB-MIMO antenna with sharp multi-stop band characteristics
Authors: Pannu Preeti
Published: June 2024

With multi-band rejection characteristics, a new low-profile antenna of size 34 × 34 mm2 is conferred in this article. It consists of quad identical monopole elements (originated orthogonally), contributing ultra-wideband characteristics in the system. The single unit of the proposed design consists of a modified spinning-top shape radiator (MSTSR), excited by a tapered microstrip line feed (TMLF) and semi-circular ground. An excellent bandwidth of 3–12.9 GHz (where S11 < − 10 dB) is obtained at each port. By inserting the structure of four spiral coils, a sharp notch ranging from 7.9 to 8.5 GHz is achieved to filter the X-band satellite communication uplink. In addition, a circular spiral slot in the radiator near the ground plane creates a stop band at 7.35–7.565 GHz band (satellite communication downlink band). Furthermore, symmetrical rectangular trapezoid resonators and inverted symmetrical rectangular trapezoid structures near the feed line are responsible for the elimination of interferences at 5.5 GHz lower WLAN and 3.5 GHz WiMAX respectively. The FR-4 substrate used for the UWB-MIMO design fabrication process and fabricated results are found in good match with the simulated results. Also, the design provides good performance metrics such as total active reflection coefficient, diversity gain, channel capacity loss, isolation, and envelope correlation coefficient.
Remote expert viewing, laboratory tests or objective metrics: which one(s) to trust?
Authors: Wien Mathias , Jung Joel
Published: June 2024

We present a study on the validity of quality assessment in the context of the development of visual media coding schemes. The work is motivated by the need for reliable means for decision-taking in standardization efforts of MPEG and JVET, i.e., the adoption or rejection of coding tools during the development process of the coding standard. The study includes results considering three means: objective quality metrics, remote expert viewing, which is a method designed in the context of MPEG standardization, and formal laboratory visual evaluation. The focus of this work is on the comparison of pairs of coded video sequences, e.g., a proposed change and an anchor scheme at a given rate point. An aggregation of performance measurements across multiple rate points, such as the Bjøntegaard Delta rate, is out of the scope of this paper. The paper details the test setup for the subjective assessment methods and the objective quality metrics under consideration. The results of the three approaches are reviewed, analyzed, and compared with respect to their suitability for the decision-taking task. The study indicates that, subject to the chosen test content and test protocols, the results of remote expert viewing using a forced-choice scale can be considered more discriminatory than the results of naïve viewers in the laboratory tests. The results further that, in general, the well-established quality metrics, such as PSNR, SSIM, or MS-SSIM, exhibit a high rate of correct decision-making when their results are compared with both types of viewing tests. Among the learning-based metrics, VMAF and AVQT appear to be most robust. For the development process of a coding standard, the selection of the most suitable means must be guided by the context, where a small number of carefully selected objective metrics, in combination with viewing tests for unclear cases, appears recommendable.
Impact of LiDAR point cloud compression on 3D object detection evaluated on the KITTI dataset
Authors: Martins Nuno A. B. , Cruz Luís A. da Silva , Lopes Fernando
Published: June 2024

The rapid growth on the amount of generated 3D data, particularly in the form of Light Detection And Ranging (LiDAR) point clouds (PCs), poses very significant challenges in terms of data storage, transmission, and processing. Point cloud (PC) representation of 3D visual information has shown to be a very flexible format with many applications ranging from multimedia immersive communication to machine vision tasks in the robotics and autonomous driving domains. In this paper, we investigate the performance of four reference 3D object detection techniques, when the input PCs are compressed with varying levels of degradation. Compression is performed using two MPEG standard coders based on 2D projections and octree decomposition, as well as two coding methods based on Deep Learning (DL). For the DL coding methods, we used a Joint Photographic Experts Group (JPEG) reference PC coder, that we adapted to accept LiDAR PCs in both Cartesian and cylindrical coordinate systems. The detection performance of the four reference 3D object detection methods was evaluated using both pre-trained models and models specifically trained using degraded PCs reconstructed from compressed representations. It is shown that LiDAR PCs can be compressed down to 6 bits per point with no significant degradation on the object detection precision. Furthermore, employing specifically trained detection models improves the detection capabilities even at compression rates as low as 2 bits per point. These results show that LiDAR PCs can be coded to enable efficient storage and transmission, without significant object detection performance loss.
‘I take the drugs… to make the sickness to move out of me’: key populations’ and service provider perspectives about facilitators and barriers to ART adherence and retention in care in Nigeria
Authors: Dirisu Osasuyi , Eluwa George I. E. , Callens Steve , Adams Eseoghene , Akinwunmi Akinola , Geibel Scott , Iyortim Isa
Published: June 2024

Background

Adherence to antiretroviral therapy (ART) has individual and public health benefits and is critical to improving life expectancy, achieving viral suppression, and reducing the risk of HIV transmission. This qualitative study explored the experience of receiving care as well as perceived facilitators and barriers of treatment initiation, retention in ART care, and adherence to treatment.

Methods

In-depth interviews were conducted among 28 men who have sex with men (MSM) and female sex workers (FSWs) receiving ART services in Lagos and Benue states. Key informant interviews were also conducted among 16 service providers engaged in counselling, clinical care, and ART treatment for MSM and FSWs. The Social Ecology Model guided the exploration of perceived barriers and facilitators of treatment initiation, retention in ART care and adherence to treatment. Qualitative data analysis was managed using NVIVO 11 software and themes were analysed using thematic analysis.

Results

We found that the key barriers to ART adherence were low motivation to comply with medication regimen, work commitments, socioeconomic factors, stigma, negative provider attitude and distance to health facilities. Facilitators of adherence identified include the desire to live a productive life, strong family support and participation in support group programs. Comprehensive adherence counselling, support group programs and an effective follow-up system were factors identified by service providers as key to facilitating adherence.

Conclusion

To be effective, ART programs must address the unique challenges key populations face in accessing treatment and achieving optimal adherence regarding establishing a strong support system and follow-up. Community level interventions that support a stigma-free environment are critical to sustaining engagement in care.
Short-chain fatty acid valerate reduces voluntary alcohol intake in male mice
Authors: Bokoliya Suresh C. , Russell Jordan , Dorsett Yair , Panier Hunter A. , Singh Vijender , Daddi Lauren , Yuan Hanshu , Dedon Liv R. , Liu Zhongmao , Zhou Yuqi , Min Zefang , Barson Jessica R. , Covault Jonathan , Bubier Jason A. , Zhou Yanjiao
Published: June 2024

Background

Despite serious health and social consequences, effective intervention strategies for habitual alcohol binge drinking are lacking. The development of novel therapeutic and preventative approaches is highly desirable. Accumulating evidence in the past several years has established associations between the gut microbiome and microbial metabolites with drinking behavior, but druggable targets and their underlying mechanism of action are understudied.

Results

Here, using a drink-in-the-dark mouse model, we identified a microbiome metabolite-based novel treatment (sodium valerate) that can reduce excessive alcohol drinking. Sodium valerate is a sodium salt of valeric acid short-chain fatty acid with a similar structure as γ-aminobutyric acid (GABA). Ten days of oral sodium valerate supplementation attenuates excessive alcohol drinking by 40%, reduces blood ethanol concentration by 53%, and improves anxiety-like or approach-avoidance behavior in male mice, without affecting overall food and water intake. Mechanistically, sodium valerate supplementation increases GABA levels across stool, blood, and amygdala. It also significantly increases H4 acetylation in the amygdala of mice. Transcriptomics analysis of the amygdala revealed that sodium valerate supplementation led to changes in gene expression associated with functional pathways including potassium voltage-gated channels, inflammation, glutamate degradation, L-DOPA degradation, and psychological behaviors. 16S microbiome profiling showed that sodium valerate supplementation shifts the gut microbiome composition and decreases microbiome-derived neuroactive compounds through GABA degradation in the gut microbiome.

Conclusion

Our findings suggest that sodium valerate holds promise as an innovative therapeutic avenue for the reduction of habitual binge drinking, potentially through multifaceted mechanisms.
Application of mendelian randomization in ocular diseases: a review
Authors: Zhang Xiran , Yuan Weichen , Xu Jun , Zhao Fangkun
Published: June 2024

Ocular disorders can significantly lower patients’ quality of life and impose an economic burden on families and society. However, for the majority of these diseases, their prevalence and mechanisms are yet unknown, making prevention, management, and therapy challenging. Although connections between exposure factors and diseases can be drawn through observational research, it is challenging to rule out the interference of confounding variables and reverse causation. Mendelian Randomization (MR), a method of research that combines genetics and epidemiology, has its advantage to solve this problem and thus has been extensively utilized in the etiological study of ophthalmic diseases. This paper reviews the implementation of MR in the research of ocular diseases and provides approaches for the investigation of related mechanisms as well as the intervention strategies.
Clinical care for severe and persistent eating disorders in pediatric populations: Perspectives of health professionals
Authors: Coelho Jennifer S. , Pardiwala Tanya , Marshall Sheila K. , Lam Pei-Yoong , Grewal Seena , Virani Alice , Olmos Pérez Alexandra , Geller Josie
Published: June 2024

Objective

Models of treatment for adults with severe and enduring eating disorders focus on harm reduction and improving quality of life. However, there is a notable gap in the pediatric literature in this area. The current study set out to assess the perspectives of health professionals regarding clinical care for young people (e.g., ages 10–25 years) with severe and enduring eating disorders, and to explore perceptions about appropriate treatment options for these presentations.

Methods

Health professionals were invited to complete a two-stage online survey about their experiences with clinical care for pediatric eating disorders through Canadian and Australian professional eating disorder networks. Survey 1 included questions about their experiences in supporting individuals with severe and enduring presentations. Participants who completed Survey 2 reviewed clinical vignettes and shared their perspectives about treatment recommendations and models of care, including for a severe and enduring presentation.

Results

A total of 85 clinicians responded to questions on Survey 1 about severe and enduring eating disorder presentations. A portion of these respondents (n = 25) also participated in Survey 2. The majority of respondents to Survey 1 reported providing clinical care for pediatric severe and enduring eating disorder presentations. Amongst respondents to Survey 2, there was low consensus amongst respondents for the clinical care that would be most appropriate for young people with a severe and enduring eating disorder presentation. Numerous challenges in models of care for severe and enduring presentations in pediatric settings were raised in responses on Survey 2, with clinicians sharing their awareness of models focusing on quality of life, while also raising concerns about the appropriateness of these models for young people.

Conclusions

The preliminary results of this study demonstrate that the majority of clinicians report that they have provided care to young people with severe and enduring presentations. There is a clear need for establishing guidance for clinicians working in pediatric eating disorder settings around models of care focused on quality of life. Engagement with interested parties, including those with lived experience, can clarify the development of terminology and clinical pathways for severe and enduring presentations of pediatric eating disorders.
Challenges and coping mechanisms of parents of children with attention deficit hyperactivity disorder in Addis Ababa, Ethiopia: a qualitative study
Authors: Mesfin Wongelawit , Habtamu Kassahun
Published: June 2024

Background

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that has manifestations of inattention, hyperactivity, and impulsivity. It affects every facet of a child’s life, including one’s own emotions, family and school life, and social interaction. The few available studies on ADHD conducted in Ethiopia focus on teachers’ awareness and the prevalence of ADHD. None of these studies has taken into account parents of children who have ADHD. The present study, therefore, aimed to find out the challenges and coping mechanisms of parents who have children with ADHD.

Methods

A phenomenological qualitative study was conducted to explore the experiences of parents who have children with ADHD. The study was carried out in Addis Ababa, the capital city of Ethiopia. Fourteen parents and two healthcare providers were involved in the study. Participants were selected using a purposive sampling technique. In-depth interviews were conducted with parents of children with ADHD (n = 8) and healthcare providers (n = 2). One focus group discussion (FGD), consisting of six members, was also conducted with parents. A topic guide for conducting the interviews and FGD was developed. Interviews and the FGD were audio-recorded. The data were transcribed verbatim, translated into English, and then analyzed using a thematic analysis approach.

Results

With regard to challenges of parents of children with ADHD, three themes emerged: social challenges, economic challenges and psychological challenges. Stigma is found to be the most common challenge. Other challenges included worry about the child’s future, lack of social support, strained relationships with others, impact on their job, and marital conflict. Concerning coping mechanisms, two themes emerged: Inward and outward means of coping. The inward means of coping included prayer and developing an optimistic mindset whereas the outward means were family support, healthcare providers’ guidance, and social avoidance.

Conclusions

The study found that parents of children with ADHD experience several aspects of psychological, social, and economic challenges. Support from healthcare professionals, family members, and the community at large is found to be useful for parents to cope with these challenges. Future research should focus on evaluating interventions that would help parents with ADHD cope with the challenges they experience.
Alpha-synuclein-induced stress sensitivity renders the Parkinson’s disease brain susceptible to neurodegeneration
Authors: Nakos Bimpos Modestos , Karali Katerina , Antoniou Christine , Palermos Dionysios , Fouka Maria , Delis Anastasios , Tzieras Iason , Chrousos George Panagiotis , Koutmani Yassemi , Stefanis Leonidas , Polissidis Alexia
Published: June 2024

A link between chronic stress and Parkinson’s disease (PD) pathogenesis is emerging. Ample evidence demonstrates that the presynaptic neuronal protein alpha-synuclein (asyn) is closely tied to PD pathogenesis. However, it is not known whether stress system dysfunction is present in PD, if asyn is involved, and if, together, they contribute to neurodegeneration. To address these questions, we assess stress axis function in transgenic rats overexpressing full-length wildtype human asyn (asyn BAC rats) and perform multi-level stress and PD phenotyping following chronic corticosterone administration. Stress signaling, namely corticotropin-releasing factor, glucocorticoid and mineralocorticoid receptor gene expression, is also examined in post-mortem PD patient brains. Overexpression of human wildtype asyn leads to HPA axis dysregulation in rats, while chronic corticosterone administration significantly aggravates nigrostriatal degeneration, serine129 phosphorylated asyn (pS129) expression and neuroinflammation, leading to phenoconversion from a prodromal to an overt motor PD phenotype. Interestingly, chronic corticosterone in asyn BAC rats induces a robust, twofold increase in pS129 expression in the hypothalamus, the master regulator of the stress response, while the hippocampus, both a regulator and a target of the stress response, also demonstrates elevated pS129 asyn levels and altered markers of stress signalling. Finally, defective hippocampal stress signalling is mirrored in human PD brains and correlates with asyn expression levels. Taken together, our results link brain stress system dysregulation with asyn and provide evidence that elevated circulating glucocorticoids can contribute to asyn-induced neurodegeneration, ultimately triggering phenoconversion from prodromal to overt PD.
Targeted sequencing of DNA/RNA combined with radiomics predicts lymph node metastasis of papillary thyroid carcinoma
Authors: Zhang Runjiao , Hu Linfei , Cheng Yanan , Chang Luchen , Dong Li , Han Lei , Yu Wenwen , Zhang Rui , Liu Pengpeng , Wei Xi , Yu Jinpu
Published: June 2024

Objective

The aim of our study is to find a better way to identify a group of papillary thyroid carcinoma (PTC) with more aggressive behaviors and to provide a prediction model for lymph node metastasis to assist in clinic practice.

Methods

Targeted sequencing of DNA/RNA was used to detect genetic alterations. Gene expression level was measured by quantitative real-time PCR, western blotting or immunohistochemistry. CCK8, transwell assay and flow cytometry were used to investigate the effects of concomitant gene alterations in PTC. LASSO-logistics regression algorithm was used to construct a nomogram model integrating radiomic features, mutated genes and clinical characteristics.

Results

172 high-risk variants and 7 fusion types were detected. The mutation frequencies in BRAF, TERT, RET, ATM and GGT1 were significantly higher in cancer tissues than benign nodules. Gene fusions were detected in 16 samples (2 at the DNA level and 14 at the RNA level). ATM mutation (ATMMUT) was frequently accompanied by BRAFMUT, TERTMUT or gene fusions. ATMMUT alone or ATM co-mutations were significantly positively correlated with lymph node metastasis. Accordingly, ATM knock-down PTC cells bearing BRAFV600E, KRASG12R or CCDC6-RET had higher proliferative ability and more aggressive potency than cells without ATM knock-down in vitro. Furthermore, combining gene alterations and clinical features significantly improved the predictive efficacy for lymph node metastasis of radiomic features, from 71.5 to 87.0%.

Conclusions

Targeted sequencing of comprehensive genetic alterations in PTC has high prognostic value. These alterations, in combination with clinical and radiomic features, may aid in predicting invasive PTC with higher accuracy.
Prognostic value of the tumor-to-liver density ratio in patients with metastatic colorectal cancer treated with bevacizumab-based chemotherapy. A post-hoc study of the STIC-AVASTIN trial
Authors: Mazard Thibault , Mollevi Caroline , Loyer Evelyne M. , Léger Julie , Chautard Romain , Bouché Olivier , Borg Christophe , Armand-Dujardin Paul , Bleuzen Aurore , Assenat Eric , Lecomte Thierry
Published: June 2024

Background

The Response Evaluation Criteria in Solid Tumors (RECIST) are often inadequate for the early assessment of the response to cancer therapy, particularly bevacizumab-based chemotherapy. In a first cohort of patients with colorectal cancer liver metastases (CRLM), we showed that variations of the tumor-to-liver density (TTLD) ratio and modified size-based criteria determined using computed tomography (CT) data at the first restaging were better prognostic criteria than the RECIST. The aims of this study were to confirm the relevance of these radiological biomarkers as early predictors of the long-term clinical outcome and to assess their correlation with contrast-enhanced ultrasound (CEUS) parameters in a new patient cohort.

Methods

In this post-hoc study of the multicenter STIC-AVASTIN trial, we retrospectively reviewed CT data of patients with CRLM treated with bevacizumab-based regimens. We determined the size, density and TTLD ratio of target liver lesions at baseline and at the first restaging and also performed a morphologic evaluation according to the MD Anderson criteria. We assessed the correlation of these parameters with progression-free survival (PFS) and overall survival (OS) using the log-rank test and a Cox proportional hazard model. We also examined the association between TTLD ratio and quantitative CEUS parameters.

Results

This analysis concerned 79 of the 137 patients included in the STIC-AVASTIN trial. PFS and OS were significantly longer in patients with tumor size reduction > 15% at first restaging, but were not correlated with TTLD ratio variations. However, PFS was longer in patients with TTLD ratio > 0.6 at baseline and first restaging than in those who did not reach this threshold. In the multivariate analysis, only baseline TTLD ratio > 0.6 was a significant survival predictor. TTLD ratio > 0.6 was associated with improved perfusion parameters.

Conclusions

Although TTLD ratio variations did not correlate with the long-term clinical outcomes, TTLD absolute values remained a good predictor of survival at baseline and first restaging, and may reflect tumor microvascular features that might influence bevacizumab-based treatment efficiency.

Trial registration

NCT00489697, registration number of the STIC-AVASTIN trial.
The combined effect of leucine-enriched essential amino acid supplements and locomotion training on physical functions and quality of life in hemodialysis patients
Authors: Kitabayashi Kou , Yamamoto Suguru , Katano Yumi , Narita Ichiei
Published: June 2024

Background

Locomotive syndrome (LS) is a condition of reduced mobility (locomotive organ impairment) that is associated with reduced quality of life (QOL) in patients undergoing hemodialysis (HD), and effective interventions for patients with LS undergoing HD are unclear. We conducted a clinical trial to assess the effects of exercise and oral nutritional supplementation (ONS) on QOL in this cohort.

Methods

This study was an open-label, randomized controlled trial. The participants were patients with LS undergoing HD. The intervention period was 3 months. The primary outcome was a change in the physical component summary (PCS) of QOL, and the secondary outcomes were changes in other QOL scores, physical function, body composition, and nutritional status assessed by using the geriatric nutritional risk index. Participants were divided into the locomotion training (LT) and LT + ONS groups. Both groups were instructed on LT that comprised one-leg standing and squats to be carried out four or more times per week. The ONS consisted of 3 g leucin-rich essential amino acids and 800 IU vitamin D per pack, and the participants in the LT + ONS group received one pack of the supplement per day.

Results

In total, 40 individuals undergoing HD were included in the study; 3 patients in the LT + ONS group were excluded from the analysis because of hospitalization and incomplete assessment. The median age was 73 years (interquartile range: 62–80 years), 23 participants were men (62%), and the duration of dialysis treatment was 6 years (interquartile range: 3–16 years). The change in PCS of the LT + ONS group did not differ from that in the LT group [LT + ONS: −1.6 (−5.3, 6.8) versus LT: −0.1 (−5.3, 6.2), p = 0.94]. In contrast, the LT + ONS group showed maintenance in mental health (MH) and improvement of the two-step value.

Conclusions

The LT + ONS group did not show an effect on PCS in QOL compared with only LT in patients with LS undergoing HD. However, maintenance of MH and improvement of two-step value were confirmed in the LT + ONS group. Future research is need to confirm whether leucine-rich essential amino acids and vitamin D help mental health and physical function in patients with LS undergoing HD with larger sample sizes and long-term interventions.

Clinical trial registration University Hospital Medical Information Network Center (UMIN 000032457).
Explore the ancient roots of the Huaxia people and Chinese civilization
Authors: Gao Xing
Published: June 2024

Chinese civilization, which stands as a shining star in human civilizations, is distinct in its nature and development path. Although it suffered numerous turns of devastation in its 5,000 years of history, it has resiliently remained uninterrupted in its growth and radiance. Characterized by continuity, innovation, unity, inclusiveness, and longstanding commitment to peace, it also exhibits strong cohesion, vitality, flexibility, and adaptability. These characteristics emerged in the Paleolithic Period, indicating that the Chinese civilization did not emerge overnight. Its roots run deep with a long history, sprouting in the Paleolithic Period, breaking ground in the late Neolithic period, and gradually growing into the towering trees it is today. How did the ancient people in China evolve into today’s Chinese nation? How did the ancient culture of prehistoric times develop into the current Chinese civilization? What are the connections between the history buried underground and the society we see today? Obviously, there is no clear answer to these questions. There are still many gaps in prehistoric China that need to be filled, and the process of and reasons for the evolution of ethnic groups and cultures still need to be further interpreted. The author tries to trace the roots of the Chinese nation and its civilization back to the Paleolithic Period, using archaeological materials to connect the survival and reproduction process of ancestors and delve into studying the ancient roots of the Huaxia people and Chinese civilization.
Detecting faults in the cooling systems by monitoring temperature and energy
Authors: Kaushik Keshav , Naik Vinayak
Published: June 2024

The cooling systems contribute to 40% of overall building energy consumption. Out of which, 40% is wasted because of faulty parts that cause anomalies in the cooling systems. We propose a three-stage, non-invasive part-level anomaly detection technique to identify anomalies in both cooling systems, a ducted-centralized and a ductless-split. We use COTS sensors to monitor temperature and energy without invading the cooling system. After identifying the anomalies, we find the cause of the anomaly. Based on the anomaly, the solution recommends a fix. If there is a technical fault, our proposed technique informs the technician regarding the faulty part, reducing the cost and time needed to repair it. In the first stage, we propose a domain-inspired time-series statistical technique to identify anomalies in cooling systems. We observe an AUC-ROC score of more than 0.93 in simulation and experimentation. In the second stage, we propose using a rule-based technique to identify the cause of the anomaly. We classify causes of anomalies into three classes. We observe an AUC-ROC score of 1. Based on the anomaly classification, we identify the faulty part of the cooling system in the third stage. We use the Nearest-Neighbour Density-Based Spatial Clustering of Applications with Noise (NN-DBSCAN) algorithm with transfer learning capabilities to train the model only once, where it learns the domain knowledge using the simulated data. The trained model is used in different environmental scenarios with both types of cooling systems. The proposed algorithm shows an accuracy score of 0.82 in simulation deployment and 0.88 in experimentation. In the simulation we used both ducted-centralized and ductless-split cooling systems and in the experimentation we evaluated the solution with ductless-split cooling systems. The overall accuracy of the three-stage technique is 0.82 and 0.86 in simulation and experimentation, respectively. We observe energy savings of up to 68% in simulation and 42% during experimentation, with a reduction of ten days in the cooling system’s downtime and up to 75% in repair cost.
Characteristics and effectiveness of deep and ultradeep tight sandstone fractures: Insights from geologic and geophysical data analysis
Authors: Zhang Guanjie , Liu Jingshou , Xu Ke , Jiang Shu , Zhang Binxin , Shi Ning
Published: June 2024

Effective natural fractures are those that contribute to reservoir storage and conductivity. In this study, the effectiveness of fractures in deep and ultradeep reservoirs (depths > 6 km) is evaluated by using geophysical image logs, cores, microstructures, mechanical tests, and geologic evidence of the tectonic context (including current in situ stress) and sedimentary faces and diagenesis. Intraformational open-mode fractures are the most common fracture type in this tectonically active region, and their effectiveness is affected by the coupling between past tectonic activity, in situ stress, and chemical reactions such as mineral precipitation or dissolution (diagenesis). Our results show that the effectiveness of fractures is mainly related to the aperture and filling, and fractures formed by early tectonic movement are more likely to be filled by minerals, reducing their effectiveness. Strata near orogenic belts in strongly cemented, tight diagenetic facies exhibit a greater abundance of mineral-filled fractures, whereas dissolution increases the fracture apertures, produces secondary pores in host rocks, and roughens the fracture walls. The effective normal stress acting on the fracture surface decreases when the fracture is parallel to the maximum horizontal stress component, so the fracture has a large aperture and, therefore, is more effective. The results of our laboratory measurements reveal that the contribution of fractures to the reservoir space is limited, and the reservoir space provided by fractures accounts for only 13% of all types of reservoir space, whereas the presence of fractures increases reservoir permeability by 1–2 orders of magnitude. Fractures improve the effectiveness of the reservoir by connecting the dispersed pores in the reservoir matrix. Fractures with a low angle to the maximum horizontal stress component have greater apertures and permeabilities and are the main channels for fluid flow.