bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabologenomics analysis of Pseudomonas sp. So3.2b, an Antarctic strain with bioactivity against Rhizoctonia solani
Authors: Maimone Naydja Moralles , Junior Mario Cezar Pozza , de Oliveira Lucianne Ferreira Paes , Rojas-Villalta Dorian , de Lira Simone Possedente , Barrientos Leticia , Núñez-Montero Kattia
Published: May 2023

Introduction

Phytopathogenic fungi are a considerable concern for agriculture, as they can threaten the productivity of several crops worldwide. Meanwhile, natural microbial products are acknowledged to play an important role in modern agriculture as they comprehend a safer alternative to synthetic pesticides. Bacterial strains from underexplored environments are a promising source of bioactive metabolites.

Methods

We applied the OSMAC (One Strain, Many Compounds) cultivation approach, in vitro bioassays, and metabolo-genomics analyses to investigate the biochemical potential of Pseudomonas sp. So3.2b, a strain isolated from Antarctica. Crude extracts from OSMAC were analyzed through HPLC-QTOF-MS/MS, molecular networking, and annotation. The antifungal potential of the extracts was confirmed against Rhizoctonia solani strains. Moreover, the whole-genome sequence was studied for biosynthetic gene clusters (BGCs) identification and phylogenetic comparison.

Results and Discussion

Molecular networking revealed that metabolite synthesis has growth media specificity, and it was reflected in bioassays results against R. solani. Bananamides, rhamnolipids, and butenolides-like molecules were annotated from the metabolome, and chemical novelty was also suggested by several unidentified compounds. Additionally, genome mining confirmed a wide variety of BGCs present in this strain, with low to no similarity with known molecules. An NRPS-encoding BGC was identified as responsible for producing the banamides-like molecules, while phylogenetic analysis demonstrated a close relationship with other rhizosphere bacteria. Therefore, by combining -omics approaches and in vitro bioassays, our study demonstrates that Pseudomonas sp. So3.2b has potential application to agriculture as a source of bioactive metabolites.
Cortical interneurons: fit for function and fit to function? Evidence from development and evolution
Authors: Keijser Joram , Sprekeler Henning
Published: May 2023

Cortical inhibitory interneurons form a broad spectrum of subtypes. This diversity suggests a division of labor, in which each cell type supports a distinct function. In the present era of optimisation-based algorithms, it is tempting to speculate that these functions were the evolutionary or developmental driving force for the spectrum of interneurons we see in the mature mammalian brain. In this study, we evaluated this hypothesis using the two most common interneuron types, parvalbumin (PV) and somatostatin (SST) expressing cells, as examples. PV and SST interneurons control the activity in the cell bodies and the apical dendrites of excitatory pyramidal cells, respectively, due to a combination of anatomical and synaptic properties. But was this compartment-specific inhibition indeed the function for which PV and SST cells originally evolved? Does the compartmental structure of pyramidal cells shape the diversification of PV and SST interneurons over development? To address these questions, we reviewed and reanalyzed publicly available data on the development and evolution of PV and SST interneurons on one hand, and pyramidal cell morphology on the other. These data speak against the idea that the compartment structure of pyramidal cells drove the diversification into PV and SST interneurons. In particular, pyramidal cells mature late, while interneurons are likely committed to a particular fate (PV vs. SST) during early development. Moreover, comparative anatomy and single cell RNA-sequencing data indicate that PV and SST cells, but not the compartment structure of pyramidal cells, existed in the last common ancestor of mammals and reptiles. Specifically, turtle and songbird SST cells also express the Elfn1 and Cbln4 genes that are thought to play a role in compartment-specific inhibition in mammals. PV and SST cells therefore evolved and developed the properties that allow them to provide compartment-specific inhibition before there was selective pressure for this function. This suggest that interneuron diversity originally resulted from a different evolutionary driving force and was only later co-opted for the compartment-specific inhibition it seems to serve in mammals today. Future experiments could further test this idea using our computational reconstruction of ancestral Elfn1 protein sequences.
Progressive multifocal leukoencephalopathy in a patient with multiple myeloma: a case report and analysis of the FDA adverse event reporting system
Authors: Jonasson Elise , Antulov Ronald , Trøllund Pedersen Per , Sejbæk Tobias
Published: May 2023

This paper demonstrates a case of progressive multifocal leukoencephalopathy (PML) in a patient with multiple myeloma (MM) treated with nine different MM therapies. This case report contributes to the already published 16 cases of PML in patients with MM. Additionally, this paper presents an analysis of cases from the United States Food and Drug Administration Adverse Event Report System database (n = 117) with a description of demographics and MM-specific therapies. Patients with MM, that developed PML, were treated with immunomodulatory drugs (97%), alkylating agents (52%), and/or proteasome inhibitors (49%). Prior to PML diagnosis, 72% of patients received two or more MM therapies. These results indicate that PML in MM is underreported and could be related to treatment with multiple immunosuppressive therapies rather than MM as a disease itself. Physicians should be aware of potential PML in the late stage of heavily treated MM patients.
Study on characteristic of epileptic multi-electroencephalograph base on Hilbert-Huang transform and brain network dynamics
Authors: Lu Xiaojie , Wang Tingting , Ye Mingquan , Huang Shoufang , Wang Maosheng , Zhang Jiqian
Published: May 2023

Lots of studies have been carried out on characteristic of epileptic Electroencephalograph (EEG). However, traditional EEG characteristic research methods lack exploration of spatial information. To study the characteristics of epileptic EEG signals from the perspective of the whole brain，this paper proposed combination methods of multi-channel characteristics from time-frequency and spatial domains. This paper was from two aspects: Firstly, signals were converted into 2D Hilbert Spectrum (HS) images which reflected the time-frequency characteristics by Hilbert-Huang Transform (HHT). These images were identified by Convolutional Neural Network (CNN) model whose sensitivity was 99.8%, accuracy was 98.7%, specificity was 97.4%, F1-score was 98.7%, and AUC-ROC was 99.9%. Secondly, the multi-channel signals were converted into brain networks which reflected the spatial characteristics by Symbolic Transfer Entropy (STE) among different channels EEG. And the results show that there are different network properties between ictal and interictal phase and the signals during the ictal enter the synchronization state more quickly, which was verified by Kuramoto model. To summarize, our results show that there was different characteristics among channels for the ictal and interictal phase, which can provide effective physical non-invasive indicators for the identification and prediction of epileptic seizures.
Characteristics and outcomes of fetal ventricular aneurysm and diverticulum: combining the use of a new technique, fetal HQ
Authors: Zhao Liqing , Wu Pengfei , Jiao Xianting , Zhang Minjie , Jing Wenhao , Wu Yurong , Chen Sun
Published: May 2023

Objectives

Congenital ventricular aneurysms or diverticulum (VA/VD) are rare cardiac anomalies with lack prenatal evaluation data. The present study aimed to provide the prenatal characteristics and outcomes from a tertiary center and the use of new techniques to evaluate the shape and contractility of these fetuses.

Methods

Ten fetuses were diagnosed with VA or VD, and 30 control fetuses were enrolled. Fetal echocardiography was performed to make the diagnosis. The prenatal echo characteristics and follow-up data were carefully reviewed. The shape and contractility measurements of the four-chamber view (4CV) and both ventricles were measured and computed using fetal fetal heart quantification (HQ).

Results

A total of 10 fetuses were enrolled, including 4 cases of left ventricular diverticulum, 5 cases of left ventricular aneurysm, and 1 case of right ventricular aneurysm (RVA). Four cases chose to terminate the pregnancy. The RVA was associated with a perimembranous ventricular septal defect. Two cases had fetal arrhythmia, and one case had pericardial effusion. After birth, one case underwent surgical resection at five years old. The 4CV global sphericity index (SI) of free-wall located ventricular outpouching (VO) was significantly lower than the apical ones and the control group (p < 0.01). Four of five apical left VOs had significant higher (>95th centile) SI in base segments, and three of four left VOs in the free-wall had significant lower (< 5th centile) SI in the majority of 24 segments. Compared to the control group, the left ventricle (LV) global longitudinal strain, ejection fraction, and fractional area change were significantly decreased (p < 0.01), while the LV cardiac output of the cases was in the normal range. The transverse fraction shortening of the affected segments of ventricles was significantly lower than the other ventricle segments (p < 0.01).

Conclusions

Fetal HQ is a promising technique to evaluate the shape and contractility of congenital ventricular aneurysm and diverticulum.
Will nanomedicine become a good solution for the cardiotoxicity of chemotherapy drugs?
Authors: Jiang Yichuan , Jiang Yueyao , Li Min , Yu Qian
Published: May 2023

Cancer is one of the leading causes of death worldwide, and with the continuous development of life sciences and pharmaceutical technology, more and more antitumor drugs are being used in clinics to benefit cancer patients. However, the incidence of chemotherapy-induced cardiotoxicity has been continuously increasing, threatening patients’ long-term survival. Cardio-oncology has become a research hot spot, and the combination of nanotechnology and biomedicine has brought about an unprecedented technological revolution. Nanomaterials have the potential to maximize the efficacy and reduce the side effects of chemotherapeutic drugs when used as their carriers, and several nano-formulations of frequently used chemotherapeutic drugs have already been approved for marketing. In this review, we summarize chemotherapeutic drugs that are highly associated with cardiotoxicity and evaluate the role of nano-delivery systems in reducing cardiotoxicity based on studies of their marketed or R&D nano-formulations. Some of the marketed chemotherapy drugs are combined with nano-delivery systems that can effectively deliver chemotherapy drugs to tumors and cannot easily penetrate the endothelial barrier of the heart, thus decreasing their distribution in the heart and reducing the cardiotoxicity to some extent. However, many chemotherapy nanomedicines that are marketed or in R&D have not received enough attention in determining their cardiotoxicity. In general, nanomedicine is an effective method to reduce the cardiotoxicity of traditional chemotherapy drugs. However, cardiovascular complications in cancer treatment are very complex diseases, requiring the application of multiple measures to achieve effective management and prevention.
A novel platelet risk score for stratifing the tumor immunophenotypes, treatment responses and prognosis in bladder carcinoma: results from real-world cohorts
Authors: Deng Dingshan , Li Xiaowen , Qi Tiezheng , Dai Yuanqing , Liu Neng , Li Huihuang
Published: May 2023

Background: Although the durable efficacy of immune checkpoint inhibitors (ICIs) in BLCA has been confirmed in numerous studies, not all patients benefit from their application in the clinic. Platelets are increasingly being found to be closely associated with cancer progression and metastasis; however, their comprehensive role in BLCA remains unclear.

Methods: We comprehensively explored platelet expression patterns in BLCA patients using an integrated set of 244 related genes. Correlations between these platelet patterns with tumor microenvironment (TME) subtypes, immune characteristics and immunotherapy efficacies were explored. In addition, a platelet risk score (PRS) was generated for individual prognosis and verified the ability to predict prognosis, precise TME phenotypes, and immunotherapy efficacies.

Results: Genes were clustered into two patterns that represented different TME phenotypes and had the ability to predict immunotherapy efficacy. We constructed a PRS that could predict individual prognosis with satisfactory accuracy using TCGA-BLCA. The results remained consistent when PRS was validated in the GSE32894 and Xiangya cohort. Moreover, we found that our PRS was positively related to tumor-infiltrating lymphocytes (TILs) in the TCGA-BLCA and Xiangya cohort. As expected, patients with higher PRS exhibited more sensitive to immunotherapy than patients with lower PRS. Finally, we discovered that a high PRS indicated a basal subtype of BLCA, whereas a low PRS indicated a luminal subtype.

Conclusion: Platelet-related genes could predict TME phenotypes in BLCA. We constructed a PRS that could predict the TME, prognosis, immunotherapy efficacy, and molecular subtypes in BLCA.
Thermal geometries and the Joule–Thomson expansion of modified charged and slowly rotating black holes
Authors: Yasir Muhammad , Lining Tong , Tiecheng Xia , Ditta Allah
Published: May 2023

Thermodynamics of charged and slowly rotating black holes in 4D Gauss–Bonnet gravity has attracted a great deal of attention due to its intrinsic complications and rich phase structures. In this paper, we revisit the thermodynamics of charged and slowly rotating black holes and provide the correct thermodynamic volume and entropy. Thermodynamic geometries are a powerful tool to study the microstructure of black holes. Based on the Hessian matrix of the black hole mass, we introduce thermodynamic geometric methods and give its scalar curvature (Ruppeiner and Weinhold). Furthermore, we investigate the Joule–Thomson expansion of slowly rotating black hole in 4D Gauss–Bonnet gravity in this research study. Interestingly, we explicitly state that the expression of the Joule–Thomson coefficient is obtained from the basic formulas of enthalpy and temperature. Then, we obtain the isenthalpic curve in the T − P graph and demonstrate the cooling–heating region by the inversion curve. The inversion temperature and inversion curves are obtained, and we investigate the similarities and differences between van der Waals fluids and charged fluids.
From helplessness to controllability: toward a neuroscience of resilience
Authors: Baratta Michael V. , Seligman Martin E. P. , Maier Steven F.
Published: May 2023

“Learned helplessness” refers to debilitating outcomes, such as passivity and increased fear, that follow an uncontrollable adverse event, but do not when that event is controllable. The original explanation argued that when events are uncontrollable the animal learns that outcomes are independent of its behavior, and that this is the active ingredient in producing the effects. Controllable adverse events, in contrast, fail to produce these outcomes because they lack the active uncontrollability element. Recent work on the neural basis of helplessness, however, takes the opposite view. Prolonged exposure to aversive stimulation per se produces the debilitation by potent activation of serotonergic neurons in the brainstem dorsal raphe nucleus. Debilitation is prevented with an instrumental controlling response, which activates prefrontal circuitry detecting control and subsequently blunting the dorsal raphe nucleus response. Furthermore, learning control alters the prefrontal response to future adverse events, thereby preventing debilitation and producing long-term resiliency. The general implications of these neuroscience findings may apply to psychological therapy and prevention, in particular by suggesting the importance of cognitions and control, rather than habits of control.
Aligning clinical research ethics with community-engaged and participatory research in the United States
Authors: Eder Milton (Mickey)
Published: May 2023

The professional role in ethical review of research in which boards review proposed research involving human beings continues to evolve. The scholarly literature on institutional review boards in academic centers of the United States, at which a majority of the community engaged and participatory research emanates and is reviewed, suggests the need to implement changes in board education, the infrastructure supporting review, and the accountability of review. The recommendations for change advanced in this perspective involve enhancing reviewer knowledge of local community contexts and developing an infrastructure that supports engagement in and dialogue among individuals involved in community-academic research to inform ethical review and the assessment of review outcomes. Additionally, recommendations regarding putting an institutional infrastructure in place are advanced in order to sustain community engaged and participatory research. The infrastructure can also support the collection and review of outcome data as the foundation of accountability. The recommendations outlined intend to improve clinical research ethics reviews of community-engaged and participatory research.
Prevalence of common chronic disease and multimorbidity patterns in Guangdong province with three typical cultures: analysis of data from the Diverse Life-Course Cohort study
Authors: Hu Yaoda , He Huijing , Ou Qiong , Nai Jing , Pan Li , Chen Xingming , Tu Ji , Zeng Xuejun , Pei Guo , Wang Longlong , Lin Binbin , Liu Qihang , Shan Guangliang
Published: May 2023

Background

Variations in the prevalence and pattern of multimorbidity might be attributable to lifestyle and environmental factors. This study was performed to determine the prevalence of common chronic diseases and to reveal multimorbidity patterns among adults in Guangdong province with Chaoshan, Hakka, and island cultures.

Methods

We used data collected at the baseline survey (April–May 2021) of the Diverse Life-Course Cohort study and included 5,655 participants aged ≥20 years. Multimorbidity was defined as the presence of two or more of the 14 chronic diseases collected by self-reports, physical examinations, and blood tests. Multimorbidity patterns were explored by association rule mining (ARM).

Results

Overall, 40.69% of participants had multimorbidity, and the prevalence among coastland (42.37%) and mountain residents (40.36%) was higher than that among island residents (37.97%). The prevalence of multimorbidity increased rapidly with higher age groups and showed an inflection point at 50 years, beyond which >50% of the middle-aged and older adults had multimorbidity. The proportion of people with two chronic diseases accounted for most cases of multimorbidity, and the strongest association was found between hyperuricemia and gout (lift of 3.26). The most prevalent multimorbidity pattern was dyslipidemia and hyperuricemia in the coastland areas and dyslipidemia combined with hypertension in the mountain and island areas. Furthermore, the most common triad combination consisted of cardiovascular diseases, gout, and hyperuricemia, which was verified in the mountain and coastal areas.

Conclusion

These observations of multimorbidity patterns, including the most frequent multimorbidity and associations, will help healthcare providers develop healthcare plans that improve the effectiveness of multimorbidity management.
Quantifying the contribution of 31 risk factors to the increasing prevalence of diabetes among US adults, 2005–2018
Authors: Huang Yue , Xu Yaqing , Qiao Yongxia , Wang Hui , Zhong Victor W.
Published: May 2023

Introduction

No study has comprehensively quantified the individual and collective contributions of various risk factors to the growing burden of diabetes in the United States.

Methods

This study aimed to determine the extent to which an increase in the prevalence of diabetes was related to concurrent changes in the distribution of diabetes-related risk factors among US adults (aged 20 years or above and not pregnant). Seven cycles of series of cross-sectional National Health and Nutrition Examination Survey data between 2005–2006 and 2017–2018 were included. The exposures were survey cycles and seven domains of risk factors, including genetic, demographic, social determinants of health, lifestyle, obesity, biological, and psychosocial domains. Using Poisson regressions, percent reduction in the β coefficient (the logarithm used to calculate the prevalence ratio for prevalence of diabetes in 2017–2018 vs. 2005–2006) was computed to assess the individual and collective contribution of the 31 prespecified risk factors and seven domains to the growing burden of diabetes.

Results

Of the 16,091 participants included, the unadjusted prevalence of diabetes increased from 12.2% in 2005–2006 to 17.1% in 2017–2018 [prevalence ratio: 1.40 (95% CI, 1.14–1.72)]. Individually, genetic domain [17.3% (95% CI, 5.4%−40.8%)], demographic domain [41.5% (95% CI, 24.4%−76.8%)], obesity domain [35.3% (95% CI, 15.8%−70.2%)], biological domain [46.2% (95% CI, 21.6%−79.1%)], and psychosocial domain [21.3% (95% CI, 9.5%−40.1%)] were significantly associated with a different percent reduction in β. After adjusting for all seven domains, the percent reduction in β was 97.3% (95% CI, 62.7%−164.8%).

Conclusion

The concurrently changing risk factors accounted for the increasing diabetes prevalence. However, the contribution of each risk factor domain varied. Findings may inform planning cost-effective and targeted public health programs for diabetes prevention.
Digital dashboards visualizing public health data: a systematic review
Authors: Schulze Annett , Brand Fabian , Geppert Johanna , Böl Gaby-Fleur
Published: May 2023

Introduction

Public health is not only threatened by diseases, pandemics, or epidemics. It is also challenged by deficits in the communication of health information. The current COVID-19 pandemic demonstrates that impressively. One way to deliver scientific data such as epidemiological findings and forecasts on disease spread are dashboards. Considering the current relevance of dashboards for public risk and crisis communication, this systematic review examines the state of research on dashboards in the context of public health risks and diseases.

Method

Nine electronic databases where searched for peer-reviewed journal articles and conference proceedings. Included articles (n= 65) were screened and assessed by three independent reviewers. Through a methodological informed differentiation between descriptive studies and user studies, the review also assessed the quality of included user studies (n= 18) by use of the Mixed Methods Appraisal Tool (MMAT).

Results

65 articles were assessed in regards to the public health issues addressed by the respective dashboards, as well as the data sources, functions and information visualizations employed by the different dashboards. Furthermore, the literature review sheds light on public health challenges and objectives and analyzes the extent to which user needs play a role in the development and evaluation of a dashboard. Overall, the literature review shows that studies that do not only describe the construction of a specific dashboard, but also evaluate its content in terms of different risk communication models or constructs (e.g., risk perception or health literacy) are comparatively rare. Furthermore, while some of the studies evaluate usability and corresponding metrics from the perspective of potential users, many of the studies are limited to a purely functionalistic evaluation of the dashboard by the respective development teams.

Conclusion

The results suggest that applied research on public health intervention tools like dashboards would gain in complexity through a theory-based integration of user-specific risk information needs.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=200178, identifier: CRD42020200178.
Long-term care units: a Portuguese study about the functional profile
Authors: Fonseca César , Ramos Ana , Morgado Bruno , Quaresma Paulo , Garcia-Alonso José , Coelho Anabela , Lopes Manuel
Published: May 2023

Aim: In this study, we analyze the relationship between the functional profile of older people admitted to long-term care units in Portugal and some demographic variables such as education level, sex, and age as well as the emotional state of mind.

Methods: A sample of 59,516 older people from the National Network of Integrated Continuous Care of Portugal were analyzed in this longitudinal study. All the retrospective data of the older people were collected during the period of hospitalization at the long-term care units. The database records of these units were analyzed, and a functional profile spanning the period of hospitalization was calculated.

Results: Activities of daily living and cognitive states improved, in the first 90 days of hospitalization, while mobility and instrumental activities of daily living worsened for the same period of 90 days. Generally, there was a decline in all domains after 450 days of hospitalization. The older women that did not attend school, those over 85 years old, and those who suffered from anxiety were pre-dominantly placed in the group of those with greater dependence (severe/complete dependence).

Conclusion: The participants hospitalized between 90 and 360 days presented the best results in the long-term care units of the National Network of Integrated Continuous Care of Portugal. With this study, we highlight the importance of evaluating the functional status of persons in long-term hospitalizations and the influence exerted by the level of education on the recovery and rehabilitation of dependence.
ChatGPT in medicine: an overview of its applications, advantages, limitations, future prospects, and ethical considerations
Authors: Dave Tirth , Athaluri Sai Anirudh , Singh Satyam
Published: May 2023

This paper presents an analysis of the advantages, limitations, ethical considerations, future prospects, and practical applications of ChatGPT and artificial intelligence (AI) in the healthcare and medical domains. ChatGPT is an advanced language model that uses deep learning techniques to produce human-like responses to natural language inputs. It is part of the family of generative pre-training transformer (GPT) models developed by OpenAI and is currently one of the largest publicly available language models. ChatGPT is capable of capturing the nuances and intricacies of human language, allowing it to generate appropriate and contextually relevant responses across a broad spectrum of prompts. The potential applications of ChatGPT in the medical field range from identifying potential research topics to assisting professionals in clinical and laboratory diagnosis. Additionally, it can be used to help medical students, doctors, nurses, and all members of the healthcare fraternity to know about updates and new developments in their respective fields. The development of virtual assistants to aid patients in managing their health is another important application of ChatGPT in medicine. Despite its potential applications, the use of ChatGPT and other AI tools in medical writing also poses ethical and legal concerns. These include possible infringement of copyright laws, medico-legal complications, and the need for transparency in AI-generated content. In conclusion, ChatGPT has several potential applications in the medical and healthcare fields. However, these applications come with several limitations and ethical considerations which are presented in detail along with future prospects in medicine and healthcare.
The memory clinic and psychosocial intervention: Translating past promise into current practices
Authors: Moniz-Cook Esme , Mountain Gail
Published: May 2023

Disproportionate negative effects since the pandemic have amplified the already limited post-diagnostic support for older people with dementia. This paper summarizes an exploratory randomized controlled study of a proactive family-based intervention compared with “usual” post-diagnostic dementia care. Memory clinic practitioners collaborated with the family doctor (GP) to coordinate this. At 12-month follow-up, positive effects on mood, behavior, carer coping and maintenance of care at home were found. Current approaches to deliver post-diagnostic support in primary care may require rethinking since (i) GP workloads have increased with low numbers of GPs per head of population in parts of England; and (ii) unlike many other long-term conditions, ongoing stigma, fear and uncertainty associated with dementia adds to the huge complexity of timely care provision. There is a case for return to a “one-stop facility”, with a single pathway of continuing multidisciplinary coordinated care for older people with dementia and families. Future longitudinal research could compare structured post-diagnostic psychosocial intervention coordinated by skilled practitioners in a single locality memory service “hub”, against other approaches such support organized mostly within primary care. Dementia-specific instruments for outcome measurement are available for use in routine practice, and should be included in such comparative studies.
Optimizing the Better Nights, Better Days for Children with Neurodevelopmental Disorders program for large scale implementation
Authors: Ilie Alzena , Orr Matt , Weiss Shelly , Smith Isabel M. , Reid Graham J. , Hanlon-Dearman Ana , Brown Cary , Constantin Evelyn , Godbout Roger , Shea Sarah , Ipsiroglu Osman S. , Corkum Penny V.
Published: May 2023

Objective

Pediatric insomnia is one of the most commonly reported disorders, especially in children with neurodevelopmental disorders.Better Nights, Better Days for Children with Neurodevelopmental Disorders(BNBD-NDD) is a transdiagnostic, self-guided, eHealth behavioral sleep intervention developed for parents of children with NDDs ages 4–12 years with insomnia. After usability testing, a randomized controlled trial (RCT) was conducted to evaluate the effectiveness of theBNBD-NDDprogram. By interviewing RCT participants after their outcome measures were collected, we sought to determine the barriers and facilitators that affect the reach, effectiveness, adoption, implementation, and maintenance of theBNBD-NDDintervention, as well as to assess whether barriers and facilitators differ across levels of engagement with the program and NDD groups.

Method

Twenty parents who had been randomized to the treatment condition of the RCT participated in this study. These parents participated in virtual semi-structured qualitative interviews about their experiences with theBNBD-NDDprogram. Rapid analysis was used, in which one researcher facilitated the interview, and another simultaneously coded the interview using the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework.

Results

Overall, more facilitators than barriers were identified for Reach, Effectiveness, Implementation, and Maintenance, whereas for Adoption more barriers emerged. Participants who were engaged reported more facilitators about theBNBD-NDDprogram design and behavior change, while unengaged participants mentioned needing more support to help facilitate their use of the program. Lastly, parents of children with ASD reported more facilitators and more barriers than did parents of children with ADHD.

Conclusion

With this feedback from participants, we can optimizeBNBD-NDDfor large-scale implementation, by modifying the program to better support parents, helping them implement the strategies effectively at home, and increasing the accessibility of this evidence-based treatment.
Phasing analysis on DRO with impulsive maneuver
Authors: Fu Honglan , Wang Ming , Zhang Hao
Published: May 2023

The cis-lunar periodic orbit exhibits some unique dynamic characteristics. Among them is the distant retrograde orbit, which has long-term stability and is one of the ideal candidate deployment orbits for cis-lunar space stations and deep-space exploration transfer stations. Orbiting, rendezvous, and docking are among the flight operations involved in space station on-orbit construction, material supply, spacecraft monitoring, and other tasks. Suitable initial conditions can be created for these operations by shortening the relative distance between spacecraft through phasing. In this study, the characteristics of a two-impulse phasing orbit on a distant retrograde orbit (DRO) are summarized, and its phasing ability is globally analyzed. Based on these analyses, a phasing optimization problem was presented and solved. Using DRO’s dynamic characteristics, a DRO multi-impulse phasing rolling solution method is presented. For accuracy purposes, the orbit determination error is also considered in this method. The simulation analysis was performed using the circular restricted three-body problem (CR3BP) dynamic model and the ephemeris model. Compared with the results of two-impulse phasing, this method reduces the offset of the end position of the DRO phasing orbit from hundreds to tens of kilometers. This result satisfies the relative distance requirements for subsequent spacecraft operations. The total pulse requirement of this phasing method for the two models was within a reasonable and feasible range.
Changes in Air Quality, Meteorology and Energy Consumption during the COVID-19 Lockdown and Unlock Periods in India
Authors: Kuttippurath Jayanarayanan , Patel Vikas Kumar , Gopikrishnan Gopalakrishna Pillai , Varikoden Hamza
Published: May 2023

The increasing population and its associated amenities demand innovative devices, infrastructure, methods, plans and policies. Regional climate has a great role in deciding the air quality and energy demand, and therefore, weather and climate have an indisputable role in its consumption and storage. Here, we present the changes in trace gases and associated regional weather in India during lockdown and unlock periods of COVID-19. We observe a reduction of about 30% in sulphur dioxide (SO2) and 10–20% in aerosols in the Indo-Gangetic Plain (IGP), large cities, industrial sites, mining areas and thermal power plants during lockdown as compared to the same period in the previous year and with respect to its climatology. However, a considerable increase in aerosols is found, particularly over IGP during Unlock 1.0 (1–30 June 2020), because of the relaxation of lockdown restrictions. The analyses also show a decrease in temperature by 1–3 °C during lockdown compared to its climatology for the same period, mainly in IGP and Central India, possibly due to the significant reduction in absorbing aerosols such as black carbon and decrease in humidity during the period. The west coast, northwest and central India show reduced wind speed when compared to its previous year and climatological values, suggesting that there was a change in regional weather due to the lockdown. Energy demand in India decreased by about 25–30% during the first phase of lockdown and about 20% during the complete lockdown period. This study thus suggests that the reduction of pollution could also modify local weather, and these results would be useful for drafting policy decisions on air pollution reduction, urban development, the energy sector, agriculture and water resources.
Wavelet Support Vector Censored Regression
Authors: Maia Mateus , Pimentel Jonatha Sousa , Ospina Raydonal , Ara Anderson
Published: May 2023

Learning methods in survival analysis have the ability to handle censored observations. The Cox model is a predictive prevalent statistical technique for survival analysis, but its use rests on the strong assumption of hazard proportionality, which can be challenging to verify, particularly when working with non-linearity and high-dimensional data. Therefore, it may be necessary to consider a more flexible and generalizable approach, such as support vector machines. This paper aims to propose a new method, namely wavelet support vector censored regression, and compare the Cox model with traditional support vector regression and traditional support vector regression for censored data models, survival models based on support vector machines. In addition, to evaluate the effectiveness of different kernel functions in the support vector censored regression approach to survival data, we conducted a series of simulations with varying number of observations and ratios of censored data. Based on the simulation results, we found that the wavelet support vector censored regression outperformed the other methods in terms of the C-index. The evaluation was performed on simulations, survival benchmarking datasets and in a biomedical real application.
Nitric Oxide Production from Nitrite plus Ascorbate during Ischemia upon Hippocampal Glutamate NMDA Receptor Stimulation
Authors: Nunes Carla , Laranjinha João
Published: May 2023

Nitric oxide (•NO), a diffusible free radical, is an intercellular messenger, playing a crucial role in several key brain physiological processes, including in neurovascular coupling (NVC). In the brain, glutamatergic activation of the neuronal nitric oxide synthase (nNOS) enzyme constitutes its main synthesis pathway. However, when oxygen (O2) supply is compromised, such as in stroke, ischemia, and aging, such •NO production pathway may be seriously impaired. In this context, evidence suggests that, as already observed in the gastric compartment, the reduction of nitrite by dietary compounds (such as ascorbate and polyphenols) or by specific enzymes may occur in the brain, constituting an important rescuing or complementary mechanism of •NO production. Here, using microsensors selective for •NO, we show that nitrite enhanced the •NO production in a concentration-dependent manner and in the presence of ascorbate evoked by N-methyl-D-aspartate (NMDA) and glutamate stimulation of rat hippocampal slices. Additionally, nitrite potentiated the •NO production induced by oxygen-glucose deprivation (OGD). Overall, these observations support the notion of a redox interaction of ascorbate with nitrite yielding •NO upon neuronal glutamatergic activation and given the critical role of NO as the direct mediator of neurovascular coupling may represents a key physiological mechanism by which •NO production for cerebral blood flow (CBF) responses to neuronal activation is sustained under hypoxic/acidic conditions in the brain.
Comparison of the Penetration Depth of 905 nm and 1064 nm Laser Light in Surface Layers of Biological Tissue Ex Vivo
Authors: Kaub Leon , Schmitz Christoph
Published: May 2023

The choice of parameters for laser beams used in the treatment of musculoskeletal diseases is of great importance. First, to reach high penetration depths into biological tissue and, secondly, to achieve the required effects on a molecular level. The penetration depth depends on the wavelength since there are multiple light-absorbing and scattering molecules in tissue with different absorption spectra. The present study is the first comparing the penetration depth of 1064 nm laser light with light of a smaller wavelength (905 nm) using high-fidelity laser measurement technology. Penetration depths in two types of tissue ex vivo (porcine skin and bovine muscle) were investigated. The transmittance of 1064 nm light through both tissue types was consistently higher than of 905 nm light. The largest differences (up to 5.9%) were seen in the upper 10 mm of tissue, while the difference vanished with increasing tissue thickness. Overall, the differences in penetration depth were comparably small. These results may be of relevance in the selection of a certain wavelength in the treatment of musculoskeletal diseases with laser therapy.
Modeling Global Genomic Instability in Chronic Myeloid Leukemia (CML) Using Patient-Derived Induced Pluripotent Stem Cells (iPSCs)
Authors: Telliam Gladys , Desterke Christophe , Imeri Jusuf , M’kacher Radhia , Oudrhiri Noufissa , Balducci Estelle , Fontaine-Arnoux Micheline , Acloque Hervé , Bennaceur-Griscelli Annelise , Turhan Ali G.
Published: May 2023

Methods: We used a patient-specific induced pluripotent stem cell (iPSC) line treated with the mutagenic agent N-ethyl-N-nitrosourea (ENU). Genomic instability was validated using γ-H2AX and micronuclei assays and CGH array for genomic events. Results: An increased number of progenitors (x5-Fold), which proliferated in liquid cultures with a blast cell morphology, was observed in the mutagenized condition as compared to the unmutagenized one. CGH array performed for both conditions in two different time points reveals several cancer genes in the ENU-treated condition, some known to be altered in leukemia (BLM, IKZF1, NCOA2, ALK, EP300, ERG, MKL1, PHF6 and TET1). Transcriptome GEO-dataset GSE4170 allowed us to associate 125 of 249 of the aberrations that we detected in CML-iPSC with the CML progression genes already described during progression from chronic and AP to BC. Among these candidates, eleven of them have been described in CML and related to tyrosine kinase inhibitor resistance and genomic instability. Conclusions: These results demonstrated that we have generated, for the first time to our knowledge, an in vitro genetic instability model, reproducing genomic events described in patients with BC.
The Validation of a Precursor Lesion of Epithelial Ovarian Cancer in Fancd2-KO Mice
Authors: Sczelecki Sarah , Pitman Janet L.
Published: May 2023

Ovarian cancer (OC) has the highest mortality rate of all gynaecological malignancies. The asymptomatic nature and limited understanding of early disease hamper research into early-stage OC. Therefore, there is an urgent need for models of early-stage OC to be characterised to improve the understanding of early neoplastic transformations. This study sought to validate a unique mouse model for early OC development. The homozygous Fanconi anaemia complementation group D2 knock-out mice (Fancd2−/−) develop multiple ovarian tumour phenotypes in a sequential manner as they age. Using immunohistochemistry, our group previously identified purported initiating precursor cells, termed ‘sex cords’, that are hypothesised to progress into epithelial OC in this model. To validate this hypothesis, the sex cords, tubulostromal adenomas and equivalent controls were isolated using laser capture microdissection for downstream multiplexed gene expression analyses using the Genome Lab GeXP Genetic Analysis System. Principal component analysis and unbiased hierarchical clustering of the resultant expression data from approximately 90 OC-related genes determined that cells from the sex cords and late-stage tumours clustered together, confirming the identity of the precursor lesion in this model. This study, therefore, provides a novel model for the investigation of initiating neoplastic events that can accelerate progress in understanding early OC.
The Role of Amplitude-Integrated Electroencephalography (aEEG) in Monitoring Infants with Neonatal Seizures and Predicting Their Neurodevelopmental Outcome
Authors: Doandes Florina Marinela , Manea Aniko Maria , Lungu Nicoleta , Brandibur Timea , Cioboata Daniela , Costescu Oana Cristina , Zaharie Mihaela , Boia Marioara
Published: May 2023

Newborn monitoring in neonatal intensive care units (NICU) is mandatory, but neurological and especially electroencephalographic (EEG) monitoring can be overlooked or delayed until the newborn is clinically stable. However, the neonatal period is associated with the highest risk of seizures in humans, and the clinical symptoms may often be discrete, but the evolution and long-term neurodevelopmental disorders in these patients may be important. In response to this issue, we conducted a study to evaluate newborns who experienced neonatal seizures (NS) in the NICU and monitored their long-term neurological development. We enrolled 73 term and preterm newborns who underwent EEG monitoring using amplitude-integrated electroencephalography (aEEG). We then followed their neurological development until around 18 months of age, with 59 patients remaining in the long-term study. A total of 22% of patients with NS developed epilepsy, 12% cerebral palsy, 19% severe neurodevelopmental disabilities, and 8.5% died within the first 18 months of life. Our findings indicate that aEEG background pattern is a strong predictor of unfavorable neurological outcomes, with an odds ratio of 20.4174 (p < 0.05). Additionally, higher Apgar scores were associated with better outcomes (p < 0.05), with the odds of unfavorable neurological outcomes decreasing by 0.7-fold for every point increase in Apgar score. Furthermore, we found a statistically significant association between preterm birth and unfavorable neurological outcomes (p = 0.0104). Our study highlights the importance of early EEG monitoring in the NICU and provides valuable insights into predictors of unfavorable neurological outcomes in newborns who experienced NS.
Progesterone Has No Impact on the Beneficial Effects of Estradiol Treatment in High-Fat-Fed Ovariectomized Mice
Authors: Talarico Carlos H. Z. , Alves Ester S. , Dos Santos Jessica D. M. , Sucupira Felipe G. S. , Araujo Layanne C. C. , Camporez João Paulo
Published: May 2023

In recent decades, clinical and experimental studies have revealed that estradiol contributes enormously to glycemic homeostasis. However, the same consensus does not exist in women during menopause who undergo replacement with progesterone or conjugated estradiol and progesterone. Since most hormone replacement treatments in menopausal women are performed with estradiol (E2) and progesterone (P4) combined, this work aimed to investigate the effects of progesterone on energy metabolism and insulin resistance in an experimental model of menopause (ovariectomized female mice—OVX mice) fed a high-fat diet (HFD). OVX mice were treated with E2 or P4 (or both combined). OVX mice treated with E2 alone or combined with P4 displayed reduced body weight after six weeks of HFD feeding compared to OVX mice and OVX mice treated with P4 alone. These data were associated with improved glucose tolerance and insulin sensitivity in OVX mice treated with E2 (alone or combined with P4) compared to OVX and P4-treated mice. Additionally, E2 treatment (alone or combined with P4) reduced both hepatic and muscle triglyceride content compared with OVX control mice and OVX + P4 mice. There were no differences between groups regarding hepatic enzymes in plasma and inflammatory markers. Therefore, our results revealed that progesterone replacement alone does not seem to influence glucose homeostasis and ectopic lipid accumulation in OVX mice. These results will help expand knowledge about hormone replacement in postmenopausal women associated with metabolic syndrome and non-alcoholic fatty liver disease.