bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel patch biomaterial treatment for colon diverticulosis in swine model
Authors: Guo Xiaomei , Patel Bhavesh , Han Ling , Van Alstine William G. , Noblet Jillian N. , Chambers Sean D. , Kassab Ghassan S.
Published: July 2023

Current leading managements for diverticular disease cannot prevent the recurrence of diverticulitis, bleeding and/or other complications. There is an immediate need for developing new minimal invasive therapeutic strategies to prevent and treat this disease. Through a biomechanical analysis of porcine colon with diverticular lesions, we proposed a novel adhesive patch concept aiming at mechanical reconstruction of the diseased colon wall. This study aims to evaluate the surgical feasibility (safety and efficacy) of pulmonary visceral pleura (PVP) patch therapy using a pig model of diverticulosis. Six female Yucatan miniature pigs underwent collagenase injection (CI) for the development of diverticular lesions. The lesions in each animal either received patch implantation (treated group, n = 40 for 6 pigs) or left intact (untreated group, n = 44 for 6 pigs). The normal colonic wall in each animal received patch implantation at two spots to serve as control (n = 12 for 6 pigs). After 3 months of observation, the performance and safety of the patch treatment were evaluated through macroscopic and histological examination. We found that 95% of pouch-like herniation of the mucosa was prevented from the colon wall with the treatment. The pouch diameter was significantly reduced in the treated group as compared to the untreated group (p < 0.001). The patch application caused a significant increase in the levels of collagen of the colon tissue as compared to the untreated and control groups (p < 0.001). No difference was found in the lymphocyte and macrophage inflammatory infiltrate between the groups. Our results suggest that patch treatment efficiently inhibits the diverticular pouch deformation and promotes the healing of the colon wall with a normal inflammatory response, which may minimize the risk of diverticulosis reoccurrence and complications over time.
Encephalitis and myositis caused by Trachipleistophora hominis diagnosed by metagenomic next-generation sequencing—a case report
Authors: Zheng Haipeng , Tan Ying , Chen Xudan , Chen Jinfeng , Li Linghua , Wang Jian
Published: July 2023

Background

Myositis is the main manifestation of Trachipleistophora hominis (T. hominis) infection and other microsporidians infection in immunocompromised patients. Clinical differential diagnosis of different microsporidians can be challenging, as the standard technique to distinguish various microsporidia species, transmission electron microscopy (TEM), is time-consuming and relies on equipment and experienced staffs who can perform the test and interpret the results.

Case presentation

We report a 37-year-old Chinese man with acquired immune deficiency syndrome (AIDS) developed headache and muscle pain in the extremities. Tramadol was used to relieve his pain. Infectious lesions in his brain were detected by cerebral magnetic resonance imaging (MRI). Oval-shaped pathogens was observed by biopsy of right gastrocnemius. Finally, T. hominis was identified by metagenomic next-generation sequencing (mNGS) in the gastrocnemius tissue and cerebrospinal fluid. After a 12-week course of antifungal treatment and antiretroviral therapy, the patient recovered from the encephalitis and myositis caused by T. hominis.

Conclusion

This report described the diagnosis and treatment of the first case of encephalitis caused by T. hominis. And mNGS is recommended for the rapid diagnosis of uncommon pathogens.
Digital participation and digital education for people with profound and multiple disabilities and complex communication needs
Authors: Keeley Caren , Bernasconi Tobias
Published: July 2023

“Digitalisation” is the buzzword of many societal as well as social changes. Participation in society is increasingly realized digitally, which is why it is important to be involved in these processes and to participate in the digital world. The UN CRPD also assigns an important role to (digital) technology as a prerequisite for inclusion and participation. Universal design, accessibility, assistive technology, and reasonable accommodation should help to avoid exclusion for people with disabilities. People with profound intellectual and multiple disabilities (PIMD), who often have complex communication needs (CCN) in addition to severe cognitive impairments, have fundamentally limited opportunities for participation. These are also visible in the context of digitalisation. At the same time, digital media also offer specific opportunities, particularly for people with PIMD and CCN. Among other things through the combined use of assistive technologies, digital media can significantly facilitate their daily lives. The present paper examines the significance, requirements and challenges as well as the potentials of digital participation and digital education in the lives of adults with PIMD and CCN and presents considerations for the design of digital education for adults. Finally, a conceptual framework for digital education for people with PIMD is presented.
Heart rate estimation from ballistocardiogram signals processing via low-cost telemedicine architectures: a comparative performance evaluation
Authors: Tramontano Adriano , Tamburis Oscar , Cioce Salvatore , Venticinque Salvatore , Magliulo Mario
Published: July 2023

Medical devices (MDs) have been designed for monitoring the parameters of patients in many sectors. Nonetheless, despite being high-performing and reliable, they often turn out to be expensive and intrusive. In addition, MDs are almost exclusively used in controlled, hospital-based environments. Paving a path of technological innovation in the clinical field, a very active line of research is currently dealing with the possibility to rely on non-medical-graded low-cost devices, to develop unattended telemedicine (TM) solutions aimed at non-invasively gathering data, signals, and images. In this article, a TM solution is proposed for monitoring the heart rate (HR) of patients during sleep. A remote patient monitoring system (RPMS) featuring a smart belt equipped with pressure sensors for ballistocardiogram (BCG) signals sampling was deployed. A field trial was then conducted over a 2-month period on 24 volunteers, who also agreed to wear a finger pulse oximeter capable of producing a photoplethysmography (PPG) signal as the gold standard, to examine the feasibility of the solution via the estimation of HR values from the collected BCG signals. For this purpose, two of the highest-performing approaches for HR estimation from BCG signals, one algorithmic and the other based on a convolutional neural network (CNN), were retrieved from the literature and updated for a TM-related use case. Finally, HR estimation performances were assessed in terms of patient-wise mean absolute error (MAE). Results retrieved from the literature (controlled environment) outperformed those achieved in the experimentation (TM environment) by 29% (MAE = 4.24 vs. 5.46, algorithmic approach) and 52% (MAE = 2.32 vs. 3.54, CNN-based approach), respectively. Nonetheless, a low packet loss ratio, restrained elaboration time of the collected biomedical big data, low-cost deployment, and positive feedback from the users, demonstrate the robustness, reliability, and applicability of the proposed TM solution. In light of this, further steps will be planned to fulfill new targets, such as evaluation of respiratory rate (RR), and pattern assessment of the movement of the participants overnight.
A study of factors influencing long-term glycemic variability in patients with type 2 diabetes: a structural equation modeling approach
Authors: Gan Yuqin , Chen Mengjie , Kong Laixi , Wu Juan , Pu Ying , Wang Xiaoxia , Zhou Jian , Fan Xinxin , Xiong Zhenzhen , Qi Hong
Published: July 2023

Aim

The present study aims to utilize structural equation modeling (SEM) to investigate the factors impacting long-term glycemic variability among patients afflicted with type 2 diabetes.

Method

The present investigation is a retrospective cohort study that involved the collection of data on patients with type 2 diabetes mellitus who received care at a hospital located in Chengdu, Sichuan Province, over a period spanning from January 1, 2013, to October 30, 2022. Inclusion criteria required patients to have had at least three laboratory test results available. Pertinent patient-related information encompassing general demographic characteristics and biochemical indicators was gathered. Variability in the dataset was defined by standard deviation (SD) and coefficient of variation (CV), with glycosylated hemoglobin variation also considering variability score (HVS). Linear regression analysis was employed to establish the structural equation models for statistically significant influences on long-term glycemic variability. Structural equation modeling was employed to analyze effects and pathways.

Results

Diabetes outpatient special disease management, uric acid variability, mean triglyceride levels, mean total cholesterol levels, total cholesterol variability, LDL variability, baseline glycated hemoglobin, and recent glycated hemoglobin were identified as significant factors influencing long-term glycemic variability. The overall fit of the structural equation model was found to be satisfactory and it was able to capture the relationship between outpatient special disease management, biochemical indicators, and glycated hemoglobin variability. According to the total effect statistics, baseline glycated hemoglobin and total cholesterol levels exhibited the strongest impact on glycated hemoglobin variability.

Conclusion

The factors that have a significant impact on the variation of glycosylated hemoglobin include glycosylated hemoglobin itself, lipids, uric acid, and outpatient special disease management for diabetes. The identification and management of these associated factors can potentially mitigate long-term glycemic variability, thereby delaying the onset of complications and enhancing patients’ quality of life.
Characterizing subsidence in used and restored peatland with Sentinel SAR data
Authors: Tarigan Suria , Kristanto Yudha , Utomo Waluyo Y.
Published: July 2023

Peatland is a fragile ecosystem in the tropical region which is prone to subsidence. Until now, there is still lack of procedure to rapidly assess a tropical peatland subsidence in a large area. Our objective was to compare subsidence in a used and restored zone in a peatland hydrological unit using synthetic aperture radar data from Sentinel-1A products (SAR data) in South Sumatra, Indonesia from the period of 2014–2021. The subsidence rate of used peatland estimated by the D-InSAR procedure were in the range of 28–80 cm year−1 in the early period of its utilization and becoming less for the consecutive year (16–48 cm year−1). Meanwhile, the subsidence rate based on the field surveys was in the range of 4–50 cm year−1 in the early period of peatland utilization. The subsidence rate in the used peatland zone (agriculture and plantations) was higher than that in the restoration zone for all SAR data pairs used in our study. The SAR data is a potential tool for the assessment, monitoring and differentiating subsidence rates among different peatland uses in a large area. This tool will help the Directorate of Peat Ecosystem Degradation Control, Directorate General of Environmental Pollution and Degradation Control, and Ministry of Environment and Forestry to plan for better peatland management and restoration.
Identification of novel gene signature for lung adenocarcinoma by machine learning to predict immunotherapy and prognosis
Authors: Shu Jianfeng , Jiang Jinni , Zhao Guofang
Published: July 2023

Background

Lung adenocarcinoma (LUAD) as a frequent type of lung cancer has a 5-year overall survival rate of lower than 20% among patients with advanced lung cancer. This study aims to construct a risk model to guide immunotherapy in LUAD patients effectively.

Materials and methods

LUAD Bulk RNA-seq data for the construction of a model, single-cell RNA sequencing (scRNA-seq) data (GSE203360) for cell cluster analysis, and microarray data (GSE31210) for validation were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. We used the Seurat R package to filter and process scRNA-seq data. Sample clustering was performed in the ConsensusClusterPlus R package. Differentially expressed genes (DEGs) between two groups were mined by the Limma R package. MCP-counter, CIBERSORT, ssGSEA, and ESTIMATE were employed to evaluate immune characteristics. Stepwise multivariate analysis, Univariate Cox analysis, and Lasso regression analysis were conducted to identify key prognostic genes and were used to construct the risk model. Key prognostic gene expressions were explored by RT-qPCR and Western blot assay.

Results

A total of 27 immune cell marker genes associated with prognosis were identified for subtyping LUAD samples into clusters C3, C2, and C1. C1 had the longest overall survival and highest immune infiltration among them, followed by C2 and C3. Oncogenic pathways such as VEGF, EFGR, and MAPK were more activated in C3 compared to the other two clusters. Based on the DEGs among clusters, we confirmed seven key prognostic genes including CPA3, S100P, PTTG1, LOXL2, MELTF, PKP2, and TMPRSS11E. Two risk groups defined by the seven-gene risk model presented distinct responses to immunotherapy and chemotherapy, immune infiltration, and prognosis. The mRNA and protein level of CPA3 was decreased, while the remaining six gene levels were increased in clinical tumor tissues.

Conclusion

Immune cell markers are effective in clustering LUAD samples into different subtypes, and they play important roles in regulating the immune microenvironment and cancer development. In addition, the seven-gene risk model may serve as a guide for assisting in personalized treatment in LUAD patients.
Long-term mechanical performance of high fluidity fiber reinforced concrete modified by metakaolin
Authors: Dou Hui , Xu Huaxin , Xie Junjie
Published: July 2023

To clarify the long-term strength and toughness of metakaolin (MK) and steel fiber (SF) modified concrete with higher fluidity and water/binder ratio, a series of tests including slump tests, compression tests, splitting tests, digital image processing and Scanning Electron Microscope (SEM) tests were performed on MK-SF concrete cured for 7–360 days. Results reveal that the slump of fresh concrete decreased with an increase in the MK and SF replacement rates. Moreover, the impact of MK on the slump of steel fiber reinforced concrete (SFRC) was more pronounced when combined with a lower water/binder ratio, resulting in increased viscosity. At the pre-peak stress region of the strain-stress curve, the compressive strength fc, tensile strength ft, Young’s modulus Ec, elastic modulus E0, and tensile strain at peak stress εt-max of high fluidity MK-SF concrete increased with increasing MK and SF admixing ratio, regardless of curing age. Notably, the coupling effects of MK and SF became more prominent after long-term curing. Without MK incorporation, the effects of SF and curing time on the above indices were relatively implicit. At the post-peak stress region of strain-stress curves, there existed a residual stage. The inclusion of MK significantly improved the long-term residual strength and strain of SFRC. Additionally, the toughness index Mc, which represents the total area of the compressive strain-stress curve containing both the pre-peak and post-peak regions, also exhibited substantial development with curing time, primarily attributed to the incorporation of MK and SF. The coupling of MK and SF led to a transformation of the concrete failure mode from brittle to ductile. Regression analysis reveals that a linear equation adequately described the long-term relationships of fc-ft, fc-Ec, fc-E0, fc-Mc, and fc-εt-max in MK-modified SFRC. Based on the testing data, a relative strength or toughness index λ and a new generalized hyperbola model were proposed to predict the long-term mechanical behavior mentioned above. Through crack morphology and microstructure analysis, the distinct roles of MK and SF in the composite material were examined.
Efficacy and safety of immune checkpoint inhibitors combined with chemotherapy as first-line treatment for extensive-stage small cell lung cancer: a meta-analysis based on mixed-effect models
Authors: Zheng Jianqing , Deng Yujie , Huang Bifen , Chen Xiaohui
Published: July 2023

Background

Extensive-stage small cell lung cancer (ES-SCLC) is a highly invasive and fatal disease with limited therapeutic options and poor prognosis. Our study aims to systematically evaluate the efficacy and safety of immune checkpoint inhibitors combined with chemotherapy (ICIs+ChT) vs. chemotherapy alone (ChT) in the first-line treatment of ES-SCLC.

Methods

A literature search was performed for randomized controlled trials (RCTs) related to “ICIs+ChT” vs. “ChT” in the first-line treatment of ES-SCLC in PubMed, Cochrane Library, Embase, CNKI, and other databases. RevMan 5.4 software was used to perform meta-analyses with hazard ratio (HR) and relative risk (RR). SAS 9.4 software was applied to conduct a mixed-effect model meta-analysis of the survival outcomes and draw survival curves.

Results

A total of 2,638 patients with ES-SCLC from 6 RCTs were included, of which 1,341 patients received “ICIs+ChT” and 1,297 received ChT. Based on the meta-analysis results provided by the mixed-effect model, patients receiving the “ICIs+ChT” regimen had a significantly longer overall survival (OS, HR = 0.800, 95% CI = 0.731–0.876, P < 0.001) and progression-free survival (PFS, HR = 0.815, 95% CI = 0.757–0.878, P <0.001) in comparison to those receiving ChT only. Compared with ChT, “ICIs+ChT” did neither improve the objective response rate (ORR, RR = 1.06, 95% CI = 1.00–1.12, P = 0.06) nor did it improve the disease control rate (DCR, RR = 0.97, 95% CI = 0.92–1.03, P = 0.35). Although the incidence of grade 3 to 5 treatment-related adverse events (trAEs) in the “ICIs+ChT” subgroup did not increase (RR = 1.16, 95% CI = 0.97–1.39, P = 0.11), the incidence of grade 3 to 5 immune-related adverse events (irAEs) increased significantly (RR = 4.29, 95% CI = 1.73–10.61, P < 0.00001).

Conclusion

ICIs+ChT regimen could significantly prolong OS and PFS in patients with ES-SCLC compared with ChT alone. Although the incidence of irAEs in “ICIs+ChT” is higher than that in the “ChT” subgroup, the incidence of trAEs is similar within the two subgroups. ICIs combined with chemotherapy demonstrated a good choice as first-line treatment for ES-SCLC.

Systematic review registration

PROSPERO, identifier: CRD42022348496.
Bioinformatics-based screening of key genes for transformation of tyrosine kinase inhibitor-resistant lung adenocarcinoma to small cell lung cancer
Authors: Zhang Ying , Chen Qiang , Huang Ting , Zhu Di , Lu Yuanzhi
Published: July 2023

Purpose

Lung adenocarcinoma (LUAD) is a common type of lung cancer. Cancer in a small number of patients with EGFR mutations will transform from LUAD to small cell lung cancer (SCLC) during epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapiesr. The purpose of the present study was to identify the core genes related to the transformation of LUAD into SCLC and to explore the associated molecular mechanisms.

Methods

GSE29016, GSE1037, GSE6044 and GSE40275 mRNA microarray datasets from Gene Expression Omnibus (GEO) were analyzed to obtain differentially expressed genes (DEGs) between LUAD and SCLC tissues, and the results were used for network analysis of protein–protein interactions (PPIs). After identifying the hub gene by STRING and Cytoscape platform, we explored the relationship between hub genes and the occurrence and development of SCLC. Finally, the obtained hub genes were validated in treated LUAD cells.

Results

A total of 41 DEGs were obtained, four hub genes (EZH2, NUSAP1, TTK and UBE2C) were identified, and related prognostic information was obtained. The coexpressed genes of the hub gene set were further screened, and the analysis identified many genes related to the cell cycle. Subsequently, LUAD cell models with TP53 and RB1 inactivation and overexpression of ASCL1 were constructed, and then the expression of hub genes was detected, the results showed that the four hub genes were all elevated in the established cell model.

Conclusion

EZH2, NUSAP1, TTK and UBE2C may affect the transformation of LUAD to SCLC and represent new candidate molecular markers for the occurrence and development of SCLC.
In vitro and in vivo antimicrobial activity of the fungal metabolite toluquinol against phytopathogenic bacteria
Authors: Chung Dawoon , Nguyen Hoa Thi , Yu Nan Hee , Yu Woon-Jong , Kwon Yong Min , Bae Seung Seob , Choi Grace , Kim Jin-Cheol
Published: July 2023

Introduction

Bacterial plant diseases cause tremendous economic losses worldwide. However, a few effective and sustainable control methods are currently available. To discover novel and effective management approaches, we screened marine fungi for their antibacterial activity against phytopathogenic bacteria in vitro and in vivo.

Methods

We screened the culture broth of 55 fungal strains isolated from various marine sources (seawater, algae, and sediment) for their in vitro antibacterial activity using the broth microdilution method. Then, only the fungal strain (designated UL-Ce9) with higher antibacterial activity in vitro was tested in an in vivo experiment against tomato bacterial wilt. The active compounds of UL-Ce9 were extracted using ethyl acetate, purified by a series of chromatography, and the structure was elucidated by nuclear magnetic resonance spectroscopy. Pesticide formulations of toluquinol were prepared as soluble concentrates and wettable powder. The disease control efficacy of toluquinol formulations was evaluated against blight of rice and the bacterial wilt of tomato.

Results and discussion

The culture broth of UL-Ce9 showed high antibacterial activity against Agrobacterium tumefaciens, Ralstonia solanacearum, and Xanthomonas arboricola pv. pruni in vitro, and we selected UL-Ce9 for the in vivo test. The UL-Ce9 culture broth completely suppressed the bacterial wilt of tomato at a dilution of 1:5. The phylogenetic analysis identified UL-Ce9 as Penicillium griseofulvum, and the antibacterial metabolites were revealed as patulin, gentisyl alcohol, and toluquinol, all of which were associated with the biosynthetic pathway of the mycotoxin patulin. Patulin exhibited the highest antibacterial activity against 16 phytopathogenic bacteria in vitro, followed by toluquinol and gentisyl alcohol. As patulin is toxic, we selected toluquinol to investigate its potential use as a pesticide against bacterial plant diseases. Compared with the chemicals currently being applied in agriculture (streptomycin and oxytetracycline), toluquinol formulations exhibited similar and higher control efficacies against bacterial leaf blight of rice and bacterial wilt of tomato, respectively. To the best of our knowledge, this is the first report of the antibacterial activity of toluquinol against phytopathogenic bacteria. Our results suggest that toluquinol is a potential candidate for the development of novel and effective pesticides for the management of bacterial plant diseases.
Re-learning mental representation of walking after a brain lesion. Effects of a cognitive-motor training with a robotic orthosis
Authors: Villa Maria-Chiara , Geminiani Giuliano C. , Zettin Marina , Cicerale Alessandro , Ronga Irene , Duca Sergio , Sacco Katiuscia
Published: July 2023

Introduction

Stroke-related deficits often include motor impairments and gait dysfunction, leading to a limitation of social activities and consequently affecting the quality of life of stroke survivors. Neurorehabilitation takes advantage of the contribution of different techniques in order to achieve more benefits for patients. Robotic devices help to improve the outcomes of physical rehabilitation. Moreover, motor imagery seems to play a role in neurological rehabilitation since it leads to the activation of the same brain areas as actual movements. This study investigates the use of a combined physical and cognitive protocol for gait rehabilitation in stroke patients.

Methods

Specifically, we tested the efficacy of a 5-week training program using a robotic orthosis (P.I.G.R.O.) in conjunction with motor imagery training. Twelve chronic stroke patients participated in the study. We evaluated balance and gait performance before and after the training. Six of them underwent fMRI examination before and after the training to assess the effects of the protocol on brain plasticity mechanisms in motor and imagery tasks.

Results

Our results show that the rehabilitation protocol can effectively improve gait performance and balance and reduce the risk of falls in stroke patients. Furthermore, the fMRI results suggest that rehabilitation is associated with cerebral plastic changes in motor networks.

Discussion

The present findings, if confirmed by future research, have the potential to advance the development of new, more effective rehabilitation approaches for stroke patients, improving their quality of life and reducing the burden of stroke-related disability.
Abnormal functional connectivity in the habenula is associated with subjective hyperarousal state in chronic insomnia disorder
Authors: Gong Liang , Cheng Fang , Li Xue , Wang Zhiqi , Wang Shuo , Xu Ronghua , Zhang Bei , Xi Chunhua
Published: July 2023

Background

The hyperarousal process model plays a central role in the physiology of chronic insomnia disorder (CID). Recent evidence has demonstrated that the habenula is involved in the arousal and sleep–wake cycle. However, whether the intrinsic habenular functional network contributes to the underlying mechanism of CID and its relationship to the arousal state in CID remains unclear.

Methods

This single-centered study included 34 patients with subjective CID and 22 matched good sleep control (GSC), and underwent a series of neuropsychological tests and resting-state functional magnetic resonance imaging scans. The habenular functional network was assessed using seed-based functional connectivity (FC) analysis. The subjective arousal state was evaluated with the hyperarousal scale (HAS). Alterations in the habenular FC network and their clinical significance in patients with CID were explored.

Results

Compared with the GSC group, the CID group showed decreased habenular FC in the left caudate nucleus and right inferior parietal lobule and increased FC in the right habenula, bilateral calcarine cortex, and posterior cingulate cortex. The decreased FC between the left habenula and caudate nucleus was associated with an increased arousal state in the CID group.

Conclusion

The present results provide evidence for a dysfunctional habenular network in patients with CID. These findings extend our understanding of the neuropathological mechanisms underlying the hyperarousal model in chronic insomnia.
Multivariate analytical approaches for investigating brain-behavior relationships
Authors: Durham E. Leighton , Ghanem Karam , Stier Andrew J. , Cardenas-Iniguez Carlos , Reimann Gabrielle E. , Jeong Hee Jung , Dupont Randolph M. , Dong Xiaoyu , Moore Tyler M. , Berman Marc G. , Lahey Benjamin B. , Bzdok Danilo , Kaczkurkin Antonia N.
Published: July 2023

Background

Many studies of brain-behavior relationships rely on univariate approaches where each variable of interest is tested independently, which does not allow for the simultaneous investigation of multiple correlated variables. Alternatively, multivariate approaches allow for examining relationships between psychopathology and neural substrates simultaneously. There are multiple multivariate methods to choose from that each have assumptions which can affect the results; however, many studies employ one method without a clear justification for its selection. Additionally, there are few studies illustrating how differences between methods manifest in examining brain-behavior relationships. The purpose of this study was to exemplify how the choice of multivariate approach can change brain-behavior interpretations.

Method

We used data from 9,027 9- to 10-year-old children from the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®) to examine brain-behavior relationships with three commonly used multivariate approaches: canonical correlation analysis (CCA), partial least squares correlation (PLSC), and partial least squares regression (PLSR). We examined the associations between psychopathology dimensions including general psychopathology, attention-deficit/hyperactivity symptoms, conduct problems, and internalizing symptoms with regional brain volumes.

Results

The results of CCA, PLSC, and PLSR showed both consistencies and differences in the relationship between psychopathology symptoms and brain structure. The leading significant component yielded by each method demonstrated similar patterns of associations between regional brain volumes and psychopathology symptoms. However, the additional significant components yielded by each method demonstrated differential brain-behavior patterns that were not consistent across methods.

Conclusion

Here we show that CCA, PLSC, and PLSR yield slightly different interpretations regarding the relationship between child psychopathology and brain volume. In demonstrating the divergence between these approaches, we exemplify the importance of carefully considering the method’s underlying assumptions when choosing a multivariate approach to delineate brain-behavior relationships.
Ultrasonic neuromodulation mediated by mechanosensitive ion channels: current and future
Authors: Song Mengyao , Zhang Mingxia , He Sixuan , Li Le , Hu Huijing
Published: July 2023

Ultrasound neuromodulation technology is a promising neuromodulation approach, with the advantages of noninvasiveness, high-resolution, deep penetration and good targeting, which aid in circumventing the side effects of drugs and invasive therapeutic interventions. Ultrasound can cause mechanical effects, activate mechanosensitive ion channels and alter neuronal excitability, producing biological effects. The structural determination of mechanosensitive ion channels will greatly contribute to our understanding of the molecular mechanisms underlying mechanosensory transduction. However, the underlying biological mechanism of ultrasonic neuromodulation remains poorly understood. Hence, this review aims to provide an outline of the properties of ultrasound, the structures of specific mechanosensitive ion channels, and their role in ultrasound neuromodulation.
Ability of metformin to deplete NAD+ contributes to cancer cell susceptibility to metformin cytotoxicity and is dependent on NAMPT expression
Authors: Zhuang Yongxian , Haugrud Allison B. , Schaefer Meg A. , Messerli Shanta M. , Miskimins W. Keith
Published: July 2023

Background

Nicotinamide adenine dinucleotide (NAD+) is vital for not only energy metabolism but also signaling pathways. A major source of NAD+ depletion is the activation of poly (ADP-ribose) polymerase (PARP) in response to DNA damage. We have previously demonstrated that metformin can cause both caspase-dependent cell death and PARP-dependent cell death in the MCF7 breast cancer cells but not in the MDA-MB-231 (231) breast cancer cells while in high-glucose media. We hypothesize that depletion of NAD+ in MCF7 cells via activation of PARP contributes to the cell death caused by metformin. Nicotinamide phosphoribosyltransferase (NAMPT), a key rate-limiting step in converting nicotinamide (vitamin B3) into NAD+, is essential for regenerating NAD+ for normal cellular processes. Evidence shows that overexpression of NAMPT is associated with tumorigenesis. We hypothesize that NAMPT expression may determine the extent to which cancer cells are sensitive to metformin.

Results

In this study, we found that metformin significantly decreases NAD+ levels over time, and that this could be delayed by PARP inhibitors. Pretreatment with NAD+ in MCF7 cells also prevents cell death and the enlargement of mitochondria and protects mitochondria from losing membrane potential caused by metformin. This leads to MCF7 cell resistance to metformin cytotoxicity in a manner similar to 231 cells. By studying the differences in NAD+ regulation in these two breast cancer cell lines, we demonstrate that NAMPT is expressed at higher levels in 231 cells than in MCF7 cells. When NAMPT is genetically repressed in 231 cells, they become much more sensitive to metformin-induced cell death. Conversely, overexpressing NAMPT in HEK-293 (293) cells causes the cells to be more resistant to metformin’s growth inhibitory effects. The addition of a NAMPT activator also decreased the sensitivity of MCF7 cells to metformin, while the NAMPT activator, P7C3, protects against metformin-induced cytotoxicity.

Conclusions

Depletion of cellular NAD+ is a key aspect of sensitivity of cancer cells to the cytotoxic effects of metformin. NAMPT plays a key role in maintaining sufficient levels of NAD+, and cells that express elevated levels of NAMPT are resistant to killing by metformin.
Early and stable difficulties of everyday executive functions predict autism symptoms and emotional/behavioral problems in preschool age children with autism: a 2-year longitudinal study
Authors: Lupi Elisabetta , Tucci Federico , Casula Laura , Novello Roberta Lucia , Guerrera Silvia , Vicari Stefano , Valeri Giovanni
Published: July 2023

Introduction

Longitudinal studies of autistic children show that autism symptoms and emotional/behavioral problems vary and change over time. However, the factors that affect this variability remain far from certain and very little is known about what take place in the preschool period and the role of executive functions (EF).

Methods

Here, we test the influence of stable difficulties in everyday executive functioning (EEF) during early childhood across 2 years on autistic symptoms and emotional and behavioral problems. Twenty-nine autistic children (24 males and 5 females) were assessed twice within the space of 2 years. At baseline (M = 29 months, SD =5.6 months), participants were assessed for EEF, cognitive development, autistic symptoms, and emotional/behavioral problems. At follow-up, we repeated the same assessment except for cognitive development.

Results

The group with stable difficulties (across 2 years) in EEF during early childhood showed a worsening in the severity of autistic symptoms and emotional and behavioral problems compared with children without EEF difficulties (p < 0.05), and these effects cannot be attributable to cognitive development.

Discussion

Our results suggest that early and stable EEF plays the role of a modifier by interacting with the core domains of autism, in particular with the social affect domain (SA CSS), influencing social cognition and exacerbating or lessening symptom expression and emotional behavioral problems. These short-term longitudinal and preliminary findings underscore the importance of EEF as necessary target for early intervention in children with autism.
Means substitutability in personal significance restoration
Authors: Contu Federico , Ellenberg Molly , Kruglanski Arie W. , Pierro Antonio
Published: July 2023

Drawing on Significance Quest Theory, we hypothesized that when people experience a loss of significance related to a specific life domain, they will aim to restore their significance by acting in an extreme manner in a different life domain. To test this hypothesis, we ran two cross-sectional studies using samples of employed people in romantic relationships. Study 1 tested if people experiencing a loss of significance in the romantic relationship domain were more prone to extremism at work. Study 2 tested whether people experiencing work-related significance loss were more prone to engage in obsessive relational intrusion (ORI) toward their romantic partner. Results from both studies confirmed our hypothesis, suggesting that both amorous relationships and careers are perceived as fruitful in maintaining or restoring ones’ sense of personal significance, even if the original loss of significance is derived from an unrelated domain. Notably, this research represents one of the first tests of the key assumption of Significance Quest Theory entailing the substitutability of means through which one can attain or renew their sense of significance.
The development of a glossary of contemporary Chinese values and its initial application
Authors: Pan Li , Huang Xiting
Published: July 2023

A value is an outward or inward view of what is “worthwhile” and is a belief system that people uses to distinguish between good and bad and to guide their behavior. Values vary from culture to culture and from time to time. In order to develop a vocabulary for measuring the values of contemporary Chinese, an open-ended survey was conducted in Study 1 to collect the value vocabulary of the Chinese public, and a text analysis was conducted in Study 2 to acquire the value vocabulary of the Chinese society. In Study 3, a word list of contemporary Chinese values was developed by integrating the words obtained from the above two studies and combining words from previous studies, and a preliminary application of the word list was conducted. The results revealed that Chinese values include four dimensions: self-fulfillment, self-cultivation, social development, and interpersonal ethics. Chinese values are characterized by diversity, and some of the socially advocated values have been internalized into the value system of individuals.
The effectiveness of Interpersonal Psychotherapy-Adolescent Skills Training for adolescents with depression: a systematic review and meta-analysis
Authors: Zheng Kewei , Xu Huimin , Qu Chunhui , Sun Xianghong , Xu Na , Sun Ping
Published: July 2023

Background

Interpersonal Psychotherapy-Adolescent Skills Training (IPT-AST) is a standardized depression prevention program for adolescents conducted in campus settings. The purpose of this review is to examine the randomized controlled trials of IPT-AST for the prevention of adolescent depression in the past 20 years.

Methods

A systematic search of relevant electronic databases (PubMed, WOS, Embase, PsycINFO, the Cochrane Library, CNKI and WANFANG DATA) and study reference lists was conducted. Any study investigating the effectiveness of IPT-AST in 12- to 20-year-olds with depressive symptoms was eligible. Synthesis was via narrative summary and meta-analysis.

Results

A total of 6 studies met the inclusion criteria. Meta-analysis results showed a remarkable improvement in patients’ depressive symptoms after IPT-AST intervention (WMD = −5.05, 95% CI = −8.11 to −1.98, p < 0.05, I2 = 77%). Six month follow-up data showed that the intervention outcomes of IPT-AST remained significant (WMD = −3.09, 95% CI: −5.23 to −0.94, p < 0.05, I2 = 57%).

Conclusion

This meta-analysis showed that IPT-AST was effective in adolescents with depressive symptoms at post-prevention and at 6-month follow-up. However, these conclusions are cautious, as they are based on a small number of studies and the presence of author duplication. Future studies should use multi-center, large-sample randomized controlled trials to evaluate the efficacy of IPT-AST for preventing depression in adolescents.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42023393047.
Ryan White HIV/AIDS Part B and AIDS Drug Assistance Programs during COVID-19: safety net public health programs’ challenges and innovations
Authors: McManus Kathleen A. , Strumpf Andrew M. , Killelea Amy , Horn Tim , Steen Amber , An Zixiao , Schurman Elizabeth , Hamp Auntré , Keim-Malpass Jessica
Published: July 2023

Introduction

We characterized the challenges and innovations of states’ Ryan White HIV/AIDS Program (RWHAP) Part B programs, including AIDS Drug Assistance Programs (ADAPs), during the COVID-19 pandemic. In the United States, these are important safety net programs for HIV healthcare, providing essential medical and support services, and medications, to people with HIV with low incomes who are uninsured/underinsured.

Methods

Data were collected via the 2021-2022 NASTAD National RWHAP Part B and ADAP Monitoring Project Report, a cross-sectional survey of state, district, and territorial programs through a mixed method study design. For quantitative data, we used descriptive statistics. Qualitative responses were coded and analyzed using content analysis.

Results

Forty-seven RWHAP Part B and ADAPs responded (92% response rate). The majority of respondents reported that maintaining client eligibility (78%) and working remotely (70%) were the most challenging aspects of the pandemic, particularly in regards to implementing new telehealth and e-certification platforms. In response to COVID-19, programs introduced enrollment “grace periods” (19%), bolstered client outreach (11%), allowed more than a 30 day supply of medications (79%), and supported medication home delivery for clients (80%).

Discussion

Despite the challenges of the COVID-19 pandemic, RWHAP Part B and ADAPs implemented several operational innovations in order to continue providing essential medicines and services. Other public health programs may adopt similar innovations, including digital innovations, for greater public health benefit. Future studies should assess the retention of policy innovations over time, their impact on the individual client level satisfaction or health outcomes, and what factors may improve the acceptability of telehealth and e-certification platforms.
Primary care biomarkers and dementia in people of the Torres Strait, Australia: extended data analysis
Authors: Thompson Fintan , Russell Sarah , Quigley Rachel , McDonald Malcolm , Sagigi Betty , Taylor Sean , Campbell Sandy , Schmidt Barbara , Esterman Adrian , Harriss Linton R. , Miller Gavin , Mills Phillip , Strivens Edward , McDermott Robyn
Published: July 2023

Objective

Dementia disproportionately affects First Nations populations. Biomarkers collected in primary care may assist with determining dementia risk. Our previous underpowered study showed some suggestive associations between baseline biomarkers with follow-up dementia or cognitive impairment. The current study extended this work with a larger linked dataset.

Study design and setting

Probabilistic data linkage was used to combine four baseline datasets with one follow-up assessment of dementia status 0–20 years later in a First Nations population in Australia. Mixed Effects Generalized Linear Regression models were used to test associations between baseline measures and follow-up status, accounting for repeated measures within individuals.

Results

Linked data were available for 88 individuals, with 101–279 baseline observations, depending on the type of measure. Higher urinary albumin to creatine ratio was associated with greater risk of cognitive impairment/dementia, whereas body weight and key lipid markers were negatively associated. There was no clear trend when these associations were examined by timing of measurement (i.e., ≤10 years or >10 years before a dementia assessment).

Conclusions

The results of this study support findings from our previous work and indicate that microalbuminuria can be an early indicator of dementia risk in this population. The weight and lipid profile findings reflect the mixed results in the published literature and require further investigation and interpretation.
Generation of site-specific ubiquitinated histones through chemical ligation to probe the specificities of histone deubiquitinases
Authors: AlAfaleq Nouf Omar , Choi Yun-Seok , Atanassov Boyko S. , Cohen Robert E. , Yao Tingting
Published: July 2023

The attachment of mono-ubiquitin to histones as a post-translational modification plays important roles in regulating chromatin structure and function. Like other epigenetic modifications, the site of ubiquitin attachment is critically important in determining its functional outcome. Depending on the type of histone and the specific lysine residue that is modified, ubiquitination acts in diverse pathways including DNA damage repair, transcription elongation, and transcription repression. Specific reader, writer and eraser activities have evolved to distinguish nucleosomes by ubiquitination of different sites. To facilitate biochemical studies of ubiquitinated nucleosomes, we have developed an efficient strategy to chemically ligate intact ubiquitin and histone proteins at specific sites to generate near-native ubiquitin-histone conjugates. Because these chemically-ligated ubiquitin conjugates are hydrolysable, they enabled us to characterize in vitro the specificities of several histone deubiquitinases. To gain insight into the mechanisms that contribute to the specificities of these deubiquitinases, we used a free Ub sensor-based real-time assay to determine their Michaelis-Menten kinetics. Our results confirmed previously reported specificities of BAP1 and USP22, but also revealed specificities of other histone deubiquitinases that have been less well defined in the literature.
Oral HIV pre-exposure prophylaxis use among pregnant and postpartum women: results from real-world implementation in Lesotho
Authors: Masenyetse Lieketseng J. , Greenberg Lauren , Samonyane Felleng , Sekepe Bokang , Mokone Majoalane , Mokone Mafusi J. , Tukei Vincent J. , Beres Laura K.
Published: July 2023

Introduction

Lesotho has reached epidemic control, PrEP is an important component in maintaining that and in reaching the goal of eliminating mother-to-child transmission.

Methods

We conducted a retrospective review of existing, routine PrEP health records in 26 health facilities in Lesotho. PrEP visit data were collected for pregnant and postpartum women screened for PrEP and/or enrolled in PrEP programs from 1 January 2019 through 30 June 2021 with follow-up data collected up to the date of data abstraction per site between October 2021 and May 2022. Poisson regression with robust variance was used to evaluate the association between patient characteristics and continuation of PrEP.

Results

Indications for starting PrEP were significantly associated with continuation in PrEP use. Women starting PrEP due to having a partner known to be living with HIV were the most likely to return for follow-up. In all age groups, the most common reason for starting PrEP was being in a serodiscordant relationship, though the proportion varies by age.

Conclusion

As Lesotho is now in the process of optimizing PrEP use among pregnant and postpartum women, it is critical to revise data sources to capture information that will link PrEP records and ANC/PNC records and document pregnancy/postpartum status in order to better understand PrEP use and gaps in this population.