bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring accommodations along the education to employment pathway for deaf and hard of hearing healthcare professionals
Authors: Moreland C. J. , Meeks L. M. , Nahid M. , Panzer K. , Fancher T. L.
Published: May 2022

Background

Deaf and hard of hearing (DHH) people are an underserved population and underrepresented among healthcare professionals. A major barrier to success for DHH healthcare professionals is obtaining effective accommodations during education and employment. Our objective: describe DHH individuals’ experiences with accommodations in healthcare education.

Methods

We used an online survey and multipronged snowball sampling to recruit participants who identify as DHH and who had applied to a U.S. health professional school (regardless of acceptance status). One hundred forty-eight individuals representing multiple professions responded; 51 had completed their training. Over 80% had been accepted to, were currently enrolled, or had completed health professions schools or residency programs, and/or were employed. The survey included questions addressing experiences applying to health professions programs and employment; satisfaction with accommodations in school and training; having worked with a disability resource professional (DRP); and depression screening.

Results

Use and type of accommodation varied widely. While in school, respondents reported spending a mean of 2.1 h weekly managing their accommodations. Only 50% were highly satisfied with the accommodations provided by their programs. Use of disability resource providers (DRPs) for accommodations was highest during school (56%) and less frequent during post-graduate training (20%) and employment (14%). Respondents who transitioned directly from school to employment (versus via additional training) were more satisfied with their accommodations during school and were more likely to find employment (p = 0.02). Seventeen respondents screened positive for risk of depression; a positive screen was statistically associated with lower school accommodation satisfaction.

Conclusions

DHH people study and practice across many health professions. While respondents were mostly successful in entering health professions programs, accommodation experiences and satisfaction varied. Satisfaction with accommodations was related to successful employment and wellness. Low satisfaction was associated with higher likelihood of depression symptoms. To increase representation in the workforce, healthcare professional schools, training programs, and employers should enhance support for the learning and working climates for people with disabilities.
“Many roads lead to Rome and the Artificial Intelligence only shows me one road”: an interview study on physician attitudes regarding the implementation of computerised clinical decision support systems
Authors: Van Cauwenberge Daan , Van Biesen Wim , Decruyenaere Johan , Leune Tamara , Sterckx Sigrid
Published: May 2022

Research regarding the drivers of acceptance of clinical decision support systems (CDSS) by physicians is still rather limited. The literature that does exist, however, tends to focus on problems regarding the user-friendliness of CDSS. We have performed a thematic analysis of 24 interviews with physicians concerning specific clinical case vignettes, in order to explore their underlying opinions and attitudes regarding the introduction of CDSS in clinical practice, to allow a more in-depth analysis of factors underlying (non-)acceptance of CDSS. We identified three general themes from the results. First, ‘the perceived role of the AI’, including items referring to the tasks that may properly be assigned to the CDSS according to the respondents. Second, ‘the perceived role of the physician’, referring to the aspects of clinical practice that were seen as being fundamentally ‘human’ or non-automatable. Third, ‘concerns regarding AI’, including items referring to more general issues that were raised by the respondents regarding the introduction of CDSS in general and/or in clinical medicine in particular. Apart from the overall concerns expressed by the respondents regarding user-friendliness, we will explain how our results indicate that our respondents were primarily occupied by distinguishing between parts of their job that should be automated and aspects that should be kept in human hands. We refer to this distinction as ‘the division of clinical labor.’ This division is not based on knowledge regarding AI or medicine, but rather on which parts of a physician’s job were seen by the respondents as being central to who they are as physicians and as human beings. Often the respondents’ view that certain core parts of their job ought to be shielded from automation was closely linked to claims concerning the uniqueness of medicine as a domain. Finally, although almost all respondents claimed that they highly value their final responsibility, a closer investigation of this concept suggests that their view of ‘final responsibility’ was not that demanding after all.
Contributing factors to healthcare costs in individuals with autism spectrum disorder: a systematic review
Authors: Matin Behzad Karami , Byford Sarah , Soltani Shahin , Kazemi-Karyani Ali , Atafar Zahra , Zereshki Ehsan , Soofi Moslem , Rezaei Satar , Rakhshan Shiva Tolouei , Jahangiri Parvin
Published: May 2022

Background

Individuals with autism spectrum disorder (ASD) are more likely to use healthcare than their counterparts without disabilities, which imposes high medical costs to families and health systems. This study aimed to investigate healthcare costs and its determinants among individuals with ASD.

Methods

In this systematic review, we searched online databases (Web of Science, Medline through PubMed and Scopus) for observational and experimental studies that included data on service use and costs associated with ASD and published between January 2000 and May 2021. Exclusion criteria included non-English language articles, duplicates, abstracts, qualitative studies, gray literature, and non-original papers (e.g., letters to editors, editorials, reviews, etc.).

Results

Our searches yielded 4015 articles screened according to PRISMA guidelines. Of 4015 studies identified, 37 articles from 10 countries were eligible for final inclusion. Therapeutic interventions, outpatient visits and medications constituted the largest proportion of direct medical expenditure on individuals with ASD. Included studies suggest lack of health insurance, having associated morbidities, more severe symptoms, younger age groups and lower socioeconomic status (SES) are associated with higher medical expenditure in individuals with ASD.

Conclusions

This systematic review identified a range of factors, including lower SES and lack of health insurance, which are associated with higher healthcare costs in people with ASD. Our study supports the formulation of policy options to reduce financial risks in families of individuals with ASD in countries which do not have a tax-based or universal health coverage system.
Moving beyond referrals to strengthen late-life depression care: a qualitative examination of primary care clinic and community-based organization partnerships
Authors: Wagner Jenny , Henderson Stuart , Hoeft Theresa J. , Gosdin Melissa , Hinton Ladson
Published: May 2022

Background

National guidelines have called for greater integration of primary care and behavioral health services, with more recent attention to social care and community-based services. Under growing resource constraints healthcare organizations have tended to rely on referrals to external entities to address social care needs. Traditional referral models, however, may not be equipped to provide for the complex needs of older adults with depression. The Care Partners Project was designed to strengthen late-life depression care through integrated partnerships between primary care clinics and community-based organizations. We sought to understand how these integrated partnerships, with shared tasks and accountability across organizations, changed the nature of depression care for older adults.

Methods

We conducted 65 in-depth, semi-structured interviews and six focus groups with service providers involved in the project, including care managers, primary care providers, and psychiatric consultants, and applied inductive and deductive qualitative thematic analysis to develop themes around participants’ experiences with the partnered initiative.

Results

We found the partnerships established by the Care Partners Project reshaped late-life depression care in two ways: (1) bidirectional communication across organizations facilitated greater recognition among providers of intersecting medical and social needs associated with late-life depression; and (2) depression care became more coordinated and effective as care teams established or strengthened relationships across organizations.

Conclusions

These findings highlight the ways cross-organizational health and social care partnerships that move beyond traditional referrals can strengthen late-life depression care and enhance organizational capacities.
Challenges and opportunities of telehealth digital equity to manage HIV and comorbidities for older persons living with HIV in New York State
Authors: Baim-Lance Abigail , Angulo Matthew , Chiasson Mary Ann , Lekas Helen-Maria , Schenkel Rachel , Villarreal Jason , Cantos Anyelina , Kerr Christine , Nagaraja Aarthi , Yin Michael T. , Gordon Peter
Published: May 2022

Background

Older persons living with HIV (PLWH) need routine healthcare to manage HIV and other comorbidities. This mixed methods study investigated digital equity, constituted as access, use and quality, of HIV and specialty telehealth services for PLWH > 50 years during the initial wave of the COVID-19 pandemic when services transitioned to remote care.

Methods

A survey of closed and open-ended questions was administered to 80 English (N = 63) and Spanish (N = 17) speaking PLWH receiving HIV care at an Academic Medical Center (N = 50) or a Federally Qualified Health Center (N = 30) in New York State. Quantitative analyses examined characteristics predicting telehealth use and visit quality. Qualitative analyses utilized thematic coding to reveal common experiences. Results were integrated to deepen the interpretation.

Results

Telehealth access and use were shaped by multiple related and unstable factors including devices and connectivity, technology literacy, and comfort including privacy concerns. Participants demonstrated their substantial effort to achieve the visit. The majority of patients with a telehealth visit perceived it as worse than an in-person visit by describing it as less interpersonal, and resulting in poorer outcomes, particularly participants with less formal education. Technology was not only a barrier to access, but also influenced perceptions of quality.

Conclusions

In the COVID-19 pandemic initial wave, barriers to using telehealth were unequally distributed to those with more significant access and use challenges. Beyond these barriers, examining the components of equity indicate further challenges replicating in-person care using telehealth formats for older PLWH. Work remains to establish telehealth as both equitable and desirable for this population.
Symbiont transmission in marine sponges: reproduction, development, and metamorphosis
Authors: Carrier Tyler J. , Maldonado Manuel , Schmittmann Lara , Pita Lucía , Bosch Thomas C. G. , Hentschel Ute
Published: May 2022

Marine sponges (phylum Porifera) form symbioses with diverse microbial communities that can be transmitted between generations through their developmental stages. Here, we integrate embryology and microbiology to review how symbiotic microorganisms are transmitted in this early-diverging lineage. We describe that vertical transmission is widespread but not universal, that microbes are vertically transmitted during a select developmental window, and that properties of the developmental microbiome depends on whether a species is a high or low microbial abundance sponge. Reproduction, development, and symbiosis are thus deeply rooted, but why these partnerships form remains the central and elusive tenet of these developmental symbioses.
Phase II study of anlotinib in combination with oxaliplatin and capecitabine for patients with RAS/BRAF wild-type metastatic colorectal adenocarcinoma as the first-line therapy
Authors: Liu Yue , Xiao Qian , He Jinjie , Hu Hanguang , Du Jinlin , Zhu Yuping , Chen Jiaqi , Liu Zhuo , Wang Jianping , Sun Lifeng , Xu Dong , Li Jun , Liao Xiujun , Wang Jianwei , Cai Yibo , Cai Cheng , Jin Zhekang , Wang Liuhong , Yuan Ying , Ding Kefeng
Published: May 2022

Background

Anlotinib, an oral small molecule tyrosine kinase inhibitor targeting VEGFR 1/2/3, FGFR 1-4, PDGFR a/β, and c-kit, had demonstrated prolonged progression-free survival (PFS) in refractory metastatic colorectal cancer (mCRC). This multicenter, single-arm, phase II, exploratory study was conducted to evaluate the efficacy and safety of anlotinib combined with capecitabine and oxaliplatin as first-line treatment for unresectable RAS/BRAF wild-type mCRC.

Methods

Patients aged 18–75 with RAS/BRAF wild-type unresectable mCRC, without prior systemic treatment, and ECOG performance status ≤1 were enrolled. Eligible patients received capecitabine (850 mg/m2, p.o., bid, on day 1–14 every 21 days), oxaliplatin (130 mg/m2, i.v., on day 1 every 21 days), and anlotinib (12 mg, p.o., qd, on days 1–14 every 21 days) as induction therapy. Following 6 cycles of therapy, patients who achieved response or stable disease received capecitabine and anlotinib as maintenance therapy until tumor progression. The primary endpoint was objective response rate (ORR) according to RECIST (version: 1.1), and the secondary endpoints were PFS, disease control rate (DCR), duration of response (DOR), and safety.

Results

Between November 2019 and February 2021, 31 patients were enrolled. One patient was excluded for refusing treatment. The primary endpoint of ORR was 76.7% (95% CI, 57.7–90.1) with 1 patient achieving a complete response and 22 patients partial response. DCR was 93.3% (95% CI, 77.9–99.2). At a median follow-up of 14.1 months (95% CI, 9.9–18.3), median PFS was 11.3 months (95% CI, 7.1–14.1), and DOR was 7.9 months (95% CI, 5.5–12.7). Twenty-five (83.3%) patients experienced grade 3 or 4 treatment-emergent adverse events (TEAEs). No grade 5 TEAE was reported. The most common grade 3 or 4 TEAEs (>10%) were hypertension (15/30; 50%), neutrophil count decreased (8/30; 26.7%), and diarrhea (4/30; 13.3%). A total of 18 (60%) patients had TEAEs that resulted in dose reduction, interruptions, or delays.

Conclusions

Anlotinib combined with capecitabine and oxaliplatin showed considerable ORR, DCR, PFS, and DOR in the first-line therapy of mCRC with manageable toxicity profiles.

Trial registration

ClinicalTrials.gov: NCT04080843
Integrated analysis of lncRNAs and mRNAs by RNA-Seq in secondary hair follicle development and cycling (anagen, catagen and telogen) of Jiangnan cashmere goat (Capra hircus)
Authors: Wu Cuiling , Qin Chongkai , Fu Xuefeng , Huang Xixia , Tian Kechuan
Published: May 2022

Background

Among the world’s finest natural fiber composites is derived from the secondary hair follicles (SHFs) of cashmere goats yield one of the world's best natural fibres. Their development and cycling are characterized by photoperiodism with diverse, well-orchestrated stimulatory and inhibitory signals. Long non-coding RNA (lncRNAs) and mRNAs play important roles in hair follicle (HF) development. However, not many studies have explored their specific functions in cashmere development and cycling. This study detected mRNAs and lncRNAs with their candidate genes and related pathways in SHF development and cycling of cashmere goat. We utilized RNA sequencing (RNA-Seq) and bioinformatics analysis on lncRNA and mRNA expressions in goat hair follicles to discover candidate genes and metabolic pathways that could affect development and cycling (anagen, catagen, and telogen).

Results

We identified 228 differentially expressed (DE) mRNAs and 256 DE lncRNA. For mRNAs, catagen and anagen had 16 upregulated and 35 downregulated DEGs, catagen and telogen had 18 upregulated and 9 downregulated DEGs and telogen and anagen had 52 upregulated and 98 downregulated DEGs. LncRNA witnessed 22 upregulated and 39 downregulated DEGs for catagen and anagen, 36 upregulated and 29 downregulated DEGs for catagen and telogen as well as 66 upregulated and 97 downregulated DEGs for telogen and anagen. Several key genes, including MSTRG.5451.2, MSTRG.45465.3, MSTRG.11609.2, CHST1, SH3BP4, CDKN1A, GAREM1, GSK-3β, DEFB103A KRTAP9–2, YAP1, S100A7A, FA2H, LOC102190037, LOC102179090, LOC102173866, KRT2, KRT39, FAM167A, FAT4 and EGFL6 were shown to be potentially important in hair follicle development and cycling. They were related to, WNT/β-catenin, mTORC1, ERK/MAPK, Hedgehog, TGFβ, NFkB/p38MAPK, caspase-1, and interleukin (IL)-1a signaling pathways.

Conclusion

This work adds to existing understanding of the regulation of HF development and cycling in cashmere goats via lncRNAs and mRNAs. It also serves as theoretical foundation for future SHF research in cashmere goats.
Effects of diabetes mellitus on left ventricular function and remodeling in hypertensive patients with heart failure with reduced ejection fraction: assessment with 3.0 T MRI feature tracking
Authors: Zhang Ge , Shi Ke , Yan Wei-Feng , Li Xue-Ming , Li Yuan , Guo Ying-Kun , Yang Zhi-Gang
Published: May 2022

Background

Heart failure with reduced ejection fraction (HFrEF) is a major health burden worldwide with high morbidity and mortality. Comorbidities of HFrEF complicate treatment and lead to poor prognosis, among which hypertension (HTN) and diabetes mellitus (DM) are common and frequently cooccur. DM was found to have additive effects on cardiac function and structure in hypertensive patients, while its effects on the HFrEF cohort in the context of HTN remain unclear.

Methods

A total of 171 patients with HFrEF were enrolled in our study, consisting of 51 HFrEF controls, 72 hypertensive HFrEF patients (HTN-HFrEF [DM−]) and 48 hypertensive HFrEF patients with comorbid DM (HTN-HFrEF [DM+]). Cardiac MRI-derived left ventricular (LV) strains, including global radial (GRPS), circumferential (GCPS) and longitudinal (GLPS) peak strain, and remodeling parameters were measured and compared among groups. The determinants of impaired LV function and LV remodeling in HFrEF patients were investigated by multivariable linear regression analyses.

Results

Despite a similar LV ejection fraction, patients in the HTN-HFrEF (DM+) and HTN-HFrEF (DM−) groups showed a higher LV mass index and LV remodeling index than those in the HFrEF control group (all p < 0.05). Compared with the HTN-HFrEF (DM−) and HFrEF control groups, the HTN-HFrEF (DM+) group exhibited the most severe GLPS impairment (p < 0.001). After adjustment for covariates in HFrEF patients, DM was found to be an independent determinant of impaired LV strains in all three directions (GRPS [β = − 0.189; p = 0.011], GCPS [β = 0.217; p = 0.005], GLPS [β = 0.237; p = 0.002]). HTN was associated with impaired GLPS (β = 0.185; p = 0.016) only. However, HTN rather than DM was associated with LV remodeling in HFrEF patients in the multivariable regression analysis (p < 0.05).

Conclusions

DM aggravated LV longitudinal dysfunction in hypertensive HFrEF patients without further changes in LV remodeling, indicating that HFrEF patients with comorbid HTN and DM may have a hidden high-risk phenotype of heart failure that requires more advanced and personalized management.
Tetraspanin 7 promotes osteosarcoma cell invasion and metastasis by inducing EMT and activating the FAK-Src-Ras-ERK1/2 signaling pathway
Authors: Shao Shijie , Piao Lianhua , Guo Liwei , Wang Jiangsong , Wang Luhui , Wang Jiawen , Tong Lei , Yuan Xiaofeng , Zhu Junke , Fang Sheng , Wang Yimin
Published: May 2022

Background

Tetraspanins are members of the 4-transmembrane protein superfamily (TM4SF) that function by recruiting many cell surface receptors and signaling proteins into tetraspanin-enriched microdomains (TEMs) that play vital roles in the regulation of key cellular processes including adhesion, motility, and proliferation. Tetraspanin7 (Tspan7) is a member of this superfamily that plays documented roles in hippocampal neurogenesis, synaptic transmission, and malignant transformation in certain tumor types. How Tspan7 influences the onset or progression of osteosarcoma (OS), however, remains to be defined. Herein, this study aimed to explore the relationship between Tspan7 and the malignant progression of OS, and its underlying mechanism of action.

Methods

In this study, the levels of Tspan7 expression in human OS cell lines were evaluated via qRT-PCR and western blotting. The effect of Tspan7 on proliferation was examined using CCK-8 and colony formation assays, while metastatic role of Tspan7 was assessed by functional assays both in vitro and in vivo. In addition, mass spectrometry and co-immunoprecipitation were performed to verify the interaction between Tspan7 and β1 integrin, and western blotting was used to explore the mechanisms of Tspan7 in OS progresses.

Results

We found that Tspan7 is highly expressed in primary OS tumors and OS cell lines. Downregulation of Tspan7 significantly suppressed OS growth, metastasis, and attenuated epithelial-mesenchymal transition (EMT), while its overexpression had the opposite effects in vitro. Furthermore, it exhibited reduced OS pulmonary metastases in Tspan7-deleted mice comparing control mice in vivo. Additionally, we proved that Tspan7 interacted with β1 integrin to facilitate OS metastasis through the activation of integrin-mediated downstream FAK-Src-Ras-ERK1/2 signaling pathway.

Conclusion

In summary, this study demonstrates for the first time that Tspan7 promotes OS metastasis via interacting with β1 integrin and activating the FAK-Src-Ras-ERK1/2 pathway, which could provide rationale for a new therapeutic strategy for OS.
Dietary fiber and prevalence of abdominal aortic calcification in the United States (from the national health and nutrition examination survey data [2013–2014])
Authors: Sun YuJiao , Zhang HuanRui , Tian Wen
Published: May 2022

Background

Abdominal aortic calcification (AAC) is recognized as a valuable predictor of cardiovascular diseases (CVDs). Dietary fiber is strongly correlated with CVDs. However, the effect of dietary fiber on AAC in the population is not well understood.

Objective

To assess the relationship between dietary fiber intake and AAC in the US adult population.

Methods

A total of 2671 individuals with both dietary fiber intake and AAC score data were enrolled from the 2013–2014 National Health and Nutrition Examination Survey (NHANES), a cross-sectional health examination in the US. Multinomial logistic regression was used to calculate the odds ratio (OR), with 95% confidence interval (CI). To reveal the relationship between dietary fiber intake and AAC, restricted cubic spline was also applied.

Results

Out of the total participants, 241 (9%) had severe AAC and 550 (20%) had mild-moderate AAC. Multinomial logistic regression indicated that higher intake of dietary fiber was associated with lower risk of severe AAC, but not with lower risk of mild-moderate AAC. For every one standard deviation increase (9.4 g/day) in dietary fiber intake, the odds of severe AAC were reduced by 28% [OR 0.72 (95% CI, 0.57–0.90), p = 0.004], after adjusting for confounding factors. Dose–response relationship revealed that dietary fiber intake was negatively correlated with severe AAC (p for linear < 0.001, p for nonlinear = 0.695).

Conclusions

Dietary fiber intake was negatively associated with severe AAC, and showed a dose–response relationship in US adults.
Effects of Benzo[a]pyrene-DNA adducts, dietary vitamins, folate, and carotene intakes on preterm birth: a nested case–control study from the birth cohort in China
Authors: Zhao Nan , Wu Weiwei , Cui Shiwei , Li Haibin , Feng Yongliang , Guo Ling , Zhang Yawei , Wang Suping
Published: May 2022

Background

Polycyclic aromatic hydrocarbons (PAHs) and its DNA adducts has been suggested to increase the risk of preterm birth (PB). Yet, few studies have been conducted to investigate this association, and the role of dietary nutrients intakes including vitamins, folate, and carotene during pre- and post-conception on this association has not been studied.

Methods

Building upon a birth cohort in Taiyuan China, we conducted a nested case control study including 83 PB and 82 term births. Benzo[a]pyrene (BaP)-DNA adducts were measured by an improved LC-MC/MC analytic method. Dietary nutrient intakes were estimated from food frequency questionnaire using the Chinese Standard Tables of Food Consumption. Multivariable logistic regression model was used to examine the associations.

Results

Increased risk of PB was observed as per interquartile increase in maternal BaP-DNA adduct level (OR = 1.27, 95%CI 0.95–1.67). Compared to low level (below mean) of maternal adducts, high level (above mean) of adducts was associated with the risk of PB (OR = 2.05, 95%CI 1.05–4.01). After stratified by dietary nutrients intakes, high adducts levels were associated with approximately 2–fourfold times increases in risk of PB among women with low vitamin A, C, E, folate, and carotene intakes during pre- and/or post-conception. Stronger stratified associations were consistently seen during preconception. Similar patterns were observed after additional adjustment for supplementation.

Conclusions

Our study supports the hypothesis that high level of maternal PAHs exposure was significantly associated with increased risk of PB, and provides the first evidence that dietary vitamins, carotene, and folate intake levels may modify this association during different pregnancy windows. Our findings are relevant to identify recommendation for environment management and prenatal nutrition regarding pregnant women and newborns. Further investigation in other populations is warranted.
Conductive nanocomposite hydrogel and mesenchymal stem cells for the treatment of myocardial infarction and non-invasive monitoring via PET/CT
Authors: Zhu Ke , Jiang Dawei , Wang Kun , Zheng Danzha , Zhu Ziyang , Shao Fuqiang , Qian Ruijie , Lan Xiaoli , Qin Chunxia
Published: May 2022

Background

Injectable hydrogels have great promise in the treatment of myocardial infarction (MI); however, the lack of electromechanical coupling of the hydrogel to the host myocardial tissue and the inability to monitor the implantation may compromise a successful treatment. The introduction of conductive biomaterials and mesenchymal stem cells (MSCs) may solve the problem of electromechanical coupling and they have been used to treat MI. In this study, we developed an injectable conductive nanocomposite hydrogel (GNR@SN/Gel) fabricated by gold nanorods (GNRs), synthetic silicate nanoplatelets (SNs), and poly(lactide-co-glycolide)-b-poly (ethylene glycol)-b-poly(lactide-co-glycolide) (PLGA-PEG-PLGA). The hydrogel was used to encapsulate MSCs and 68Ga3+ cations, and was then injected into the myocardium of MI rats to monitor the initial hydrogel placement and to study the therapeutic effect via 18F-FDG myocardial PET imaging.

Results

Our data showed that SNs can act as a sterically stabilized protective shield for GNRs, and that mixing SNs with GNRs yields uniformly dispersed and stabilized GNR dispersions (GNR@SN) that meet the requirements of conductive nanofillers. We successfully constructed a thermosensitive conductive nanocomposite hydrogel by crosslinking GNR@SN with PLGA2000-PEG3400-PLGA2000, where SNs support the proliferation of MSCs. The cation-exchange capability of SNs was used to adsorb 68Ga3+ to locate the implanted hydrogel in myocardium via PET/CT. The combination of MSCs and the conductive hydrogel had a protective effect on both myocardial viability and cardiac function in MI rats compared with controls, as revealed by 18F-FDG myocardial PET imaging in early and late stages and ultrasound; this was further validated by histopathological investigations.

Conclusions

The combination of MSCs and the GNR@SN/Gel conductive nanocomposite hydrogel offers a promising strategy for MI treatment.

Graphical Abstract
ROS-responsive liposomes as an inhaled drug delivery nanoplatform for idiopathic pulmonary fibrosis treatment via Nrf2 signaling
Authors: Liu Junzhao , Wu Zuohong , Liu Yadong , Zhan Zhu , Yang Liping , Wang Can , Jiang Qinqin , Ran Haitao , Li Pan , Wang Zhigang
Published: May 2022

Background

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disease with pathophysiological characteristics of transforming growth factor-β (TGF-β), and reactive oxygen species (ROS)-induced excessive fibroblast-to-myofibroblast transition and extracellular matrix deposition. Macrophages are closely involved in the development of fibrosis. Nuclear factor erythroid 2 related factor 2 (Nrf2) is a key molecule regulating ROS and TGF-β expression. Therefore, Nrf2 signaling modulation might be a promising therapy for fibrosis. The inhalation-based drug delivery can reduce systemic side effects and improve therapeutic effects, and is currently receiving increasing attention, but direct inhaled drugs are easily cleared and difficult to exert their efficacy. Therefore, we aimed to design a ROS-responsive liposome for the Nrf2 agonist dimethyl fumarate (DMF) delivery in the fibrotic lung. Moreover, we explored its therapeutic effect on pulmonary fibrosis and macrophage activation.

Results

We synthesized DMF-loaded ROS-responsive DSPE-TK-PEG@DMF liposomes (DTP@DMF NPs). DTP@DMF NPs had suitable size and negative zeta potential and excellent capability to rapidly release DMF in a high-ROS environment. We found that macrophage accumulation and polarization were closely related to fibrosis development, while DTP@DMF NPs could attenuate macrophage activity and fibrosis in mice. RAW264.7 and NIH-3T3 cells coculture revealed that DTP@DMF NPs could promote Nrf2 and downstream heme oxygenase-1 (HO-1) expression and suppress TGF-β and ROS production in macrophages, thereby reducing fibroblast-to-myofibroblast transition and collagen production by NIH-3T3 cells. In vivo experiments confirmed the above findings. Compared with direct DMF instillation, DTP@DMF NPs treatment presented enhanced antifibrotic effect. DTP@DMF NPs also had a prolonged residence time in the lung as well as excellent biocompatibility.

Conclusions

DTP@DMF NPs can reduce macrophage-mediated fibroblast-to-myofibroblast transition and extracellular matrix deposition to attenuate lung fibrosis by upregulating Nrf2 signaling. This ROS-responsive liposome is clinically promising as an ideal delivery system for inhaled drug delivery.

Graphical Abstract
Two-photon responsive porphyrinic metal-organic framework involving Fenton-like reaction for enhanced photodynamic and sonodynamic therapy
Authors: Duan Wenyao , Li Bo , Zhang Wen , Li Jiaqi , Yao Xin , Tian Yupeng , Zheng Jun , Li Dandan
Published: May 2022

Designing new oxygenation nanomaterials by oxygen-generating or oxygen-carrying strategies in hypoxia-associated anti-tumor therapy is a high priority target yet challenge. In this work, we fabricated a nanoplatform involving Fenton-like reaction, Pd@MOF-525@HA, to relieve tumor hypoxia via oxygen-generating strategy for enhanced oxygen-dependent anti-tumor therapy. Thereinto, the porphyrinic MOF-525 can produce singlet oxygen (1O2) via light or ultrasonic irradiation for photodynamic and sonodynamic therapy. Notably, the well-dispersed Pd nanocubes within MOF-525 can convert H2O2 into O2 to mitigate the hypoxic environment for enhanced therapy outcome. Moreover, the two-photon activity and cancer cell specific targeting capability of Pd@MOF-525@HA gave rise to deeper tissue penetration and near-infrared light-induced fluorescence imaging to achieve precise guidance for cancer therapy. This work provides a feasible way in designing new oxygenation nanomaterials to relieve tumor hypoxia for enhanced cancer treatment.

Graphical Abstract
Three birds with one stone: co-encapsulation of diclofenac and DL-menthol for realizing enhanced energy deposition, glycolysis inhibition and anti-inflammation in HIFU surgery
Authors: Wu Haitao , Zhou Hu , Zhang Wenjie , Jin Ping , Shi Qianqian , Miao Zhaohua , Wang Hua , Zha Zhengbao
Published: May 2022

Despite attracting increasing attention in clinic, non-invasive high-intensity focused ultrasound (HIFU) surgery still commonly suffers from tumor recurrence and even matastasis due to the generation of thermo-resistance in non-apoptotic tumor cells and adverse therapy-induced inflammation with enhanced secretion of growth factors in irradiated region. In this work, inspired by the intrinsic property that the expression of thermo-resistant heat shock proteins (HSPs) is highly dependent with adenosine triphosphate (ATP), dual-functionalized diclofenac (DC) with anti-inflammation and glycolysis-inhibition abilities was successfully co-encapsulated with phase-change dl-menthol (DLM) in poly(lactic-co-glycolic acid) nanoparticles (DC/DLM@PLGA NPs) to realize improved HIFU surgery without causing adverse inflammation. Both in vitro and in vivo studies demonstrated the great potential of DC/DLM@PLGA NPs for serving as an efficient synergistic agent for HIFU surgery, which can not only amplify HIFU ablation efficacy through DLM vaporization-induced energy deposition but also simultaneously sensitize tumor cells to hyperthermia by glycolysis inhibition as well as diminished inflammation. Thus, our study provides an efficient strategy for simultaneously improving the curative efficiency and diminishing the harmful inflammatory responses of clinical HIFU surgery.

Graphical Abstract
Association of inflammatory markers with cerebral small vessel disease in community-based population
Authors: Jiang Lingling , Cai Xueli , Yao Dongxiao , Jing Jing , Mei Lerong , Yang Yingying , Li Shan , Jin Aoming , Meng Xia , Li Hao , Wei Tiemin , Wang Yongjun , Pan Yuesong , Wang Yilong
Published: May 2022

Background

This study investigated the relationships of neutrophil count (NC), neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) with cerebral small vessel disease (CSVD).

Methods

A total of 3052 community-dwelling residents from the Poly-vasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study were involved in this cross-sectional study. CSVD burden and imaging markers, including white matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces in basal ganglia (BG-EPVS), were assessed according to total CSVD burden score. The associations of NC, NLR and SII with CSVD and imaging markers were evaluated using logistic regression models. Furthermore, two-sample Mendelian randomization (MR) analysis was performed to investigate the genetically predicted effect of NC on CSVD. The prognostic performances of NC, NLR and SII for the presence of CSVD were assessed.

Results

At baseline, the mean age was 61.2 ± 6.7 years, and 53.5% of the participants were female. Higher NC was suggestively associated with increased total CSVD burden and modified total CSVD burden (Q4 vs. Q1: common odds ratio (cOR) 1.33, 95% CI 1.05–1.70; cOR 1.28, 95% CI 1.02–1.60) and marginally correlated with the presence of CSVD (OR 1.29, 95% CI 1.00–1.66). Furthermore, elevated NC was linked to a higher risk of lacune (OR 2.13, 95% CI 1.25–3.62) and moderate-to-severe BG-EPVS (OR 1.67, 95% CI 1.14–2.44). A greater NLR was related to moderate-to-severe BG-EPVS (OR 1.68, 95% CI 1.16–2.45). Individuals with a higher SII had an increased risk of modified WMH burden (OR 1.35, 95% CI 1.08–1.69) and moderate-to-severe BG-EPVS (OR 1.70, 95% CI 1.20–2.41). MR analysis showed that genetically predicted higher NC was associated with an increased risk of lacunar stroke (OR 1.20, 95% CI 1.04–1.39) and small vessel stroke (OR 1.21, 95% CI 1.06–1.38). The addition of NC to the basic model with traditional risk factors improved the predictive ability for the presence of CSVD, as validated by the net reclassification index and integrated discrimination index (all p < 0.05).

Conclusions

This community-based population study found a suggestive association between NC and CSVD, especially for BG-EPVS and lacune, and provided evidence supporting the prognostic significance of NC.
Molecular characterization of CTNS mutations in Tunisian patients with ocular cystinosis
Authors: Chkioua Latifa , Amri Yessine , Saheli Chaima , Mili Wassila , Mabrouk Sameh , Chabchoub Imen , Boudabous Hela , Azzouz Wissem Ben , Turkia Hadhami Ben , Ferchichi Salima , Tebib Neji , Massoud Taieb , Ghorbel Mohamed , Laradi Sandrine
Published: May 2022

Background

Ocular cystinosis is a rare autosomal recessive disorder characterized by intralysosomal cystine accumulation in renal, ophthalmic (cornea, conjunctiva), and other organ abnormalities. Patients with ocular cystinosis are mostly asymptomatic and typically experience mild photophobia due to cystine crystals in the cornea observed accidently during a routine ocular examination. The ocular cystinosis is associated with different mutations in CTNS gene. Cysteamine therapy mostly corrects the organ abnormalities.

Methods

This study was performed in collaboration with the department of ophthalmology of Farhat Hached Hospital. The Optical Coherence Tomography (OCT) of the cornea and retinal photography were used to search cystine crystals within the corneas and conjunctiva in eight Tunisian patients. Screening for the common 57-kb deletion was performed by standard multiplex PCR, followed by direct sequencing of the entire CTNS gene.

Results

The studied patients were found to have cystine crystal limited anterior corneal stroma and the conjunctiva associated with retinal crystals accumulation. CTNS gene sequencing disclosed 7 mutations: three missense mutations (G308R, p.Q88K, and p.S139Y); one duplication (C.829dup), one framshift mutation (p.G258f), one splice site mutation (c.681 + 7delC) and a large deletion (20,327-bp deletion). Crystallographic structure analysis suggests that the novel mutation p.S139Y is buried in a first transmembrane helix closed to the lipid bilayer polar region, introducing a difference in hydrophobicity which could affect the hydrophobic interactions with the membrane lipids. The second novel mutation p.Q88K which is located in the lysosomal lumen close to the lipid membrane polar head region, introduced a basic amino acid in a region which tolerate only uncharged residue. The third missense mutation introduces a positive change in nonpolar tail region of the phospholipid bilayer membrane affecting the folding and stability of the protein in the lipid bilayer.

Conclusions

Our data demonstrate that impaired transport of cystine out of lysosomes is the most common, which is obviously associated with the mutations of transmembrane domains of cystinosine resulting from a total loss of its activity.
Application of gas flow headspace liquid phase micro extraction coupled with gas chromatography-mass spectrometry for determination of 4-methylimidazole in food samples employing experimental design optimization
Authors: Rafiei jam Mahdiye , Nezhadali Azizollah , Kaykhaii Massoud
Published: May 2022

Background

4-Methylimidazole (4-MeI) or 4-methyl-1H-imidazole, a slightly yellowish solid with molecular formula C4H6N2, is a heterocyclic compound which supposedly does not exist as a natural product and is formed when carbohydrates are heating with ammonium compounds. This compound is used in pharmaceuticals, agriculture and photography chemicals, dyes and pigments, and rubber manufacturing. In the present study, a simple and efficient sample preparation method designated gas flow headspace liquid phase microextraction (GF-HS-SDME) was employed for the extraction and preconcentration of 4-methylimidazole (4-MeI) from food and beverage samples, before its determination by gas chromatography-mass spectrometry.

Result

To investigate the optimal conditions for the extraction process in GF-HS-SDME method, factors affecting extraction, including selection of extraction solvent, vial volume, extraction solvent ratio, position of extracting solvent, drop volume, sample volume, stirring speed, temperature, extraction time, sample pH, ionic strength of the sample solution and gas flow rate were optimized by utilizing both one-variable-at-a-time method and Plackett–Burman design. The investigation of protocol was carried out by using a standard solution containing 100.0 μg L−1 of 4-MeI in deionized water.

Conclusion

In this study, a simple and green analytical method based on GF-HS-SDME was proposed for the extraction and preconcentration of 4-MeI from foodstuffs, followed by GC–MS determination. The main advantage of this method is its high preconcentration factor and fastness due to the application of an inert gas stream during microextraction.
Intelligent metasurfaces: control, communication and computing
Authors: Li Lianlin , Zhao Hanting , Liu Che , Li Long , Cui Tie Jun
Published: May 2022

Controlling electromagnetic waves and information simultaneously by information metasurfaces is of central importance in modern society. Intelligent metasurfaces are smart platforms to manipulate the wave–information–matter interactions without manual intervention by synergizing engineered ultrathin structures with active devices and algorithms, which evolve from the passive composite materials for tailoring wave–matter interactions that cannot be achieved in nature. Here, we review the recent progress of intelligent metasurfaces in wave–information–matter controls by providing the historical background and underlying physical mechanisms. Then we explore the application of intelligent metasurfaces in developing novel wireless communication architectures, with particular emphasis on metasurface-modulated backscatter wireless communications. We also explore the wave-based computing by using the intelligent metasurfaces, focusing on the emerging research direction in intelligent sensing. Finally, we comment on the challenges and highlight the potential routes for the further developments of the intelligent metasurfaces for controls, communications and computing.
Revisiting 2013–2014 Azle seismicity to understand the role of Barnett production on stress propagation and fault stability
Authors: Bubshait Abdulrahman , Jha Birendra
Published: May 2022

Propagation of production- and injection-induced stresses from reservoir layers to basement faults is not well understood, especially in reservoirs with hydraulically segregated production and injection units situated across low-permeability structural or stratigraphic boundaries. This is one of the challenges in understanding the 2013–2014 Azle-Reno earthquake sequence (maximum magnitude M w 3.8) in the Fort Worth Basin of Texas, which occurred after several billion cubic meters of gas and several million cubic meters of brine were produced from the Barnett Shale and several million cubic meters of water was injected into the Ellenburger Formation below the Barnett. The effect of Barnett production on induced stress and reactivation of the synthetic-antithetic fault pair hosting the seismicity is not well understood from prior studies. The interaction among production-induced contraction, injection-induced expansion, and decrease in fault compression due to fluid diffusing from the injection layer strengthens two-way coupling among fluid flow, deformation, and fault failure processes. Using a high-resolution coupled flow-geomechanics-fault reactivation model of the Azle region and a modified corner point meshing algorithm, we integrate structural, seismic, and well data to model novel mechanisms of stress interaction and propagation. The model indicates how Barnett’s production-induced contraction interacts with Ellenburger’s injection-induced expansion in the footwall block of the antithetic fault to cause updip shear on the fault. In the hanging-wall block of the synthetic fault below Ellenburger, the model finds that the downdip shear from Ellenburger expansion colludes with the decrease in fault’s effective compression due to downdip fluid diffusion. The collusion induces normal faulting in the model. Modeling also reveals that the reorientation of the principal stresses is more severe in the Barnett compared with that in the Ellenburger. The model quantifies the impact of stress reorientation on the magnitude and location of fault reactivation events.
Resilience-enhancing interventions for antepartum depressive symptoms: systematic review
Authors: Walker Annika L. , Witteveen Anke B. , Otten René H. J. , Verhoeven Corine J. , Henrichs Jens , de Jonge Ank
Published: May 2022

Background

Antepartum depressive symptoms (ADS) are highly prevalent and may affect the mother and child. Cognitive–behavioural therapy and interpersonal therapy are effective psychological interventions for depression. However, low adherence and high attrition rates in studies of prevention and treatment of antepartum depression suggest that these approaches might not be entirely suitable for women with mild/moderate ADS. Considering the protective association between resilience and ADS, women with ADS might benefit more from interventions focusing on promotion of mental well-being and resilience.

Aims

We aimed to provide an overview of studies evaluating the effectiveness of antepartum resilience-enhancing interventions targeting the improvement of ante- and postpartum depressive symptoms. We also investigated whether these interventions improve resilience and resilience factors in the peripartum period.

Method

We conducted a systematic review, using PRISMA guidelines. Studies were eligible for inclusion when they utilised a randomised controlled trial or quasi-experimental design, studied pregnant women with ADS, and implemented psychological interventions that (a) aimed to reduce maternal ADS and/or prevent peripartum major depression, and (b) addressed one or more psychological resilience factors.

Results

Five of the six included cognitive–behavioural therapy interventions and all four mindfulness-based interventions were effective in reducing peripartum depressive symptoms and/or the incidence of depression. However, the methodological quality of most of the included studies was low to moderate. Only three studies assessed change in resilience factors.

Conclusions

Resilience-enhancing interventions might be beneficial for mental well-being of pregnant women with ADS, although more rigorously designed intervention studies are needed.
High-Risk and Relapsed Neuroblastoma: Toward More Cures and Better Outcomes
Authors: DuBois Steven G. , Macy, Margaret E. , Henderson Tara O.
Published: May 2022

Approximately half of the patients diagnosed with neuroblastoma are classified as having high-risk disease. This group continues to have inadequate cure rates despite multiagent chemotherapy, surgery, high-dose chemotherapy with autologous stem cell rescue, and immunotherapy directed against GD2. We review current efforts to try to improve outcomes in patients with newly diagnosed disease by integrating novel targeted therapies earlier in the course of the disease. We further examine a growing list of options available for patients with relapsed or refractory high-risk disease, with an eye toward graduating successful strategies from a relapsed/refractory setting to the frontline setting. Last, we review efforts to study and potentially mitigate the array of late effects faced by survivors of high-risk neuroblastoma.