bluuebunny/crossref_metadata_2025 huggingface dataset:
A guide for standardized interpretation of lumbar multifidus ultrasonography; an observational study
Authors: Soer Remko , Hofste Anke , Oosterveld Frits G. J. , Hermens Hermie , van Ravensberg Ricardo , Wolff André P. , Groen Gerbrand J.
Published: July 2022

Background

Inconsistent descriptions of Lumbar multifidus (LM) morphology were previously identified, especially in research applying ultrasonography (US), hampering its clinical applicability with regard to diagnosis and therapy. The aim of this study is to determine the LM-sonoanatomy by comparing high-resolution reconstructions from a 3-D digital spine compared to standard LM-ultrasonography.

Methods

An observational study was carried out. From three deeply frozen human tissue blocks of the lumbosacral spine, a large series of consecutive photographs at 78 μm interval were acquired and reformatted into 3-D blocks. This enabled the reconstruction of (semi-)oblique cross-sections that could match US-images obtained from a healthy volunteer. Transverse and oblique short-axis views were compared from the most caudal insertion of LM to L1.

Results

Based on the anatomical reconstructions, we could distinguish the LM from the adjacent erector spinae (ES) in the standard US imaging of the lower spine. At the lumbosacral junction, LM is the only dorsal muscle facing the surface. From L5 upwards, the ES progresses from lateral to medial. A clear distinction between deep and superficial LM could not be discerned. We were only able to identify five separate bands between every lumbar spinous processes and the dorsal part of the sacrum in the caudal anatomical cross-sections, but not in the standard US images.

Conclusion

The detailed cross-sectional LM-sonoanatomy and reconstructions facilitate the interpretations of standard LM US-imaging, the position of the separate LM-bands, the details of deep interspinal muscles, and demarcation of the LM versus the ES. Guidelines for electrode positioning in EMG studies should be refined to establish reliable and verifiable findings. For clinical practice, this study can serve as a guide for a better characterisation of LM compared to ES and for a more reliable placement of US-probe in biofeedback.
Assessment of bone mineral density and bone metabolism in young men with obstructive sleep apnea: a cross-sectional study
Authors: Zhao Jian-Ming , Wang Bi-Ying , Huang Jie-Feng , Xie Han-Sheng , Chen Meng-Lan , Chen Gong-Ping
Published: July 2022

Background

Hypoxia in obstructive sleep apnea (OSA) patients during sleep may have an effect on bone metabolism. Few data regarding evaluation of bone metabolism in young individuals diagnosed with OSA. In this study, we aim to identify the association between bone mineral density and OSA in young men (≤ 40 years old of age).

Methods

Consecutive male subjects who underwent polysomnography were enrolled. Serum calcium, 25-hydroxyvitamin-D3, β-isomerized form C-terminal telopeptide of type I collagen, osteocalcin and procollagen type 1 N-propeptide were measured in all participants, and bone mineral density (BMD) at lumbar spine (L1-L4), femoral neck and hip total were determined by dual energy X-ray absorption (DXA).

Results

The population consisted of 85 subjects (mean age 35.53 years). The BMD at lumbar spine (L1-L4) in moderate OSA patients was higher than control and severe OSA group significantly (p = 0.036). After adjustment for confounding factors, stepwise multiple linear regression analyses showed LaSO2 (β = 0.340, p = 0.008) as an independent explanatory variable for Lumbar L1–L4 BMD, LaSO2 (β = 0.304, p = 0.037), BMI (β = 0.393, p = 0.008) for femur neck BMD and BMI (β = 0.720, p = 0.002) for hip total BMD. Conclusions.

Our finding indicated that there was a relationship between OSA and bone metabolism in younger men, and moderate OSA-related hypoxia positively related with BMD. This study also showed that different degrees of recurrent hypoxia had different effects on bone metabolism, a finding that required further investigation.
Adaptation, implementation, and mixed methods evaluation of an interprofessional modular clinical practice guideline for delirium management on an inpatient palliative care unit
Authors: Bush Shirley H. , Skinner Elise , Lawlor Peter G. , Dhuper Misha , Grassau Pamela A. , Pereira José L. , MacDonald Alistair R. , Parsons Henrique A. , Kabir Monisha
Published: July 2022

Background

Using delirium clinical guidelines may align interprofessional clinical practice and improve the care of delirious patients and their families. The aim of this project was to adapt, implement and evaluate an interprofessional modular delirium clinical practice guideline for an inpatient palliative care unit.

Methods

The setting was a 31-bed adult inpatient palliative care unit within a university-affiliated teaching hospital. Participants for the evaluation were interprofessional team members. Using integration of guideline adaptation and an education initiative, an interprofessional guideline adaptation group developed a face-to-face ‘starter kit’ module and four online self-learning modules. The mixed methods evaluation comprised pre-and post-implementation review of electronic patient records, an online survey, and analysis of focus groups/ interviews using an iterative, inductive thematic analysis approach.

Results

Guideline implementation took 12 months. All palliative care unit staff attended a ‘starter kit’ session. Overall completion rate of the four e-Learning modules was 80.4%. After guideline implementation, nursing documentation of non-pharmacological interventions occurring before medication administration was observed. There was 60% less scheduled antipsychotic use and an increase in ‘as needed’ midazolam use. The online survey response rate was 32% (25/77). Most participants viewed the guideline’s implementation favourably. Six key themes emerged from the qualitative analysis of interviews and focus groups with ten participants: prior delirium knowledge or experiences, challenges of facilitating change, impacts on practice, collaborative effort of change, importance of standardized guidelines, and utility of guideline elements.

Conclusions

Guideline implementation warrants concerted effort, time, and management support. Interprofessional team support facilitates the modular approach of guideline adaptation and implementation, leading to a change in clinical practice.
Implementing Advance Care Planning for dialysis patients: HIGHway project
Authors: Rodriguez de Sosa Giselle , Nicklas Amanda , Thamer Mae , Anderson Elizabeth , Reddy Naveena , Stevelos JoAnn , Germain Michael J. , Unruh Mark L. , Lupu Dale E.
Published: July 2022

Background

Patients undergoing hemodialysis have a high mortality rate and yet underutilize palliative care and hospice resources. The Shared Decision Making-Renal Supportive Care (SDM-RSC) intervention focused on goals of care conversations between patients and family members with the nephrologist and social worker. The intervention targeted deficiencies in communication, estimating prognosis, and transition planning for seriously ill dialysis patients. The intervention showed capacity to increase substantially completion of advance care directives. The HIGHway Project, adapted from the previous SDM-RSC, scale up training social workers or nurses in dialysis center in advance care planning (ACP), and then support them for a subsequent 9-month action period, to engage in ACP conversations with patients at their dialysis center regarding their preferences for end-of-life care.

Methods

We will train between 50–60 dialysis teams, led by social workers or nurses, to engage in ACP conversations with patients at their dialysis center regarding their preferences for end-of-life care. This implementation project uses the Knowledge to Action (KTA) Framework within the Consolidated Framework for Implementation Research (CFIR) to increase adoption and sustainability in the participating dialysis centers. This includes a curriculum about how to hold ACP conversation and coaching with monthly teleconferences through case discussion and mentoring. An application software will guide on the process and provide resources for holding ACP conversations. Our project will focus on implementation outcomes. Success will be determined by adoption and effective use of the ACP approach. Patient and provider outcomes will be measured by the number of ACP conversations held and documented; the quality and fidelity of ACP conversations to the HIGHway process as taught during education sessions; impact on knowledge and skills; content, relevance, and significance of ACP intervention for patients, and Supportive Kidney Care (SKC) App usage. Currently HIGHway is in the recruitment stage.

Discussion

Effective changes to advance care planning processes in dialysis centers can lead to institutional policy and protocol changes, providing a model for patients receiving dialysis treatment in the US. The result will be a widespread improvement in advance care planning, thereby remedying one of the current barriers to patient-centered, goal-concordant care for dialysis patients.

Trial registration

The George Washington University Protocol Record NCR213481, Honoring Individual Goals and Hopes: Implementing Advance Care Planning for Persons with Kidney Disease on Dialysis, is registered in ClinicalTrials.gov Identifier: NCT05324878 on April 11th, 2022.
Resveratrol pre-treatment alleviated caerulein-induced acute pancreatitis in high-fat diet-feeding mice via suppressing the NF-κB proinflammatory signaling and improving the gut microbiota
Authors: Zhang Xiaoying , Yang Guodong , Chen Yulin , Mu Zhao , Zhou Haiyue , Zhang Luoyao
Published: July 2022

Background

hyperlipidemia acute pancreatitis (HTG-AP) is a major hidden danger affecting human health, however, whether there is a protective effect of resveratrol on HTG-AP is unclear. Therefore our study was aimed to investigate the preventive effect and the underlying mechanism of resveratrol in the HTG-AP mice model.

Methods

This research was divided into two parts. In the first part, mice were adaptively fed with normal chow or HFD for 6 weeks. From the second week, resveratrol-treated mice were in intragastric administration with resveratrol (45 mg/kg/d) for 4 weeks. In the second part, the procedures were the same as the first part. After the last intragastric administration with resveratrol, all mice were intraperitoneal injections of cerulean.

Results

We found resveratrol effectively inhibited pancreatic pathological injury in the HFD, AP, and HTG-AP mice. Resveratrol reduced the LPS, IL-6, TNF-α, and MCP-1 expressions in the HFD mice. Resveratrol also reduced TNF-α, MDA, and MCP-1 expressions and increased SOD and T-AOC expressions in the AP and HTG-AP mice. Furthermore, resveratrol suppressed the NF-κB pro-inflammatory signaling pathway in pancreatic tissues in the AP and HTG-AP mice. Moreover, resveratrol improved the gut microbiota in the HFD mice.

Conclusion

The resveratrol pre-treatment could attenuate pancreas injury, inflammation, and oxidative stress in the HTG-AP mice, via restraining the NF-κB signaling pathway and regulating gut microbiota. Therefore, Our study proved that the resveratrol pre-treatment had a preventive effect on HTG-AP.
Identification of core genes associated with the anti-atherosclerotic effects of Salvianolic acid B and immune cell infiltration characteristics using bioinformatics analysis
Authors: Jin Zheng , Zhao Huanyi , Luo Yuan , Li Xiushen , Cui Jiayan , Yan Jing , Yang Pingzhen
Published: July 2022

Background

Atherosclerosis (AS) is the greatest contributor to pathogenesis of atherosclerotic cardiovascular disease (ASCVD), which is associated with increased mortality and reduced quality of life. Early intervention to mitigate AS is key to prevention of ASCVD. Salvianolic acid B (Sal B) is mainly extracted from root and rhizome of Salvia Miltiorrhiza Bunge, and exerts anti-atherosclerotic effect. The purpose of this study was to screen for anti-AS targets of Sal B and to characterize immune cell infiltration in AS.

Methods

We identified targets of Sal B using SEA (http://sea.bkslab.org/) and SIB (https://www.sib.swiss/) databases. GSE28829 and GSE43292 datasets were obtained from Gene Expression Omnibus database. We identified differentially expressed genes (DEGs) and performed enrichment analysis. Weighted gene co-expression network analysis (WGCNA) was used to determine the most relevant module associated with atherosclerotic plaque stability. Intersecting candidate genes were evaluated by generating receiver operating characteristic (ROC) curves and molecular docking. Then, immune cell types were identified using CIBERSOFT and single-sample gene set enrichment analysis (ssGSEA), the relationship between candidate genes and immune cell infiltration was evaluated. Finally, a network-based approach to explore the candidate genes relationship with microRNAs (miRNAs) and Transcription factors (TFs).

Results

MMP9 and MMP12 were been selected as candidate genes from 64 Sal B-related genes, 81 DEGs and turquoise module with 220 genes. ROC curve results showed that MMP9 (AUC = 0.815, P<0.001) and MMP12 (AUC = 0.763, P<0.001) were positively associated with advanced atherosclerotic plaques. The results of immune infiltration showed that B cells naive, B cells memory, Plasma cells, T cells CD8, T cells CD4 memory resting, T cells CD4 memory activated, T cells regulatory (Tregs), T cells gamma delta, NK cells activated, Monocytes, and Macrophages M0 may be involved in development of AS, and the candidate genes MMP9 and MMP12 were associated with these immune cells to different degrees. What’ s more, miR-34a-5p and FOXC1, JUN maybe the most important miRNA and TFs.

Conclusion

The anti-AS effects of Sal B may be related to MMP9 and MMP12 and associated with immune cell infiltration, which is expected to be used in the early intervention of AS.
Development and implementation of a formative instructional coaching program using the Teaching Practices Inventory within a health professions program
Authors: Olsen Amanda A. , Morbitzer Kathryn A. , Zambrano Skye , Zeeman Jacqueline M. , Persky Adam M. , Bush Antonio , McLaughlin Jacqueline E.
Published: July 2022

Background

A growing body of literature describes teaching practices that are positively associated with student achievement. Observing, characterizing, and providing feedback on these teaching practices is a necessary, yet significant challenge to improving teaching quality. This study describes the design, implementation, and evaluation of an instructional coaching program created to provide formative feedback to instructors based on their use of evidence-based teaching practices.

Methods

The program was designed for formative purposes utilizing an instrument adapted from the Teaching Practices Inventory. All faculty were invited to participate in the program on a voluntary basis when the program launched in Fall 2019. Program coaches included any School personnel who completed required training. Two rounds of instrument development were conducted with multiple observers and assessed using Krippendorff’s Alpha. The program was evaluated using an anonymous post-session survey.

Results

Interrater reliability of the form improved over two rounds of piloting and no differences were found in scoring between trainees and education professionals. Seventeen observations were completed by nine coaches. Instructors indicated that feedback was practical, timely, specific, and collegial, suggesting that including student perspectives (e.g., focus groups, student course evaluations) in the coaching program might be helpful.

Conclusions

Creating programs that emphasize and foster the use of evidence-based teaching are critical for health professions education. Additional research is needed to further develop coaching programs that ensure teaching practices in the health professions are optimizing student learning.
Perceptions on the current content and pedagogical approaches used in end-of-life care education among undergraduate nursing students: a qualitative, descriptive study
Authors: Cao Wenjing , Li Chunyan , Zhang Qianqian , Tong Huiru
Published: July 2022

Background

With the aging of the population, high rates of cancer and comorbidity complexity, the end-of-life care for patients will be ever more important. Nurses have always played an essential role in end-of-life care. Insufficient education and training in end-of-life care has been regarded as a major reason of inadequate symptom recognition, symptom management, and communication which results in mental trauma for both the patient’s family and attending health care providers. Undergraduate nurses do end-of-life care as part of their clinical learning. However, undergraduate nurses’ perceptions of the education they received about end-of-life care are not documented.

Objective

This study aimed to critically explore the current state of education regarding end-of-life care from the perspectives of undergraduate nurses.

Methods

We used a descriptive qualitative design. Face-to-face semi-structured interviews were conducted from May to August 2020, with a purposive sample of 15 fourth-year undergraduate nurses who finished the internship. Data were transcribed verbatim and analyzed using content analysis.

Findings

Three main themes relating to undergraduate nurses’ experiences of end-of-life care education emerged from the thematic analysis: 1) Universities provide foundational knowledge about end-of-life care, but it still needs improvement; 2) Clinical practice consolidates and drives undergraduate nurses’ knowledge, skills and confidence about end-of-life care; and 3) cultural attitudes of patients’ family toward disease and death sometimes impedes learning and knowledge translation about end-of-life care.

Conclusion

Undergraduate nursing students benefit from not only theoretical content delivered in the university setting but also practice happened on clinical placement. The current undergraduate curriculum, related to end-of-life care, is disjointed. Meanwhile, undergraduate nurses’ learning and knowledge translation of end-of-life care are impeded by cultural attitudes toward disease and death.
Identification of Mycobacterium avium subspecies paratuberculosis in sheep farms in Bayannaoer, Inner Mongolia, China (short communication)
Authors: Yu Yuandi , Zhang Suhui , Xu Guoyang , Xu Dengfeng , Zheng Hua , Li Bo , Shen Kefei , Fu Lizhi
Published: July 2022

Background

Paratuberculosis is a widespread chronic infection of Mycobacterium avium subspecies paratuberculosis (MAP) that causes significant economic losses to the sheep industry. The current study investigated this disease, which causes diarrhea in sheep, particularly, in Bayannaoer, Inner Mongolia, China. Diagnosis was based on clinical symptoms, pathological autopsy, histopathological inspection, and serological and molecular methods.

Results

MAP was confirmed using polymerase chain reaction using DNA extracted from tissue and fecal samples. Serum samples from 472 individual sheep were obtained to detect antibodies against MAP using an enzyme-linked immunosorbent assay. MAP antibodies were separately detected in 17.86% (35/196) and 18.48% (51/276) of sheep herds at approximately 6 months and ≥ 1 year of age, respectively. The tissue lesion and pathological section results were consistent with paratuberculosis infection.

Conclusions

To our knowledge, this is the first report of Mycobacterium avium subspecies paratuberculosis seroprevalence in Bayannaoer sheep in Inner Mongolia. Our findings show that MAP is not only prevalent, but also a potential threat to this region. Further investigations, including long-term epidemiological surveillance and isolation are needed for the awareness and effective treatment of paratuberculosis in sheep of Inner Mongolia.
Identification of six novel variants from nine Chinese families with hypophosphatemic rickets
Authors: Cao Yixuan , You Yi , Wang Qiong , Ren Xiuzhi , Li Shan , Li Lulu , Xia Weibo , Guan Xin , Yang Tao , Ikegawa Shiro , Wang Zheng , Zhao Xiuli
Published: July 2022

Background

Hypophosphatemic rickets (HR) is a rare genetic disorder associated with renal phosphate wasting and characterized by bone defects. Inactivating mutations in the phosphate regulating endopeptidase homolog X‑linked gene (PHEX) account for most cases of HR. The aim of this study was to identify causative variants in nine unrelated Chinese families associated with HR, and to determine potential pathogenicity of the identified variants.

Methods

Genomic DNA was isolated from the peripheral blood of HR patients and their healthy relatives, followed by next-generation sequencing and/or Sanger sequencing. In silico prediction combined with conservation analysis was performed to assess the effects of the variants, and 3D protein modeling was conducted to predict the functional effects on the encoded protein.

Results

All HR patients recruited in this study displayed bone deformities and tooth agenesis, as well as reduced serum phosphate levels and elevated urine phosphate levels. Nine PHEX variants were identified in eight families, including four novel variants (c.1661_1726del, c.980A > G, c.1078A > T, and c.1017_1051dup). Of the nine identified PHEX variants, five caused a truncated protein, two caused an altered amino acid, and the other two were the canonical splicing variants. Novel variants c.1336G > A and c.1364 T > C in SLC34A3 were also found in one family. Conservation analysis showed that all the amino acids corresponding to the missense variants were highly conserved. In silico analysis and 3D protein structure modeling confirmed the pathogenicity of these variants.

Conclusions

This study identified four novel variants in PHEX and two novel variants in SLC34A3 in a Chinese cohort with HR. Our findings highlight the dominant role of PHEX in HR, and expand the genotypic and phenotypic spectra of this disorder.
Efficient and scalable synthesis of 1,5-diamino-2-hydroxy-pentane from l-lysine via cascade catalysis using engineered Escherichia coli
Authors: Li Yangyang , Zhang Alei , Hu Shewei , Chen Kequan , Ouyang Pingkai
Published: July 2022

Background

1,5-Diamino-2-hydroxy-pentane (2-OH-PDA), as a new type of aliphatic amino alcohol, has potential applications in the pharmaceutical, chemical, and materials industries. Currently, 2-OH-PDA production has only been realized via pure enzyme catalysis from lysine hydroxylation and decarboxylation, which faces great challenges for scale-up production. However, the use of a cell factory is very promising for the production of 2-OH-PDA for industrial applications, but the substrate transport rate, appropriate catalytic environment (pH, temperature, ions) and separation method restrict its efficient synthesis. Here, a strategy was developed to produce 2-OH-PDA via an efficient, green and sustainable biosynthetic method on an industrial scale.

Results

In this study, an approach was created for efficient 2-OH-PDA production from l-lysine using engineered E. coli BL21 (DE3) cell catalysis by a two-stage hydroxylation and decarboxylation process. In the hydroxylation stage, strain B14 coexpressing l-lysine 3-hydroxylase K3H and the lysine transporter CadB-argT enhanced the biosynthesis of (2S,3S)-3-hydroxylysine (hydroxylysine) compared with strain B1 overexpressing K3H. The titre of hydroxylysine synthesized by B14 was 2.1 times higher than that synthesized by B1. Then, in the decarboxylation stage, CadA showed the highest hydroxylysine activity among the four decarboxylases investigated. Based on the results from three feeding strategies, l-lysine was employed to produce 110.5 g/L hydroxylysine, which was subsequently decarboxylated to generate a 2-OH-PDA titre of 80.5 g/L with 62.6% molar yield in a 5-L fermenter. In addition, 2-OH-PDA with 95.6% purity was obtained by solid-phase extraction. Thus, the proposed two-stage whole-cell biocatalysis approach is a green and effective method for producing 2-OH-PDA on an industrial scale.

Conclusions

The whole-cell catalytic system showed a sufficiently high capability to convert lysine into 2-OH-PDA. Furthermore, the high titre of 2-OH-PDA is conducive to separation and possesses the prospect of industrial scale production by whole-cell catalysis.
Bioprocess development as a sustainable platform for eco-friendly alkaline phosphatase production: an approach towards crab shells waste management
Authors: Abdelgalil Soad A. , Abo-Zaid Gaber A.
Published: July 2022

Background

There are substantial environmental and health risks associated with the seafood industry's waste of crab shells. In light of these facts, shellfish waste management is critical for environmental protection against hazardous waste produced from the processing industries. Undoubtedly, improved green production strategies, which are based on the notion of "Green Chemistry," are receiving a lot of attention. Therefore, this investigation shed light on green remediation of the potential hazardous crab shell waste for eco-friendly production of bacterial alkaline phosphatase (ALP) through bioprocessing development strategies.

Results

It was discovered that by utilizing sequential statistical experimental designs, commencing with Plackett–Burman design and ending with spherical central composite design, and then followed by pH-uncontrolled cultivation conditions in a 7 L bench-top bioreactor, an innovative medium formulation could be developed that boosted ALP production fromBacillus licheniformisstrain ALP3 to 212 U L−1. The highest yield of ALP was obtained after 22 h of incubation time with yield coefficientYp/sof 795 U g−1, which was 4.35-fold higher than those obtained in the shake-flask system. ALP activity has a substantial impact on the volatilization of crab shell particles, as shown by the results of several analytical techniques such as atomic absorption spectrometry, TGA, DSC, EDS, FTIR, and XRD.

Conclusions

We highlighted in the current study that the biovalorization of crab shell waste and the production of cost-effective ALP were being combined and that this was accomplished via the use of a new and innovative medium formulation design for seafood waste management as well as scaling up production of ALP on the bench-top scale.
Exploring the multi-level regulation of lignocellulases in the filamentous fungus Trichoderma guizhouense NJAU4742 from an omics perspective
Authors: Xia Yanwei , Wang Jingfan , Guo Chuanxu , Xu Huanhuan , Wang Wei , Yang Mingzhu , Shen Qirong , Zhang Ruifu , Miao Youzhi
Published: July 2022

Background

Filamentous fungi are highly efficient at deconstructing plant biomass by secreting a variety of enzymes, but the complex enzymatic regulation underlying this process is not conserved and remains unclear.

Results

In this study, cellulases and xylanases could specifically respond to Avicel- and xylan-induction, respectively, in lignocellulose-degrading strain Trichoderma guizhouense NJAU4742, however, the differentially regulated cellulases and xylanases were both under the absolute control of the same TgXyr1-mediated pathway. Further analysis showed that Avicel could specifically induce cellulase expression, which supported the existence of an unknown specific regulator of cellulases in strain NJAU4742. The xylanase secretion is very complex, GH10 endoxylanases could only be induced by Avicel, while, other major xylanases were significantly induced by both Avicel and xylan. For GH10 xylanases, an unknown specific regulator was also deduced to exist. Meanwhile, the post-transcriptional inhibition was subsequently suggested to stop the Avicel-induced xylanases secretion, which explained the specifically high xylanase activities when induced by xylan in strain NJAU4742. Additionally, an economical strategy used by strain NJAU4742 was proposed to sense the environmental lignocellulose under the carbon starvation condition, that only slightly activating 4 lignocellulose-degrading genes before largely secreting all 33 TgXyr1-controlled lignocellulases if confirming the existence of lignocellulose components.

Conclusions

This study, aiming to explore the unknown mechanisms of plant biomass-degrading enzymes regulation through the combined omics analysis, will open directions for in-depth understanding the complex carbon utilization in filamentous fungi.
Advancing behavioral interventions for African American/Black and Latino persons living with HIV using a new conceptual model that integrates critical race theory, harm reduction, and self-determination theory: a qualitative exploratory study
Authors: Gwadz Marya , Cluesman Sabrina R. , Freeman Robert , Collins Linda M. , Dorsen Caroline , Hawkins Robert L. , Cleland Charles M. , Wilton Leo , Ritchie Amanda S. , Torbjornsen Karen , Leonard Noelle R. , Martinez Belkis Y. , Silverman Elizabeth , Israel Khadija , Kutnick Alexandra
Published: July 2022

Background

Rates of participation in HIV care, medication uptake, and viral suppression are improving among persons living with HIV (PLWH) in the United States. Yet, disparities among African American/Black and Latino PLWH are persistent, signaling the need for new conceptual approaches. To address gaps in services and research (e.g., insufficient attention to structural/systemic factors, inadequate harm reduction services and autonomy support) and improve behavioral interventions, we integrated critical race theory, harm reduction, and self-determination theory into a new conceptual model, then used the model to develop a set of six intervention components which were tested in a larger study. The present qualitative study explores participants’ perspectives on the study’s acceptability, feasibility, and impact, and the conceptual model’s contribution to these experiences.

Methods

Participants in the larger study were African American/Black and Latino PLWH poorly engaged in HIV care and with non-suppressed HIV viral load in New York City (N = 512). We randomly selected N = 46 for in-depth semi-structured interviews on their experiences with and perspectives on the study. Interviews were audio-recorded and professionally transcribed verbatim, and data were analyzed using directed qualitative content analysis.

Results

On average, participants were 49 years old (SD = 9) and had lived with HIV for 19 years (SD = 7). Most were male (78%) and African American/Black (76%). All had taken HIV medication previously. Challenging life contexts were the norm, including poverty, poor quality/unstable housing, trauma histories exacerbated by current trauma, health comorbidities, and substance use. Participants found the study highly acceptable. We organized results into four themes focused on participants’ experiences of: 1) being understood as a whole person and in their structural/systemic context; 2) trustworthiness and trust; 3) opportunities for self-reflection; and 4) support of personal autonomy. The salience of nonjudgment was prominent in each theme. Themes reflected grounding in the conceptual model. Participants reported these characteristics were lacking in HIV care settings.

Conclusions

The new conceptual model emphasizes the salience of systemic/structural and social factors that drive health behavior and the resultant interventions foster trust, self-reflection, engagement, and behavior change. The model has potential to enhance intervention acceptability, feasibility, and effectiveness with African American/Black and Latino PLWH.
Blood speckle imaging compared with conventional Doppler ultrasound for transvalvular pressure drop estimation in an aortic flow phantom
Authors: Dockerill Cameron , Gill Harminder , Fernandes Joao Filipe , Nio Amanda Q. X. , Rajani Ronak , Lamata Pablo
Published: July 2022

Background

Transvalvular pressure drops are assessed using Doppler echocardiography for the diagnosis of heart valve disease. However, this method is highly user-dependent and may overestimate transvalvular pressure drops by up to 54%. This work aimed to assess transvalvular pressure drops using velocity fields derived from blood speckle imaging (BSI), as a potential alternative to Doppler. 

Methods

A silicone 3D-printed aortic valve model, segmented from a healthy CT scan, was placed within a silicone tube. A CardioFlow 5000MR flow pump was used to circulate blood mimicking fluid to create eight different stenotic conditions. Eight PendoTech pressure sensors were embedded along the tube wall to record ground-truth pressures (10 kHz). The simplified Bernoulli equation with measured probe angle correction was used to estimate pressure drop from maximum velocity values acquired across the valve using Doppler and BSI with a GE Vivid E95 ultrasound machine and 6S-D cardiac phased array transducer.

Results

There were no significant differences between pressure drops estimated by Doppler, BSI and ground-truth at the lowest stenotic condition (10.4 ± 1.76, 10.3 ± 1.63 vs. 10.5 ± 1.00 mmHg, respectively; p > 0.05). Significant differences were observed between the pressure drops estimated by the three methods at the greatest stenotic condition (26.4 ± 1.52, 14.5 ± 2.14 vs. 20.9 ± 1.92 mmHg for Doppler, BSI and ground-truth, respectively; p < 0.05). Across all conditions, Doppler overestimated pressure drop (Bias = 3.92 mmHg), while BSI underestimated pressure drop (Bias = -3.31 mmHg).

Conclusions

BSI accurately estimated pressure drops only up to 10.5 mmHg in controlled phantom conditions of low stenotic burden. Doppler overestimated pressure drops of 20.9 mmHg. Although BSI offers a number of theoretical advantages to conventional Doppler echocardiography, further refinements and clinical studies are required with BSI before it can be used to improve transvalvular pressure drop estimation in the clinical evaluation of aortic stenosis.
Human monocytes differentiate into tumor-associated macrophages upon SKOV3 cells coculture and/or lysophosphatidic acid stimulation
Authors: Feng Ying , Xiao Meizhu , Cao Guangming , Liu Hao , Li Yanfang , Wang Shuzhen , Zijtveld Stan , Delvoux Bert , Xanthoulea Sofia , Romano Andrea , Liu Chongdong , Zhang Zhenyu
Published: July 2022

Background

Serous ovarian carcinoma is the most common type of ovarian carcinoma. Tumor-associated macrophages (TAMs) promote ovarian cancer progression. Most macrophages are generated by monocyte differentiation. Lysophosphatidic acid (LPA) levels are high in blood, tissues and ascites of patients with ovarian cancer. This study investigated whether human monocytes can directly differentiate into TAMs in the serous ovarian carcinoma microenvironment.

Methods

Human monocytes were isolated and purified from umbilical cord blood. A serous ovarian carcinoma-like microenvironment was generated by coculturing monocytes and SKOV3 cells in 0.4-μm-pore-size Transwell chambers. Additionally, the effect of LPA was assessed. The two cultured cell types and supernatants were evaluated.

Results

The morphology and function of monocytes cocultured with SKOV3 cells and/or stimulated with LPA were significantly changed compared with those of non-stimulated monocytes. The CD14 + CD163 + and CD206 + phenotype indicated that stimulated cells were TAMs. The induced cells promoted SKOV3 cell proliferation and invasion, further proving that they were TAMs. The level of the cytokine interleukin-6R in the supernatant was significantly elevated in the treatment groups compared to the control monocyte group. Pathway enrichment analysis of ELISA results showed a strong influence of interleukin-6 family signaling, especially the JAK-STAT signaling pathway, further confirming the importance of IL-6R.

Conclusion

Monocytes can differentiate into TAMs under coculture with SKOV3 cells and/or LPA stimulation. The induced TAMs promote SKOV3 cell proliferation and invasion. The cytokine receptor IL-6sR and the JAK-STAT signaling pathway play an important role in the differentiation of monocytes into TAMs.
Supporting a review of the benefits package of the National Health Insurance Scheme in Ghana
Authors: Vellekoop Heleen , Odame Emmanuel , Ochalek Jessica
Published: July 2022

Background

Although Ghana is lauded for its National Health Insurance Scheme (NHIS), concerns exist about the scheme’s functioning and sustainability. An often-cited issue—contributing to the scheme’s decreasing membership, long-standing financial deficit, and frequent out-of-pocket payments among members—is the large benefits package (BP). While, on paper, the BP covers over 95% of the conditions occurring in Ghana, its design was not informed by any budget analysis, nor any systematic prioritization of interventions. This paper aims to provide evidence-based input into ongoing discussions regarding a review of the NHIS benefits package.

Methods

An existing analytic framework is used to calculate net health benefit (NHB) for a range of interventions in order to assess their cost-effectiveness and enable the prioritization of ‘best buys’. The framework is expanded upon by incorporating concerns for financial protection, and practical feasibility, as well as the political economy challenges of disinvesting in currently funded activities. Five different options for the benefits package, each based on policy discourse in Ghana’s health sector, are presented and evaluated.

Results

Implementing all interventions for which data was available to 100% of the population in need was estimated to cost GH₵4323 million (US$994 million), while the available NHIS budget was only GH₵970 million (US$223 million). Options for the benefits package that focussed on cost-effectiveness and primary care provision achieved the best health outcomes, while options reflecting the status quo and allowing for co-payments included a higher number of healthcare interventions. Apart from the package option focussing on primary care, all packages were faced with physician shortages.

Conclusions

Current funding to the NHIS is insufficient to provide the historical benefits package, which promises to cover over 95% of disease conditions occurring in Ghana, to the total population. Shifting the NHIS focus from intervention coverage to population coverage is likely to lead to better health outcomes. A primary care package may be most feasible in the short-term, though additional physicians should be trained to provide higher-level care that is highly cost-effective, such as emergency neonatal care.
Inhibition of AMPK/PFKFB3 mediated glycolysis synergizes with penfluridol to suppress gallbladder cancer growth
Authors: Hu Jiahao , Cao Jiasheng , Jin Ren’an , Zhang Bin , Topatana Win , Juengpanich Sarun , Li Shijie , Chen Tian’en , Lu Ziyi , Cai Xiujun , Chen Mingyu
Published: July 2022

Background

Penfluridol (PF) is an FDA-approved antipsychotic drug that has recently been shown to have anticancer activity. However, the anticancer effects and underlying mechanisms of PF are not well-established in gallbladder cancer (GBC).

Methods

The anticancer efficacy of PF on GBC was investigated via a series of cell functions experiments, including cell viability, colony formation, apoptosis assays, and so on. The corresponding signaling changes after PF treatment were explored by western blotting. Then, nude mice were utilized to study and test the anticancer activity of PF in vivo. Besides, glucose consumption and lactic production assays were used to detect the glycolysis alteration.

Results

In this study, we discovered that PF greatly inhibited the proliferation and invasion ability of GBC cells (GBCs). The glucose consumption and lactic generation ability of GBCs were dramatically elevated following PF treatment. Additionally, we discovered that inhibiting glycolysis could improve PF's anticancer efficacy. Further studies established that the activation of the AMPK/PFKFB3 signaling pathway medicated glycolysis after PF treatment. We proved mechanistically that inhibition of AMPK/PFKFB3 singling pathway mediated glycolysis was a potential synergetic strategy to improve the anticancer efficacy of PF on GBC.

Conclusions

By inhibiting AMPK, the anticancer effects of PF on GBCs were amplified. As a result, our investigations shed new light on the possibility of repurposing PF as an anticancer drug for GBC, and AMPK inhibition in combination with PF may represent a novel therapeutic strategy for GBC.

Graphical abstract
A comprehensive evaluation of the immune system response and type-I Interferon signaling pathway in hospitalized COVID-19 patients
Authors: Soltani-Zangbar Mohammad Sadegh , Parhizkar Forough , Ghaedi Elham , Tarbiat Ali , Motavalli Roza , Alizadegan Amin , Aghebati-Maleki Leili , Rostamzadeh Davoud , Yousefzadeh Yousef , Jadideslam Golamreza , Farid Sima Shahmohammadi , Roshangar Leila , Mahmoodpoor Ata , Heris Javad Ahmadian , Miahipour Abolfazl , Yousefi Mehdi
Published: July 2022

Background

The COVID-19 pandemic has become the world’s main life-threatening challenge in the third decade of the twenty-first century. Numerous studies have been conducted on SARS-CoV2 virus structure and pathogenesis to find reliable treatments and vaccines. The present study aimed to evaluate the immune-phenotype and IFN-I signaling pathways of COVID-19 patients with mild and severe conditions.

Material and methods

A total of 100 COVID-19 patients (50 with mild and 50 with severe conditions) were enrolled in this study. The frequency of CD4 + T, CD8 + T, Th17, Treg, and B lymphocytes beside NK cells was evaluated using flow cytometry. IFN-I downstream signaling molecules, including JAK-1, TYK-2, STAT-1, and STAT-2, and Interferon regulatory factors (IRF) 3 and 7 expressions at RNA and protein status were investigated using real-time PCR and western blotting techniques, respectively. Immune levels of cytokines (e.g., IL-1β, IL-6, IL-17, TNF-α, IL-2R, IL-10, IFN-α, and IFN-β) and the existence of anti-IFN-α autoantibodies were evaluated via enzyme-linked immunosorbent assay (ELISA).

Results

Immune-phenotyping results showed a significant decrease in the absolute count of NK cells, CD4 + T, CD8 + T, and B lymphocytes in COVID-19 patients. The frequency of Th17 and Treg cells showed a remarkable increase and decrease, respectively. All signaling molecules of the IFN-I downstream pathway and IRFs (i.e., JAK-1, TYK-2, STAT-1, STAT-2, IRF-3, and IRF-7) showed very reduced expression levels in COVID-19 patients with the severe condition compared to healthy individuals at both RNA and protein levels. Of 50 patients with severe conditions, 14 had anti-IFN-α autoantibodies in sera. Meanwhile, this result was 2 and 0 for patients with mild symptoms and healthy controls, respectively.

Conclusion

Our results indicate a positive association of the existence of anti-IFN-α autoantibodies and immune cells dysregulation with the severity of illness in COVID-19 patients. However, comprehensive studies are necessary to find out more about this context.
TA-MSCs, TA-MSCs-EVs, MIF: their crosstalk in immunosuppressive tumor microenvironment
Authors: Zhang Zhenghou , Zhou Xiangyu , Guo Jinshuai , Zhang Fusheng , Qian Yiping , Wang Guang , Duan Meiqi , Wang Yutian , Zhao Haiying , Yang Zhi , Liu Zunpeng , Jiang Xiaofeng
Published: July 2022

As an important component of the immunosuppressive tumor microenvironment (TME), it has been established that mesenchymal stem cells (MSCs) promote the progression of tumor cells. MSCs can directly promote the proliferation, migration, and invasion of tumor cells via cytokines and chemokines, as well as promote tumor progression by regulating the functions of anti-tumor immune and immunosuppressive cells. MSCs-derived extracellular vesicles (MSCs-EVs) contain part of the plasma membrane and signaling factors from MSCs; therefore, they display similar effects on tumors in the immunosuppressive TME. The tumor-promoting role of macrophage migration inhibitory factor (MIF) in the immunosuppressive TME has also been revealed. Interestingly, MIF exerts similar effects to those of MSCs in the immunosuppressive TME. In this review, we summarized the main effects and related mechanisms of tumor-associated MSCs (TA-MSCs), TA-MSCs-EVs, and MIF on tumors, and described their relationships. On this basis, we hypothesized that TA-MSCs-EVs, the MIF axis, and TA-MSCs form a positive feedback loop with tumor cells, influencing the occurrence and development of tumors. The functions of these three factors in the TME may undergo dynamic changes with tumor growth and continuously affect tumor development. This provides a new idea for the targeted treatment of tumors with EVs carrying MIF inhibitors.
Delayed administration of nafamostat mesylate inhibits thrombin-mediated blood–spinal cord barrier breakdown during acute spinal cord injury in rats
Authors: Zhao Chenxi , Zhou Tiangang , Zhao Xiaoqing , Pang Yilin , Li Wenxiang , Fan Baoyou , Li Ming , Liu Xinjie , Ma Lei , Zhang Jiawei , Sun Chao , Shen Wenyuan , Kong Xiaohong , Yao Xue , Feng Shiqing
Published: July 2022

Background

Nafamostat mesylate (nafamostat, NM) is an FDA-approved serine protease inhibitor that exerts anti-neuroinflammation and neuroprotective effects following rat spinal cord injury (SCI). However, clinical translation of nafamostat has been limited by an unclear administration time window and mechanism of action.

Methods

Time to first dose of nafamostat administration was tested on rats after contusive SCI. The optimal time window of nafamostat was screened by evaluating hindlimb locomotion and electrophysiology. As nafamostat is a serine protease inhibitor known to target thrombin, we used argatroban (Arg), a thrombin-specific inhibitor, as a positive control in the time window experiments. Western blot and immunofluorescence of thrombin expression level and its enzymatic activity were assayed at different time points, as well its receptor, the protease activated receptor 1 (PAR1) and downstream protein matrix metalloproteinase-9 (MMP9). Blood–spinal cord barrier (BSCB) permeability leakage indicator Evans Blue and fibrinogen were analyzed along these time points. The infiltration of peripheral inflammatory cell was observed by immunofluorescence.

Results

The optimal administration time window of nafamostat was 2–12 h post-injury. Argatroban, the thrombin-specific inhibitor, had a similar pattern. Thrombin expression peaked at 12 h and returned to normal level at 7 days post-SCI. PAR1, the thrombin receptor, and MMP9 were significantly upregulated after SCI. The most significant increase of thrombin expression was detected in vascular endothelial cells (ECs). Nafamostat and argatroban significantly downregulated thrombin and MMP9 expression as well as thrombin activity in the spinal cord. Nafamostat inhibited thrombin enrichment in endothelial cells. Nafamostat administration at 2–12 h after SCI inhibited the leakage of Evans Blue in the epicenter and upregulated tight junction proteins (TJPs) expression. Nafamostat administration 8 h post-SCI effectively inhibited the infiltration of peripheral macrophages and neutrophils to the injury site.

Conclusions

Our study provides preclinical information of nafamostat about the administration time window of 2–12 h post-injury in contusive SCI. We revealed that nafamostat functions through inhibiting the thrombin-mediated BSCB breakdown and subsequent peripheral immune cells infiltration.