Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeted Deletion of CXCR2 in Myeloid Cells Alters the Tumor Immune Environment to Improve Antitumor Immunity

Myeloid cell CXCR2 affects not only suppressive MDSCs but also B cells, especially the B1b subset. CXCL11-producing B cells are key and impact infiltration and activation of effector CD8+ T cells in the tumor microenvironment. Recruitment of myeloid-derived suppressor cells (MDSC) into the tumor microenvironment (TME) contributes to cancer immune evasion. MDSCs express the chemokine receptor CXCR2, and inhibiting CXCR2 suppresses the recruitment of MDSCs into the tumor and the premetastatic niche. Here, we compared the growth and metastasis of melanoma and breast cancer xenografts in mice exhibiting or not exhibiting targeted deletion of Cxcr2 in myeloid cells (CXCR2myeΔ/Δ vs. CXCR2myeWT). Detailed analysis of leukocyte populations in peripheral blood and in tumors from CXCR2myeΔ/Δ mice revealed that loss of CXCR2 signaling in myeloid cells resulted in reduced intratumoral MDSCs and increased intratumoral CXCL11. The increase in intratumoral CXCL11 was derived in part from tumor-infiltrating B1b cells. The reduction in intratumoral MDSCs coupled with an increase in intratumoral B1b cells expressing CXCL11 resulted in enhanced infiltration and activation of effector CD8+ T cells in the TME of CXCR2myeΔ/Δ mice, accompanied by inhibition of tumor growth in CXCR2myeΔ/Δ mice compared with CXCR2myeWT littermates. Treatment of tumor-bearing mice with a CXCR2 antagonist (SX-682) also inhibited tumor growth, reduced intratumoral MDSCs, and increased intratumoral B1b cells expressing CXCL11, leading to an increase in activated CD8+ T cells in the tumor. Depletion of B220+ cells or depletion of CD8+ T cells reversed the tumor-inhibitory properties in CXCR2myeΔ/Δ mice. These data revealed a mechanism by which loss of CXCR2 signaling in myeloid cells modulates antitumor immunity through decreasing MDSCs and enriching CXCL11-producing B1b cells in the TME, which in turn increases CD8+ T-cell recruitment and activation in tumors.
Using Exploratory Structural Equation Modeling (ESEM) to Examine the Internal Structure of Posttraumatic Stress Disorder Symptoms

Abstract Several studies have reported the factor structure of posttraumatic stress disorder (PTSD) using confirmatory factor analysis (CFA). The results show models with different number of factors, high correlations between factors, and symptoms that belong to different factors in different models without affecting the fit index. These elements could suppose the existence of considerable item cross-loading, the overlap of different factors or even the presence of a general factor that explains the items common source of variance. The aim is to provide new evidence regarding the factor structure of PTSD using CFA and exploratory structural equation modeling (ESEM). In a sample of 1,372 undergraduate students, we tested six different models using CFA and two models using ESEM and ESEM bifactor analysis. Trauma event and past-month PTSD symptoms were assessed with Life Events Checklist for DSM-5 (LEC–5) and PTSD Checklist for DSM-5 (PCL–5). All six tested CFA models showed good fit indexes (RMSEA = .051–.056, CFI = .969–.977, TLI = .965–.970), with high correlations between factors (M = .77, SD = .09 to M = .80, SD = .09). The ESEM models showed good fit indexes (RMSEA = .027–.036, CFI = .991–.996, TLI = .985–.992). These models confirmed the presence of cross-loadings on several items as well as loads on a general factor that explained 76.3% of the common variance. The results showed that most of the items do not meet the assumption of dimensional exclusivity, showing the need to expand the analysis strategies to study the symptomatic organization of PTSD.
RNA-seq analysis identifies cytoskeletal structural genes and pathways for meat quality in beef

RNA sequencing (RNA-seq) has allowed for transcriptional profiling of biological systems through the identification of differentially expressed (DE) genes and pathways. A total of 80 steers with extreme phenotypes were selected from the University of Florida multibreed Angus-Brahman herd. The average slaughter age was 12.91±8.69 months. Tenderness, juiciness and connective tissue assessed by sensory panel, along with marbling, Warner-Bratzler Shear Force (WBSF) and cooking loss, were measured in longissimus dorsi muscle. Total RNA was extracted from muscle and one RNA-seq library per sample was constructed, multiplexed, and sequenced based on protocols by Illumina HiSeq-3000 platform to generate 2×101 bp paired-end reads. The overall read mapping rate using the Btau_4. 6.1 reference genome was 63%. A total of 8,799 genes were analyzed using two different methodologies, an expression association and a DE analysis. A gene and exon expression association analysis was carried out using a meat quality index on all 80 samples as a continuous response variable. The expression of 208 genes and 3,280 exons from 1,565 genes was associated with the meat quality index (p-value ≤ 0.05). A gene and isoform DE evaluation was performed analyzing two groups with extreme WBSF, tenderness and marbling. A total of 676 (adjusted p-value≤0.05), 70 (adjusted p-value≤0.1) and 198 (adjusted p-value≤0.1) genes were DE for WBSF, tenderness and marbling, respectively. A total of 106 isoforms from 98 genes for WBSF, 13 isoforms from 13 genes for tenderness and 43 isoforms from 42 genes for marbling (FDR≤0.1) were DE. Cytoskeletal and transmembrane anchoring genes and pathways were identified in the expression association, DE and the gene enrichment analyses; these proteins can have a direct effect on meat quality. Cytoskeletal proteins and transmembrane anchoring molecules can influence meat quality by allowing cytoskeletal interaction with myocyte and organelle membranes, contributing to cytoskeletal structure and architecture maintenance postmortem.
Enabling Advance Care Planning in Dementia Care: A Primary Care Approach

Background: Lack of tools to support advance care planning (ACP) has been identified as a significant barrier to implementing these discussions. Aim: We pilot tested an ACP framework tool for use with persons living with dementia (PLWD) in primary care-based memory clinics and an Adult Day Program; this study describes user and recipient experiences with this framework. Methods: We used a mixed methods approach. Health professionals completed an online survey following pilot testing and PLWD and substitute decision makers (SDM) completed survey immediately following the ACP discussion assessing their satisfaction (5-point scale) with the framework and exploring potential outcomes. Interviews with health professionals, PLWD, and SDM were conducted to gather more in-depth information on their perceptions of the ACP framework/ discussion. Results: Surveys were completed by 12 health professionals, 13 PLWD, and 16 SDM. While PLWD and SDM were satisfied with the ACP discussion (M = 4.0/5), health professionals were minimally satisfied with the ease of use of the framework (M = 2.0/5), acceptability for patients (M = 2.4/5) and feasibility in practice (M = 1.9/5). Sixteen interviews were completed with 8 health professionals, 1 PLWD, and 7 SDM. While health professionals valued ACP, lack of time and training were identified barriers to framework use. SDM felt better prepared for future decisions and PLWD were put at ease, knowing that their wishes for care were understood. Conclusion: PLWD and SDM value the opportunity for ACP, and although health professionals identified some concerns with framework administration, they acknowledge the value and importance of ACP. Continuing efforts to refine ACP processes are justified.
Applications of compressive sensing in spatial frequency domain imaging

Abstract. Significance: Spatial frequency domain imaging (SFDI) is an imaging modality that projects spatially modulated light patterns to determine optical property maps for absorption and reduced scattering of biological tissue via a pixel-by-pixel data acquisition and analysis procedure. Compressive sensing (CS) is a signal processing methodology which aims to reproduce the original signal with a reduced number of measurements, addressing the pixel-wise nature of SFDI. These methodologies have been combined for complex heterogenous data in both the image detection and data analysis stage in a compressive sensing SFDI (cs-SFDI) approach, showing reduction in both the data acquisition and overall computational time. Aim: Application of CS in SFDI data acquisition and image reconstruction significantly improves data collection and image recovery time without loss of quantitative accuracy. Approach: cs-SFDI has been applied to an increased heterogenic sample from the AppSFDI data set (back of the hand), highlighting the increased number of CS measurements required as compared to simple phantoms to accurately obtain optical property maps. A novel application of CS to the parameter recovery stage of image analysis has also been developed and validated. Results: Dimensionality reduction has been demonstrated using the increased heterogenic sample at both the acquisition and analysis stages. A data reduction of 30% for the cs-SFDI and up to 80% for the parameter recover was achieved as compared to traditional SFDI, while maintaining an error of <10 % for the recovered optical property maps. Conclusion: The application of data reduction through CS demonstrates additional capabilities for multi- and hyperspectral SFDI, providing advanced optical and physiological property maps.
Pilot Study of Compassion Meditation Training to Improve Well-being Among Older Adults

ABSTRACT Objectives Compassion meditation (CM) training has demonstrated potential in improving well-being and psychosocial functioning. However, most prior studies of CM training have focused on younger adults. The generalizability of the effectiveness of CM training with older adults requires further study. This pilot study was intended to inform future randomized controlled studies of CM training in older adults. Methods Participants included 24 older adults who attended a 10-week group CM training. Exploratory outcome measures were administered prior to, during, and after the intervention. Participants also completed logs of mood and meditation practice, and provided descriptive comments in response to open-ended questions administered at the end of treatment. Results High treatment completion rates (87.5%) and reported adherence (85.7% of assigned meditation) were observed. Descriptive feedback from participants indicated older adults are interested in and capable of learning and applying new concepts and skills in support of their well-being. Pre- to post-intervention changes were explored with a variety of self-report measures. Weekly journals suggested increased feelings of love, closeness, or trust, and decreased feelings of stress, nervousness, or being overwhelmed. Conclusions These findings provide preliminary support for the feasibility of CM training in community-dwelling older adults, and suggest the need for future efficacy and effectiveness clinical trials. Clinical Implications CM training offers potential benefits for improving well-being among older adults, and, as an example of a strengths-based approach, can be tailored to the specific needs of older adults.
Early Patient Experiences of Primary Above-the-Knee Amputation From Vascular Etiologies: A Phenomenological Study

The aim of this study was to explore the different meanings of the experience of lower-limb amputation due to vascular causes in the time period from the fifth to twelfth week post-amputation. A phenomenological study involving semi-structured interviews was carried out. Data collection took place in a Public Hospital in Spain and included a convenience sample of 20 patients who had undergone amputation. The study highlighted patients’ fears related to mobility, pain, dependence, and autonomy. Moreover, patients experience of the rehabilitation process and resources for adaptation were described as well as all the changes related to the social environment. The figure of a nurse was considered essential after amputation by the patients. This study provides a deep understanding of their experiences at the immediate time after amputation considering patients demographical associations and the etiology of the vascular pathology. This could be the starting point to understand patients’ immediate needs upon discharge.
Umbilical cord blood-derived mesenchymal stem cells in treating a critically ill COVID-19 patient.

INTRODUCTION The coronavirus disease 2019 (COVID-19) pandemic is spreading rapidly. Critically ill cases of COVID-19 can rapidly progress to acute respiratory distress syndrome and multiple organ failures. However, no effective drugs have been available till now, leading to more than 300,000 deaths up to 29 April 2020. Here, we present a critically ill case utilizing umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs). CASE PRESENTATION A 72-year-old man was admitted, with the diagnosis of COVID-19, ARDS, type-2 diabetes, diabetic nephropathy, renal insufficiency, and hypertension. His clinical condition continually developed to be life-threatening even receiving various treatment options including antiviral therapy and extracorporeal membrane oxygenation. Between 28 February and 8 March 2020, the patient was given 5-time intravenous infusions of UCB-MSCs. His hematological and biochemical indexes, including lymphocytes and renal function improved. Pulmonary static compliance increased significantly and PaO2/FiO2 ratio maintained stable. On March 10, he received lung transplantation. CONCLUSIONS Our current findings suggested that UCB-MSCs therapy may show some positive effect in treating critical COVID-19 to some extent, for its delaying deterioration of the disease and efficacy in respiratory and renal function, though limited.
Nuclear F-actin Cytology in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma

Oral cavity cancer has a low 5-y survival rate, but outcomes improve when the disease is detected early. Cytology is a less invasive method to assess oral potentially malignant disorders relative to the gold-standard scalpel biopsy and histopathology. In this report, we aimed to determine the utility of cytological signatures, including nuclear F-actin cell phenotypes, for classifying the entire spectrum of oral epithelial dysplasia and oral squamous cell carcinoma. We enrolled subjects with oral potentially malignant disorders, subjects with previously diagnosed malignant lesions, and healthy volunteers without lesions and obtained brush cytology specimens and matched scalpel biopsies from 486 subjects. Histopathological assessment of the scalpel biopsy specimens classified lesions into 6 categories. Brush cytology specimens were analyzed by machine learning classifiers trained to identify relevant cytological features. Multimodal diagnostic models were developed using cytology results, lesion characteristics, and risk factors. Squamous cells with nuclear F-actin staining were associated with early disease (i.e., lower proportions in benign lesions than in more severe lesions), whereas small round parabasal-like cells and leukocytes were associated with late disease (i.e., higher proportions in severe dysplasia and carcinoma than in less severe lesions). Lesions with the impression of oral lichen planus were unlikely to be either dysplastic or malignant. Cytological features substantially improved upon lesion appearance and risk factors in predicting squamous cell carcinoma. Diagnostic models accurately discriminated early and late disease with AUCs (95% CI) of 0.82 (0.77 to 0.87) and 0.93 (0.88 to 0.97), respectively. The cytological features identified here have the potential to improve screening and surveillance of the entire spectrum of oral potentially malignant disorders in multiple care settings.
The LAIs Are Coming! Implementation Science Considerations for Long-Acting Injectable Antiretroviral Therapy in the United States: A Scoping Review.

INTRODUCTION Long-acting injectable antiretroviral therapy (LAI-ART) is one of the latest advancements in HIV control with the potential to overcome oral ART barriers to adherence. The objective of this paper is to anticipate and examine implementation considerations for LAI-ART using components of the PRISM model, a Practical, Robust Implementation and Sustainability Model for integrating research findings into practice. METHODS We conducted a scoping review from January to August 2020 of the growing literature on LAI-ART implementation and other fields employing long-acting injectable therapies. Key considerations regarding LAI-ART were parsed from the searches and entered into the PRISM implementation science framework. DISCUSSION The PRISM framework posed multiple questions for consideration in the development of an optimal implementation strategy for LAI-ART in the United States. These questions revealed the necessity for more data including acceptability of LAI-ART among many different sub-groups of people living with HIV (PLWH), cost effectiveness, patient satisfaction, and patient-reported outcomes, as well as more detailed information related to the external environment for optimal LAI-ART implementation. Ethical considerations of LAI-ART will also need to be considered. CONCLUSION The anticipation of and excitement for LAI-ART represent the hope for a new direction for HIV treatment that reduces adherence barriers and improvements in prognoses for PLWH. We have a unique window of opportunity to anticipate implementation considerations for LAI-ART so this new therapy can be used to its fullest potential. Outstanding questions remain, however, that need to be addressed to help achieve HIV suppression goals in diverse populations.
Further delineation of MYO18B‐related autosomal recessive Klippel‐Feil syndrome with myopathy and facial dysmorphism

Klippel‐Feil syndrome 4 (KFS4; MIM# 616549) is an autosomal recessive disorder caused by biallelic pathogenic variants in MYO18B and comprises, in addition to Klippel‐Feil anomaly (KFA), nemaline myopathy, facial dysmorphism, and short stature. We aim to outline the natural history of KFS4 and provide an updated description of its clinical, radiological, laboratory, and molecular findings. We comprehensively analyzed the medical records of 6 Saudi and 1 American patients (including 5 previously unpublished cases) with a molecularly confirmed diagnosis of KFS4. All patients had myopathy of varying severity that followed a slowly progressive or non‐progressive course, affecting primarily the proximal musculature of the lower limb although hand involvement with distal arthrogryposis and abnormal interphalangeal creases was also observed. KFA and characteristic dysmorphic features, including ptosis and bulbous nose, were observed in all but two patients. The causal MYO18B variants were a founder NM_032608. 5:c.6905C>A; p.(Ser2302*) variant in the Saudi patients (P1‐P6) and a novel MYO18B homozygous variant (c.6660_6670del;p.[Arg2220Serfs*74]) in the American Caucasian patient (P7). We report the phenotypic and genetic findings in seven patients with KFS4. We describe the natural history of this disease, confirm myopathy as a universal feature and describe its pattern and progression, and note interesting differences between the phenotypes observed in patients with KFA and those without.
CD34+ Hematopoietic Progenitor Cell Subsets Exhibit Differential Ability To Maintain Human Cytomegalovirus Latency and Persistence

Human cytomegalovirus infection is associated with severe disease in transplant patients, and understanding how latency and reactivation occur in stem cell populations is essential to understand disease. CD34+ hematopoietic progenitor cells (HPCs) are a critical viral reservoir; however, these cells are a heterogeneous pool with donor-to-donor variation in functional, genetic, and phenotypic characteristics. ABSTRACT In human cytomegalovirus (HCMV)-seropositive patients, CD34+ hematopoietic progenitor cells (HPCs) provide an important source of latent virus that reactivates following cellular differentiation into tissue macrophages. Multiple groups have used primary CD34+ HPCs to investigate mechanisms of viral latency. However, analyses of mechanisms of HCMV latency have been hampered by the genetic variability of CD34+ HPCs from different donors, availability of cells, and low frequency of reactivation. In addition, multiple progenitor cell types express surface CD34, and the frequencies of these populations differ depending on the tissue source of the cells and culture conditions in vitro. In this study, we generated CD34+ progenitor cells from two different embryonic stem cell (ESC) lines, WA01 and WA09, to circumvent limitations associated with primary CD34+ HPCs. HCMV infection of CD34+ HPCs derived from either WA01 or WA09 ESCs supported HCMV latency and induced myelosuppression similar to infection of primary CD34+ HPCs. Analysis of HCMV-infected primary or ESC-derived CD34+ HPC subpopulations indicated that HCMV was able to establish latency and reactivate in CD38+ CD90+ and CD38+/low CD90− HPCs but persistently infected CD38− CD90+ cells to produce infectious virus. These results indicate that ESC-derived CD34+ HPCs can be used as a model for HCMV latency and that the virus either latently or persistently infects specific subpopulations of CD34+ cells. IMPORTANCE Human cytomegalovirus infection is associated with severe disease in transplant patients and understanding how latency and reactivation occur in stem cell populations is essential to understand disease. CD34+ hematopoietic progenitor cells (HPCs) are a critical viral reservoir; however, these cells are a heterogeneous pool with donor-to-donor variation in functional, genetic, and phenotypic characteristics. We generated a novel system using embryonic stem cell lines to model HCMV latency and reactivation in HPCs with a consistent cellular background. Our study defined three key stem cell subsets with differentially regulated latent and replicative states, which provide cellular candidates for isolation and treatment of transplant-mediated disease. This work provides a direction toward developing strategies to control the switch between latency and reactivation.
Serum Levels of Soluble Platelet Endothelial Cell Adhesion Molecule 1 in COVID-19 Patients Are Associated With Disease Severity

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