Mesenchymal stem cells promote ovarian reconstruction in mice.

BACKGROUND: Studies have shown that chemotherapy and radiotherapy can cause premature ovarian failure and loss of fertility in female cancer patients. Ovarian cortex cryopreservation is a good choice to preserve female fertility before cancer treatment. Following the remission of the disease, the thawed ovarian tissue can be transplanted back and restore fertility of the patient. However, there is a risk to reintroduce cancer cells in the body and leads to the recurrence of cancer. Given the low success rate of current in vitro culture techniques for obtaining mature oocytes from primordial follicles, an artificial ovary with primordial follicles may be a good way to solve this problem. METHODS: In the study, we established an artificial ovary model based on the participation of mesenchymal stem cells (MSCs) to evaluate the effect of MSCs on follicular development and oocyte maturation. P2.5 mouse ovaries were digested into single cell suspensions and mixed with bone marrow derived mesenchymal stem cells (BM-MSCs) at a 1:1 ratio. The reconstituted ovarian model was then generated by using phytohemagglutinin. The phenotype and mechanism studies were explored by follicle counting, immunohistochemistry, immunofluorescence, in vitro maturation (IVM), in vitro fertilization (IVF), real-time quantitative polymerase chain reaction (RT-PCR), and Terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL) assay. RESULTS: Our study found that the addition of BM-MSCs to the reconstituted ovary can enhance the survival of oocytes and promote the growth and development of follicles. After transplanting the reconstituted ovaries under kidney capsules of the recipient mice, we observed normal folliculogenesis and oocyte maturation. Interestingly, we found that BM-MSCs did not contribute to the formation of follicles in ovarian aggregation, nor did they undergo proliferation during follicle growth. Instead, the cells were found to be located around growing follicles in the reconstituted ovary. When theca cells were labeled with CYP17a1, we found some overlapped staining with green fluorescent protein(GFP)-labeled BM-MSCs. The results suggest that BM-MSCs may participate in directing the differentiation of theca layer in the reconstituted ovary. CONCLUSIONS: The presence of BM-MSCs in the artificial ovary was found to promote the survival of ovarian cells, as well as facilitate follicle formation and development. Since the cells didn't proliferate in the reconstituted ovary, this discovery suggests a potential new and safe method for the application of MSCs in clinical fertility preservation by enhancing the success rate of cryo-thawed ovarian tissues after transplantation.

Virtual Care: Perspectives From Family Physicians.

BACKGROUND: During the COVID-19 pandemic, virtual care expanded rapidly at Michigan Medicine and other health systems. From family physicians' perspectives, this shift to virtual care has the potential to affect workflow, job satisfaction, and patient communication. As clinics reopened and care delivery models shifted to a combination of in-person and virtual care, the need to understand physician experiences with virtual care arose in order to improve both patient and provider experiences. This study investigated Michigan Medicine family medicine physicians' perceptions of virtual care through qualitative interviews to better understand how to improve the quality and effectiveness of virtual care for both patients and physicians. METHODS: We employed a qualitative descriptive design to examine physician perspectives through semistructured interviews. We coded and analyzed transcripts using thematic analysis, facilitated by MAXQDA (VERBI) software. RESULTS: The results of the analysis identified four major themes: (a) chief concerns that are appropriate for virtual evaluation, (b) physician perceptions of patient benefits, (c) focused but contextually enriched patient-physician communication, and (d) structural support needed for high-quality virtual care. CONCLUSIONS: These findings can help further direct the discussion of how to make use of resources to improve the quality and effectiveness of virtual care.

A lightweight YOLOv7 insulator defect detection algorithm based on DSC-SE.

As the UAV(Unmanned Aerial Vehicle) carrying target detection algorithm in transmission line insulator inspection, we propose a lightweight YOLOv7 insulator defect detection algorithm for the problems of inferior insulator defect detection speed and high model complexity. Firstly, a lightweight DSC-SE module is designed using a DSC(Depthwise Separable Convolution) fused SE channel attention mechanism to substitute the SC(Standard Convolution) of the YOLOv7 backbone extraction network to decrease the number of parameters in the network as well as to strengthen the shallow network's ability to obtain information about target features. Then, in the feature fusion part, GSConv(Grid Sensitive Convolution) is used instead of standard convolution to further lessen the number of parameters and the computational effort of the network. EIoU-loss(Efficient-IoU) is performed in the prediction head part to make the model converge faster. According to the experimental results, the recognition accuracy rate of the improved model is 95.2%, with a model size of 7.9M. Compared with YOLOv7, the GFLOPs are reduced by 54.5%, the model size is compressed by 37.8%, and the accuracy is improved by 4.9%. The single image detection time on the Jetson Nano is 105ms and the capture rate is 13FPS. With guaranteed accuracy and detection speed, it meets the demands of real-time detection.

Pharmacovigilance for rare diseases: a bibliometrics and knowledge-map analysis based on web of science.

OBJECTIVES: The aims of this paper is to search and explore publications in the field of pharmacovigilance for rare diseases and to visualize general information, research hotspots, frontiers and future trends in the field using the bibliometric tool CiteSpace to provide evidence-based evidence for scholars. METHODS: We searched the Web of Science Core Collection (WoSCC) for studies related to pharmacovigilance for rare diseases, spanning January 1, 1997-October 25, 2022. CiteSpace software was utilized to discuss countries/regions, institutions, authors, journals, and keywords. RESULTS: After screening, a total of 599 valid publications were included in this study, with a significant upward trend in the number of publications. These studies were from 68 countries/regions with the United States and the United Kingdom making the largest contributions to the field. 4,806 research scholars from 493 institutions conducted studies on pharmacovigilance for rare diseases. Harvard University and University of California were the top two productive institutions in the research field. He Dian of the Affiliated Hospital of Guizhou Medical University and Peter G.M. Mol of the University of Groningen, The Netherlands, were the two most prolific researchers. The Cochrane Database of Systematic Reviews and the New England Journal of Medicine were the journals with the highest number of articles and co-citation frequency respectively. Clinical trial, therapy and adverse event were the top three most cited keywords. CONCLUSIONS: Based on keywords co-occurrence analysis, four research topics were identified: orphan drug clinical trials, postmarketing ADR surveillance for orphan drugs, rare diseases and orphan drug management, and diagnosis and treatment of rare diseases. Immune-related adverse reactions and benefit-risk assessment of enzyme replacement therapy were at the forefront of research in this field. Treatment outcomes, early diagnosis and natural history studies of rare diseases may become hotspots for future research.

Identifying Inequities in Video and Audio Telehealth Services for Primary Care Encounters During COVID-19: Repeated Cross-Sectional, Observational Study.

BACKGROUND: The COVID-19 pandemic resulted in rapid changes in how patient care was provided, particularly through the expansion of telehealth and audio-only phone-based care. OBJECTIVE: The goal of this study was to evaluate inequities in video and audio-only care during various time points including the initial wave of the COVID-19 pandemic, later stages of the pandemic, and a historical control. We sought to understand the characteristics of care during this time for a variety of different groups of patients that may experience health care inequities. METHODS: We conducted a retrospective analysis of electronic health record (EHR) data from encounters from 34 family medicine and internal medicine primary care clinics in a large, Midwestern health system, using a repeated cross-sectional, observational study design. These data included patient demographic data, as well as encounter, diagnosis, and procedure records. Data were obtained for all in-person and telehealth encounters (including audio-only phone-based care) that occurred during 3 separate time periods: an initial COVID-19 period (T2: March 16, 2020, to May 3, 2020), a later COVID-19 period (T3: May 4, 2020, to September 30, 2020), and a historical control period from the previous year (T1: March 16, 2019, to September 30, 2019). Primary analysis focused on the status of each encounter in terms of whether it was completed as scheduled, it was canceled, or the patient missed the appointment. A secondary analysis was performed to evaluate the likelihood of an encounter being completed based on visit modality (phone, video, in-person). RESULTS: In total, there were 938,040 scheduled encounters during the 3 time periods, with 178,747 unique patients, that were included for analysis. Patients with completed encounters were more likely to be younger than 65 years old (71.8%-74.1%), be female (58.8%-61.8%), be White (75.6%-76.7%), and have no significant comorbidities (63.2%-66.8%) or disabilities (53.2%-61.1%) in all time periods than those who had only canceled or missed encounters. Effects on different subpopulations are discussed herein. CONCLUSIONS: Findings from this study demonstrate that primary care utilization across delivery modalities (in person, video, and phone) was not equivalent across all groups before and during the COVID-19 pandemic and different groups were differentially impacted at different points. Understanding how different groups of patients responded to these rapid changes and how health care inequities may have been affected is an important step in better understanding implementation strategies for digital solutions in the future.

Equity in virtual care: A mixed methods study of perspectives from physicians.

BACKGROUND: Virtual care expanded rapidly during the COVID-19 pandemic, and how this shift affected healthcare disparities among subgroups of patients is of concern. Racial and ethnic minorities, older adults, individuals with less education, and lower-income households have lower rates of home broadband, smartphone ownership, and patient portal adoption, which may directly affect access to virtual care. Because primary care is a major access point to healthcare, perspectives of primary care providers are critical to inform the implementation of equitable virtual care. OBJECTIVE: The aim of this mixed methods study was to explore primary care physician experiences and perceptions of barriers and facilitators to equitable virtual care. DESIGN: We used an explanatory sequential mixed methods design, which consists of first collecting and analyzing quantitative survey data, then using those results to inform a qualitative follow-up phase to explain and expand on results. PARTICIPANTS: Primary care physicians in a family medicine department at an academic medical center responded to surveys (n = 38) and participated in interviews (n = 16). APPROACH: Participants completed a survey concerning frequency and preferences about video visits, pros and cons of video visits, communication aspects, and sufficiency of the technology. A purposeful sample of participants completed semi-structured interviews about their virtual care experiences with a focus on equity for subpopulations. KEY RESULTS: The results indicated that physicians have observed equity issues for unique patient populations. The results add to the understanding of nuanced ways in which virtual care can increase and decrease healthcare access for unique populations. Patients with limited English proficiency were particularly affected by inequity in virtual care access. CONCLUSION: Additional research and interventions are needed to improve portal access for those with limited English proficiency. Improvements should focus on health system interventions that expand access without requiring increased patient burden.

Performance evaluation of a prescription medication image classification model: an observational cohort.

Technology assistance of pharmacist verification tasks through the use of machine intelligence has the potential to detect dangerous and costly pharmacy dispensing errors. National Drug Codes (NDC) are unique numeric identifiers of prescription drug products for the United States Food and Drug Administration. The physical form of the medication, often tablets and capsules, captures the unique features of the NDC product to help ensure patients receive the same medication product inside their prescription bottle as is found on the label from a pharmacy. We report and evaluate using an automated check to predict the shape, color, and NDC for images showing a pile of pills inside a prescription bottle. In a test set containing 65,274 images of 345 NDC classes, overall macro-average precision was 98.5%. Patterns of incorrect NDC predictions based on similar colors, shapes, and imprints of pills were identified and recommendations to improve the model are provided.

Single-cell RNA-Seq reveals a highly coordinated transcriptional program in mouse germ cells during primordial follicle formation.

The assembly of primordial follicles in mammals represents one of the most critical processes in ovarian biology. It directly affects the number of oocytes available to a female throughout her reproductive life. Premature depletion of primordial follicles contributes to the ovarian pathology primary ovarian insufficiency (POI). To delineate the developmental trajectory and regulatory mechanisms of oocytes during the process, we performed RNA-seq on single germ cells from newborn (P0.5) ovaries. Three cell clusters were classified which corresponded to three cell states (germ cell cyst, cyst breakdown, and follicle) in the newborn ovary. By Monocle analysis, a uniform trajectory of oocyte development was built with a series of genes showed dynamic changes along the pseudo-timeline. Gene Ontology term enrichment revealed a significant decrease in meiosis-related genes and a dramatic increase in oocyte-specific genes which marked the transition from a germ cell to a functional oocyte. We then established a network of regulons by using single-cell regulatory network inference and clustering (SCENIC) algorithm and identified possible candidate transcription factors that may maintain transcription programs during follicle formation. Following functional studies further revealed the differential regulation of the identified regulon Id2 and its family member Id1, on the establishment of primordial follicle pool by using siRNA knockdown and genetic modified mouse models. In summary, our study systematically reconstructed molecular cascades in oocytes and identified a series of genes and molecular pathways in follicle formation and development.

Human versus machine editing of electronic prescription directions.

BACKGROUND: Pharmacy staff are responsible for editing poor-quality and difficult-to-read electronic prescription (e-prescription) directions. Machine translation (MT) models are capable of translating free text from 1 sequence into another. However, the quality of MTs of e-prescriptions into pharmacy label directions is unknown. OBJECTIVE: To determine the types and frequencies of e-prescription direction component errors made by an MT model, pharmacy staff, and prescribers. METHODS: A prospective evaluation was conducted on a random sample of 300 patient directions in a test set of e-prescriptions from a mail-order pharmacy. Each row included directions produced by (1) prescribers on e-prescriptions, (2) pharmacy staff on prescription labels, and (3) an open neural MT model. Annotators labeled direction sets for missing direction components, use of abbreviations and medical jargon, and incorrect information (e.g., changing the number of tablets to be taken). The longest common subsequence (LCS) compared the amount of pharmacy staff editing with and without MT. RESULTS: Out of 279 direction sets labeled, the MT model directions contained no quality issues in 196 (70.3%) samples compared with 187 (67.0%) and 83 (29.8%) samples for pharmacy staff directions and prescriber directions, respectively. The MT model directions contained more incorrect components (n = 23). Median LCS was greater without MT (30.0 vs. 18.5, P < 0.01, Wilcoxon signed-rank test), indicating more editing was needed. CONCLUSION: MT could be used to improve the quality of e-prescription directions; however, MT makes high-risk mistakes such as incorrectly predicting the tapering regimen for prednisone. The use of semiautomated MT, where pharmacy staff can review model predictions to detect and resolve quality issues, should be considered to improve safety and decrease total work time compared with current practice. MT has strengths and weaknesses for improving the editing process of the patient directions compared with pharmacy staff alone.

Advances in Bone Turnover Markers (PINP and CTX) in Optimizing Anti-resorptive and Anabolic Therapies Against Osteoporosis.

Osteoporosis has been a major health problem for many elderly people and postmenopausal women with poor prognosis. Bone turnover markers (BTMs) reflecting bone metabolisms are applied to evaluating clinical results and monitoring of compliance in anti-resorptive and anabolic therapy for osteoporosis. The numerical changes and clinical significance of BTMs in two therapies are summarized and the practical application and potential value of PINP and CTX as therapeutic target, threshold of follow-up therapy, and evaluation of fracture risk in different regimes such as bisphosphonates, denosumab, raloxifene, teriparatide, abaloparatide, and romosozumab are reviewed in this paper. The application of BTMs is expected to improve the efficacy of the treatments and reduce the rate of osteoporotic fracture in clinical practice.

Advances of aptamers screened by Cell-SELEX in selection procedure, cancer diagnostics and therapeutics.

Aptamers are a class of short artificial single-stranded oligo(deoxy) nucleotides that can bind to different targets, which generated by Systematic Evolution of Ligands by Exponential Enrichment (SELEX). Due to excellent selectivity and high affinity to targets, aptamers hold considerable potential as molecular probe in diverse applications ranging from ensuring food safety, monitoring environment, disease diagnosis to therapy. This review highlights recent development and challenges about aptamers screened by Cell-SELEX, and its application about cancer diagnostics and therapeutics. Advances about some operation methods such as seperation method and culture method in aptamers selection procedure were summarized in this paper. Some common challenges and technological difficulties such as nonspecific binding and biostability were discussed. Up to now, the recent endeavors about cancer diagnostic and therapeutic applications of aptamers are summarized and expatiated. Most of aptamers screened by Cell-SELEX took tumor cells as target cells, and such aptamers have been assembled to various aptasensor for cancer diagnosis. Aptamers conjugated various drugs or nanomaterials are functioned for cancer target therapy to improve drugs delivery efficiency and reduce side effects. Furthermore, the duplexed aptamer is discussed to be applied for cancer cells detection and some conflicts of theories about duplexed aptamer designs are analyzed.

HucMSC-Derived Exosomes Mitigate the Age-Related Retardation of Fertility in Female Mice.

In mammals, resting primordial follicles serve as the ovarian reserve. The decline in ovarian function with aging is characterized by a gradual decrease in both the quantity and quality of the oocytes residing within the primordial follicles. Many reports show that mesenchymal stem cells have the ability to recover ovarian function in premature ovarian insufficiency (POI) or natural aging animal models; however, the underlying mechanism remains unclear. In this study, using exosomes derived from human umbilical cord mesenchymal stem cells (HucMSC-exos), we found the specific accumulation of exosomes in primordial oocytes. The stimulating effects of exosomes on primordial follicles were manifested as the activation of the oocyte phosphatidylinositol 3-kinase (PI3K)/mTOR signaling pathway and the acceleration of follicular development after kidney capsule transplantation. Further analysis revealed the stimulatory effects of HucMSC-exos on primordial follicles were through carrying functional microRNAs, such as miR-146a-5p or miR-21-5p. In aged female mice, the intrabursal injection of HucMSC-exos demonstrated the recovery of decreased fertility with increased oocyte production and improved oocyte quality. Although assisted reproductive technologies have been widely used to treat infertility, their overall success rates remain low, especially for women in advanced maternal age. We propose HucMSC-exos as a new approach to mitigate the age-related retardation of fertility in women.

Short-term rapamycin treatment increases ovarian lifespan in young and middle-aged female mice.

Although age-related ovarian failure in female mammals cannot be reversed, recent strategies have focused on improving reproductive capacity with age, and rapamycin is one such intervention that has shown a potential for preserving the ovarian follicle pool and preventing premature ovarian failure. However, the application is limited because of its detrimental effects on follicular development and ovulation during long-term treatment. Herein, we shortened the rapamycin administration to 2 weeks and applied the protocol to both young (8 weeks) and middle-aged (8 months) mouse models. Results showed disturbances in ovarian function during and shortly after treatment; however, all the treated animals returned to normal fertility 2 months later. Following natural mating, we observed prolongation of ovarian lifespan in both mouse models, with the most prominent effect occurring in mice older than 12 months. The effects of transient rapamycin treatment on ovarian lifespan were reflected in the preservation of primordial follicles, increases in oocyte quality, and improvement in the ovarian microenvironment. These data indicate that short-term rapamycin treatment exhibits persistent effects on prolonging ovarian lifespan no matter the age at initiation of treatment. In order not to disturb fertility in young adults, investigators should in the future consider applying the protocol later in life so as to delay menopause in women, and at the same time increase ovarian lifespan.