bluuebunny/crossref_metadata_2025 huggingface dataset:
The correlation between hip alpha angle and acetabular labral tear location and size: A cross-sectional study
Authors: Lin Han-Ying , Chiang En-Rung , Wu Shang-Liang , Wu Ching-Lan , Chiou Hong-Jen , Wu Hung-Ta
Published: November 2023

Background:

Explore the correlation between hip morphology and labral tear location/size.

Methods:

This retrospective study analyzed patients with hip pain who received magnetic resonance (MR) arthrography at our institution, between January 2017 and December 2020. Imaging analysis includes labral tear location and size, and hip morphology measurement with alpha angle, lateral center-edge (CE) angle, anterior CE angle, and femoral neck version. The correlation between hip morphology angles and labral tear location/size was evaluated using multiple regression, followed by stratification analysis with Chi-square test to investigate interactions between the variables.

Results:

A total of 103 patients (105 hips) with hip pain who received MR arthrography (mean age, 50 years ± 15 [SD]) were included, with mean alpha angle of 57.7° ± 9.9° [SD], mean lateral CE angle of 32.6° ± 6.8° [SD], mean anterior CE angle of 58.2° ± 8.1° [SD], mean femoral neck version of 17.1° ± 8.2° [SD]. Large alpha angle (>57°) and older age were both correlated with superior and posterosuperior labral tear incidence (p < 0.05) and larger tear size (p < 0.05). Furthermore, alpha angle is significantly correlated with superior labral tear incidence in young-age subgroup (age <45 years) (p < 0.05), also significantly correlated with posterosuperior labral tear incidence and larger tear size in middle-age subgroup (45 ≤ age ≤ 60 years) (p < 0.05).

Conclusion:

A large alpha angle (>57°) is significantly correlated with increased incidence of superior and posterosuperior labral tear, and larger tear size in patients with hip pain, and the relationships depend on age.
Strategies to Eliminate Inequity in PrEP Services in the US South and Rural Communities
Authors: Kamitani Emiko , Mizuno Yuko , Koenig Linda J.
Published: November 2023

Inequity in preexposure prophylaxis (PrEP) care in the US South and rural communities is likely attributed to Social Determinants of Health and structural issues beyond individuals' control. We describe three approaches to modify PrEP care practice models to make access easier—“normalizing,” “digitalizing,” and “simplifying.” “Normalizing” approaches are defined as practice models where medical providers who have access to PrEP candidates prescribe PrEP routinely (e.g., primary care providers, community pharmacists); these approaches are found to be highly applicable in real-world settings. Telehealth and other dHealth tools are examples of “digitalizing” PrEP, and their use has been increasing rapidly since the COVID-19 pandemic. “Simplifying” PrEP care (e.g., with HIV self-testing, on-demand PrEP) is highlighted in the most recent World Health Organization PrEP guideline. Identifying, implementing, and scaling up these new strategies can allow PrEP candidates to access it, potentially addressing inequities and promoting HIV risk reduction in the US South and rural communities.
Hypertriglyceridemia and acute pancreatitis: clinical and basic research—a narrative review
Authors: Gao Lin , Li Weiqin
Published: November 2023

Hypertriglyceridemia (HTG) is the third most common cause of acute pancreatitis (AP), and the incidence of HTG-induced AP (HTG-AP) is rising worldwide as a result of changes in lifestyle and dietary habits. In China, HTG accounts for 10% to 20% of the causes of AP, even becoming the second leading cause of AP. The presentation and diagnosis of HTG-AP is similar to that of AP from other causes, however, the complication rates and severe AP are significantly higher in patients with HTG-AP than in patients with other etiologies. Regarding the management of HTG-AP, the initial management is similar to that of AP from other causes and mainly includes fluid resuscitation, pain control, and nutritional support. In addition to supportive care, it is necessary to take appropriate measures to decrease serum TG levels, in order to alleviate the progression of AP and prevent recurrence. This review aims to summarize existing clinical and basic research evidence of HTG-AP and seeks to highlight the epidemiology, definition, pathogenesis, clinical course, diagnosis, management, prevention of recurrence, and specific clinical scenarios, such as HTG-AP during pregnancy, HTG-AP with diabetic ketoacidosis.
Myocardial Recovery With HeartMate 3 Left Ventricular Assist Device: An Attainable Goal That Needs Better Precision
Authors: Liang Lusha W. , Ladanyi Annamaria , Kennel Peter J. , Axsom Kelly M. , Sayer Gabriel T. , Takeda Koji , Sekulic Miroslav , Uriel Nir , Drakos Stavros , Colombo Paolo C. , Yuzefpolskaya Melana
Published: November 2023

Despite advances in our understanding of myocardial recovery among left ventricular assist device (LVAD) patients, with 10–30% of patients achieving substantial myocardial improvement, the rates of LVAD support cessation remain extremely low (1–2%). These numbers are in stark contrast to clinical trial data where successful LVAD cessation is reported in up to 47% of patients. The majority of LVAD programs lack structured recovery programs and targeted protocols, likely underscoring the heterogeneity that exists among LVAD patients with myocardial recovery. This perspective summarizes the current medical and surgical challenges with respect to 1) identifying the appropriate candidates for LVAD cessation; 2) methods to wean LVAD support; 3) reviewing surgical techniques for cessation of current generation HeartMate 3 LVAD; and 4) approaching shared decision making for LVAD cessation between patients and providers given the uncertainties that remain in the field.
Building Data Infrastructure for Disease-Focused Health Economics Research
Authors: Bradley Cathy J. , Liang Rifei , Lindrooth Richard C. , Sabik Lindsay M. , Perraillon Marcelo C.
Published: November 2023

Background:

Data infrastructure for cancer research is centered on registries that are often augmented with payer or hospital discharge databases, but these linkages are limited. A recent alternative in some states is to augment registry data with All-Payer Claims Databases (APCDs). These linkages capture patient-centered economic outcomes, including those driven by insurance and influence health equity, and can serve as a prototype for health economics research.

Objectives:

To describe and assess the utility of a linkage between the Colorado APCD and Colorado Central Cancer Registry (CCCR) data for 2012–2017.

Research Design, Participants, and Measures:

This cohort study of 91,883 insured patients evaluated the Colorado APCD-CCCR linkage on its suitability to assess demographics, area-level data, insurance, and out-of-pocket expenses 3 and 6 months after cancer diagnosis.

Results:

The linkage had high validity, with over 90% of patients in the CCCR linked to the APCD, but gaps in APCD health plans limited available claims at diagnosis. We highlight the advantages of the CCCR-APCD, such as granular race and ethnicity classification, area-level data, the ability to capture supplemental plans, medical and pharmacy out-of-pocket expenses, and transitions in insurance plans.

Conclusions:

Linked data between registries and APCDs can be a cornerstone of a robust data infrastructure and spur innovations in health economics research on cost, quality, and outcomes. A larger infrastructure could comprise a network of state APCDs that maintain linkages for research and surveillance.
Using Address Data to Track Household Financial Burden of Disease
Authors: Nicholas Lauren Hersch
Published: November 2023

The financial burden of illness cannot be correctly characterized without accounting for the impacts across healthy and sick members of a household. Currently, we have very few large, nationally representative data resources to facilitate such work. This paper describes ways to move the field forward through a novel application of address data.
Commentary
Authors: Palatucci John S. , Chakravarty Sujoy , Kratchman Amy L. , Harris Jill , Pizzi Laura T. , Coffield Caroline N. , Ibitamuno Grace , Spitalnik Deborah M.
Published: November 2023

Background:

The 2020–2029 strategic plan for the Patient-Centered Outcomes Research Trust Fund calls for addressing data infrastructure gaps that are critical for studying issues around intellectual and developmental disabilities (I/DD). Specifically, the plan calls for data collection on economic factors that affect person-centered approaches to health care decision-making. Among people with I/DD and their caregivers, such economic factors may include financial costs of care, decreased opportunities for leisure and recreation, income losses associated with caregiving, and foregone opportunities for skill acquisition or other human capital investments.

Objective:

This commentary supports responsiveness to the Patient-Centered Outcomes

Research Trust Fund (PCORTF) calls by conceptualizing and operationalizing a framework for identifying preferences on economic factors that are relevant to people with I/DD and their caregivers.

Main Arguments:

The framework outlined in this commentary addresses barriers to data collection that hinder measure development in the study of I/DD. This work is significant and timely given the continued movement to integrate and maintain people with I/DD within communities and recent methodological advances for eliciting preferences among people with I/DD.

Relevance to the Special Issue:

Readers will be introduced to a framework for building data capacity in the study of economic outcomes among a population that is a high research priority for federal funding agencies. This commentary aims to be useful to researchers in planning, developing, and initiating projects in this area.
Do Hospital Characteristics Predict Racial-and-Ethnic Disparities in Patient Experience? National Results From the HCAHPS Survey
Authors: Beckett Megan K. , Elliott Marc N. , Hambarsoomian Katrin , Tamayo Loida , Lehrman William G. , Agniel Denis , Khau Meagan , Goldstein Elizabeth , Giordano Laura A. , Ng Judy H. , Martino Steven C.
Published: November 2023

Objective:

Assess whether hospital characteristics associated with better patient experiences overall are also associated with smaller racial-and-ethnic disparities in inpatient experience.

Background:

Hospitals that are smaller, non-profit, and serve high proportions of White patients tend to be high-performing overall, but it is not known whether these hospitals also have smaller racial-and-ethnic disparities in care.

Research Design:

We used linear mixed-effect regression models to predict a summary measure that averaged eight Hospital CAHPS (HCAHPS) measures (Nurse Communication, Doctor Communication, Staff Responsiveness, Communication about Medicines, Discharge Information, Care Coordination, Hospital Cleanliness, and Quietness) from patient race-and-ethnicity, hospital characteristics (size, ownership, racial-and-ethnic patient-mix), and interactions of race-and-ethnicity with hospital characteristics.

Subjects:

Inpatients discharged from 4,365 hospitals in 2021 who completed an HCAHPS survey (N=2,288,862).

Results:

While hospitals serving larger proportions of Black and Hispanic patients scored lower on all measures, racial-and-ethnic disparities were generally smaller for Black and Hispanic patients who received care from hospitals serving higher proportions of patients in their racial-and-ethnic group. Experiences overall were better in smaller and non-profit hospitals, but racial-and-ethnic differences were slightly larger.

Conclusions:

Large, for-profit hospitals and hospitals serving higher proportions of Black and Hispanic patients tend to be lower performing overall but have smaller disparities in patient experience. High-performing hospitals might look at low-performing hospitals for how to provide less disparate care whereas low-performing hospitals may look to high-performing hospitals for how to improve patient experience overall.
Recent advances in the treatment of childhood cancers
Authors: Ohlsen Timothy J.D. , Martos Melissa R. , Hawkins Douglas S.
Published: November 2023

Purpose of review

Although cancer remains the leading nonaccidental cause of mortality in children, substantial advances in care have led to 5-year overall survival exceeding 85%. However, improvements in outcomes have not been uniform across malignancies or strata of social determinants of health. The current review highlights recent areas of advancement and anticipated directions for future progress.

Recent findings

Incorporation of rational targeted agents into upfront treatment regimens has led to incremental improvements in event-free survival for many children, sometimes with potential reductions in late effects. For rare or challenging-to-treat cancers, the increasing feasibility of molecular profiling has provided specific treatment options to patients with some of the greatest needs. Simultaneously, increased focus is being given to patient-reported outcomes and social determinants of health, the importance of

which are becoming readily recognized in providing equitable, quality care. Finally, as survival from malignant diseases improves, breakthroughs in the prevention and management of adverse late effects will promote long-term quality of life.

Multi-institutional collaboration and risk-adapted approaches have been crucial to recent advancements in the care of children with cancer and inform potential directions for future investigation.
Leveraging behavioral modification technology for the prevention of kidney stones
Authors: Aksenov Leonid I. , Streeper Necole M. , Scales Charles D.
Published: November 2023

Purpose of review

The purpose of this review is to examine the use of technology to help promote and maintain behaviors that decrease stone recurrence.

Recent findings

Behavior change is a complex process with various interacting components. Recent developments have sought to utilize technology in combination with behavioral change techniques to promote behavior that lowers stone recurrence risk. Smart water bottles are becoming a popular way to accurately measure fluid intake with variable impact on adherence to the recommended daily fluid intake. Mobile apps have also been explored as a method to improve fluid intake. Interventions that combine smart water bottles, mobile apps, and behavioral change techniques have shown the most promise in promoting increased daily fluid intake. Other technologies, such as smart pill dispensers and hydration monitors, have potential applications in promoting behavioral change for stone disease but have yet to be evaluated for this purpose.

There is a limited number of studies exploring technology as a means to promote and maintain behaviors that decrease urinary stone recurrence. Future research is needed to elucidate how to maximize the potential of these technologies and better understand which behavioral change techniques best promote habit formation for the prevention of stones.
Virtual reality vs. physical models in surgical skills training. An update of the evidence
Authors: Chahal Baldev , Aydin Abdullatif , Ahmed Kamran
Published: November 2023

Purpose of review

Simulation is a key component of surgical training, enabling trainees to develop their skills in a safe environment. With simulators broadly grouped into physical models and virtual-reality (VR) simulators, it is important to evaluate the comparative effectiveness of the simulator types in terms of validity as well as cost. The review aims to compare the benefits and drawbacks of novel VR and physical simulators within the broader themes of endourology, laparoscopic and robotic operations, and other urological procedures.

Recent findings

Key benefits of bench models include their comparatively lower cost, easy access and provision of haptic feedback, whereas VR simulators are generally self-sufficient, reusable and enable skills of haemostasis to be practised. The advent of perfused 3D printed simulators across a range of urological procedures may replace cadavers as the traditional gold-standard simulation modality.

Although possessing differing strengths and downsides, VR and physical simulators when used together can have an additive effect due to skill transferability across the platforms. Further comparative studies are required to directly quantify the differences between physical models and VR simulators in terms of performance metrics and cost-effectiveness. There is lack of validated VR simulators for open and reconstructive procedures.
ChatGPT in urology practice: revolutionizing efficiency and patient care with generative artificial intelligence
Authors: Nedbal Carlotta , Naik Nitesh , Castellani Daniele , Gauhar Vineet , Geraghty Robert , Somani Bhaskar Kumar
Published: November 2023

Purpose of review

ChatGPT has emerged as a potentially useful tool for healthcare. Its role in urology is in its infancy and has much potential for research, clinical practice and for patient assistance. With this narrative review, we want to draw a picture of what is known about ChatGPT's integration in urology, alongside future promises and challenges.

Recent findings

The use of ChatGPT can ease the administrative work, helping urologists with note-taking and clinical documentation such as discharge summaries and clinical notes. It can improve patient engagement through increasing awareness and facilitating communication, as it has especially been investigated for uro-oncological diseases. Its ability to understand human emotions makes ChatGPT an empathic and thoughtful interactive tool or source for urological patients and their relatives. Currently, its role in clinical diagnosis and treatment decisions is uncertain, as concerns have been raised about misinterpretation, hallucination and out-of-date information. Moreover, a mandatory regulatory process for ChatGPT in urology is yet to be established.

ChatGPT has the potential to contribute to precision medicine and tailored practice by its quick, structured responses. However, this will depend on how well information can be obtained by seeking appropriate responses and asking the pertinent questions. The key lies in being able to validate the responses, regulating the information shared and avoiding misuse of the same to protect the data and patient privacy. Its successful integration into mainstream urology needs educational bodies to provide guidelines or best practice recommendations for the same.
Development of an Institution-Wide Pediatric End-of-Life Summit
Authors: Edson JoEllen , Abecassis Leah , Beke Dorothy M. , McGorman Tara
Published: November 2023

End-of-life (EOL) care in pediatrics is a unique subspecialty lacking adequate provider education and training. Patient and family outcomes may improve when clinicians are provided with training in this care. Recognizing the need for this specialized education, a small group of bereavement coordinators created an institution-wide pediatric EOL summit at a large urban pediatric teaching hospital. One hundred forty-five clinicians from 14 diverse disciplines attended the first annual pediatric EOL summit. A survey was sent to the participants for feedback. The survey results suggested an overwhelmingly positive response to the summit. Continuing to provide this educational conference is critical to improving care for patients and families, particularly at the end of life.
Experiences of Pediatric Palliative Care Among Bereaved Parents Who Lost a Child With Leukemia in South Korea
Authors: Oh Seung Jin , Min Haeyoung , Choi Sunhee , Hwang Hye-lyung , Kim Sujeong
Published: November 2023

Pediatric palliative care was introduced in South Korea in 2018, with an increased need for care of children with life-limiting conditions, such as leukemia. However, the perspective of parents, who are the primary caregivers, regarding pediatric palliative care has not been explored. This study aimed to describe the pediatric palliative care–related experiences of parents who had lost a child to leukemia to better understand their needs and care outcomes. Ten mothers of children who received pediatric palliative care were recruited. Individual in-depth interviews were conducted. Phenomenology was applied to elucidate parents' experiences during their children's illness and after bereavement. From 179 main statements and 46 meaningful units, 22 themes were derived and grouped into 11 theme clusters and 4 categories. The participants described that the pediatric palliative care team had an indispensable role in providing emotional support to them and their children; this support continued even after the child's death. In addition, the participants were satisfied with their choice to receive pediatric palliative care and hoped that more regions could benefit from the services. The study findings could contribute to advances and the popularization of pediatric palliative care in South Korea.
Moving towards online-based STI testing and treatment services for young people: Who will use it and what do they want?
Authors: Ludwick Teralynn , Walsh Olivia , Cardwell Trey , Chang Shanton , Kong Fabian , Hocking Jane S.
Published: November 2023

Introduction

The market for online STI services is rapidly expanding. Online health services often have unequal uptake among different demographics of the population. There is a need to understand how different online delivery options for STI testing may appeal to different groups of young people, particularly young people who have higher rates of STI diagnoses or access barriers.

Materials and methods

An online survey of young Australians aged 16-29 was conducted to understand service preferences regarding: consultation (telehealth, fully automated questionnaire); testing (electronic pathology form, at-home self-sampling); treatment (e-prescriptions, mailed oral tablets); and partner notification (web tools). Multivariable multinomial logistic regression examined associations between user characteristics and service preferences and adjusted relative risk ratios (aRRR) and 95% confidence intervals are presented.

Results

Among 905 respondents, rural youth were more likely to prefer fully automated questionnaires (aRRR = 1.9; 95% CI 1.0 to 3.5) over telehealth consultations, whereas culturally and linguistically diverse youth (CALD) were less likely (aRRR = 0.4; 95% CI 0.2 to 0.7). Rural youth preferred at-home self-sampling kits (aRRR = 1.9; 95% CI 1.3, 2.7) over electronic forms for on-site collection at pathology centres, with the opposite for CALD youth (aRRR = 0.7; 95% CI 0.5,1.0). Receiving oral antibiotics by mail was preferred by rural youth (aRRR:2.3 95% CI 1.1, 4.6) over for in-clinic treatment, but not for CALD youth (aRRR = 0.5; 95% CI 0.4, 0.8).

Discussion

Our findings suggest that rural youth tend to prefer self-navigated and automated options whereas CALD prefer options with greater provider engagement. Online STI service providers should consider how different service options may affect equitable uptake across the population, and implications for addressing disparities in testing and treatment.
Identifying the Need for and Availability of Evidence-Based Care for Sexually Transmitted Infections in Rural Primary Care Clinics
Authors: Merrell Melinda A. , Crouch Elizabeth , Harrison Sayward , Brown Monique J. , Brown Tony , Pearson William S.
Published: November 2023

Background

Increasing rates of bacterial sexually transmitted infections (STI) may lead to increased HIV rates, as the STI and HIV epidemics are syndemic. Centers for Disease Control and Prevention (CDC) guidelines recommend including extragenital (i.e., rectal and/or pharyngeal) STI screenings for certain populations at increased risk for STIs and concurrent infections with HIV.

Methods

A descriptive study was conducted by interviewing staff members from four rural primary care clinics in areas of high need for STI and HIV services in South Carolina. Qualitative data about their clinical practices in 2021 was obtained. The primary outcome was to determine the awareness and availability of health care services associated with STI and HIV care in these locations.

Results

Clinics in target counties provided limited STI and HIV testing and treatment services, especially for populations at risk of infection, indicating the need for additional clinical training and professional development for all clinic staff. Specifically, only one of four clinics provided extragenital STI testing, and no clinics reported prescribing Pre-Exposure Prophylaxis (PrEP).

Conclusions

Rural primary care clinics can fill important gaps in the availability of STI and HIV services with appropriate support and incentives. Findings from this study may aid in facilitating policy (state Medicaid agencies) and program (state health department) decisions related to STI and HIV testing and treatment.
Not Quite Meeting the Mark: College Experiences for Patients With Celiac Disease
Authors: Khan Narmeen , Keenan Kate , Jericho Hilary
Published: November 2023

Strict adherence to a gluten-free diet (GFD), the current treatment for celiac disease (CD), is socially challenging for adolescents, especially in the college setting. We conducted a survey of factors contributing to GFD adherence during college among patients meeting the ESPGHAN criteria for CD. One-hundred-one young adults (18 years and older) were contacted; 59 completed the survey, of which 47 were enrolled or had attended college. The survey was developed by the study team. Most patients were able to maintain strict adherence to the GFD, whereas at college and reported that GF food was available and consistent with expectations. Nearly all participants reported a lack of resources for students with CD. Strong family support helped, and school stress and lack of peer support impeded diet adherence. Although colleges may meet the basic needs of celiac students, the availability and quality of gluten-free options, and improved campus resources are needed.
18F-FDG PET/CT Versus 18F-FAPI PET/CT in a Case of Recurrent Malignant Phyllodes Breast Tumor
Authors: Jiang Shuqin , Jiang Ming , Rao Songquan , Liang Jiucen , Zhang Rusen
Published: November 2023

A 52-year-old woman with medical history of surgery for left malignant phyllodes breast tumor found a mass on the left chest 3 months ago. A suspicion of recurrent malignant phyllodes breast tumor was made. The patient was enrolled in the clinical trial of 18F-FAPI PET/CT in recurrent sarcoma (no. NCT05485792). 18F-FAPI PET/CT and 18F-FDG PET/CT were performed, and the images demonstrated intense uptake in a huge mass in the left anterior chest wall. Then the patient underwent extended resection of left chest wall tumor. The tumor proved to be recurrent malignant phyllodes breast tumor pathologically.
Management of Human Bites in a Rural Kenyan Setting
Authors: Rhodes Isaiah J. , Mwangi Mark W. , Romeo Dominic J. , Rhodes WR , Rohde Christine
Published: November 2023

Introduction

The treatment of human bites is a common issue facing healthcare practitioners in the developing countries of Sub-Saharan Africa where it has been noted as a growing public health concern. Generally, the desired outcomes from surgical management are healing, function, and aesthetics. We share our 8-year experience at Kapsowar Hospital in Kenya with the presentation, management, and outcome of human bites. We are uniquely situated to do so given the prevalence of human biting in our community and the full-time presence of a plastic surgeon at our institution. To the best of our knowledge, this study is the first to present human bite surgical management by a plastic surgeon certified by the American Board of Surgery working full-time on the African continent.

Methods

A retrospective chart review was conducted on all patients who presented to the operating theater at Kapsowar Hospital with a human bite between 2013–2021. After identification of eligible patients, charts were reviewed assessing parameters including age, gender, timing from injury to presentation at hospital, localization of bite, severity of facial wounds using Lackmann's classification, surgical procedure(s), postoperative complications, surgical revisions, antibiotics administered, and circumstance of incident. Data were analyzed using SPSS 29.0.0.0.

Results

Forty-four patients were identified. Seventeen (38.6%) were female and 27 (61.4%) were male. Thirty-one patients had facial bites and 13 patients had bites to other parts of the body. Of facial bites, 70.3% resulted in amputation of the affected part while 29.7% were lacerations. Using Lackmann's classification for facial bite severity, IIIA bites (complete avulsion) were most common for both males (9) and females (7). Females comprised 68.4% of total lip bite victims. Bites to the extremity were associated with late presentation and infection. We report a salvage rate of 85.7% for infected digits.

Conclusions

Compared with most other studies on human bites, our patient population presents with a higher rate of avulsive lip injuries, most commonly among women. Our postoperative infection rate is lower than many others reported in the literature. Satisfactory cosmetic outcome with low risk of infection can be achieved by following well-established principles of wound healing and tension-free closure.
SINGLE-CELL TRANSCRIPTOME ANALYSIS IN HEALTH AND DISEASE
Authors: Bhattachan Punit , Jeschke Marc G.
Published: November 2023

The analysis of the single-cell transcriptome has emerged as a powerful tool to gain insights of the basic mechanisms of health and disease. It is widely used to reveal the cellular diversity and complexity of tissues at cellular resolution by RNA sequencing of the whole transcriptome from a single cell. Equally, it is applied to discover an unknown, rare population of cells in the tissue. The prime advantage of single-cell transcriptome analysis is the detection of stochastic nature of gene expression of the cell in tissue. Moreover, the availability of multiple platforms for the single-cell transcriptome has broadened its approaches to using cells of different sizes and shapes, including the capture of short or full-length transcripts, which is helpful in the analysis of challenging biological samples. And with the development of numerous packages in R and Python, new directions in the computational analysis of single-cell transcriptomes can be taken to characterize healthy versus diseased tissues to obtain novel pathological insights. To further examine the biology of different cell types, downstream analysis such as differential gene expression analysis, GO term analysis, KEGG pathway analysis, cell-cell interaction analysis, and trajectory analysis has become standard practice in the workflow of single-cell transcriptome analysis. Here, we provide a broad overview of single-cell transcriptome analysis in health and disease conditions currently applied in various studies.
Renal Angptl4 is a key fibrogenic molecule in progressive diabetic kidney disease
Authors: Srivastava Swayam Prakash , Zhou Han , Shenoi Rachel , Morris Myshal , Goedeke Leigh , Rajendran Barani Kumar , Setia Ocean , Aryal Binod , Kanasaki Keizo , Koya Daisuke , Dardik Alan , Bell Thomas , Hernando Carlos Fernández- , Shulman Gerald I. , Goodwin Julie E.
Published: November 2023

Angiopoietin-like 4 (ANGPTL4) is the key protein involved in lipoprotein metabolism and has been shown to have diverse effects on tissue protection. In clinical settings, there is a reported association between higher levels of plasma Angptl4 and features of diabetic kidney disease, however, the association between kidney Angptl4 with features of diabetic kidney disease has not been well investigated. We show that both podocyte-and tubule-specific ANGPTL4 are crucial fibrogenic molecules in diabetes. Results from mRNA-array analysis in control (non-fibrotic) and diabetic (fibrotic) kidneys suggest time-dependent emergence ofAngplt4expression. Diabetes accelerates the fibrogenic phenotype in control mice but not in ANGPTL4 mutant mice. The protective effect observed in ANGPTL4 mutant mice is correlated with a reduction in the levels of pro-inflammatory cytokines, epithelial-to-mesenchymal transition, endothelial-to-mesenchymal transition and augmented fatty acid oxidation. Mechanistically, we demonstrate that podocyte-or tubule-secretedAngptl4interacts with Integrin-β1 and influences the association between dipeptidyl-4 with Integrin-β1 and promotes heterodimerization of transforming growth factor-β receptor 1 (TGFβR1) andTGFβR2in cultured cells. This in turn results inSmad3phosphorylation and subsequent downregulation of the expression of genes involved in fatty acid oxidation; these cumulative effects led to the activation of fibrogenic phenotypes. We demonstrate the utility of a targeted pharmacologic therapy that specifically inhibitsAngptl4gene expression in the kidneys and protects diabetic kidneys from proteinuria and fibrosis. Importantly, use of this kidney-specific targeted strategy is beneficial and does not cause any harmful effect suggesting it can be used as a novel drug molecule for treatment of diabetic kidney disease. Taken together, these data demonstrate that podocyte-and tubule-derivedAngptl4is fibrogenic in diabetic kidneys.
Insights into spinach domestication from genomes sequences of two wild spinach progenitors,Spinacia turkestanicaandS. tetrandra
Authors: She Hongbing , Liu Zhiyuan , Xu Zhaosheng , Zhang Helong , Wu Jian , Wang Xiaowu , Cheng Feng , Charlesworth Deborah , Qian Wei
Published: November 2023

Cultivated spinach (Spinacia oleracea) is a dioecious species (with male and female flowers on separate individuals). We report high-quality genome assemblies for its two closest wild relatives,S. turkestanicaandS. tetrandra, which are also dioecious, to study the genetics of spinach domestication. Using a combination of genomic approaches, we assembled genome sequences of both these species, and analysed them in comparison to the previously assembledS. oleraceagenome. These species diverged approximately 6.3 million years ago (Mya), while cultivated spinach split fromS. turkestanica(its probable direct progenitor) 0.8 Mya. A common feature of all three species is that all six chromosomes include very large gene-poor, repeat-rich regions. InS. oleracea, these correspond with pericentromeric regions with very low recombination rates in both male and female genetic maps, and we infer that the similar pericentromeric regions in the wild species also recombine rarely. Although these regions include a low proportion ofSpinaciagenes, many genes are nevertheless within them, and they must be considered when analyzing selection during domestication. As a first approach to the difficult question of detecting genes involved in spinach domestication, we characterized 282 structural variants (SVs) whose frequencies are higher in a set of spinach accessions than in the wild species, suggesting that they mark genome regions that have been selected during domestication. These regions include genes associated with leaf margin type and flowering time. We also describe evidence that the downy mildew resistance loci of cultivated spinach are derived from introgression from both wild spinach species.
Design of parallelβ-sheet nanofibrils using Monte-Carlo search, coarse-grained simulations, and experimental testing
Authors: Sarma Sudeep , Sudarshan Tarunya Rao , Nguyen Van , Robang Alicia S. , Xiao Xingqing , Le Justin V. , Helmicki Michael E. , Paravastu Anant K. , Hall Carol K.
Published: November 2023

Peptide self-assembly into amyloid fibrils provides numerous applications in drug delivery and biomedical engineering applications. We augment our previously-established computational screening technique along with experimental biophysical characterization to discover 7-mer peptides that self-assemble into “parallel β-sheets”, i.e., β-sheets with N-terminus-to-C-terminusβ-strand vectors oriented in parallel. To accomplish the desired β-strand organization, we applied thePepADamino acid sequence design software to the Class-1 cross-β spine defined by Sawaya et al. This molecular configuration includes two layers of parallel β-sheets stacked such that N-terminus-to-C-terminus vectors are oriented antiparallel for molecules on adjacent β-sheets. The first cohort ofPepADidentified peptides were examined for their fibrillation behavior in DMD/PRIME20 simulations, and the top performing sequence was selected as a prototype for a subsequent round of sequence refinement. The two rounds of design resulted in a library of eight 7-mer peptides. In DMD/PRIME20 simulations, five of these peptides spontaneously formed fibril-like structures with a predominantly parallelβ-sheet arrangement, two formed fibril-like structure with <50% in parallelβ-sheet arrangement and one remained a random coil. Among the eight candidate peptides produced by PepAD and DMD/PRIME20, five were synthesized and purified. All five assembled into amyloid fibrils composed of parallel β-sheets based on Fourier Transform Infrared Spectroscopy, Circular Dichroism, Electron Microscopy, and Thioflavin-T fluorescence spectroscopy measurements.
Characterising the contribution of auditory and somatosensory inputs to TMS-evoked potentials following stimulation of prefrontal, premotor and parietal cortex
Authors: Biabani Mana , Fornito Alex , Goldsworthy Mitchell , Thompson Sarah , Graetz Lynton , Semmler John G. , Opie George M. , Bellgrove Mark A. , Rogasch Nigel C.
Published: November 2023

Transcranial magnetic stimulation (TMS) results in a series of evoked potentials (TEPs) in electroencephalography (EEG) recordings. However, it remains unclear whether these responses reflect neural activity resulting from transcranial stimulation of the cortex, or from the sensory experiences of TMS. Across three experiments (total n = 135), we recorded EEG activity following TMS to the dorsolateral prefrontal cortex, premotor cortex, and parietal cortex as well as a sensory control condition (stimulation of the shoulder or electrical stimulation of the scalp with a click sound). We found that TEPs showed a stereotypical frontocentral N100/P200 complex following TMS of all cortical sites and control conditions, regardless of TMS intensity or the type of sensory control. In contrast, earlier TEPs (<60 ms) showed site-specific characteristics which were largest at the site of stimulation. Self-reported sensory experiences differed across sites, with prefrontal stimulation resulting in stronger auditory (click sound perception) and somatosensory input (scalp muscle twitch, discomfort) than premotor or parietal stimulation, a pattern that was reflected in the amplitude of later (N100/P200), but not earlier (<60 ms) TEP peak amplitudes. Later TEPs were also larger in individuals who experienced stronger click sound perception and, to a lesser extent, TMS-evoked scalp muscle twitches. Increasing click sound perception by removing auditory masking increased N100/P200 amplitudes without altering earlier peaks, an effect which was more prominent at sites with more successful masking. Together, these findings suggest that the frontocentral N100/P200 complex represents a generalised sensory response resulting from TMS-related auditory and somatosensory input. In contrast, early TEP peaks likely reflect activity resulting from transcranial stimulation of the cortex. The results have important implications for designing and interpreting TEP studies, especially when comparing TEPs between stimulation sites and participant groups showing differences in sensory experiences following TMS.
Sensory-memory interactions via modular structure explain errors in visual working memory
Authors: Yang Jun , Zhang Hanqi , Lim Sukbin
Published: November 2023

Errors in stimulus estimation reveal how stimulus representation changes during cognitive processes. Repulsive bias and minimum variance observed near cardinal axes are well-known error patterns typically associated with visual orientation perception. Recent experiments suggest that these errors continuously evolve during working memory, posing a challenge that neither static sensory models nor traditional memory models can address. Here, we demonstrate that these evolving errors, maintaining characteristic shapes, require network interaction between two distinct modules. Each module fulfills efficient sensory encoding and memory maintenance, which cannot be achieved simultaneously in a single-module network. The sensory module exhibits heterogeneous tuning with strong inhibitory modulation reflecting natural orientation statistics. While the memory module, operating alone, supports homogeneous representation via continuous attractor dynamics, the fully connected network forms discrete attractors with moderate drift speed and nonuniform diffusion processes. Together, our work underscores the significance of sensory-memory interaction in continuously shaping stimulus representation during working memory.
Quantifyingin vivocollagen reorganization during immunotherapy in murine melanoma with second harmonic generation imaging
Authors: Heaton Alexa R. , Burkard Nathaniel J. , Sondel Paul M. , Skala Melissa C.
Published: November 2023

Significance

Increased collagen linearization and deposition during tumorigenesis can impede immune cell infiltration and lead to tumor metastasis. Although melanoma is well studied in immunotherapy research, studies that quantify collagen changes during melanoma progression and treatment are lacking.

Aim

Imagein vivocollagen in preclinical melanoma models during immunotherapy and quantify the collagen phenotype in treated and control mice.

Approach

Second harmonic generation imaging of collagen was performed in mouse melanoma tumorsin vivoover a treatment time-course. Animals were treated with a curative radiation and immunotherapy combination. Collagen morphology was quantified over time at an image and single fiber level using CurveAlign and CT-FIRE software.

Results

In immunotherapy-treated mice, collagen reorganized toward a healthy phenotype, including shorter, wider, curlier collagen fibers, with modestly higher collagen density. Temporally, collagen fiber straightness and length changed late in treatment (Day 9 and 12) while width and density changed early (Day 6) compared to control mice. Single fiber level collagen analysis was most sensitive to the changes between treatment groups compared to image level analysis.

Conclusions

Quantitative second harmonic generation imaging can provide insight into collagen dynamicsin vivoduring immunotherapy, with key implications in improving immunotherapy response in melanoma and other cancers.
The greening-causing agent alters the behavioral and electrophysiological responses of the Asian citrus psyllid to a putative sex pheromone
Authors: Volpe Haroldo X. L. , Carmo-Sousa Michele , Luvizotto Rejane A. G. , de Freitas Renato , Esperança Victoria , Darolt Josiane C. , Pegoraro Abner A. L. , Magalhães Diego M. , Favaris Arodi P. , Wulff Nelson A. , Miranda Marcelo P. , Bento José Maurício S. , Leal Walter S.
Published: November 2023

The Asian Citrus Psyllid (ACP),Diaphorina citri,is a vector of the pathological bacteriumCandidatusLiberibacter asiaticus (CLas), which causes the most devastating disease to the citrus industry worldwide, known as greening or huanglongbing (HLB). Earlier field tests with an acetic acid-based lure in greening-free, ‘Valencia’ citrus orange groves in California showed promising results. The same type of lures tested in São Paulo, Brazil, showed unsettling results. During the unsuccessful trials, we noticed a relatively large proportion of females in the field, ultimately leading us to test field-collected males and females forWolbachiaand CLas. The results showed high rates ofWolbachiaand CLas infection in field populations. We then compared the olfactory responses of laboratory-raised, CLas-free, and CLas-infected males to acetic acid. As previously reported, CLas-uninfected males responded to acetic acid at 1 µg. Surprisingly, CLas-infected males required 50x higher doses of the putative sex pheromone, thus explaining the failure to capture CLas-infected males in the field. CLas infection was also manifested in electrophysiological responses. Electroantennogram responses from CLas-infected ACP males were significantly higher than those obtained with uninfected males. To the best of our knowledge, this is the first report of a pathogen infection affecting a vector’s response to a sex attractant.
Single-cell transcriptomic analysis of immune cell dynamics in the healthy human endometrium
Authors: Chen Kaixing , Yu Qiaoni , Sha Qing , Wang Junyu , Fang Jingwen , Li Xin , Shen Xiaokun , Fu Binqing , Guo Chuang
Published: November 2023

The microenvironment of the endometrial immune system is crucial to the success of placental implantation and healthy pregnancy. However, the functionalities of immune cells across various stages of the reproductive cycle have yet to be fully comprehended. To address this, we conducted advanced bioinformatic analyses on 230,049 high-quality single-cell transcriptomes from healthy endometrial samples obtained during the proliferative, secretory, early pregnancy, and late pregnancy stages. Our investigation revealed that proliferative natural killer (NK) cells, a potential source of endometrial NK cells, exhibit the most robust proliferative and differentiation potential during non-pregnant stages. During early pregnancy, NK cells display high oxidative phosphorylation metabolism activity, and together with macrophages and T cells, exhibit a strong type II interferon response. Based on our cell-cell interaction analyses, we identify a large majority of interaction pairs to occur in late pregnancy. Finally, we explored the correlation between stage-specific alterations in transcriptomics and the risk genes of common reproductive diseases, unveiling that MHC class I/II molecules, along withTGFBR1, exhibited the potential to serve as biomarkers. Our study provides insights into the dynamics of the endometrial immune microenvironment during different reproductive cycle stages, thus serving as a reference for detecting pathological changes during pregnancy.
Mind the gap: exploring the usefulness of historical data to assess the impacts of land-use change on bird diversity in a farmland mosaic of Northeastern Portugal (1980-2000)
Authors: Múrias Tiago , Ribeiro Sérgio B. , Lomba Angela , Ferrand De Almeida Nuno
Published: November 2023

Agriculture intensification and land abandonment are the main threats to bird communities in farmlands. Although they represent the opposite endpoints of a gradient of land-use change, they are usually examined separately. In this study, we assessed the effects of the occurrence of both drivers in space and in time, on bird assemblages. The study was performed in a Mediterranean vineyard-dominated farmland mosaic located in North-Eastern Portugal, where land abandonment and (mechanized) intensification coexisted for twenty years. The aims of this study were (1) to describe the temporal patterns of land-use change; (2) to investigate whether these changes affected the local bird species composition and ecological guild structure; and (3) to assess which species/ecological traits were more responsive to land-use changes. We compared the occurrence of birds before (1979-84) and after (2002-03) the triggering of the land-use change proccess. Results showed the prevalence of three interacting gradients of land-use change: land intensification, and direct and indirect effects of land abandonment. While the composition and ecological structure of the bird communities remained stable during the period analyzed, trait and species-specific analysis showed significant correlations with the gradients of change. This suggest that the local bird communities were able to cope with the synergic dynamics of the land-use change, possibly due to a combination of a resilient pre-change bird assemblage and the buffering effect of the competing drivers. The pros and cons of the approach adopted and the utility of past datasets as baselines to assess and monitor the impacts of environmental change on farmland bird diversity are discussed.