bluuebunny/crossref_metadata_2025 huggingface dataset:
Digital spatial profiling of human parathyroid tumors reveals cellular and molecular alterations linked to vitamin D deficiency
Authors: Tu Chia-Ling , Chang Wenhan , Sosa Julie A , Koh James
Published: March 2023

Primary hyperparathyroidism (PHPT) is a common endocrine neoplastic disorder characterized by disrupted calcium homeostasis secondary to inappropriately elevated parathyroid hormone (PTH) secretion. Low levels of serum 25-hydroxyvitamin D (25OHD) are significantly more prevalent in PHPT patients than in the general population (1–3), but the basis for this association remains unclear. We employed a spatially defined in situ whole-transcriptomics and selective proteomics profiling approach to compare gene expression patterns and cellular composition in parathyroid adenomas from vitamin D-deficient or vitamin D-replete PHPT patients. A cross-sectional panel of eucalcemic cadaveric donor parathyroid glands was examined in parallel as normal tissue controls. Here, we report that parathyroid tumors from vitamin D-deficient PHPT patients (Def-Ts) are intrinsically different from those of vitamin D-replete patients (Rep-Ts) of similar age and preoperative clinical presentation. The parathyroid oxyphil cell content is markedly higher in Def-Ts (47.8%) relative to Rep-Ts (17.8%) and normal donor glands (7.7%). Vitamin D deficiency is associated with increased expression of electron transport chain and oxidative phosphorylation pathway components. Parathyroid oxyphil cells, while morphologically distinct, are comparable to chief cells at the transcriptional level, and vitamin D deficiency affects the transcriptional profiles of both cell types in a similar manner. These data suggest that oxyphil cells are derived from chief cells and imply that their increased abundance may be induced by low vitamin D status. Gene set enrichment analysis reveals that pathways altered in Def-Ts are distinct from Rep-Ts, suggesting alternative tumor etiologies in these groups. Increased oxyphil content may thus be a morphological indicator of tumor-predisposing cellular stress.
Post-yield softening of bending-dominated metal metamaterials
Authors: Zhong H Z , Li C W , Das R , Gu J F , Qian M
Published: March 2023

Post-yield softening (PYS) plays an important role in guiding the design of high-performance energy-absorbing lattice materials. PYS is usually restricted to lattice materials that are stretching dominated according to the Gibson–Ashby model. Contrary to this long-held assumption, this work shows that PYS can also occur in various bending-dominated Ti-6Al-4V lattices with increasing relative density. The underlying mechanism for this unusual property is elucidated using the Timoshenko beam theory. It is attributed to the increase in stretching and shear deformation with increasing relative density, thereby increasing the tendency towards PYS. The finding of this work extends perspectives on PYS for the design of high-performance energy-absorbing lattice materials.
Google Trends as a predictive tool in the era of COVID-19: a scoping review
Authors: Zayed Berlanty A , Talaia Ahmed M , Gaaboobah Mohamed A , Amer Samar M , Mansour Fotouh R
Published: March 2023

Google Trends has been extensively used in different sectors from finance to tourism, the economy, fashion, the fun industry, the oil trade, and healthcare. This scoping review aims to summarize the role of Google Trends as a monitoring and a predicting tool in the COVID-19 pandemic. Inclusion criteria for this scoping review were original English-language peer-reviewed research articles on the COVID-19 pandemic conducted in 2020 using Google Trends as a search tool. Articles that were in a language other than English, were only in abstract form, or did not discuss the role of Google Trends during the COVID-19 pandemic were excluded. According to these criteria, a total of 81 studies were included to cover the period of the first year after the emergence of the crisis. Google Trends can potentially help health authorities to plan and control pandemics earlier and to decrease the risk of infection among people.
Gender diversity and publication activity—an analysis of STEM in the UK
Authors: Sarabi Yasaman , Smith Matthew
Published: March 2023

Gender diversity in STEM remains a significant issue, as the field continues to be a male dominated one, despite increased attention on the subject. This article examines the interplay between gender diversity on projects funded by a major UK research council, the Engineering and Physical Sciences Research Council, and the publication activity of a project, as measured by the average journal quality of project publication output, over a 10-year period. The proportion of female representation and leadership on these projects remains very low. For the projects examined as part of this study, over 70% of these projects have no female representation, and less than 15% have a female lead. This study does not find a significant relationship between gender diversity and journal quality output. This study highlights that an important avenue for future work is the development of alternative metrics to assess the performance of research projects in a discipline characterized by very low levels of gender diversity, to fully unpack the impact of project team gender diversity on project output activity.
Cajanus Scarabaeoides Yellow Mosaic Virus, a New Bipartite Begomovirus Causing Yellow Mosaic Disease in Cajanus scarabaeoides in India
Authors: Dokka Narasimham , Marathe Ashish , Sahu Bhimeshwari , Kaushal Pankaj , Ghosh Probir Kumar , Sivalingam Palaiyur Nanjappan
Published: March 2023

Yellow mosaic disease of Cajanus scarabaeoides (L.) Thouars (CsYMD) was observed in up to 46% of C. scarabaeoides plants in the mungbean, urdbean, and pigeon pea fields from 22 districts of Chhattisgarh State, India, during 2017 to 2019. The symptoms were characterized by yellow mosaic on green leaves and yellow discoloration of leaves in advanced stages of the disease. Severely infected plants showed shortened internodal length and reduced leaf size. CsYMD was transmissible to healthy C. scarabaeoides and C. cajan by whitefly (Bemisia tabaci). The infected plants developed typical yellow mosaic symptoms on their leaves within 16 and 22 days of inoculation, respectively, suggesting a begomovirus etiology. Molecular analysis revealed that this begomovirus has a bipartite genome composed of DNA-A (2,729 nucleotides) and DNA-B (2,630 nucleotides). Sequence and phylogenetic analyses revealed that the nucleotide sequence of the DNA-A component had the highest identity of 81.1% with DNA-A of Rhynchosia yellow mosaic virus (RhYMV; NC_038885), followed by mungbean yellow mosaic virus (MN602427; 75.3%). DNA-B had the highest identity of 74.0% with DNA-B of RhYMV (NC_038886). As per ICTV guidelines, this isolate had <91% nucleotide identity with DNA-A of any of the begomoviruses reported; so, it is proposed as a new begomovirus species, tentatively named C. scarabaeoides yellow mosaic virus (CsYMV). After agroinoculation with DNA-A and DNA-B clones of CsYMV, all Nicotiana benthamiana plants developed leaf curl symptoms along with light yellowing symptoms 8 to 10 days after inoculation (DAI), while ∼60% of the C. scarabaeoides plants developed yellow mosaic symptoms similar to those observed in the field 18 DAI, thus fulfilling Koch’s postulates. From these agro-infected C. scarabaeoides plants, CsYMV was transmissible to healthy C. scarabaeoides plants by B. tabaci. Apart from these hosts, CsYMV also infected and caused symptoms in mungbean and pigeon pea.
Identification and Chemical and Biological Management of Fusarium Root and Crown Rot Disease of Oakleaf Hydrangea
Authors: Neupane Sandhya , Avin Farhat A. , Liyanapathiranage Prabha , Simmons Terri , Baysal-Gurel Fulya
Published: March 2023

Oakleaf hydrangea (Hydrangea quercifolia) is an important ornamental plant grown in Tennessee. In May 2018, after late spring frost, cultivars Pee Wee and Queen of Hearts showed root and crown rot symptoms and identification and management of the disease was a major concern. The objective of this research was to identify the causal organism of this disease and develop management recommendations for nursery growers. Isolates from the infected root and crown parts were subjected to microscopy, and the morphology of fungi resembled Fusarium. Molecular analysis was conducted by amplifying the internal transcribed spacer of ribosomal DNA, β-tubulin, and translation elongation factor 1-α regions. Fusarium oxysporum was identified as a causal organism based on molecular analysis. A pathogenicity test was done to complete the Koch’s postulates by drenching containerized oakleaf hydrangea with a conidial suspension. Experiments were conducted to evaluate different chemical fungicides and biological products with different rates for Fusarium root and crown rot management in container-grown Queen of Hearts. Plants were inoculated by drenching containerized oakleaf hydrangea with 150-ml conidial suspensions of F. oxysporum, maintaining the concentration of 1 × 106 conidia/ml. Root and crown rot were assessed using a scale of 0 to 100%. Recovery of F. oxysporum was recorded by plating root and crown sections. Chemical fungicides such as mefentrifluconazole (BAS75002F), the low rate (1.09 ml/liter) of difenoconazole + pydiflumetofen (Postiva), and the high rate (1.32 ml/liter) of isofetamid (Astun) and biopesticide were applied; the high rate (1.64 g/liter) of ningnanmycin (SP2700 WP) effectively reduced Fusarium root rot severity and pyraclostrobin effectively reduced Fusarium crown rot severity in both trials.
Phenotypic and Genotypic Diversity of Puccinia sorghi in Eastern Australia: Implications for Maize Breeding Programs
Authors: Quade Aurelie , Park Robert F. , Stodart Benjamin J. , Ding Yi , Zhang Peng , Thang Mike , Poudel Barsha , Vaghefi Niloofar , Ash Gavin J.
Published: March 2023

Common rust of maize (CR), caused by Puccinia sorghi Schwein., is found in all maize growing regions across the globe. In recent years, an increase in the incidence and severity of CR has been observed in Australia. The challenges posed by a diverse population of P. sorghi to maize breeding programs and the strategies required to deploy durable resistance were explored. Preliminary studies of diversity were conducted by phenotyping the five most diverse isolates against maize lines carrying no resistance genes and one to four resistance genes. The results showed that further genotyping studies were required. Short reads of 17 CR isolates were collected from an array of agroecological regions in Eastern Australia, and these were mapped back against the hybrid assembly of Isolate 1. A hybrid assembly between short (Illumina paired-end) and long (PacBio) reads was conducted in MaSuRCA of the first isolate collected. A draft genome of 145,963,792 bp was obtained after QUAST analysis, with a total length of 145,815,044 bp (when removing base pairs below ≥1,000). The prediction from the BRAKER pipeline identified 20,438 gene models. All 17 isolates sequenced represented unique genotypes, and no clones were detected. The 17 isolates grouped into three clusters. The diversity observed within the population of P. sorghi in Australia suggests that monogenic resistance might not be durable.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Incidence, risk factors, and consequences of radiographic pin migration after pinning of pediatric supracondylar humeral fractures
Authors: Badin Daniel , Boustany Mickael , Lee R. Jay , Varghese Ranjit , Sponseller Paul D.
Published: March 2023

Current literature on pin migration is inconsistent and its significance is not understood. We aimed to investigate the incidence, magnitude, predictors, and consequences of radiographic pin migration after pediatric supracondylar humeral fractures (SCHF). We retrospectively reviewed pediatric patients treated with reduction and pinning of SCHF at our institution. Baseline and clinical data were collected. Pin migration was assessed by measuring the change in distance between pin tip and humeral cortex on sequential radiographs. Factors associated with pin migration and loss of reduction (LOR) were assessed. Six hundred forty-eight patients and 1506 pins were included; 21%, 5%, and 1% of patients had pin migration ≥5 mm, ≥10 mm, and ≥20 mm respectively. Mean migration in symptomatic patients was 20 mm compared to a migration of 5 mm in all patients with non-negligible migration (P < 0.001). Pin migration > 10 mm was strongly associated with LOR [odds ratio (OR) = 6.91; confidence interval (CI), 2.70–17.68]. Factors associated with increased migration included increased days to pin removal (β = 0.022; CI, 0.002–0.043), migration outwards versus inwards ( = 1.02; CI, 0.21–1.80), and BMI > 95th percentile (OR = 1.63; [1.06–2.50]). Factors not associated with migration included cross-pinning, number of pins, and fracture grade. We identified a 5% incidence of radiographic pin migration ≥ 10 mm and determined the factors associated with it. Pin migration became radiographically significant at >10 mm where it was strongly associated with LOR. Our findings contribute to the understanding of pin migration and suggest that interventions targeting pin migration may decrease the risk of LOR. Level of Evidence: Level III – Retrospective Cohort Study
Pakistan’s struggle to tame hepatitis: an ongoing threat
Authors: Shaikh Omer Ahmed , Aaqil Syeda Ilsa , Kumar Pelash , Basit Jawad
Published: March 2023

A potentially deadly liver illnesses Hepatitis B & C are causing a major concern for public health. Hepatitis B is thought to be responsible for 563,000 annual mortality, compared to Hepatitis C’s 366,000. Pakistan is second in terms of the prevalence of chronic HCV infection, with 9.8 million affected. Blood transfusions, hospital stays, dental work, usage of injections, and prior surgery are major risk factors for the spread of the hepatitis C virus. Strong prevention interventions and rigorous management programs are necessary in densely populated, low-income nations like Pakistan to tackle the burden of HBV and HCV patients.
Threading the Needle: A Case of Periorbital Gold Threading
Authors: Froines Colin P. , Godbout Erin E. , Yu Jennifer T. , Tang Lawrence D. , Lu G. Nina , Chambers Christopher B. , Zhang Matthew M.
Published: March 2023

While a rare periorbital finding, the aesthetic practice of gold threading is increasingly identified in Western care setting and may be misidentified as the practice of inserting charm needles (susuk). The authors present a unique case of gold threading discovered incidentally during workup of chronic sinusitis and report a rarely seen delayed local site reaction. The practice of gold threading and mimickers including the practice of inserting charm needles (susuk) are reviewed with emphasis on clinical and radiographic differentiation by oculoplastic surgeons.
Effect of Arsenic Exposure and Cigarette Smoking on Total and Cause-Specific Mortality
Authors: Jia Xin-Hua , Li Yu-Fei , Fan Ya-Guang , Zhou Qing-Hua , Zhao Fang-Hui , Qiao You-Lin , Lalley Marja
Published: March 2023

Background

The relationship between arsenic exposure and all-cause mortality and the joint effects of arsenic exposure and smoking have been poorly described in previous studies.

Methods

After 27 years of follow-up, a total of 1738 miners were included in the analysis. Different statistical methods were used to explore the relationship between arsenic exposure and smoking and the risk of all-cause mortality and various causes of death.

Results

A total of 694 deaths occurred during the 36,199.79 person-years of follow-up. Cancer was the leading cause of death, and arsenic-exposed workers had significantly higher mortality rates for all-cause, cancer, and cerebrovascular disease. All-cause, cancer, cerebrovascular disease, and respiratory disease increased with cumulative arsenic exposure.

Conclusions

We demonstrated the negative effects of smoking and arsenic exposure on all-cause mortality. More effective actions should be taken to reduce arsenic exposure in miners.
Measuring the Health Related Quality of Life and Economic Burden of Illness Among Migrant Workers With Pneumoconiosis
Authors: Zhang Boling , Wang Qian , Wang Yuhao , Tong Ruipeng
Published: March 2023

Objective

The aim of the study is to evaluate the living status of migrant workers with pneumoconiosis (MWP) in China with regard to health-related quality of life (QOL) and economic burden of illness.

Methods

An on-site investigation of 685 respondents in 7 provinces is conducted. Quality of life scores are derived using the self-made scale, and human capital method and disability-adjusted life year are applied to value the economic loss. Multiple linear regression and K-means clustering analysis are performed for further investigation.

Results

Respondents have an overall lower QOL of 64.85 ± 7.04 and significant average loss of Ұ344.5 thousand per capita, where age and provincial heterogeneity generally exist. Pneumoconiosis stage and assistance condition are 2 significant predictors affecting MWP’s living conditions.

Conclusions

The evaluation of QOL and economic loss would contribute to the formulation of targeted countermeasures for MWP to enhance their well-being.
Association Between Serum Trace Heavy Metals and Liver Function Among Adolescents
Authors: Yang Daheng , Zhu Haobo , Chen Hongjian , Long Guangfeng
Published: March 2023

Background

Exposure to metals has been associated with liver-related disease. Few studies have explored the effect of sex stratification on adolescent liver function.

Method

From the National Health and Nutrition Examination Survey (2011–2016), 1143 subjects aged 12–19 years were selected for analysis. The outcome variables were the levels of alanine aminotransferase (ALT), aspartate aminotransferase, and gamma-glutamyl transpeptidase.

Results

The results showed a positive association between serum zinc and ALT in boys (odds ratio [OR], 2.37; 95% confidence interval [CI], 1.11–5.06). Serum mercury was associated with an increase in ALT level in girls (OR, 2.73; 95% CI, 1.14–6.57). Mechanistically, the efficacy mediated by total cholesterol accounted for 24.38% and 6.19% of the association between serum zinc and ALT.

Conclusions

The results imply that serum heavy metals were associated with the risk of liver injury, possibly mediated by serum cholesterol, in adolescents.
An Investigation of Latex Sensitivity and Respiratory Complaints in Workers in a Rubber-Based Material Manufacturing Industry
Authors: Elverişli Mehmet Fatih , Yildiz Gülhan Pinar , Mungan Dilşad , Erçelik Merve , Şahin İbrahim Ethem , Güleç Balbay Ege , Çoban Seyit , Karav Halil Mehmet , Arbak Peri Meram
Published: March 2023

Objective

To present study aimed to investigate the prevalence of latex sensitivity in a workplace that produced rubber-based vehicle seals.

Method

The serum latex-specific IgE levels, respiratory complaints, PFT, serum interleukin (IL)-4, IL-5, IL-8, IL-10, IL-13 levels of all male workers (n = 108) exposed to latex in the workplace, which produced rubber seals, were compared with the control group (n = 52).

Results

The rates of latex-specific IgE >0.10 kU/L in the workers and control group were 12.3% and 4.1%, respectively (P = 0.147). There was no difference in IL-4, IL-5, IL-10, and IL-13 levels between latex-specific IgE-positive, and -negative participants.

Conclusion

Latex sensitivity was higher in workers who used rubber as a raw material than in the control group but it was not statistically significant.
Prophylactic acid suppression and enteral nutrition
Authors: Barletta Jeffrey F.
Published: March 2023

Purpose of review

Stress ulcer prophylaxis (SUP) is routinely administered to critically ill patients who are at high-risk for clinically important gastrointestinal bleeding. Recent evidence however has highlighted adverse effects with acid suppressive therapy, particularly proton pump inhibitors where associations with higher mortality have been reported. Enteral nutrition may provide benefits in reducing the incidence of stress ulceration and may mitigate the need for acid suppressive therapy. This manuscript will describe the most recent evidence evaluating enteral nutrition for the provision of SUP.

Recent findings

There are limited data evaluating enteral nutrition for SUP. The available studies compare enteral nutrition with or without acid suppressive therapy rather than enteral nutrition vs. placebo. Although data exist demonstrating similar clinically important bleeding rates in patients on enteral nutrition who receive SUP vs. no SUP, these studies are underpowered for this endpoint. In the largest placebo-controlled trial conducted to date, lower bleeding rates were observed with SUP and most patients were receiving enteral nutrition. Pooled analyses had also described benefit with SUP vs. placebo and enteral nutrition did not change the impact of these therapies.

Although enteral nutrition may provide some benefit as SUP, existing data are not strong enough to validate their use in place of acid suppressive therapy. Clinicians should continue to prescribe acid suppressive therapy for SUP in critically ill patients who are at high risk for clinically important bleeding even when enteral nutrition is being provided.
Disparities in Telemedicine Use Among Louisiana Medicaid Beneficiaries During the COVID-19 Pandemic
Authors: Callison Kevin , Anderson Andrew , Shao Yixue , LaVeist Thomas A. , Walker Brigham
Published: March 2023

Background:

The COVID-19 pandemic led to an increased reliance on telemedicine. Whether this exacerbated existing disparities within vulnerable populations is not yet known.

Objectives:

Characterize changes in outpatient telemedicine evaluation and management (E&M) services for Louisiana Medicaid beneficiaries by race, ethnicity, and rurality during the COVID-19 pandemic.

Research Design:

Interrupted time series regression models estimated pre-COVID-19 trends and changes in E&M service use at the April and July 2020 peaks in COVID-19 infections in Louisiana and in December 2020 after those peaks had subsided.

Subjects:

Louisiana Medicaid beneficiaries continuously enrolled between January 2018 and December 2020 who were not also enrolled in Medicare.

Measures:

Monthly outpatient E&M claims per 1000 beneficiaries.

Results:

Prepandemic differences in service use between non-Hispanic White and non-Hispanic Black beneficiaries narrowed by 34% through December 2020 (95% CI: 17.6%–50.6%), while differences between non-Hispanic White and Hispanic beneficiaries increased by 10.5% (95% CI: 0.1%–20.7%). Non-Hispanic White beneficiaries used telemedicine at higher rates than non-Hispanic Black (difference=24.9 claims per 1000 beneficiaries, 95% CI: 22.3–27.4) and Hispanic beneficiaries (difference=42.3 claims per 1000 beneficiaries, 95% CI: 39.1–45.5) during the first wave of COVID-19 infections in Louisiana. Telemedicine use increased slightly for rural beneficiaries compared with urban beneficiaries (difference=5.3 claims per 1000 beneficiaries, 95% CI: 4.0–6.6).

Conclusions:

The COVID-19 pandemic narrowed gaps in outpatient E&M service use between non-Hispanic White and non-Hispanic Black Louisiana Medicaid beneficiaries, though gaps in telemedicine use emerged. Hispanic beneficiaries experienced large reductions in service use and relatively small increases in telemedicine use.
Virtual Care and Urinary Tract Infection Management
Authors: Gander Jennifer C. , Goodrich Glenn , McDonald Bennet , McCracken Courtney E. , Tavel Heather M. , Davis Teaniese L. , Weinfield Nancy S. , Ritzwoller Debra P. , Roblin Douglas W.
Published: March 2023

Background:

During the COVID-19 pandemic, more health care issues were being managed remotely. Urinary tract infections (UTIs) are being managed more often using telehealth although few reports compare the rate of UTI ancillary service orders placed and fulfilled during these visits.

Objectives:

We aimed to evaluate and compare the rate of ancillary service orders and order fulfillments in incident UTI diagnoses between virtual and in-person encounters.

Research Design:

The retrospective cohort study involved 3 integrated health care systems: Kaiser Permanente (KP) Colorado, KP Georgia, and KP Mid-Atlantic States.

Subjects:

We included incident UTI encounters from adult primary care data from January 2019 to June 2021.

Measures:

Data were categorized as: prepandemic (January 2019–March 2020), COVID-19 Era 1 (April 2020–June 2020), and COVID-19 Era 2 (July 2020–June 2021). UTI-specific ancillary services included medication, laboratory, and imaging. Orders and order fulfillments were dichotomized for analyses. Weighted percentages for orders and fulfillments were calculated using inverse probability treatment weighting from logistic regression and compared between virtual and in-person encounters using χ2 tests.

Results:

We identified 123,907 incident encounters. Virtual encounters increased from 13.4% prepandemic to 39.1% in COVID-19 Era 2. Ancillary service orders from virtual encounters were not placed as often as in-person encounters. However, the weighted percentage for ancillary service order fulfillment across all services remained above 65.3% across sites and eras, with many fulfillment percentages above 90%.

Conclusions:

Our study reported a high rate of order fulfillment for both virtual and in-person encounters. Health care systems should encourage providers to place ancillary service orders for uncomplicated diagnoses, such as UTI, to provide enhanced access to patient-centered care.
Racial and Ethnic Segregation in Primary Care and Association of Practice Composition With Quality of Care
Authors: Ding Dong , Zhu Benjamin , Glied Sherry
Published: March 2023

Objective:

To assess the extent of segregation between racial and ethnic minority and White patients across primary care physicians and the association of practice panel racial/ethnic composition with the quality of care delivered.

Research Design:

We examined the degree of racial/ethnic dissimilarity (a measure of segregation) in visits and the allocation of patient visits by different groups across primary care physicians (PCPs). We assessed the regression-adjusted relationship between the racial/ethnic composition of PCP practices and measures of the quality of care delivered. We compared outcomes in the pre-Affordable Care Act (ACA) and post-ACA (2006–2010/2011–2016) periods.

Subjects:

We analyzed data on all primary care visits to office-based practitioners in the 2006–2016 National Ambulatory Medical Care Survey. PCPs were defined as general/family practice or internal medicine physicians. We excluded cases with imputed race or ethnicity information. For the quality of care analyses, we limited the sample to adults.

Results:

Racial and ethnic minority patients remain concentrated within a small group of PCPs: 35% of PCPs accounted for 80% of non-White patients’ visits; 63% of non-White (or White) patients would need to switch physicians to make the distribution of visits across PCPs proportional between the groups. We observed little correlation between the PCPs panel’s racial/ethnic composition and quality of care. These patterns did not change substantially over time.

Conclusions:

PCPs remain segregated, but the racial/ethnic composition of a practice panel is not associated with the quality of health care that individual patients receive in either the pre or post-ACA passage periods.
Using Explainable Artificial Intelligence to Predict Potentially Preventable Hospitalizations
Authors: Riis Anders Hammerich , Kristensen Pia Kjær , Lauritsen Simon Meyer , Thiesson Bo , Jørgensen Marianne Johansson
Published: March 2023

Background:

The increasing aging population and limited health care resources have placed new demands on the healthcare sector. Reducing the number of hospitalizations has become a political priority in many countries, and special focus has been directed at potentially preventable hospitalizations.

Objectives:

We aimed to develop an artificial intelligence (AI) prediction model for potentially preventable hospitalizations in the coming year, and to apply explainable AI to identify predictors of hospitalization and their interaction.

Methods:

We used the Danish CROSS-TRACKS cohort and included citizens in 2016-2017. We predicted potentially preventable hospitalizations within the following year using the citizens’ sociodemographic characteristics, clinical characteristics, and health care utilization as predictors. Extreme gradient boosting was used to predict potentially preventable hospitalizations with Shapley additive explanations values serving to explain the impact of each predictor. We reported the area under the receiver operating characteristic curve, the area under the precision-recall curve, and 95% confidence intervals (CI) based on five-fold cross-validation.

Results:

The best performing prediction model showed an area under the receiver operating characteristic curve of 0.789 (CI: 0.782–0.795) and an area under the precision-recall curve of 0.232 (CI: 0.219–0.246). The predictors with the highest impact on the prediction model were age, prescription drugs for obstructive airway diseases, antibiotics, and use of municipality services. We found an interaction between age and use of municipality services, suggesting that citizens aged 75+ years receiving municipality services had a lower risk of potentially preventable hospitalization.

Conclusion:

AI is suitable for predicting potentially preventable hospitalizations. The municipality-based health services seem to have a preventive effect on potentially preventable hospitalizations.
Development of a Common Data Model for a Multisite and Multiyear Study of Virtual Visit Implementation
Authors: Roblin Douglas W. , Rubenstein Kevin B. , Tavel Heather M. , Goodrich Glenn K. , Ritzwoller Debra P. , Certa Julia M. , Basra Sundeep S. , Weinfield Nancy S. , Cromwell Lee A. , McDonald Bennett , Davis Teaniese L. , Gander Jennifer C. , McCracken Courtney E.
Published: March 2023

Background/Objective:

In multisite studies, a common data model (CDM) standardizes dataset organization, variable definitions, and variable code structures and can support distributed data processing. We describe the development of a CDM for a study of virtual visit implementation in 3 Kaiser Permanente (KP) regions.

Methods:

We conducted several scoping reviews to inform our study’s CDM design: (1) virtual visit mode, implementation timing, and scope (targeted clinical conditions and departments); and (2) extant sources of electronic health record data to specify study measures. Our study covered the period from 2017 through June 2021. Integrity of the CDM was assessed by a chart review of random samples of virtual and in-person visits, overall and by specific conditions of interest (neck or back pain, urinary tract infection, major depression).

Results:

The scoping reviews identified a need to address differences in virtual visit programs across the 3 KP regionsto harmonize measurement specifications for our research analyses. The final CDM contained patient-level, provider-level, and system-level measures on 7,476,604 person-years for KP members aged 19 years and above. Utilization included 2,966,112 virtual visits (synchronous chats, telephone visits, video visits) and 10,004,195 in-person visits. Chart review indicated the CDM correctly identified visit mode on>96% (n=444) of visits, and presenting diagnosis on >91% (n=482) of visits.

Conclusions:

Upfront design and implementation of CDMs may be resource intensive. Once implemented, CDMs, like the one we developed for our study, provide downstream programming and analytic efficiencies by harmonizing, in a consistent framework, otherwise idiosyncratic temporal and study site differences in source data.
Quantum Theory for Infectious Diseases: Insights, Prospects, and Challenges
Authors: Gazi Sevcan Zehra
Published: March 2023

The continuous manifestations of emerging and reemerging infectious diseases across the world is championed by microorganisms particularly, viruses and bacteria. These manifestations consistently keep researchers at work in establishing approaches towards minimising the burden of infectious diseases both locally and internationally. Microorganisms, especially bacteria and viruses, possess very disparate features like the presence of sensors, in-built biological engines, immaculate communication means, processing architecture, among others. Researchers are introducing these biological entities into the quantum theory network where their dynamical physical properties and concepts can be used to develop response mechanisms during infection stages. This article aims to review and present an account of quantum approaches derived from quantum mechanics as an emerging fundamental enabler and a novel concept in the treatment of infectious diseases. It also looks at the possible application of these quantum approaches in revolutionising discovery, development, and production of vaccines at a quantum scale and speed. A descriptive review of the literature was conducted by searching these electronic databases: Web of Science, PubMed, and SciELO. Findings in this article show that through the advent of single-particle approaches and high-resolution techniques, viral dynamics can be scrutinised during and after their assembly towards studying their infection development pathway. Additionally, quantum information in biological entities has been found to provide hereditary information insights supporting genetic studies in relation to infectious diseases. The introduction of quantum-inspired genetic algorithms towards predicting the secondary structures of RNA depicts certain superiority over strategies currently in existence. Ongoing research is putting quantum-based studies in an ideal direction towards shaping the understanding and perhaps treatment of infectious diseases.
What are the best indicators of myoelectric manifestation of fatigue?
Authors: Fegni Ndam Elvige Ornella , Goubault Étienne , Moyen-Sylvestre Béatrice , Côté Julie N. , Bouffard Jason , Maso Fabien Dal
Published: March 2023

The myoelectric manifestation of fatigue (MMF) is predominantly assessed using median frequency and amplitude of electromyographic (EMG) signals. However, EMG has complex features so that fractals, correlation, entropy, and chaos MMF indicators were introduced to detect alteration of EMG features caused by muscle fatigue that may not be detected by linear indicators. The aim of this study was to determine the best MMF indicators. Twenty-four participants were equipped with EMG sensors on 9 shoulder muscles and performed a repetitive pointing task. They reported their rate of perceived exertion every 30 seconds and were stopped when they reached 8 or higher on the CR10 Borg scale. Partial least square regression was used to predict perceived exertion through 15 MMF indicators. In addition, the proportion of participants with a significant change between task initiation and termination was determined for each MMF indicator and muscle. The PLSR model explained 73% of the perceived exertion variance. Median frequency, mobility, spectral entropy, fuzzy entropy, and Higuchi fractal dimension had the greatest importance to predict perceived exertion and changed for 83.5% participants on average between task initiation and termination for the anterior and medial deltoids. The amplitude, activity, approximate, sample, and multiscale entropy, degree of multifractality, percent determinism and recurrent, correlation dimension, and largest Lyapunov exponent analysis MMF indicators were not efficient to assess MMF. Mobility, spectral entropy, fuzzy entropy, and Higuchi fractal dimension should be further considered to assess muscle fatigue and their combination with median frequency may further improve the assessment of muscle fatigue.
Computation of longitudinal phenotypes in 466 individuals with a developmental and epileptic encephalopathy enables clinical trial readiness
Authors: Brimble Elise , Kim Joseph , Martin Richard L. , McKnight Dianalee , Lacoste Alix M. B.
Published: March 2023

Electronic health records (EHRs) represent a rich data source to support precision medicine, particularly in disorders with small and heterogeneous populations where longitudinal phenotypes are poorly characterized. However, the impact of EHR data is often limited by incomplete or imperfect source documentation and the inability to leverage unstructured data. Here, we address these shortcomings through a computational analysis of one of the largest cohorts of developmental and epileptic encephalopathies (DEEs), representing 466 individuals across six genetically defined conditions. The DEEs encompass debilitating pediatric-onset disorders with high unmet needs for which treatment development is ongoing. By applying a platform approach to data curation and annotation of 18 clinical data entities from comprehensive medical records, we characterize variation in longitudinal clinical journeys. Assessments of the relative enrichment of phenotypes and semantic similarity analysis highlight commonalities and differences between the six cohorts. Evaluation of medication use reflects unmet needs, particularly in the management of movement disorders. We also present a novel composite measure of seizure severity that is more robust than existing measures of seizure frequency alone. Finally, we show that the attainment of developmental outcomes, including the ability to sit independently and the ability to walk, is correlated with seizure severity scores. Overall, the combined analyses demonstrate that patient-centric real world data generation, including structuring of medical records, holds promise to improve clinical trial success in rare disorders. Applications of this approach support improved understanding of baseline disease progression, selection of relevant endpoints, and definition of inclusion and exclusion criteria.
Values and Preferences Related to Workplace Mental Health Programs and Interventions: An International Survey
Authors: Murphy J.K. , Noble J.M. , Chakraborty P.A. , Michlig G. , Michalak E.E , Greenshaw A.J. , Lam R.W.
Published: March 2023

Introduction

This study explores the perspectives of workers and managers on workplace programs and interventions that seek to promote mental wellbeing, and prevent and treat mental health conditions The results contributed supporting evidence for the development of the WHO’s first global guidelines for mental health and work, which provide evidence-based recommendations to support the implementation of workplace mental health programs and supports, to improve their acceptability, appropriateness, and uptake.

Methods

A survey was used to examine the values and preferences among workers and employers related to workplace mental health prevention, protection, promotion, and support programs and services. The survey was made available in English, French, and Spanish. Descriptive statistics were used to analyse the survey data. Rapid thematic analysis was used to analyse the results of qualitative questions.

Results

These results provide a unique international perspective on programs and supports for mental health at work, from the standpoint of employees, including managers. Results suggest that employees value interventions developed in consultation with workers (including indicated, selective and universal interventions), increased training and capacity building among managers, and targeted interventions to address the pervasive impact of stigma on perceptions about mental health at work and help-seeking. The findings of this study seek to reflect the perspectives of workers, including managers, and therein to promote improved access, availability and uptake of mental health programs and supports at work and – ultimately- to support the potential of workplaces as environments that promote and support mental health.
Immune Microenvironment Profiling of Normal Appearing Colorectal Mucosa Biopsied Over Repeat Patient Visits Reproduciably Separates Lynch Syndrome Patients Based on Their History of Colon Cancer
Authors: Brand Rhonda M. , Dudley Beth , Karloski Eve , Zyhowski Ashley , Raphael Rebecca , Pitlor Danielle , Metter E. Jeffrey , Pai Reet , Lee Kenneth , Brand Randall E. , Uttam Shikhar
Published: March 2023

Introduction

Lynch syndrome (LS) is the most common hereditary cause of colorectal cancer (CRC), increasing lifetime risk of CRC by up to 70%. Despite this higher lifetime risk, disease penetrance in LS patients is highly variable and most LS patients undergoing CRC surveillance will not develop CRC. Therefore, biomarkers that can correctly and consistently predict CRC risk in LS patients are needed to both optimize LS patient surveillance and help identify better prevention strategies that reduce risk of CRC development in the subset of high-risk LS patients.

Methods

Normal-appearing colorectal tissue biopsies were obtained during repeat surveillance colonoscopies of LS patients with and without a history of CRC, healthy controls (HC), and patients with a history of sporadic CRC. Biopsies were cultured in anex-vivoexplant system and their supernatants were assayed via multiplexed ELISA to profile the local immune signaling microenvironment. High quality cytokine signatures were identified usingrxCOV fidelity metric. These signatures were used to perform biomarker selection by computing their selection probability based on penalized logistic regression.

Results

Our study demonstrated that cytokine based local immune microenvironment profiling was reproducible over repeat visits and sensitive to patient LS-status and CRC history. Furthermore, we identified sets of biomarkers whose differential expression was predictive of LS-status in patients when compared to sporadic CRC patients and in identifying those LS patients with or without a history of CRC. Enrichment analysis based on these biomarkers revealed an LS and CRC status dependent constitutive inflammatory state of the normal appearing colonic mucosa.

Discussion

This prospective pilot study demonstrated that immune profiling of normal appearing colonic mucosa discriminates LS patients with a prior history of CRC from those without it, as well as patients with a history of sporadic CRC from HC. Importantly, it suggests existence of immune signatures specific to LS-status and CRC history. We anticipate that our findings have the potential to assess CRC risk in individuals with LS and help in preemptively mitigating it by optimizing surveillance and identifying candidate prevention targets. Further studies are required to validate our findings in an independent cohort of LS patients over multiple visits.
Cellos: High-throughput deconvolution of 3D organoid dynamics at cellular resolution for cancer pharmacology
Authors: Mukashyaka Patience , Kumar Pooja , Mellert David J. , Nicholas Shadae , Noorbakhsh Javad , Brugiolo Mattia , Anczukow Olga , Liu Edison T. , Chuang Jeffrey H.
Published: March 2023

Three-dimensional (3D) culture models, such as organoids, are flexible systems to interrogate cellular growth and morphology, multicellular spatial architecture, and cell interactions in response to drug treatment. However, new computational methods to segment and analyze 3D models at cellular resolution with sufficiently high throughput are needed to realize these possibilities. Here we reportCellos(Cell and Organoid Segmentation), an accurate, high throughput image analysis pipeline for 3D organoid and nuclear segmentation analysis.Cellossegments organoids in 3D using classical algorithms and segments nuclei using a Stardist-3D convolutional neural network which we trained on a manually annotated dataset of 3,862 cells from 36 organoids confocally imaged at 5 μm z-resolution. To evaluate the capabilities ofCelloswe then analyzed 74,450 organoids with 1.65 million cells, from multiple experiments on triple negative breast cancer organoids containing clonal mixtures with complex cisplatin sensitivities.Celloswas able to accurately distinguish ratios of distinct fluorescently labelled cell populations in organoids, with <3% deviation from the seeding ratios in each well and was effective for both fluorescently labelled nuclei and independent DAPI stained datasets.Celloswas able to recapitulate traditional luminescence-based drug response quantifications by analyzing 3D images, including parallel analysis of multiple cancer clones in the same well. Moreover,Celloswas able to identify organoid and nuclear morphology feature changes associated with treatment. Finally,Cellosenables 3D analysis of cell spatial relationships, which we used to detect ecological affinity between cancer cells beyond what arises from local cell division or organoid composition.Cellosprovides powerful tools to perform high throughput analysis for pharmacological testing and biological investigation of organoids based on 3D imaging.
Targeted therapies prime oncogene-driven lung cancers for macrophage-mediated destruction
Authors: Vaccaro Kyle , Allen Juliet , Whitfield Troy W. , Maoz Asaf , Reeves Sarah , Velarde José , Yang Dian , Phan Nicole , Bell George W. , Hata Aaron N. , Weiskopf Kipp
Published: March 2023

Macrophage immune checkpoint inhibitors, such as anti-CD47 antibodies, show promise in clinical trials for solid and hematologic malignancies. However, the best strategies to use these therapies remain unknown and ongoing studies suggest they may be most effective when used in combination with other anticancer agents. Here, we developed a novel screening platform to identify drugs that render lung cancer cells more vulnerable to macrophage attack, and we identified therapeutic synergy exists between genotype-directed therapies and anti-CD47 antibodies. In validation studies, we found the combination of genotype-directed therapies and CD47 blockade elicited robust phagocytosis and eliminated persister cells in vitro and maximized anti-tumor responses in vivo. Importantly, these findings broadly applied to lung cancers with various RTK/MAPK pathway alterations—includingEGFRmutations,ALKfusions, orKRASG12Cmutations. We observed downregulation of β2-microglobulin and CD73 as molecular mechanisms contributing to enhanced sensitivity to macrophage attack. Our findings demonstrate that dual inhibition of the RTK/MAPK pathway and the CD47/SIRPa axis is a promising immunotherapeutic strategy. Our study provides strong rationale for testing this therapeutic combination in patients with lung cancers bearing driver mutations.

Brief summary

Unbiased drug screens identify targeted therapies as drugs that make lung cancers with driver mutations more vulnerable to macrophage attack.