bluuebunny/crossref_metadata_2025 huggingface dataset:
Uterine Tumor Resembling Ovarian Sex Cord Tumors: 23 Cases Indicating Molecular Heterogeneity With Variable Biological Behavior
Authors: Bi Rui , Yao Qianlan , Ji Gang , Bai Qianming , Li Anqi , Liu Zebing , Cheng Yufan , Tu Xiaoyu , Yu Lin , Chang Bin , Huang Dan , Ge Huijuan , Zuo Ke , Li Hui , Chang Heng , Cai Xu , Jiang Wenhua , Zhou Xiaoyan , Yang Wentao
Published: May 2023

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare mesenchymal neoplasm that mainly harborsNCOA1-3rearrangements with partner genesESR1orGREB1. Here, we explored 23 UTROSCTs by targeted RNA sequencing. The association between molecular diversity and clinicopathologic features was investigated. The mean age of our cohort was 43 years (23–65 y). Only 15 patients (65%) were originally diagnosed with UTROSCTs. Mitotic figures ranged from 1 to 7/10 high power fields, of primary tumors and increased from 1 to 9/10 high power fields in recurrent tumors. Five types of gene fusions were identified in these patients, includingGREB1::NCOA2(n=7),GREB1::NCOA1(n=5),ESR1::NCOA2(n=3),ESR1::NCOA3(n=7), andGTF2A1::NCOA2(n=1). To our knowledge, our group included the largest cohort of tumors withGREB1::NCOA2fusions. Recurrences were most common in patients withGREB1::NCOA2fusion (57%), followed by 40% (GREB1::NCOA1), 33% (ESR1::NCOA2), and 14% (ESR1::NCOA3). The recurrent patient who harboredan ESR1::NCOA2fusion was characterized by extensive rhabdoid features. Both of the recurrent patients who harboredGREB1::NCOA1andESR1::NCOA3had the largest tumor sizes in their own gene alteration groups, and another recurrentGREB1::NCOA1patient had extrauterine involvement. TheGREB1-rearranged patients were of older age, larger tumor size, and higher stage than non-GREB1-rearranged patients (P=0.004, 0.028, and 0.016, respectively). In addition, theGREB1-rearranged tumors presented more commonly as intramural masses rather than non-GREB1-rearranged tumors presenting as polypoid/submucosal masses (P=0.021). Microscopically, nested and whorled patterns were frequently seen inGREB1-rearranged patients (P=0.006). Of note, estrogen receptor expression was weaker than progesterone receptor in all 12GREB1-rearranged tumors, whereas the similar staining intensity of estrogen receptor and progesterone receptor was observed in all 11 non-GREB1-rearranged tumors (P<0.0001). This study demonstrated that UTROSCTs were present at a younger age in the Chinese population. The genetic heterogeneity of UTROSCTs was correlated with variable recurrence rate. Tumors withGREB1::NCOA2fusions are more likely to recur compared with those with other genetic alterations.
Building Machine Learning Models to Correct Self-Reported Anthropometric Measures
Authors: An Ruopeng , Ji Mengmeng
Published: May 2023

Monitoring population obesity risk primarily depends on self-reported anthropometric data prone to recall error and bias. This study developed machine learning (ML) models to correct self-reported height and weight and estimate obesity prevalence in US adults. Individual-level data from 50 274 adults were retrieved from the National Health and Nutrition Examination Survey (NHANES) 1999-2020 waves. Large, statistically significant differences between self-reported and objectively measured anthropometric data were present. Using their self-reported counterparts, we applied 9 ML models to predict objectively measured height, weight, and body mass index. Model performances were assessed using root-mean-square error. Adopting the best performing models reduced the discrepancy between self-reported and objectively measured sample average height by 22.08%, weight by 2.02%, body mass index by 11.14%, and obesity prevalence by 99.52%. The difference between predicted (36.05%) and objectively measured obesity prevalence (36.03%) was statistically nonsignificant. The models may be used to reliably estimate obesity prevalence in US adults using data from population health surveys.
A Decade of Nipple-Sparing Mastectomy: Lessons Learned in 3035 Immediate Implant-based Breast Reconstructions
Authors: Lin Alex M. , Lorenzi Roberto , Van Der Hulst Juliette E. , Liao Eric C. , Austen William G. , Webster Alexandra , Smith Barbara L. , Colwell Amy S.
Published: May 2023

Background

Nipple-sparing mastectomy is commonly performed for breast cancer treatment or prevention. We present one of the largest breast reconstruction series in the literature.

Methods

A single institution retrospective review was conducted 2007-2019.

Results

Our query identified 3,035 implant-based breast reconstructions after nipple-sparing mastectomy including 2043 direct-to-implant and 992 tissue expander-implant reconstructions. The overall major complication rate was 9.15% and nipple necrosis rate 1.20%. Therapeutic mastectomy was associated with higher overall complications and explantations compared to prophylactic mastectomy (p<0.01). Comparing unilateral and bilateral procedures, bilateral mastectomy had increased risk for complications (OR 1.46, C.I. 0.997-2.145, p=0.05). Tissue-expander reconstructions had higher rates of nipple necrosis (1.9% vs. 0.88%, p=0.015), infection (4.2% vs. 2.8%, p=0.04), and explantation (5.1% vs. 3.5%, p=0.04) compared to direct-to-implant reconstruction. When assessing plane of reconstruction, we found similar rates of complications between subpectoral dual plane and prepectoral reconstruction. There was no difference in complications between reconstruction with acellular dermal matrix or mesh compared to total or partial muscle coverage without ADM/mesh (OR 0.749, 95% C.I. 0.404-1.391, p=0.361). Multivariable regression analysis revealed preoperative radiotherapy (OR 2.465, 95% C.I. 1.579-3.848, p<0.001), smoking (2.53, 95% C.I. 1.581-4.054, p<0.001), and a periareolar incision (OR 3.657, 95% C.I. 2.276-5.875, p<0.001) to be the strongest predictors of complications and nipple necrosis (p<0.05).

Conclusions

Nipple-sparing mastectomy and immediate breast reconstruction has a low rate of complications. In this series, radiation, smoking, and incision choice predicted overall complications and nipple necrosis while direct-to-implant reconstruction and acellular dermal matrix or mesh did not increase risk.
Improving Facial Fat Graft Survival Using Stromal Vascular Fraction-Enriched Lipotransfer: A Prospective Multicenter, Randomized Controlled Study
Authors: Wufuer Maierdanjiang , Choi Tae Hyun , Najmiddinov Bakhtiyor , Kim Junhyung , Choi Jaehoon , Kim Taeyoung , Park Yongsoo , Kim Ji-hoon , Jeon Heejung , Kim Byung Jun
Published: May 2023

Background

Although previous clinical studies have reported that cell-assisted lipotransfer increases the fat survival rate in facial fat transplants, most were case studies without quantitative evaluation. A multi-center, prospective, randomized, controlled study was performed to evaluate the safety and efficacy of the stromal vascular fraction (SVF) in facial fat grafts.

Methods

Twenty-three participants were enrolled for autologous fat transfer in the face, and randomly assigned to the experimental (n=11) and control (n=12) groups. Fat survival was assessed using magnetic resonance imaging at 6 and 24 weeks postoperatively. Subjective evaluations were performed by the patients and surgeons. To address safety concerns, results of an SVF culture and the postoperative complications were recorded.

Results

The overall fat survival rate was significantly higher in the experimental group than in the control group (6 weeks: 74.5±9.99% vs. 66.55±13.77%, p<0.025; 24 weeks: 71.27±10.43% vs. 61.98±13.46%, p<0.012). Specifically, graft survival in the forehead was 12.82% higher in the experimental group when compared with that in the control group at 6 weeks (p<0.023). Furthermore, graft survival in the forehead (p<0.021) and cheeks (p<0.035) was superior in the experimental group at 24 weeks. At 24 weeks, the aesthetic scores given by the surgeons were higher in the experimental group than in the control group (p<0.03); however, no significant intergroup differences were noted in the patient-evaluated scores. Neither bacterial growth from SVF cultures nor postoperative complications were noted.

Conclusions

SVF enrichment for autologous fat grafting can be a safe and effective technique for increasing the fat retention rate.
Cognitive Impairment and the Associated Factors Among Older People in Rural Central Tanzania
Authors: Masika Golden M. , Nyundo Azan , Msisiri Laidi
Published: May 2023

Aim:

This study examined the profile of cognitive impairment and associated factors among older people in rural central Tanzania.

Methods:

We conducted a cross-sectional study involving 462 community-dwelling older adults. We performed cognitive, psychosocial, and clinical assessments and face-to-face interviews with all older adults. Descriptive, bivariate and multivariate linear regression analyses were performed to determine the participant’s cognitive performance and the associated factors.

Results:

The mean cognitive score on the Identification and Intervention for Dementia in Elderly Africans cognitive test was 11.04 (SD=2.89). Per the proposed cut-off scores to define probable and possible dementia, 13.2% of the population had probable dementia and another 13.9% had possible dementia. Increase in age was associated with poor cognitive performance (β=−0.076, 95% CI=−0.109 to −0.043, P<0.001); whereas male sex (β=0.989, 95% CI=0.333 to 1.645, P=0.003), higher educational attainment (β=2.575, 95% CI=0.557 to 4.594, P=0.013) and performance in instrumental activities of daily living (β=0.552, 95% CI=0.376 to 0.729, P<0.001) were associated with higher cognitive performance.

Discussion:

Older people in rural settings of central Tanzania have poor cognitive functions and are at high risk of further cognitive decline. Preventive and therapeutic programs for the affected older people are warranted to prevent further decline and maintain quality of life.
HSD3B1 is an oxysterol 3β-hydroxysteroid dehydrogenase in human placenta
Authors: Dickson Alison , Yutuc Eylan , Thornton Catherine A. , Dunford James E. , Oppermann Udo , Wang Yuqin , Griffiths William J.
Published: May 2023

Most biologically active oxysterols have a 3β-hydroxy-5-ene function in the ring system with an additional site of oxidation at C-7 or on the side-chain. In blood plasma oxysterols with a 7α-hydroxy group are also observed with the alternative 3-oxo-4-ene function in the ring system formed by ubiquitously expressed 3β-hydroxy-Δ
5
-C
27
-steroid oxidoreductase Δ
5
-isomerase, HSD3B7. However, oxysterols without a 7α-hydroxy group are not substrates for HSD3B7 and are not usually observed with the 3-oxo-4-ene function. Here we report the unexpected identification of oxysterols in plasma derived from umbilical cord blood and blood from pregnant women taken before delivery at 37+ weeks of gestation, of side-chain oxysterols with a 3-oxo-4-ene function but no 7α-hydroxy group. These 3-oxo-4-ene oxysterols were also identified in placenta, leading to the hypothesis that they may be formed by a previously unrecognized 3β-hydroxy-Δ
5
-C
27
-steroid oxidoreductase Δ
5
-isomerase activity of HSD3B1, an enzyme which is highly expressed in placenta. Proof-of-principle experiments confirmed that HSD3B1 has this activity. We speculate that HSD3B1 in placenta is the source of the unexpected 3-oxo-4-ene oxysterols in cord and pregnant women's plasma and may have a role in controlling the abundance of biologically active oxysterols delivered to the fetus.
Opium alkaloids, biosynthesis, pharmacology and association with cancer occurrence
Authors: Vadhel Agrataben , Bashir Sabreen , Mir Ashiq Hussain , Girdhar Madhuri , Kumar Deepak , Kumar Anil , Mohan Aradhana , Malik Tabarak , Mohan Anand
Published: May 2023

Papaver somniferumL. (Family: Papaveraceae) is a species well known for its diverse alkaloids (100 different benzylisoquinoline alkaloids (BIAs)). L-tyrosine serves as a precursor of several specific metabolites like BIAs. It has been used as an antitussive and potent analgesic to alleviate mild to extreme pain since ancient times. The extraction of pharmaceutically important alkaloids like morphine and codeine from poppy plant reflects the need for the most suitable and standard methods. Several analytical and extraction techniques have been reported in open literature for morphine, codeine and other important alkaloids which play a vital function in drug development and drug discovery. Many studies suggest that opioids are also responsible for adverse effects or secondary complications like dependence and withdrawal. In recent years, opium consumption and addiction are the most important risk factors. Many evidence-based reviews suggest that opium consumption is directly linked or acts as a risk factor for different cancers. In this review, we highlight significant efforts related to research which have been done over the past 5 decades and the complete information onPapaver somniferumincluding its phytochemistry, pharmacological actions, biosynthetic pathways and analytical techniques of opium alkaloid extraction and the link between opium consumption and cancer-related updates.
Shiga toxin-producing Escherichia coli (STEC) and atypical enteropathogenic E. coli (aEPEC) in Swedish retail wheat flour
Authors: Söderlund Robert , Flink Catarina , Aspán Anna , Eriksson Erik
Published: May 2023

Wheat flour has been identified as the source of multiple outbreaks of gastrointestinal disease caused by shiga toxin-producing

Escherichia coli

(STEC). We have investigated the presence and genomic characteristics of STEC and related atypical enteropathogenic

E. coli

(aEPEC) in 200 bags of Swedish-produced retail wheat flour, representing 87 products and 25 brands. Samples were enriched in modified tryptone soya broth (mTSB) and screened with real-time PCR targeting stx1
, stx2
and eae, and the serogroups O157, O121 and O26. Isolation was performed by immunomagnetic separation (IMS) for suspected STEC/aEPEC O157, O121 and O26, and by screening pools of colonies for other STEC. Real-time PCR after enrichment revealed 12 % of samples to be positive for shiga toxin genes (stx1
and/or stx2
) and 11 % to be positive for intimin (eae). Organic production, small-scale production or whole grain did not significantly influence shiga toxin gene presence or absence in a generalized linear mixed model analysis. Eight isolates of STEC were recovered, all of which were intimin-negative. Multiple serotype/sequence type/shiga toxin subtype combinations that have also been found in flour samples in other European countries were recovered. Most STEC types recovered were associated with sporadic cases of STEC among humans in Sweden, but no types known to have caused outbreaks or severe cases of disease (i.e. haemolytic uraemic syndrome) were found. The most common finding was O187:H28 ST200 with stx2g
, with possible links to cervid hosts. Wildlife associated with crop damage is a plausible explanation for at least some of the surprisingly high frequency of STEC in wheat flour.
Improved characterization of circulating tumor cells and cancer-associated fibroblasts in breast cancer patients using imaging flow cytometry
Authors: Muchlińska Anna , Wenta Robert , Ścińska Wiktoria , Markiewicz Aleksandra , Suchodolska Grażyna , Senkus Elżbieta , Żaczek Anna J , Bednarz-Knoll Natalia
Published: May 2023

Circulating tumor cells (CTCs) and circulating cancer-associated fibroblasts (cCAFs) have been individually considered as strong indicators of cancer progression. However, technical limitations have prevented their simultaneous analysis in the context of CTC phenotypes different from epithelial. This study aimed to analyze CTCs and cCAFs simultaneously in peripheral blood of 210 breast cancer patients using DAPI/pan-keratin (K)/vimentin (V)/alpha-SMA/CD29/CD45/CD31 immunofluorescent staining and novel technology - imaging flow cytometry (imFC). Single and clustered CTCs of different sizes and phenotypes (i.e. epithelial phenotype K+/V-, and epithelial-mesenchymal transition (EMT)-related such as K+/V+, K-/V+ and K-/V-) were detected in 27.6% of the samples and correlated with metastases. EMT-related CTCs interacted more frequently with normal cells and tended to occur in patients with tumors progressing during therapy, while cCAFs coincided with CTCs (mainly K+/V- and K-/V-) in 7 (3.3%) patients and seemed to correlate with the presence of metastases, particularly visceral ones. This study emphasizes advantages of imFC in the field of liquid biopsy and highlights the importance of multimarker detailed analysis of different subpopulations and phenotypes of cancer progression-related cells i.e. CTCs and cCAFs. Co-detection of CTCs and cCAFs might improve the identification of patients at higher risk of progression and their monitoring during therapy.

Simple Summary

Liquid biopsy is promising but challenging tool potentially upgrading cancer patients diagnostics and bringing new insights into tumor biology. Here, we applied a unique approach to detect CTCs and cCAFs in one-tube assay using imaging flow cytometry enabling improved enumeration, multimarker-based phenotyping and detailed morhopological characterization of those rare cells. We showed that EMT-related CTCs might contribute to breast cancer progression, whereas coincidence of CTCs and cCAFs might be signature of metastasis.
Two sample Mendelian Randomisation using an outcome from a multilevel model of disease progression
Authors: Lawton Michael , Ben-Shlomo Yoav , Gkatzionis Apostolos , Hu Michele T. , Grosset Donald , Tilling Kate
Published: May 2023

Identifying factors that are causes of disease progression, especially in neurodegenerative diseases, is of considerable interest. Disease progression can be described as a trajectory of outcome over time - for example, a linear trajectory having both an intercept (severity at time zero) and a slope (rate of change). A technique for identifying causal relationships between one exposure and one outcome in observational data whilst avoiding bias due to confounding is two sample Mendelian Randomisation (2SMR). We consider a multivariate approach to 2SMR using a multilevel model for disease progression to estimate the causal effect an exposure has on the intercept and slope. We carry out a simulation study comparing a naïve univariate 2SMR approach to a multivariate 2SMR approach with one exposure that effects both the intercept and slope of an outcome that changes linearly with time since diagnosis. The simulation study results for both approaches were similar and approximately unbiased (bias for intercept ranges from -1.6% to 1.5% and the slope -0.7% to 4.1%) with appropriate coverage of the 95% confidence intervals (for intercept 94.1%-96.2% and the slope 94.7%-96.0%). The multivariate approach gives a better joint coverage of both the intercept and slope effects (93.3%-95.8% for multivariate approach compared to 89.0%-92.5% for the naïve approach). We also apply our method to two Parkinson’s cohorts to examine the effect body mass index has on disease progression. There was no strong evidence that BMI affects disease progression, however the confidence intervals for both intercept and slope were wide.
Backscattering amplitude in Ultrasound Localization Microscopy
Authors: Renaudin Noemi , Pezet Sophie , Ialy-Radio Nathalie , Demene Charlie , Tanter Mickael
Published: May 2023

In the last decade, Ultrafast Ultrasound Localisation Microscopy has taken non-invasive deep vascular imaging down to the microscopic level. By imaging diluted suspensions of circulating microbubbles in the blood stream at kHz framerate and localising the center of their individual point spread function with a sub-resolution precision, it enabled to break the unvanquished trade-off between depth of imaging and resolution by microscopically mapping the microbubbles flux and velocities deep into tissue. However, ULM also suffers limitations. Many small vessels are not visible in the ULM images due to the noise level in areas dimly explored by the microbubbles. Moreover, as the vast majority of studies are performed using 2D imaging, quantification is limited to in-plane velocity or flux measurements which hinders the accurate velocity determination and quantification. Here we show that the backscattering amplitude of each individual microbubble can also be exploited to produce backscattering images of the vascularization with a higher sensitivity compared to conventional ULM images. By providing valuable information about the relative distance of the microbubble to the 2D imaging plane in the out-of-plane direction, backscattering ULM images introduces a physically relevant 3D rendering perception in the vascular maps. It also retrieves the missing information about the out-of-plane motion of microbubbles and provides a way to improve 3D flow and velocity quantification using 2D ULM. These results pave the way to improved visualization and quantification for 2D and 3D ULM.
A novel web-based 24-hour dietary recall tool in line with the Nova food processing classification: description and evaluation
Authors: Neri Daniela , Gabe Kamila Tiemann , Santos Costa Caroline Dos , Steele Euridice Martinez , Rauber Fernanda , Marchioni Dirce Maria , Louzada Maria Laura , Levy Renata Bertazzi , Monteiro Carlos Augusto
Published: May 2023

Objective

This paper describes the first web-based self-completed 24-hour recall designed to categorize food intake according to Nova groups - Nova24h – and its agreement with a reference tool in estimating the dietary relative contribution of the four Nova food groups (% of total energy intake).

Design

Comparisons of estimates of dietary relative contributions of Nova groups obtained by Nova24h and one standard interviewer-led 24-hour recall.

Setting

Nationwide adult cohort study in Brazil.

Participants

The subjects were 186 participants of the NutriNet Brasil Cohort Study (n=186).

Results

No statistically significant differences were observed between the Nova24h and the reference tool mean contributions of unprocessed or minimally processed foods (52.3% vs. 52.6%), processed culinary ingredients (11.6% vs. 11.9%), processed foods (17.1% vs. 14.7%) and ultra-processed foods (19.0% vs. 20.9%). Intraclass correlation coefficients between individual estimates obtained for each Nova group showed moderate to good agreement (0.54-0.78). Substantial or almost perfect agreement between the tools was seen regarding the ability to rank participants according to quintiles of contribution of each Nova group (PABAK 0.69-0.81).

Conclusions

Nova24h is a suitable tool for estimating the dietary relative energy contribution of Nova food groups in the NutriNet Brasil cohort. New studies are necessary to verify its adequacy in other populations.
Estimated Effects of Amyloid Reduction on Cognitive Change: A Bayesian Update across a Range of Priors
Authors: Ackley Sarah F. , Wang Jingxuan , Chen Ruijia , Power Melinda C. , Allen Isabel Elaine , Glymour M. Maria
Published: May 2023

Introduction

Results of the CLARITY-AD and GRADUATE I and II trials rekindled discussion on the impact of amyloid-targeting drugs. We use a Bayesian approach to quantify how a rational observer would have updated their prior beliefs based on new trial results.

Methods

We used publicly available data from the CLARITY-AD and GRADUATE I & II trials to estimate the effect of reducing amyloid on CDR-SB score. A range of prior positions were then updated according to Bayes Theorem using these estimates.

Results

After updating with new trial data, a wide range of starting positions resulted in credible intervals that did not include no effect of amyloid reduction on CDR-SB.

Discussion

For a range of starting beliefs and assuming veracity of underlying data, rational observers would conclude there is a small benefit of amyloid-reductions on cognition. This benefit must be weighed against opportunity cost and side effect risk.
Genetic liability for cardiovascular disease, physical activity, and mortality – findings from The Finnish Twin Cohort
Authors: Joensuu Laura , Waller Katja , Kankaanpää Anna , Palviainen Teemu , Kaprio Jaakko , Sillanpää Elina
Published: May 2023

Background

An overall healthy lifestyle may mitigate the risk of all-cause and cardiovascular disease (CVD) mortality despite the inherited risk for CVD. We assessed if similar phenomenon is observed independently with physical activity (PA).

Methods

In a prospective older Finnish Twin Cohort, genetic liability for coronary heart disease, systolic and diastolic blood pressure was estimated with polygenic risk scores (PRSs) derived from the Pan UK Biobank (N≈400,000) and >1,000,000 genetic variants, and leisure-time PA longitudinally with validated and structured questionnaires three times during 1975–1990 among 4,897 participants aged 33–60-years (54.3% women). Interactions of PRSs and PA with mortality and the independent main effects of different PA metrics with mortality were evaluated with Cox proportional hazards models. A co-twin control design with 180 monozygotic twin pairs discordant for physical activity was used for causal inference.

Results

During the 17.4-y (mean) follow-up (85,136 person-years), 1,195 participants died with 389 CVD deaths. Although the favorable associations of an overall healthy lifestyle with mortality risk reduction replicated in the cohort, no interactions or significant independent main effects were observed with any of the assessed PA metrics. Adherence to World Health Organizations PA guidelines or vigorous PA during the 15-year observational period did not decrease mortality in more active twins compared to their less active identical twin brother or sister. The findings did not vary with genetic CVD risk.

Conclusions

No evidence was found that PA mitigates inherited CVD risk or is causally associated with mortality challenging some of our current understanding.
Excellent reliability of the six-minute walking distance measured by FeetMe®insoles at home
Authors: Mostovov Andrey , Jacobs Damien , Farid Leila , Dhellin Paul , Baille Guillaume
Published: May 2023

Background

Wearable technology provides an opportunity for new ways of monitoring patient gait remotely, through at-home self-administered six-minute walk tests (6MWTs). The purpose of this study was to evaluate the reliability and repeatability of FeetMe®insoles, a wearable gait assessment device, for measuring the six-minute walking distance (6MWD) during tests conducted independently at home by healthy volunteers.

Methods

Participants (n=21) performed two 6MWTs at home while wearing the FeetMe®insoles, and two 6MWTs at hospital while wearing FeetMe®insoles and being assessed by a rater. All assessments were performed with a one-week interval between tests, no assistance was provided to the participants at home.

Results and conclusion

The agreement between the 6MWD measurements made at baseline and at Week 1 was good for all test configurations and was highest for the at-home FeetMe®measurements, with an intraclass correlation coefficient (ICC) of 0.95, standard error of the measurement (SEM) of 15.02 m and coefficient of variation (CV) of 3.33%, compared to ICCs of 0.79 and 0.78, SEMs of 25.65 and 26.65 and CVs of 6.24% and 6.10% for the rater and FeetMe®measurements at hospital, respectively. Our work demonstrates that the FeetMe®system could provide a reliable solution allowing individuals to self-administer 6MWTs independently at home.

Author Summary

At-home patients monitoring using wearable tools presents numerous advantages for regular care and clinical studies. Patients benefit from the convenience of not having to travel to a clinic for assessments, which is particularly helpful for those in remote areas or with mobility issues. Besides, at-home monitoring allows for more frequent assessments, leading to more accurate clinical decision-making and timely intervention, which ultimately results in enhanced patient care. For the same reasons, it can improve patients recruitment and retention in clinical studies.

The six-minute walk test (6MWT) is a commonly used standardized assessment of functional capacity in patients with various diseases. We evaluated the reliability and repeatability of FeetMe®insoles, a wearable gait assessment device, for measuring the six-minute walking distance (6MWD) at home. Our analysis of the data from 21 healthy volunteers showed that the FeetMe®insoles were as reliable at home as they were in the standard clinical setting and as a conventional way of assessing the 6MWD. In addition, the insoles provided extensive gait analysis, which may allow for more precise conclusions regarding the patient’s state and its evolution than the 6MWD alone. We conclude that the FeetMe®device is an excellent tool for at-home patients monitoring.
Discovery of Novel Digital Biomarkers for Type 2 Diabetic Nephropathy Classification via Integration of Urinary Proteomics and Pathology
Authors: Lucarelli Nicholas , Yun Donghwan , Han Dohyun , Ginley Brandon , Moon Kyung Chul , Rosenberg Avi Z. , Tomaszewski John E. , Zee Jarcy , Jen Kuang-Yu , Han Seung Seok , Sarder Pinaki
Published: May 2023

Background

The heterogeneous phenotype of diabetic nephropathy (DN) from type 2 diabetes complicates appropriate treatment approaches and outcome prediction. Kidney histology helps diagnose DN and predict its outcomes, and an artificial intelligence (AI)- based approach will maximize clinical utility of histopathological evaluation. Herein, we addressed whether AI-based integration of urine proteomics and image features improves DN classification and its outcome prediction, altogether augmenting and advancing pathology practice.

Methods

We studied whole slide images (WSIs) of periodic acid-Schiff-stained kidney biopsies from 56 DN patients with associated urinary proteomics data. We identified urinary proteins differentially expressed in patients who developed end-stage kidney disease (ESKD) within two years of biopsy. Extending our previously published human-AI-loop pipeline, six renal sub-compartments were computationally segmented from each WSI. Hand-engineered image features for glomeruli and tubules, and urinary protein measurements, were used as inputs to deep-learning frameworks to predict ESKD outcome. Differential expression was correlated with digital image features using the Spearman rank sum coefficient.

Results

A total of 45 urinary proteins were differentially detected in progressors, which was most predictive of ESKD (AUC=0.95), while tubular and glomerular features were less predictive (AUC=0.71 andAUC=0.63, respectively). Accordingly, a correlation map between canonical cell-type proteins, such as epidermal growth factor and secreted phosphoprotein 1, and AI-based image features was obtained, which supports previous pathobiological results.Conclusions:Computational method-based integration of urinary and image biomarkers may improve the pathophysiological understanding of DN progression as well as carry clinical implications in histopathological evaluation.

Significance Statement

The complex phenotype of diabetic nephropathy from type 2 diabetes complicates diagnosis and prognosis of patients. Kidney histology may help overcome this difficult situation, particularly if it further suggests molecular profiles. This study describes a method using panoptic segmentation and deep learning to interrogate both urinary proteomics and histomorphometric image features to predict whether patients progress to end-stage kidney disease since biopsy date. A subset of urinary proteomics had the most predictive power in identifying progressors, which could annotate significant tubular and glomerular features related to outcomes. This computational method, which aligns molecular profiles and histology, may improve our understanding of pathophysiological progression of diabetic nephropathy as well as carry clinical implications in histopathological evaluation.
Types of Traumatic Experiences in Drug Overdose-Related Deaths: An Exploratory Latent Class Analysis
Authors: Hong Judy H. , de Dios Constanza , Badawi Jessica C. , Tonkin Sarah S. , Schmitz Joy M. , Walss-Bass Consuelo , Meyer Thomas D.
Published: May 2023

Aim

Drug overdose related-deaths in the US are increasing, with over 100,000 deaths occurring in 2020, an increase of 30% from the previous year and the highest number recorded in a single year. It is widely known that experiences of trauma and substance use very often co-occur, but little is known about the role of trauma in the context of drug overdose-related deaths. Latent class analysis (LCA) was used to classify drug overdose-related deaths based on type of traumatic experiences and individual, social, and substance use characteristics.

Methods

Psychological autopsy data were obtained from the University of Texas Health Science Center at Houston (UTHealth) Brain Collection. A total of 31 drug overdose-related deaths collected from January 2016 through March 2022 were included in this study. LCA was used to identify latent factors via experience of four trauma categories (illness/accidents, sexual/interpersonal violence, death/trauma to another, other situations where life was in danger). Generalized linear modeling (GLM) was used to explore differences on demographic, social, substance use, and psychiatric variables between the latent classes in separate models.

Results

LCA identified 2 classes: C1 (n=12; 39%) was characterized by higher incidence of overall trauma exposure as well as variation in trauma type; C2 (n=19; 61%) had lower levels of overall trauma exposure with sexual/interpersonal violence as the most frequent. GLMs indicated that C1 membership was associated with higher incidence of polysubstance use, being married, and having suicidal ideation compared to C2 membership (ps<0.05).

Conclusion

Among individuals who died by drug overdose, the exploratory LCA identified two distinct subgroups that differed in type of trauma experienced and substance use pattern, the first group having more “typical” characteristics of drug overdoses cases, the other group less typical. This suggests that those at risk of drug overdose may not always exhibit high-risk characteristics.
Vasectomy workforce and utilization in the United States, 2019
Authors: Bodas Mandar , Strasser Julia , Banawa Rachel , Luo Qian , Schenk Ellen , Chen Candice
Published: May 2023

Objective

To examine the workforce that provides vasectomies in the United States using national-level medical claims data (IQVIA Dx, 2019).

Methods

We combined IQVIA Dx 2019 data on medical claims with information on clinician characteristics and clinician type from the National Plan and Provider Enumeration System (NPPES) and the American Medical Association (AMA) Masterfile. We assessed state-level trends in vasectomy provision. We used multivariate regressions to evaluate the association between clinician characteristics and two outcomes: providing at least one vasectomy and total volume of vasectomies in 2019.

Results

We found total of 147,618 vasectomies performed by 7,592 clinicians in the IQVIA Dx 2019 data. About 76% clinicians were urologists, 16% family medicine specialists, and about 8% were general surgeons. Urologists performed about 91% of all vasectomies. Overall, about 92% of clinicians were located in urban areas. Multivariate regression analysis showed that clinicians that were female (Odds Ratio (OR) 0.12, 95% Confidence Interval (95% CI) (0.09 - 0.15)), graduated from osteopathic schools (OR 0.77, 95% CI (0.60 - 0.98)) had lower odds of providing vasectomies.

Conclusions

Clinicians from multiple specialties performed vasectomies in the U.S. Most often, this procedure was performed by male urologists practicing in urban areas. Wide state-level variations exist in vasectomy provision. Clinicians’ gender, location and type of medical degree received were associated with their vasectomy provision.
Radiogenomic profiling of prostate tumors prior to external beam radiotherapy converges on a transcriptomic signature of TGF-β activity driving tumor recurrence
Authors: Ku Anson T. , Shankavaram Uma , Trostel Shana Y. , Zhang Hong , Sater Houssein A. , Harmon Stephanie A. , Carrabba Nicole V. , Liu Yang , Wood Bradford J. , Pinto Peter A. , Choyke Peter L. , Stoyanova Radka , Davicioni Elai , Pollack Alan , Turkbey Baris , Sowalsky Adam G. , Citrin Deborah E.
Published: May 2023

STRUCTURED ABSTRACT

Background

Patients with localized prostate cancer have historically been assigned to clinical risk groups based on local disease extent, serum prostate specific antigen (PSA), and tumor grade. Clinical risk grouping is used to determine the intensity of treatment with external beam radiotherapy (EBRT) and androgen deprivation therapy (ADT), yet a substantial proportion of patients with intermediate and high risk localized prostate cancer will develop biochemical recurrence (BCR) and require salvage therapy. Prospective identification of patients destined to experience BCR would allow treatment intensification or selection of alternative therapeutic strategies.

Methods

Twenty-nine individuals with intermediate or high risk prostate cancer were prospectively recruited to a clinical trial designed to profile the molecular and imaging features of prostate cancer in patients undergoing EBRT and ADT. Whole transcriptome cDNA microarray and whole exome sequencing were performed on pretreatment targeted biopsy of prostate tumors (n=60). All patients underwent pretreatment and 6-month post EBRT multiparametric MRI (mpMRI), and were followed with serial PSA to assess presence or absence of BCR. Genes differentially expressed in the tumor of patients with and without BCR were investigated using pathways analysis tools and were similarly explored in alternative datasets. Differential gene expression and predicted pathway activation were evaluated in relation to tumor response on mpMRI and tumor genomic profile. A novel TGF-β gene signature was developed in the discovery dataset and applied to a validation dataset.

Findings

Baseline MRI lesion volume andPTEN/TP53status in prostate tumor biopsies correlated with the activation state of TGF-β signaling measured using pathway analysis. All three measures correlated with the risk of BCR after definitive RT. A prostate cancer-specific TGF-β signature discriminated between patients that experienced BCR vs. those that did not. The signature retained prognostic utility in an independent cohort.

Interpretation

TGF-β activity is a dominant feature of intermediate-to-unfavorable risk prostate tumors prone to biochemical failure after EBRT with ADT. TGF-β activity may serve as a prognostic biomarker independent of existing risk factors and clinical decision-making criteria.

Funding

This research was supported by the Prostate Cancer Foundation, the Department of Defense Congressionally Directed Medical Research Program, National Cancer Institute, and the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.
United States’ qualifying conditions compared to evidence of the 2017 National Academy of Sciences Report
Authors: Stains Elena L. , Kennalley Amy L. , Tian Maria , Boehnke Kevin F. , Kraus Chadd K. , Piper Brian J.
Published: May 2023

Objective

To compare the 2017 National Academies of Sciences, Engineering, and Medicine (NAS) report to state medical cannabis (MC) laws defining approved qualifying conditions (QC) from 2017 to 2024 and to determine if there exist gaps in evidence-based decision making.

Methods

The 2017 NAS report assessed therapeutic evidence for over twenty medical conditions treated with MC. We identified the QCs of 38 states (including Washington, D.C.) where MC was legal in 2024. We also identified the QCs that these states used in 2017. QCs were then categorized based on NAS-established level of evidence: substantial/conclusive evidence of effectiveness, moderate evidence of effectiveness, limited evidence of effectiveness, limited evidence of ineffectiveness, and no/insufficient evidence to support or refute effectiveness. This study was completed between January 31, 2023 through May 20, 2024.

Results

Most states listed at least one QC with substantial evidence—80.0% of states in 2017 and 97.0% in 2024. However, in 2024 only 8.3% of the QCs on states’ QC lists met the standard of substantial evidence. Of the 20 most popular QCs in the country in 2017 and 2024, one only (chronic pain) was categorized by the NAS as having substantial evidence for effectiveness. However, seven (ALS, Alzheimer’s disease, epilepsy, glaucoma, Huntington’s disease, Parkinson’s disease, spastic spinal cord damage) were rated as either ineffective or insufficient evidence.

Conclusion

Most QCs lack evidence for use based on the 2017 NAS report. Many states recommend QCs with little evidence, such as amyotrophic lateral sclerosis (ALS), or even those for which MC is ineffective, like depression. There have been insufficient updates to QCs since the NAS report. These findings highlight a disparity between state-level MC recommendations and the evidence to support them.
Rare penetrant mutations confer severe risk of common diseases
Authors: Fiziev Petko , McRae Jeremy , Ulirsch Jacob C. , Dron Jacqueline S. , Hamp Tobias , Yang Yanshen , Wainschtein Pierrick , Ni Zijian , Schraiber Joshua G. , Gao Hong , Cable Dylan , Field Yair , Aguet Francois , Fasnacht Marc , Metwally Ahmed , Rogers Jeffrey , Marques-Bonet Tomas , Rehm Heidi L. , O’Donnell-Luria Anne , Khera Amit V. , Farh Kyle Kai-How
Published: May 2023

We examined 454,712 exomes for genes associated with a wide spectrum of complex traits and common diseases and observed that rare, penetrant mutations in genes implicated by genome-wide association studies confer ∼10-fold larger effects than common variants in the same genes. Consequently, an individual at the phenotypic extreme and at the greatest risk for severe, early-onset disease is better identified by a few rare penetrant variants than by the collective action of many common variants with weak effects. By combining rare variants across phenotype-associated genes into a unified genetic risk model, we demonstrate superior portability across diverse global populations compared to common variant polygenic risk scores, greatly improving the clinical utility of genetic-based risk prediction.

One sentence summary

Rare variant polygenic risk scores identify individuals with outlier phenotypes in common human diseases and complex traits.
Subclinical Vascular Composites Predict Clinical Cardiovascular Disease, Stroke, and Dementia: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Hughes Timothy M. , Tanley Jordan , Chen Haiying , Schaich Christopher L. , Yeboah Joseph , Espeland Mark A. , Lima Joao A. C. , Ambale-Venkatesh Bharath , Michos Erin D. , Ding Jingzhong , Hayden Kathleen , Casanova Ramon , Craft Suzanne , Rapp Stephen R. , Luchsinger José A. , Fitzpatrick Annette L. , Heckbert Susan R. , Post Wendy S. , Burke Gregory L.
Published: May 2023

Background

Subclinical cardiovascular disease (CVD) measures may reflect biological pathways that contribute to increased risk for coronary heart disease (CHD) events, stroke, and dementia beyond conventional risk scores.

Methods

The Multi-Ethnic Study of Atherosclerosis (MESA) followed 6,814 participants (45-84 years of age) from baseline in 2000-2002 to 2018 over 6 clinical examinations and annual follow-up interviews. MESA baseline subclinical CVD procedures included: seated and supine blood pressure, coronary calcium scan, radial artery tonometry, and carotid ultrasound. Baseline subclinical CVD measures were transformed into z-scores before factor analysis to derive composite factor scores. Time to clinical event for all CVD, CHD, stroke and ICD code-based dementia events were modeled using Cox proportional hazards models reported as area under the curve (AUC) with 95% Confidence Intervals (95%CI) at 10 and 15 years of follow-up. All models included all factor scores together and adjustment for conventional risk scores for global CVD, stroke, and dementia.

Results

After factor selection, 24 subclinical measures aggregated into four distinct factors representing: blood pressure, arteriosclerosis, atherosclerosis, and cardiac factors. Each factor significantly predicted time to CVD events and dementia at 10 and 15 years independent of each other and conventional risk scores. Subclinical vascular composites of arteriosclerosis and atherosclerosis best predicted time to clinical events of CVD, CHD, stroke, and dementia. These results were consistent across sex and racial and ethnic groups.

Conclusions

Subclinical vascular composites of arteriosclerosis and atherosclerosis may be useful biomarkers to inform the vascular pathways contributing to events of CVD, CHD, stroke, and dementia.
Diverging maternal and infant cord antibody functions from SARS-CoV-2 infection and vaccination in pregnancy
Authors: Adhikari Emily H. , Lu Pei , Kang Ye jin , McDonald Ann R. , Pruszynski Jessica E. , Bates Timothy A. , McBride Savannah K. , Trank-Greene Mila , Tafesse Fikadu G. , Lu Lenette L.
Published: May 2023

Immunization in pregnancy is a critical tool that can be leveraged to protect the infant with an immature immune system but how vaccine-induced antibodies transfer to the placenta and protect the maternal-fetal dyad remains unclear. Here, we compare matched maternal-infant cord blood from individuals who in pregnancy received mRNA COVID-19 vaccine, were infected by SARS-CoV-2, or had the combination of these two immune exposures. We find that some but not all antibody neutralizing activities and Fc effector functions are enriched with vaccination compared to infection. Preferential transport to the fetus of Fc functions and not neutralization is observed. Immunization compared to infection enriches IgG1-mediated antibody functions with changes in antibody post-translational sialylation and fucosylation that impact fetal more than maternal antibody functional potency. Thus, vaccine enhanced antibody functional magnitude, potency and breadth in the fetus are driven more by antibody glycosylation and Fc effector functions compared to maternal responses, highlighting prenatal opportunities to safeguard newborns as SARS-CoV-2 becomes endemic.

One Sentence Summary

SARS-CoV-2 vaccination in pregnancy induces diverging maternal and infant cord antibody functions