bluuebunny/crossref_metadata_2025 huggingface dataset:
A scale for measuring nursing digital application skills: a development and psychometric testing study
Authors: Qin Shijia , Zhang Jianzhong , Sun Xiaomin , Meng Ge , Zhuang Xinqi , Jia Yitong , Shi Wen-Xin , Zhang Yin-Ping
Published: May 2024

Background

The adoption of digitization has emerged as a new trend in the advancement of healthcare systems. To ensure high-quality care, nurses should possess sufficient skills to assist in the digital transformation of healthcare practices. Suitable tools have seldom been developed to assess nurses’ skills in digital applications. This study aimed to develop the Nursing Digital Application Skill Scale (NDASS) and test its psychometric properties.

Methods

The Nursing Digital Application Skill Scale was developed in three phases. In Phase 1, an item pool was developed based on previous literature and the actual situation of nursing work. Phase 2 included 14 experts’ assessment of content validity and a focus group interview with 30 nurses to pretest the scale. In phase 3, 429 registered nurses were selected from March to June 2023, and item analysis, exploratory factor analysis, and confirmatory factor analysis were used to refine the number of items and explore the factor structure of the scale. Additionally, reliability was determined by internal consistency and test-retest reliability.

Results

The final version of the NDASS consisted of 12 items. The content validity index of NDASS reached 0.975 at an acceptable level. The convergent validity test showed that the average variance extracted value was 0.694 (> 0.5) and the composite reliability value was 0.964 (> 0.7), both of which met the requirements. The principal component analysis resulted in a single-factor structure explaining 74.794% of the total variance. All the fitting indices satisfied the standard based upon confirmatory factor analyses, indicating that the single-factor structure contributed to an ideal model fit. The internal consistency appeared high for the NDASS, reaching a Cronbach’s alpha value of 0.968. The test-retest reliability was 0.740, and the split-half coefficient was 0.935.

Conclusion

The final version of the NDASS, which possesses adequate psychometric properties, is a reliable and effective instrument for nurses to self-assess digital skills in nursing work and for nursing managers in designing nursing digital skill training.
Long COVID clinics and services offered by top US hospitals: an empirical analysis of clinical options as of May 2023
Authors: Haslam Alyson , Prasad Vinay
Published: May 2024

Background

The economic and health burden of COVID-19 has transformed the healthcare system in the US. Hospitals have adapted to the heterogeneity in long COVID symptoms, and the sheer number of people affected by this condition, by building long COVID centers and programs.

Objective

We sought to describe characteristics, services, and clinical trials of long COVID centers at top US hospitals.

Design

Cross-sectional analysis.

Participants

Long COVID treatment programs or centers at top US hospitals.

Exposures

Frequency of long COVID centers, eligibility for being treated, the services they provide, specialist to whom the patients may be referred, and the long COVID clinical trials in which these hospitals participate.

Findings

Most top hospitals in the US (n = 43/50; 86%) offer long COVID services. 65% (28/43) did not describe the services provided. 12 (28%) required a referral from a primary care physician. The most common services were meeting with a team member (n = 20; 47%), ordering lab and/or radiology services (n = 8; 18.6%), and administering a physical exam (n = 7; 16%). 7 (16%) centers/programs treated only adults; 5 (12%) treated both adults and children, and 31 (72%) did not specify. The most common specialists described were psychology (n = 25; 58%), neurology (n = 25; 58%), and pulmonary (n = 24; 56%). Sixty-three trials (of 134 long COVID clinical trials) had at least one top hospital listed as a study site. The median number of clinical trials that each hospital sponsored or was a study site was 2 (interquartile range: 1, 3).

Conclusions and relevance

We find that services offered at long COVID clinics at top hospitals in the US often include meeting with a team member and referrals to a wide range of specialists. The diversity in long COVID services offered parallels the diversity in long COVID symptoms, suggesting a need for better consensus in developing and delivering treatment.
Early development of local data dashboards to depict the substance use care cascade for youth involved in the legal system: qualitative findings from end users
Authors: Dir Allyson L. , O’Reilly Lauren , Pederson Casey , Schwartz Katherine , Brown Steven A. , Reda Khairi , Gillenwater Logan , Gharbi Sami , Wiehe Sarah E. , Adams Zachary W. , Hulvershorn Leslie A. , Zapolski Tamika C.B. , Boustani Malaz , Aalsma Matthew C.
Published: May 2024

Introduction

Rates of substance use are high among youth involved in the legal system (YILS); however, YILS are less likely to initiate and complete substance use treatment compared to their non legally-involved peers. There are multiple steps involved in connecting youth to needed services, from screening and referral within the juvenile legal system to treatment initiation and completion within the behavioral health system. Understanding potential gaps in the care continuum requires data and decision-making from these two systems. The current study reports on the development of data dashboards that integrate these systems’ data to help guide decisions to improve substance use screening and treatment for YILS, focusing on end-user feedback regarding dashboard utility.

Methods

Three focus groups were conducted with n = 21 end-users from juvenile legal systems and community mental health centers in front-line positions and in decision-making roles across 8 counties to gather feedback on an early version of the data dashboards; dashboards were then modified based on feedback.

Results

Qualitative analysis revealed topics related to (1) important aesthetic features of the dashboard, (2) user features such as filtering options and benchmarking to compare local data with other counties, and (3) the centrality of consistent terminology for data dashboard elements. Results also revealed the use of dashboards to facilitate collaboration between legal and behavioral health systems.

Conclusions

Feedback from end-users highlight important design elements and dashboard utility as well as the challenges of working with cross-system and cross-jurisdiction data.
Imprinted Grb10, encoding growth factor receptor bound protein 10, regulates fetal growth independently of the insulin-like growth factor type 1 receptor (Igf1r) and insulin receptor (Insr) genes
Authors: Moorwood Kim , Smith Florentia M. , Garfield Alastair S. , Ward Andrew
Published: May 2024

Background

Optimal size at birth dictates perinatal survival and long-term risk of developing common disorders such as obesity, type 2 diabetes and cardiovascular disease. The imprinted Grb10 gene encodes a signalling adaptor protein capable of inhibiting receptor tyrosine kinases, including the insulin receptor (Insr) and insulin-like growth factor type 1 receptor (Igf1r). Grb10 restricts fetal growth such that Grb10 knockout (KO) mice are at birth some 25-35% larger than wild type. Using a mouse genetic approach, we test the widely held assumption that Grb10 influences growth through interaction with Igf1r, which has a highly conserved growth promoting role.

Results

Should Grb10 interact with Igf1r to regulate growth Grb10:Igf1r double mutant mice should be indistinguishable from Igf1r KO single mutants, which are around half normal size at birth. Instead, Grb10:Igf1r double mutants were intermediate in size between Grb10 KO and Igf1r KO single mutants, indicating additive effects of the two signalling proteins having opposite actions in separate pathways. Some organs examined followed a similar pattern, though Grb10 KO neonates exhibited sparing of the brain and kidneys, whereas the influence of Igf1r extended to all organs. An interaction between Grb10 and Insr was similarly investigated. While there was no general evidence for a major interaction for fetal growth regulation, the liver was an exception. The liver in Grb10 KO mutants was disproportionately overgrown with evidence of excess lipid storage in hepatocytes, whereas Grb10:Insr double mutants were indistinguishable from Insr single mutants or wild types.

Conclusions

Grb10 acts largely independently of Igf1r or Insr to control fetal growth and has a more variable influence on individual organs. Only the disproportionate overgrowth and excess lipid storage seen in the Grb10 KO neonatal liver can be explained through an interaction between Grb10 and the Insr. Our findings are important for understanding how positive and negative influences on fetal growth dictate size and tissue proportions at birth.
Associations of prenatal blood pressure trajectory and variability with child neurodevelopment at 2 years old
Authors: Xu Luli , Cheng Jiayi , Dong Xiaohan , Guo Menglan , Chen Kai , Fan Xiaoxuan , Mu Xiaofeng , Wang Yuji , Xia Zhiguo , Li Jun , Wang Youjie , Xiong Chao , Zhou Aifen
Published: May 2024

Background

The patterns of blood pressure (BP) change throughout the pregnancy were related to adverse birth outcomes. However, little is known about the long-term effect of BP change patterns on child neurodevelopment. This study aimed to explore the relationship between the BP trajectory and BP variability during pregnancy and early childhood neurodevelopment.

Method

A total of 2797 mother-newborn pairs were derived from the Wuhan Healthy Baby Cohort Study. BP was measured during each antenatal visit, and Mental and Psychomotor Development Indexes (MDI and PDI) were assessed using the Bayley Scales of Infant Development (BSID) when the children were 2 years old. Delayed neurodevelopment was defined as scores of PDI or MDI less than − 1SD relative to the mean score of the study population. A group-based multi-trajectory model was adopted to identify multi-trajectories of systolic blood pressure (SBP) and diastolic blood pressure (DBP). Visit-to-visit BP variability was assessed by the coefficient of variation (CV), standard deviation (SD), and average real variability (ARV). Generalized linear models and multivariate logistic regressions were used to assess the associations of BP trajectories and variability with BSID scores and delayed neurodevelopment, respectively.

Results

Five distinct trajectories for SBP and DBP were identified, namely, “Low-increasing,” “Low-stable,” “Moderate-decreasing,” “Moderate-increasing,” and “High-stable” groups. Compared with the “Low-stable” group, the children whose mothers’ BP fell into the other four groups had lower PDI scores, and mothers in the “Low-increasing,” “Moderate-increasing,” and “Moderate-decreasing” groups had 43% (OR: 1.43, 95% CI: 1.01, 2.03), 48% (OR: 1.48, 95% CI: 1.05, 2.08) and 45% (OR:1.45, 95% CI: 1.03, 2.04) higher risk of having offspring with delayed psychomotor neurodevelopment, respectively. High DBP variability was associated with lower BSID scores, and delayed psychomotor neurodevelopment (OR = 1.46, 95% CI: 1.10, 1.92 for DBP-SD; OR = 1.53, 95% CI: 1.16, 2.02 for DBP-CV).

Conclusion

Our findings suggest that BP change patterns assessed by multi-trajectory and visit-to-visit variability were associated with lower BSID scores and delayed neurodevelopment. Health professionals should be aware of the influence of BP level and its oscillations during pregnancy on the risk of delayed neurodevelopment.
Distribution of sequence types and antimicrobial resistance of clinical Pseudomonas aeruginosa isolates from dogs and cats visiting a veterinary teaching hospital in Thailand
Authors: Jangsangthong Arunee , Lugsomya Kittitat , Apiratwarrasakul Sukanya , Phumthanakorn Nathita
Published: May 2024

Background

Pseudomonas aeruginosa is an important opportunistic pathogen in dogs and cats and is resistant to several antimicrobial drugs; however, data on the clonal distribution of P. aeruginosa in veterinary hospital are limited. This study aimed to investigate the clonal dissemination and antimicrobial resistance of clinical P. aeruginosa in a veterinary teaching hospital in Thailand within a 1-year period. Minimum inhibitory concentration determination and whole genome sequencing were used for antimicrobial susceptibility analysis and genetic determination, respectively.

Results

Forty-nine P. aeruginosa were isolated mostly from the skin, urinary tract, and ear canal of 39 dogs and 10 cats. These isolates belonged to 39 sequence types (STs) that included 9 strains of high-risk clones of ST235 (n = 2), ST244 (n = 2), ST274 (n = 2), ST277 (n = 1), ST308 (n = 1), and ST357 (n = 1). Overall antimicrobial resistance rate was low (< 25%), and no colistin-resistant strains were found. Two carbapenem-resistant strains belonging to ST235 and ST3405 were identified.

Conclusions

Clinical P. aeruginosa in dogs and cats represent STs diversity. High-risk clones and carbapenem-resistant strains are a public health concern. Nevertheless, this study was limited by a small number of isolates. Continuous monitoring is needed, particularly in large-scale settings with high numbers of P. aeruginosa, to restrict bacterial transfer from companion animal to humans in a veterinary hospital.
Examining the paradox: increased malaria risk in children under 5 in female-headed households in Nigeria
Authors: Xing Si-Yu , Zhang Hai-Ting , Wang Lin-Min , Lu Hong-Zheng , Peng Zhe-Yu , Liu Miao , Li Chun-Xiao , Deng Sheng-Qun
Published: May 2024

Background

Nigeria is facing a severe malaria crisis, accounting for a significant proportion of global cases and deaths of malaria. This study aimed to investigate the differences between female-headed households (FHHs) and male-headed households (MHHs) and their impact on malaria risk among children under five (U5) in Nigeria.

Methods

Data from the 2021 Nigeria Malaria Indicator Survey (NMIS) were used for this cross-sectional study. A representative sample of 10,988 households was analysed, with key variables subjected to frequency calculations, descriptive statistics, and bivariate analyses using t-tests and chi-square analyses to compare the differences between FHHs and MHHs.

Results

Among all participants, 92.1% (N = 10,126) reported residing in male-headed households, while 7.8% (N = 862) reported living in female-headed households. MHHs were significantly more likely to own insecticide-treated bed nets (ITNs) than FHHs (64.7% vs. 53.6%, P < 0.001). U5 children in MHHs had a greater likelihood of sleeping under a bed net the night before the survey than U5 children in FHHs (35.3% vs. 30.0%, P < 0.05). The prevalence of fever in the previous two weeks among U5 children was similar in MHHs and FHHs (35.4% vs. 31.4%), and the testing rates for malaria among U5 children who experienced febrile episodes were higher in MHHs than FHHs (22.4% vs. 15.4%, P < 0.05). Although not statistically significant, FHHs exhibited a higher percentage of U5 children testing positive for malaria compared to MHHs (87.8% vs. 78.9%). On the other hand, FHHs had higher education levels, overall wealth index scores, and a larger presence in urban areas compared to MHHs (P < 0.001). Moreover, FHHs reported higher adherence to malaria prevention awareness (P < 0.001).

Conclusion

In Nigeria, FHHs enjoy relatively better socioeconomic conditions and stronger awareness of malaria prevention compared to their male-headed counterparts. Contrary to expectations, FHHs are at an increased risk of malaria in children under 5 years old. This phenomenon is associated with entrenched gender inequality and the challenges women face in accessing critical assets. As women in FHHs bear the responsibility of income generation while caring for their children, it is crucial to prioritize interventions that address malaria management in FHHs to reduce both malaria incidence and mortality rates.

Graphical Abstract
Exosome-derived circUPF2 enhances resistance to targeted therapy by redeploying ferroptosis sensitivity in hepatocellular carcinoma
Authors: Dong Feng-Lin , Xu Zong-Zhen , Wang Ying-Qiao , Li Tao , Wang Xin , Li Jie
Published: May 2024

Background

Advanced hepatocellular carcinoma (HCC) can be treated with sorafenib, which is the primary choice for targeted therapy. Nevertheless, the effectiveness of sorafenib is greatly restricted due to resistance. Research has shown that exosomes and circular RNAs play a vital role in the cancer’s malignant advancement. However, the significance of exosomal circular RNAs in the development of resistance to sorafenib in HCC remains uncertain.

Methods

Ultracentrifugation was utilized to isolate exosomes (Exo-SR) from the sorafenib-resistant HCC cells’ culture medium. Transcriptome sequencing and differential expression gene analysis were used to identify the targets of Exo-SR action in HCC cells. To identify the targets of Exo-SR action in HCC cells, transcriptome sequencing and analysis of differential expression genes were employed. To evaluate the impact of exosomal circUPF2 on resistance to sorafenib in HCC, experiments involving gain-of-function and loss-of-function were conducted. RNA pull-down assays and mass spectrometry analysis were performed to identify the RNA-binding proteins interacting with circUPF2. RNA immunoprecipitation (RIP), RNA pull-down, electrophoretic mobility shift assay (EMSA), immunofluorescence (IF) -fluorescence in situ hybridization (FISH), and rescue assays were used to validate the interactions among circUPF2, IGF2BP2 and SLC7A11. Finally, a tumor xenograft assay was used to examine the biological functions and underlying mechanisms of Exo-SR and circUPF2 in vivo.

Results

A novel exosomal circRNA, circUPF2, was identified and revealed to be significantly enriched in Exo-SR. Exosomes with enriched circUPF2 enhanced sorafenib resistance by promoting SLC7A11 expression and suppressing ferroptosis in HCC cells. Mechanistically, circUPF2 acts as a framework to enhance the creation of the circUPF2-IGF2BP2-SLC7A11 ternary complex contributing to the stabilization of SLC7A11 mRNA. Consequently, exosomal circUPF2 promotes SLC7A11 expression and enhances the function of system Xc- in HCC cells, leading to decreased sensitivity to ferroptosis and resistance to sorafenib.

Conclusions

The resistance to sorafenib in HCC is facilitated by the exosomal circUPF2, which promotes the formation of the circUPF2-IGF2BP2-SLC7A11 ternary complex and increases the stability of SLC7A11 mRNA. Focusing on exosomal circUPF2 could potentially be an innovative approach for HCC treatment.

Graphical Abstract
Initial evaluation of measurement properties of the Work Environment Impact Questionnaire (WEIQ) - using Rasch analysis
Authors: Ekbladh Elin , Yngve Moa , Melin Jeanette
Published: May 2024

Background

To provide both preventive and rehabilitative conditions in a workplace, one must understand how employees experience work demands. Such an understanding can be obtained from each individual with valid and quality-assured questionnaires. The Work Environment Impact Questionnaire (WEIQ) is a new questionnaire for measuring employees’ self-perceived work ability in relation to their specific workplace environment. The purpose of this study was to assess the measurement properties in terms of construct validity of the WEIQ.

Methods

A cross-sectional survey study was conducted with 288 respondents from three different workplaces involving assisted living personnel, vocational rehabilitation personnel and personnel at a research institute. The measurement properties of the WEIQ were assessed according to Rasch Measurement Theory (RMT), including assessment of item-to-sample targeting, threshold ordering, item fit statistics, unidimensionality and reliability.

Results

Item fit, i.e., fit residuals, item characteristic curves (ICC) and chi square values, were all satisfactory, and no disordered thresholds were present after collapsing the lowest response categories. However, issues with local dependent (LD) item correlations was present in 7.6% cases, four items showed statistically significant differential item functioning (DIF), where 11% of the respondents had person fit residuals outside the recommended range of ± 2.5 and the t-test for unidimensionality did not meet the criterion of 5%. Scale-to-sample targeting and reliability (0.92) were good. LD could be resolved with testlets and at the same time maintaining fit and improving dimensionality, but then the reliability decreased to 0.82.

Conclusions

This study provides an initial validation of the WEIQ to be used for assessing employees’ self-perceived work ability. Most measurement properties were acceptable, but further exploration of LD, DIF and unidimensionality in additional work settings and with larger sample sizes is warranted.

Trial registration

Not applicable.
The value of health service-based research to health service organisations: a qualitative study with senior health service executives
Authors: Todd Angela L. , Petrunoff Nicholas , Frommer Michael , Nutbeam Don
Published: May 2024

Background

Research evidence has demonstrably improved health care practices and patient outcomes. However, systemic translation of evidence into practice is far from optimal. The reasons are complex, but often because research is not well aligned with health service priorities. The aim of this study was to explore the experiences and perspectives of senior health service executives on two issues: (1) the alignment between local research activity and the needs and priorities of their health services, and (2) the extent to which research is or can be integrated as part of usual health care practice.

Methods

In this qualitative study, semi-structured interviews were conducted with senior health leaders from four large health service organisations that are members of Sydney Health Partners (SHP), one of Australia’s nationally accredited research translation centres committed to accelerating the translation of research findings into evidence-based health care. The interviews were conducted between November 2022 and January 2023, and were either audio-recorded and transcribed verbatim or recorded in the interviewer field notes. A thematic analysis of the interview data was conducted by two researchers, using the framework method to identify common themes.

Results

Seventeen health executives were interviewed, including chief executives, directors of medical services, nursing, allied health, research, and others in executive leadership roles. Responses to issue (1) included themes on re-balancing curiosity- and priority-driven research; providing more support for research activity within health organisations; and helping health professionals and researchers discuss researchable priorities. Responses to issue (2) included identification of elements considered essential for embedding research in health care; and the need to break down silos between research and health care, as well as within health organisations.

Conclusions

Health service leaders value research but want more research that aligns with their needs and priorities. Discussions with researchers about those priorities may need some facilitation. Making research a more integrated part of health care will require strong and broad executive leadership, resources and infrastructure, and investing in capacity- and capability-building across health clinicians, managers and executive staff.
Genomic epidemiology of CVA10 in Guangdong, China, 2013–2021
Authors: Lian Huimin , Yi Lina , Qiu Ming , Li Baisheng , Sun Limei , Zeng Huiling , Zeng Biao , Yang Fen , Yang Haiyi , Yang Mingda , Xie Chunyan , Qu Lin , Lin Huifang , Hu Pengwei , Xu Shaojian , Zeng Hanri , Lu Jing
Published: May 2024

Hand, Foot and Mouth Disease (HFMD) is a highly contagious viral illness primarily affecting children globally. A significant epidemiological transition has been noted in mainland China, characterized by a substantial increase in HFMD cases caused by non-Enterovirus A71 (EV-A71) and non-Coxsackievirus A16 (CVA16) enteroviruses (EVs). Our study conducts a retrospective examination of 36,461 EV-positive specimens collected from Guangdong, China, from 2013 to 2021. Epidemiological trends suggest that, following 2013, Coxsackievirus A6 (CVA6) and Coxsackievirus A10 (CVA10) have emerged as the primary etiological agents for HFMD. In stark contrast, the incidence of EV-A71 has sharply declined, nearing extinction after 2018. Notably, cases of CVA10 infection were considerably younger, with a median age of 1.8 years, compared to 2.3 years for those with EV-A71 infections, possibly indicating accumulated EV-A71-specific herd immunity among young children. Through extensive genomic sequencing and analysis, we identified the N136D mutation in the 2 A protein, contributing to a predominant subcluster within genogroup C of CVA10 circulating in Guangdong since 2017. Additionally, a high frequency of recombination events was observed in genogroup F of CVA10, suggesting that the prevalence of this lineage might be underrecognized. The dynamic landscape of EV genotypes, along with their potential to cause outbreaks, underscores the need to broaden surveillance efforts to include a more diverse spectrum of EV genotypes. Moreover, given the shifting dominance of EV genotypes, it may be prudent to re-evaluate and optimize existing vaccination strategies, which are currently focused primarily target EV-A71.
Virological evaluation of natural and modified attapulgite against porcine epidemic diarrhoea virus
Authors: Wang Tianmin , Wen Yuan , Qian Bingxu , Tang Fang , Zhang Xiaorong , Xu Xiulong , Zhou Yanmin , Dai Jianjun , Wang Aiqin , Xue Feng
Published: May 2024

Background

The Porcine Epidemic Diarrhea Virus (PEDV) has caused significant economic losses in the global swine industry. As a potential drug for treating diarrhea, the antiviral properties of attapulgite deserve further study.

Methods

In this study, various methods such as RT-qPCR, Western blot, viral titer assay, Cytopathic Effect, immunofluorescence analysis and transmission electron microscopy were used to detect the antiviral activity of attapulgite and to assess its inhibitory effect on PEDV.

Results

When exposed to the same amount of virus, there was a significant decrease in the expression of the S protein, resulting in a viral titer reduction from 10-5.613 TCID50/mL to 10-2.90 TCID50/mL, which represents a decrease of approximately 102.6 folds. Results of cytopathic effect and indirect immunofluorescence also indicate a notable decrease in viral infectivity after attapulgite treatment. Additionally, it was observed that modified materials after acidification had weaker antiviral efficacy compared to powdered samples that underwent ultrasonic disintegration, which showed the strongest antiviral effects.

Conclusion

As a result, Attapulgite powders can trap and adsorb viruses to inhibit PEDV in vitro, leading to loss of viral infectivity. This study provides new materials for the development of novel disinfectants and antiviral additives.
One spinal manipulation session reduces local pain sensitivity but does not affect postural stability in individuals with chronic low back pain: a randomised, placebo-controlled trial
Authors: Freitas João Paulo , Corrêa Leticia Amaral , Bittencourt Juliana Valentim , Armstrong Karine Marcondes , Meziat-Filho Ney , Nogueira Leandro Alberto Calazans
Published: May 2024

Background

Clinical practice guidelines recommend spinal manipulation for patients with low back pain. However, the effects of spinal manipulation have contradictory findings compared to placebo intervention. Therefore, this study investigated the immediate effects of lumbar spinal manipulation on pressure pain threshold (PPT) and postural stability in people with chronic low back pain (cLBP). Second, we investigated the immediate effect of lumbar spinal manipulation on pain intensity and the interference of the participant beliefs about which treatment was received in the PPT, postural stability, and pain intensity.

Methods

A two-arm, randomised, placebo-controlled, double-blind trial was performed. Eighty participants with nonspecific cLPB and a minimum score of 3 on the Numeric Pain Rating Scale received one session of lumbar spinal manipulation (n = 40) or simulated lumbar spinal manipulation (n = 40). Primary outcomes were local and remote PPTs and postural stability. Secondary outcomes were pain intensity and participant’s perceived treatment allocation. Between-group mean differences and their 95% confidence intervals (CIs) estimated the treatment effect. One-way analysis of covariance (ANCOVA) was performed to assess whether beliefs about which treatment was received influenced the outcomes.

Results

Participants had a mean (SD) age of 34.9 (10.5) years, and 50 (62.5%) were women. Right L5 [between-group mean difference = 0.55 (95%CI 0.19 to 0.90)], left L5 [between-group mean difference = 0.45 (95%CI 0.13 to 0.76)], right L1 [between-group mean difference = 0.41 (95%CI 0.05 to 0.78)], left L1 [between-group mean difference = 0.57 (95%CI 0.15 to 0.99)], left DT [between-group mean difference = 0.35 (95%CI 0.04 to 0.65)], and right LE [between-group mean difference = 0.34 (95%CI 0.08 to 0.60)] showed superior treatment effect in the spinal manipulation group than sham. Neither intervention altered postural stability. Self-reported pain intensity showed clinically significant decreases in both groups after the intervention. A higher proportion of participants in the spinal manipulation group achieved more than two points of pain relief (spinal manipulation = 90%; sham = 60%). The participants’ perceived treatment allocation did not affect the outcomes.

Conclusion

One spinal manipulation session reduces lumbar pain sensitivity but does not affect postural stability compared to a sham session in individuals with cLPB. Self-reported pain intensity lowered in both groups and a higher proportion of participants in the spinal manipulation group reached clinically significant pain relief. The participant’s belief in receiving the manipulation did not appear to have influenced the outcomes since the adjusted model revealed similar findings.
Evaluation of multiple-vendor AI autocontouring solutions
Authors: Goddard Lee , Velten Christian , Tang Justin , Skalina Karin A. , Boyd Robert , Martin William , Basavatia Amar , Garg Madhur , Tomé Wolfgang A.
Published: May 2024

Background

Multiple artificial intelligence (AI)-based autocontouring solutions have become available, each promising high accuracy and time savings compared with manual contouring. Before implementing AI-driven autocontouring into clinical practice, three commercially available CT-based solutions were evaluated.

Materials and methods

The following solutions were evaluated in this work: MIM-ProtégéAI+ (MIM), Radformation-AutoContour (RAD), and Siemens-DirectORGANS (SIE). Sixteen organs were identified that could be contoured by all solutions. For each organ, ten patients that had manually generated contours approved by the treating physician (AP) were identified, totaling forty-seven different patients. CT scans in the supine position were acquired using a Siemens-SOMATOMgo 64-slice helical scanner and used to generate autocontours. Physician scoring of contour accuracy was performed by at least three physicians using a five-point Likert scale. Dice similarity coefficient (DSC), Hausdorff distance (HD) and mean distance to agreement (MDA) were calculated comparing AI contours to “ground truth” AP contours.

Results

The average physician score ranged from 1.00, indicating that all physicians reviewed the contour as clinically acceptable with no modifications necessary, to 3.70, indicating changes are required and that the time taken to modify the structures would likely take as long or longer than manually generating the contour. When averaged across all sixteen structures, the AP contours had a physician score of 2.02, MIM 2.07, RAD 1.96 and SIE 1.99. DSC ranged from 0.37 to 0.98, with 41/48 (85.4%) contours having an average DSC ≥ 0.7. Average HD ranged from 2.9 to 43.3 mm. Average MDA ranged from 0.6 to 26.1 mm.

Conclusions

The results of our comparison demonstrate that each vendor’s AI contouring solution exhibited capabilities similar to those of manual contouring. There were a small number of cases where unusual anatomy led to poor scores with one or more of the solutions. The consistency and comparable performance of all three vendors’ solutions suggest that radiation oncology centers can confidently choose any of the evaluated solutions based on individual preferences, resource availability, and compatibility with their existing clinical workflows. Although AI-based contouring may result in high-quality contours for the majority of patients, a minority of patients require manual contouring and more in-depth physician review.
Soluble immune checkpoints: implications for cancer prognosis and response to immune checkpoint therapy and conventional therapies
Authors: Pitts Stephanie C. , Schlom Jeffrey , Donahue Renee N.
Published: May 2024

Longitudinal sampling of tumor tissue from patients with solid cancers, aside from melanoma and a few other cases, is often unfeasible, and thus may not capture the plasticity of interactions between the tumor and immune system under selective pressure of a given therapy. Peripheral blood analyses provide salient information about the human peripheral immunome while offering technical and practical advantages over traditional tumor biopsies, and should be utilized where possible alongside interrogation of the tumor. Some common blood-based biomarkers used to study the immune response include immune cell subsets, circulating tumor DNA, and protein analytes such as cytokines. With the recent explosion of immune checkpoint inhibitors (ICI) as a modality of treatment in multiple cancer types, soluble immune checkpoints have become a relevant area of investigation for peripheral immune-based biomarkers. However, the exact functions of soluble immune checkpoints and their roles in cancer for the most part remain unclear. This review discusses current literature on the production, function, and expression of nine soluble immune checkpoints – sPD-L1, sPD-1, sCTLA4, sCD80, sTIM3, sLAG3, sB7-H3, sBTLA, and sHVEM – in patients with solid tumors, and explores their role as biomarkers of response to ICI as well as to conventional therapies (chemotherapy, radiotherapy, targeted therapy, and surgery) in cancer patients.
Ovarian aging: energy metabolism of oocytes
Authors: Bao Shenglan , Yin Tailang , Liu Su
Published: May 2024

In women who are getting older, the quantity and quality of their follicles or oocytes and decline. This is characterized by decreased ovarian reserve function (DOR), fewer remaining oocytes, and lower quality oocytes. As more women choose to delay childbirth, the decline in fertility associated with age has become a significant concern for modern women. The decline in oocyte quality is a key indicator of ovarian aging. Many studies suggest that age-related changes in oocyte energy metabolism may impact oocyte quality. Changes in oocyte energy metabolism affect adenosine 5'-triphosphate (ATP) production, but how related products and proteins influence oocyte quality remains largely unknown. This review focuses on oocyte metabolism in age-related ovarian aging and its potential impact on oocyte quality, as well as therapeutic strategies that may partially influence oocyte metabolism. This research aims to enhance our understanding of age-related changes in oocyte energy metabolism, and the identification of biomarkers and treatment methods.
Reproductive characteristics, menopausal status, race and ethnicity, and risk of breast cancer subtypes defined by ER, PR and HER2 status: the Breast Cancer Etiology in Minorities study
Authors: John Esther M. , Koo Jocelyn , Phipps Amanda I. , Longacre Teri A. , Kurian Allison W. , Ingles Sue A. , Wu Anna H. , Hines Lisa M.
Published: May 2024

Background

Associations between reproductive factors and risk of breast cancer differ by subtype defined by joint estrogen receptor (ER), progesterone receptor (PR), and HER2 expression status. Racial and ethnic differences in the incidence of breast cancer subtypes suggest etiologic heterogeneity, yet data are limited because most studies have included non-Hispanic White women only.

Methods

We analyzed harmonized data for 2,794 breast cancer cases and 4,579 controls, of whom 90% self-identified as African American, Asian American or Hispanic. Questionnaire data were pooled from three population-based studies conducted in California and data on tumor characteristics were obtained from the California Cancer Registry. The study sample included 1,530 luminal A (ER-positive and/or PR-positive, HER2-negative), 442 luminal B (ER-positive and/or PR-positive, HER2-positive), 578 triple-negative (TN; ER-negative, PR-negative, HER2-negative), and 244 HER2-enriched (ER-negative, PR-negative, HER2-positive) cases. We used multivariable unconditional logistic regression models to estimate subtype-specific ORs and 95% confidence intervals associated with parity, breast-feeding, and other reproductive characteristics by menopausal status and race and ethnicity.

Results

Subtype-specific associations with reproductive factors revealed some notable differences by menopausal status and race and ethnicity. Specifically, higher parity without breast-feeding was associated with higher risk of luminal A and TN subtypes among premenopausal African American women. In contrast, among Asian American and Hispanic women, regardless of menopausal status, higher parity with a breast-feeding history was associated with lower risk of luminal A subtype. Among premenopausal women only, luminal A subtype was associated with older age at first full-term pregnancy (FTP), longer interval between menarche and first FTP, and shorter interval since last FTP, with similar OR estimates across the three racial and ethnic groups.

Conclusions

Subtype-specific associations with reproductive factors overall and by menopausal status, and race and ethnicity, showed some differences, underscoring that understanding etiologic heterogeneity in racially and ethnically diverse study samples is essential. Breast-feeding is likely the only reproductive factor that is potentially modifiable. Targeted efforts to promote and facilitate breast-feeding could help mitigate the adverse effects of higher parity among premenopausal African American women.
High-throughput functional mapping of variants in an arrhythmia gene, KCNE1, reveals novel biology
Authors: Muhammad Ayesha , Calandranis Maria E. , Li Bian , Yang Tao , Blackwell Daniel J. , Harvey M. Lorena , Smith Jeremy E. , Daniel Zerubabell A. , Chew Ashli E. , Capra John A. , Matreyek Kenneth A. , Fowler Douglas M. , Roden Dan M. , Glazer Andrew M.
Published: May 2024

Background

KCNE1 encodes a 129-residue cardiac potassium channel (IKs) subunit. KCNE1 variants are associated with long QT syndrome and atrial fibrillation. However, most variants have insufficient evidence of clinical consequences and thus limited clinical utility.

Methods

In this study, we leveraged the power of variant effect mapping, which couples saturation mutagenesis with high-throughput sequencing, to ascertain the function of thousands of protein-coding KCNE1 variants.

Results

We comprehensively assayed KCNE1 variant cell surface expression (2554/2709 possible single-amino-acid variants) and function (2534 variants). Our study identified 470 loss- or partial loss-of-surface expression and 574 loss- or partial loss-of-function variants. Of the 574 loss- or partial loss-of-function variants, 152 (26.5%) had reduced cell surface expression, indicating that most functionally deleterious variants affect channel gating. Nonsense variants at residues 56–104 generally had WT-like trafficking scores but decreased functional scores, indicating that the latter half of the protein is dispensable for protein trafficking but essential for channel function. 22 of the 30 KCNE1 residues (73%) highly intolerant of variation (with > 70% loss-of-function variants) were in predicted close contact with binding partners KCNQ1 or calmodulin. Our functional assay data were consistent with gold standard electrophysiological data (ρ =  − 0.64), population and patient cohorts (32/38 presumed benign or pathogenic variants with consistent scores), and computational predictors (ρ =  − 0.62). Our data provide moderate-strength evidence for the American College of Medical Genetics/Association of Molecular Pathology functional criteria for benign and pathogenic variants.

Conclusions

Comprehensive variant effect maps of KCNE1 can both provide insight into IKs channel biology and help reclassify variants of uncertain significance.
Online vs in-person musculoskeletal ultrasound course: a cohort comparison study
Authors: Lake Shirley , Brydges Ryan , Penney Chris , Wilson Diane , Sweezie Raquel , Bagovich Maria , Bong David , Barr Susan , Stroud Lynfa
Published: May 2024

Background

Point-of-care musculoskeletal (MSK) ultrasound (US) courses are typically held in-person. The COVID-19 pandemic guidelines forced courses to switch to online delivery. To determine this impact, we conducted an observational cohort study, comparing homework completion and image quality between an Online and a historical In-person cohort.

Methods

The In-person (n = 27) and Online (n = 24) cohorts attended two learning sessions spaced six months apart. The course content was the same, while the process of delivery differed. As homework, participants submitted US images biweekly for up to five months after each session. Expert faculty provided written feedback to all participants, and two independent reviewers rated the image quality for a subset of participants in each group who had completed at least 70% of their homework (In-person, n = 9; Online, n = 9). Participants self-reported their satisfaction through post-course evaluation.

Results

63% of In-Person and 71% of Online cohort participants submitted their homework images. We observed no differences in the mean amount of homework images submitted for In-person (M = 37.3%, SD = 42.6%) and Online cohorts (M = 48.1%, SD = 38.8%; p > 0.05, Mann-Whitney U Test). At course end, the cohorts did not differ in overall image quality (p > 0.05, Wilcoxon Signed-rank Test). All participants reported high levels of satisfaction.

Conclusions

A convenience sample of participants attending a basic MSK US course in-person and online did not differ statistically in homework completion, quality of submitted US images, or course satisfaction. We add to literature suggesting online learning remains a viable option post-pandemic.
FdeC expression regulates motility and adhesion of the avian pathogenic Escherichia coli strain IMT5155
Authors: Aleksandrowicz Adrianna , Kjærup Rikke Brødsgaard , Grzymajło Krzysztof , Martinez Fernando Garcia , Muñoz Javier , Borowska Dominika , Sives Samantha , Vervelde Lonneke , Dalgaard Tina Sørensen , Kingsley Robert A. , Kolenda Rafał
Published: May 2024

Adaptation of avian pathogenic E. coli (APEC) to changing host environments including virulence factors expression is vital for disease progression. FdeC is an autotransporter adhesin that plays a role in uropathogenic Escherichia coli (UPEC) adhesion to epithelial cells. Expression of fdeC is known to be regulated by environmental conditions in UPEC and Shiga toxin-producing E. coli (STEC). The observation in a previous study that an APEC strain IMT5155 in which the fdeC gene was disrupted by a transposon insertion resulted in elevated adhesion to chicken intestinal cells prompted us to further explore the role of fdeC in infection. We found that the fdeC gene prevalence and FdeC variant prevalence differed between APEC and nonpathogenic E. coli genomes. Expression of the fdeC gene was induced at host body temperature, an infection relevant condition. Disruption of fdeC resulted in greater adhesion to CHIC-8E11 cells and increased motility at 42 °C compared to wild type (WT) and higher expression of multiple transporter proteins that increased inorganic ion export. Increased motility may be related to increased inorganic ion export since this resulted in downregulation of YbjN, a protein known to supress motility. Inactivation of fdeC in APEC strain IMT5155 resulted in a weaker immune response in chickens compared to WT in experimental infections. Our findings suggest that FdeC is upregulated in the host and contributes to interactions with the host by down-modulating motility during colonization. A thorough understanding of the regulation and function of FdeC could provide novel insights into E. coli pathogenesis.
Utilization of early supported discharge and outpatient rehabilitation services following inpatient stroke rehabilitation
Authors: Razavilar Negar , Tran Dat T. , Dukelow Sean P. , Round Jeff
Published: May 2024

Background

Studies examining factors associated with patient referral to early supported discharge (ESD)/outpatient rehabilitation (OPR) programs and utilization of ESD/OPR services after discharge from inpatient stroke rehabilitation (IPR) are scarce. Accordingly, we examined utilization of ESD/OPR services following discharge from IPR and patient factors associated with service utilization.

Methods

Stroke patients discharged from IPR facilities in Alberta between April 2014 and March 2016 were included and followed for one year for ESD/OPR service utilization. Multivariable linear and negative binomial regressions were used to examine association of patients’ factors with ESD/OPR use.

Results

We included 752 patients (34.4% of 2,187 patients discharged from IPR) who had 40,772 ESD/OPR visits during one year of follow-up in the analysis. Mean and median ESD/OPR visits were 54.2 and 36 visits, respectively. Unadjusted ESD/OPR visits were lower in females and patients aged ≥ 60 years but were similar between urban and rural areas. After adjustment for patient factors, patients in urban areas and discharged home after IPR were associated with 83.5% and 61.9%, respectively, increase in ESD/OPR visits, while having a right-body stroke was associated with 23.5% increase. Older patients used ESD/OPR less than their younger counterparts (1.4% decrease per one year of older age). Available factors explained 12.3% of variation in ESD/OPR use.

Conclusion

ESD/OPR utilization after IPR in Alberta was low and varied across age and geographic locations. Factors associated with use of ESD/OPR were identified but they could not fully explain variation of ESD/OPR use.