bluuebunny/crossref_metadata_2025 huggingface dataset:
Persistence without essence
Authors: Leech Jessica
Published: July 2024

Questions of persistence and change are central to metaphysics. There is almost always a role for sortal or essential properties to play in theories of persistence. However, one might reasonably be suspicious of many of the claims about sortal properties and essential properties on which so many accounts of persistence conditions rest. The aim of this paper is to think through what persistence looks like if we don't help ourselves to these assumptions. In so doing, we shall uncover a deep and difficult problem when it comes to identity facts and their relation to qualitative facts. Towards the end of the paper, I sketch a potential line of response that builds upon our seeming awareness of a genuinely persisting self.
Photon Emission by an Electron in a Constant Background Field Modeling a Lorentz-Noninvariant Vacuum
Authors: Borisov Anatoly V
Published: July 2024

We considered the radiative transition of an electron due to its spin-flip in a constant background field of the quasielectric type, which models the Lorentz-noninvariant vacuum. The power and probability of radiation and the degree of its linear polarization are calculated. It is shown that this radiative transition leads to the complete polarization of the initially unpolarized electron beam. The investigated effects increase with increasing electron energy.
Optimizing Total Knee Arthroplasty Rehabilitation With Telehealth Physical Activity Behavior Change Intervention: A Randomized Clinical Trial
Authors: Christiansen Cory L , Kline Paul W , Anderson Chelsey B , Melanson Edward L , Sullivan William J , Richardson Vanessa L , Juarez-Colunga Elizabeth , Stevens-Lapsley Jennifer E
Published: July 2024

Objective

Conventional total knee arthroplasty (TKA) rehabilitation has little impact on sedentary lifestyles that have negative long-term health consequences. The purpose of this trial was to determine the effect of telehealth-based physical activity behavior change intervention on physical activity and functional outcomes following TKA.

Methods

This study was a 2-arm, parallel randomized controlled superiority trial at a regional Veterans Affairs medical center. The participants were 92 US military veterans (mean age = 65.7 [SD =7.8] y) undergoing unilateral TKA. The Physical Activity Behavior Change (PABC) intervention included telehealth-based self-management training (10 30-minute sessions) delivered over 12 weeks. The control intervention included telehealth-based health education sessions that matched PABC frequency and duration. Both groups participated in standardized conventional outpatient rehabilitation. Physical activity, measured as average daily step count, was the primary outcome. Secondary outcomes were Life-Space Assessment questionnaire, 30-Second Chair-Stand test, Timed “Up & Go” Test, 6-Minute Walk Test, Western Ontario and McMaster Universities Osteoarthritis Index, and Veterans RAND 12-Item Health Survey. The Self Efficacy for Exercise scale and daily time spent in different postures (sitting/lying, standing, stepping) were exploratory variables. Outcomes were measured at baseline (before surgery), mid-intervention (8 weeks after surgery), after the intervention (14 weeks after surgery; primary endpoint), and follow-up (38 weeks after surgery).

Results

The PABC group had an estimated 931 (95% CI = 42–1819) more daily steps than the control group from baseline to 14 weeks, though a between-group effect was not sustained at 38 weeks. There were no group differences in secondary outcomes. Participants included only military veterans using Veterans Health Administration services. The intervention targeted self-management and did not include peer support.

Conclusion

The PABC intervention improved physical activity for veterans recovering from unilateral TKA at 14 weeks after surgery, though the effect was not sustained at 38 weeks. Physical function improved with rehabilitation but was not different between groups, indicating that physical function was not a primary driver of physical activity behavior.

Impact

Conventional TKA rehabilitation has a negligible effect on free-living physical activity, which is relevant to long-term health outcomes. This trial identified telehealth physical activity self-management as effective in addressing activity behaviors, separate from conventional rehabilitation strategies.
Training an Anti-Ableist Physical Therapist Workforce: Critical Perspectives of Health Care Education That Contribute to Health Inequities for People With Disabilities
Authors: Whalen Smith Cara N , Havercamp Susan M , Tosun Leyla , Shetterly Samantha , Munir Armin , Kennedy Winston , Feldner Heather A , Herrman Deana , Sloane Bethany M , Weinstein Faye H
Published: July 2024

Americans with disabilities represent the largest historically underserved and marginalized health disparity population in the United States. This perspective piece will raise the awareness of physical therapist faculty and clinicians on gaps in health care provider knowledge about disability and provide actionable strategies, frameworks, and resources available to improve disability competence to make changes in clinical education and practice. In this perspective piece, 3 contributions are made. First, health disparities experienced by Americans with disabilities as a result of health care providers’ biased assumptions about disability and lack of disability competence are described through an in-depth illustration of lived experiences of people with disabilities. Second, a discussion of disability competence in physical therapist education is provided. Finally, critical and evidence–based insights and actionable frameworks and resources to address disability competence training gaps and to promote anti-ableist practice are provided.
Training a convolutional neural network for real–bogus classification in the ATLAS survey
Authors: Weston J G , Smith K W , Smartt S J , Tonry J L , Stevance H F
Published: July 2024

We present a convolutional neural network (CNN) for use in the real–bogus classification of transient detections made by the Asteroid Terrestrial-impact Last Alert System (ATLAS) and subsequent efforts to improve performance since initial development. In transient detection surveys, the number of alerts made outstrips the capacity for human scanning, necessitating the use of machine learning aids to reduce the number of false positives presented to annotators. We take a sample of recently annotated data from each of the three operating ATLAS telescope with $\sim$340 000 real (known transients) and $\sim$1030 000 bogus detections per model. We retrained the CNN architecture with these data specific to each ATLAS unit, achieving a median false positive rate (FPR) of 0.72 per cent for a 1.00 per cent missed detection rate. Further investigations indicate that if we reduce the input image size it results in increased FPR. Finally architecture adjustments and comparisons to contemporary CNNs indicate that our retrained classifier is providing an optimal FPR. We conclude that the periodic retraining and readjustment of classification models on survey data can yield significant improvements as data drift arising from changes in the optical and detector performance can lead to new features in the model and subsequent deteriorations in performance.
Long-term outcomes of childhood-onset systemic lupus erythematosus
Authors: Mirguet Anne , Aeschlimann Florence A , Lemelle Irene , Jaussaud Roland , Decker Paul , Moulinet Thomas , Mohamed Shirine , Quartier Pierre , Hofer Michael , Boyer Olivia , Belot Alexandre , Hummel Aurélie , Costedoat-Chalumeau Nathalie , Bader-Meunier Brigitte
Published: July 2024

Objective

Data on the long-term outcome of patients with childhood-onset SLE (cSLE) are scarce. Aims of this study were to describe the long-term outcomes of cSLE and to identify factors associated with the development of damage and persistent disease activity.

Methods

We conducted a retrospective multicentre study using data from the PEDIALUP registry of the Juvenile Inflammatory Rheumatism (JIR) cohort database. Demographic characteristics, clinical manifestations, laboratory, radiological, histological and treatment data were collected from medical records during follow-up.

Results

A total of 138 patients with cSLE, diagnosed between 1971 and 2015, were included. With a median follow-up of 15.4 [9.6–22.4] years, 51% of patients had a SLICC-damage index (DI) score ≥1 at last follow-up with the musculoskeletal, cutaneous, renal, neurological and cardiovascular damage being the most common manifestations. The proportion of patients with a SLICC-DI score ≥1 increased significantly with the duration of the follow-up (P < 0.001). On multivariate analysis, duration of follow-up was associated with increased risk of cumulative damage (OR 1.08, 95% CI 1.01, 1.15, P = 0.035). At the last visit, 34% of patients still had active disease with a SLEDAI score of ≥6. On multivariate analysis, sub-Saharan African ethnicity was associated with 7-fold increased odds of having active disease at the last visit compared with Caucasians (OR 7.44, 95% CI 2.24, 24.74, P = 0.0002).

Conclusion

The prevalence of damage remains high in patients with cSLE even when the diagnosis of cSLE has been made in the recent decades.
A double-blind, placebo-controlled, randomized multiple dose phase 1b trial of a CDK4/6 inhibitor, TCK-276, in patients with active rheumatoid arthritis
Authors: Tasaki Daisuke , Tsuruda Kazuoki , Sun Shosho , Tsumura Yoshinori , Asano Satoshi , Suzuki Yuki , Tsujimoto Shunsuke , Miura Daishiro , Sato Hiroaki
Published: July 2024

Objective

The purpose of this study was to evaluate the safety, tolerability, pharmacokinetics and efficacy (as an exploratory endpoint) of TCK-276, a novel CDK4/6 inhibitor, after multiple oral doses for 7 days in patients with active RA.

Methods

This multicentre, randomized, placebo-controlled, dose-ascending, double-blind, phase 1b, multiple-dose study included 32 patients with active RA in four cohorts of 8 patients (6 active and 2 matching placebo), each receiving an oral dose of TCK-276 or matching placebo for 7 days (once daily). The doses of TCK-276 were 10, 25, 75 and 175 mg/day. Safety and pharmacokinetic endpoints, and exploratory disease activity parameters for RA were assessed.

Results

There were no deaths, serious adverse events, notable clinically meaningful laboratory findings (including haematological changes), clinically meaningful vital sign changes or clinically meaningful ECG or cardiac telemetry changes. TCK-276 was rapidly absorbed and the half-life time ranged approximately from 6 to 12 h. No obvious accumulation was observed, and the increase in TCK-276 exposure was dose proportional. At day 7, DAS28-CRP responses (EULAR good or moderate responses) were observed in 40%, 80% and 66.7% at 25, 75 and 175 mg/day TCK-276, respectively, vs 12.5% in placebo; ACR20 responses were 33.3%, 60% and 50%, respectively, vs none in placebo.

Conclusion

TCK-276 (≤175 mg) was well tolerated with no clinically meaningful safety signals in patients with active RA. Together with the preliminary efficacy (≥25 mg/day), these data warrant further study of TCK-276 for the treatment of active RA.

Trial registration

ClinicalTrails.gov, NCT05437419.
The impact of periodontitis and periodontal treatment on rheumatoid arthritis outcomes: an exploratory clinical trial
Authors: Silva Daniela S , de Vries Charlotte , Rovisco João , Serra Sara , Kaminska Marta , Mydel Piotr , Lundberg Karin , da Silva José António P , Baptista Isabel P
Published: July 2024

Objective

Studies suggest RA patients could benefit from periodontal treatment. However, published data are inconsistent, and there is a need for better-controlled research. Our study aims to address these limitations.

Methods

In this exploratory randomized delayed-start study, 22 RA patients with moderate/severe periodontitis were subjected to full-mouth debridement. Periodontal and rheumatological assessments, including measuring anti-cyclic citrullinated peptide 2 (CCP2) IgG levels, were performed at baseline (V1), 2 months (V2) and 6 months (V3) after steps 1 and 2 of periodontal therapy. Primary outcome was changes in DAS for 28 joints (DAS28) between V2 and V1. Secondary outcomes were changes in other rheumatological or periodontal clinical parameters (V2 or V3-V1).

Results

RA disease activity was significantly higher in RA patients with severe periodontitis compared with moderate periodontitis at baseline, with significant positive correlations between several rheumatological and periodontal parameters. After periodontal treatment, RA patients with severe, but not moderate, periodontitis demonstrated significant improvements in DAS28 (ΔV2-V1, P = 0.042; ΔV3-V1, P = 0.001) and significant reduction in anti-CCP2 IgG levels at V3 (P = 0.032).

Conclusion

Periodontal treatment is locally effective in patients with RA and impacts RA disease activity and anti-CCP2 antibody levels in patients with severe periodontitis. Hence, our data suggest that periodontal assessment and treatment should be integrated in the management of RA patients within a treat-to-target strategy.

Trial registration

isrctn.com, http://www.isrctn.com, ISRCTN 17950307.
Avacopan for anti-neutrophil cytoplasm antibodies-associated vasculitis: a multicentre real-world study
Authors: Gabilan Charlotte , Belliere Julie , Moranne Olivier , Pfirmann Pierre , Samson Maxime , Delattre Vincent , Thoreau Benjamin , Gueutin Victor , Boyer Annabel , Leurs Amélie , Astouati Quentin , Ronsin Charles , Quemeneur Thomas , Ribes David , Karras Alexandre , Faguer Stanislas
Published: July 2024

Objectives

Avacopan, a selective C5aR1 inhibitor, recently emerged as a glucocorticoid (GCs) sparing agent in anti-neutrophil cytoplasm antibodies (ANCA)-associated vasculitis (AAV). We aim to evaluate the tolerance and efficacy of avacopan given outside randomized clinical trials or with severe kidney involvement.

Methods

In this multicentre retrospective study, we reviewed the clinical charts of patients with AAV and contraindication to high dose of GCs who received avacopan 30 mg b.i.d plus standard-of-care regimen owing to the French early access program between 2020 and 2023. Efficacy and safety data were recorded using a standardized case report form.

Results

Among the 31 patients (median age 72 years), 10 had a relapsing AAV, 20 had anti-myeloperoxidase antibodies and 30 had kidney vasculitis. Induction regimen included rituximab (n = 27), cyclophosphamide (n = 2) or both (n = 2). Five patients did not receive GCs. Despite rapid GCs tapering (which were withdrawn in 23 patients before month 3), 25 patients (81%) had a favourable outcome and no severe adverse event. The estimated glomerular filtration rate increased from 19 [15; 34] to 35 mL/min/1.73 m2 [23; 45] at month 12 (P < 0.05), independently of kidney biopsies findings. One patient developed refractory AAV and two had a relapse while receiving avacopan. At month 12, ANCA remained positive in 10/18 patients (55.5%). Two patients developed severe adverse events leading to a withdrawal of avacopan (hepatitis and age-related macular degeneration).

Conclusions

The GCs’ sparing effect of avacopan was confirmed, even in patients with severe kidney vasculitis, but further studies are required to identify the optimal dosing of GCs when avacopan is used.
Contracting when enforcement is weak: evidence from an audit study
Authors: Iyer Rajkamal , Schoar Antoinette
Published: July 2024

How are contracts structured in the presence of relationship-specific investments when legal enforcement is weak? Using a new audit methodology, we show that simple financial contracts in combination with social norms and reputation concerns can sustain relationship-specific transactions. Wholesalers in the market for pens in India use upfront payments rather than increased risk premiums to mitigate risks arising from relationship-specific investments. Upfront payments for printed pens cover only 40 percent of the production costs, highlighting the importance of upfront payments as a screening device. Ex-post, renegotiation is more likely for printed pens, but in a substantial fraction of cases, renegotiation fails.
Societal guardrails for AI? Perspectives on what we know about public opinion on artificial intelligence
Authors: Eom Dayeon , Newman Todd , Brossard Dominique , Scheufele Dietram A
Published: July 2024

Artificial intelligence (AI) not only holds immense potential for improving quality of life but also creates complex ethical, legal, and societal challenges. AI has gained significant attention recently, particularly by introducing ChatGPT and other emerging applications. This paper offers a comprehensive overview of public opinion trends on AI, drawing from fifteen surveys conducted in the USA over the past 4 years. The findings reveal a divided American public regarding AI’s applications. Americans generally call for more regulation and government oversight, expressing a need for increased measures before fully embracing AI. While specific AI applications, such as skin cancer screening, have been welcomed, most Americans emphasize the importance of addressing societal concerns such as racial bias and inequities before the widespread implementation of AI. The evolving landscape of AI necessitates ongoing monitoring of public sentiment and the consideration of societal implications.
Conspiracy theories and the COVID-19 pandemic in Japan: the rise, radicalization, and fall (?) of YamatoQ-kai
Authors: Demelius Yoko , Szczepanska Kamila
Published: July 2024

This article investigates how conspiracy theories, spirituality, and resistance against pandemic-mitigation measures became intertwined during the coronavirus disease 2019 (COVID-19) crisis in Japan. Utilizing selected concepts from social movement theories (SMT), this case study-driven exploratory analysis focuses on the activities of YamatoQ-kai, a civil society organization that originated in a group of conspiracy-theory influencers and whose activities included the dissemination of an anti-immunization agenda. By analysing online posts on the organization’s homepage and journalistic reports on the organization, the article illuminates the underlying implications of the conspiracy theorists’ activism and demonstrates how the group adopted QAnon’s conspiracy rhetoric whilst taking a Japanized form. Second, it explains YamatoQ’s pivotal place amongst the Japanese societal actors espousing vaccine-hesitant attitudes. Finally, it shows how the group—as an unconventional case of conspirituality—created tangible experiences for followers and demonstrates the affective impact of group solidarity. In this way, the article’s findings contribute to closing the research gaps in scholarship on conspiracy theories, vaccine scepticism, and conspirituality.
Austria: Private foundations in Austria—between consolidation and reform
Authors: Schauer Martin , Nueber Michael
Published: July 2024

Austrian private foundation law, which was 30 years old in 2023, is currently going through a phase of consolidation. Private foundations are also a constant concern for the Austrian courts in conflict situations. In this article the authors take a closer look at the Austrian private foundation as an instrument of asset protection in case of divorce, the interpretation of foundation documents, and the composition of a possible council. They also make an assessment of the way ahead.
Artificial intelligence system for outcome evaluations of human in vitro fertilization-derived embryos
Authors: Sun Ling , Li Jiahui , Zeng Simiao , Luo Qiangxiang , Miao Hanpei , Liang Yunhao , Cheng Linling , Sun Zhuo , Tai Wa Hou , Han Yibing , Yin Yun , Wu Keliang , Zhang Kang
Published: July 2024

Background:

In vitro fertilization (IVF) has emerged as a transformative solution for infertility. However, achieving favorable live-birth outcomes remains challenging. Current clinical IVF practices in IVF involve the collection of heterogeneous embryo data through diverse methods, including static images and temporal videos. However, traditional embryo selection methods, primarily reliant on visual inspection of morphology, exhibit variability and are contingent on the experience of practitioners. Therefore, an automated system that can evaluate heterogeneous embryo data to predict the final outcomes of live births is highly desirable.

Methods:

We employed artificial intelligence (AI) for embryo morphological grading, blastocyst embryo selection, aneuploidy prediction, and final live-birth outcome prediction. We developed and validated the AI models using multitask learning for embryo morphological assessment, including pronucleus type on day 1 and the number of blastomeres, asymmetry, and fragmentation of blastomeres on day 3, using 19,201 embryo photographs from 8271 patients. A neural network was trained on embryo and clinical metadata to identify good-quality embryos for implantation on day 3 or day 5, and predict live-birth outcomes. Additionally, a 3D convolutional neural network was trained on 418 time-lapse videos of preimplantation genetic testing (PGT)-based ploidy outcomes for the prediction of aneuploidy and consequent live-birth outcomes.

Results:

These two approaches enabled us to automatically assess the implantation potential. By combining embryo and maternal metrics in an ensemble AI model, we evaluated live-birth outcomes in a prospective cohort that achieved higher accuracy than experienced embryologists (46.1% vs. 30.7% on day 3, 55.0% vs. 40.7% on day 5). Our results demonstrate the potential for AI-based selection of embryos based on characteristics beyond the observational abilities of human clinicians (area under the curve: 0.769, 95% confidence interval: 0.709–0.820). These findings could potentially provide a noninvasive, high-throughput, and low-cost screening tool to facilitate embryo selection and achieve better outcomes.

Conclusions:

Our study underscores the AI model’s ability to provide interpretable evidence for clinicians in assisted reproduction, highlighting its potential as a noninvasive, efficient, and cost-effective tool for improved embryo selection and enhanced IVF outcomes. The convergence of cutting-edge technology and reproductive medicine has opened new avenues for addressing infertility challenges and optimizing IVF success rates.
Is unicompartmental knee arthroplasty a better choice than total knee arthroplasty for unicompartmental osteoarthritis? A systematic review and meta-analysis of randomized controlled trials
Authors: Xia Kuanyu , Min Lang , Xie Wenqing , Yang Guang , Yon Dong Keon , Lee Seung Won , Koyanagi Ai , Jacob Louis , Smith Lee , Shin Jae Il , Rahmati Masoud , Xiao Wenfeng , Li Yusheng
Published: July 2024

Background:

The choice of unicompartmental knee arthroplasty (UKA) vs. total knee arthroplasty (TKA) in the surgical treatment of knee osteoarthritis (KOA) remains controversial. This study aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the clinical results of UKA and TKA for treating unicompartmental KOA.

Methods:

PubMed, Embase, and the Cochrane Library were systematically searched for articles published up to January 2, 2023. The literature was rigorously screened to include only RCTs comparing UKA and TKA for unicompartmental KOA. A systematic review and meta-analysis were performed to calculate the mean difference (MD), relative risk (RR), and 95% confidence interval (CI) according to the Cochrane standards.

Results:

Thirteen publications involving 683 UKAs and 683 TKAs were analyzed. Except for one study with a follow-up period of 15 years, all outcome measures reported were within 5 years of follow-up. Meta-analysis showed better knee recovery (MD: 1.23; 95% CI: 1.01–1.45; P <0.00001), greater knee function (MD: 1.78; 95% CI: 0.34–3.22; P = 0.02), less pain (MD: 0.75; 95% CI: 0.43–1.06; P <0.00001), and better health status (MD: 3.75; 95% CI: 0.81–6.69; P = 0.01) after UKA than TKA. However, considering the minimal clinically important difference values for these variables, the findings were not clinically relevant. Moreover, UKA patients had fewer complications (RR: 0.59; 95% CI: 0.45–0.78; P = 0.0002) and shorter hospital stays (MD: –0.89; 95% CI: –1.57 to –0.22; P = 0.009) than did TKA patients. There were no statistically significant differences in terms of postoperative range of movement, revision, failure, operation time, and patient satisfaction.

Conclusions:

In terms of clinical efficacy, there was no obvious advantage of UKA over TKA in the surgical treatment of knee OA when considering the minimal clinically important difference. The main advantage of UKA over TKA is that it leads to fewer complications and a shorter length of hospital stay. It is ideal to perform prospective studies with longer follow-up periods to fully evaluate the long-term efficacy and safety of the two procedures in the future.
Association between coronary artery stenosis and myocardial injury in patients with acute pulmonary embolism: A case-control study
Authors: Yang Yinjian , Liu Chao , Ma Jieling , Zhu Xijie , Ma Jingsi , Lu Dan , Yan Xinxin , Gao Xuan , Wang Jia , Wang Liting , Zhang Sijin , Li Xianmei , Wu Bingxiang , Sun Kai , Mao Yimin , Xu Xiqi , Lian Tianyu , Cheng Chunyan , Jing Zhicheng
Published: July 2024

Background:

The potential impact of pre-existing coronary artery stenosis (CAS) on acute pulmonary embolism (PE) episodes remains underexplored. This study aimed to investigate the association between pre-existing CAS and the elevation of high-sensitivity cardiac troponin I (hs-cTnI) levels in patients with PE.

Methods:

In this multicenter, prospective case-control study, 88 cases and 163 controls matched for age, sex, and study center were enrolled. Cases were patients with PE with elevated hs-cTnI. Controls were patients with PE with normal hs-cTnI. Coronary artery assessment utilized coronary computed tomographic angiography or invasive coronary angiography. CAS was defined as ≥50% stenosis of the lumen diameter in any coronary vessel >2.0 mm in diameter. Conditional logistic regression was used to evaluate the association between CAS and hs-cTnI elevation.

Results:

The percentage of CAS was higher in the case group compared to the control group (44.3% [39/88] vs. 30.1% [49/163]; P = 0.024). In multivariable conditional logistic regression model 1, CAS (adjusted odds ratio [OR], 2.680; 95% confidence interval [CI], 1.243–5.779), heart rate >75 beats/min (OR, 2.306; 95% CI, 1.056–5.036) and N-terminal pro-B type natriuretic peptide (NT-proBNP) >420 pg/mL (OR, 12.169; 95% CI, 4.792–30.900) were independently associated with elevated hs-cTnI. In model 2, right CAS (OR, 3.615; 95% CI, 1.467–8.909) and NT-proBNP >420 pg/mL (OR, 13.890; 95% CI, 5.288–36.484) were independently associated with elevated hs-cTnI.

Conclusions:

CAS was independently associated with myocardial injury in patients with PE. Vigilance towards CAS is warranted in patients with PE with elevated cardiac troponin levels.
Perceptions of general surgery residents at military treatment facilities: Excellent training with crisis of confidence
Authors: West Erin , Green Kristina , Horton John , Gillern Suzanne M. , Faler Byron , Krell Robert W. , Nelson Daniel , Krzyzaniak Michael J. , Vicente Diego , Choi Pamela M.
Published: July 2024

BACKGROUND

The declining operative volume at Military Treatment Facilities (MTFs) has resulted in Program Directors finding alternate civilian sites for resident rotations. The continued shift away from MTFs for surgical training is likely to have unintended negative consequences.

METHODS

An anonymous survey was generated and sent to the program directors of military general surgery training programs for distribution to their residents.

RESULTS

A total of 42 residents responded (response rate 21%) with adequate representation from all PGY years. Ninety-five percent of residents believed that their programs provided the training needed to be a competent general surgeon. However, when asked about career choices, only 30.9% reported being likely/extremely likely to remain in the military beyond their initial service obligation, while 54.7% reported that it was unlikely/extremely unlikely and 19% reported uncertainty. Eighty-eight percent reported that decreasing MTF surgical volume directly influenced their decision to stay in the military, and half of respondents regretted joining the military. When asked to assess their confidence in the military to provide opportunities for skill sustainment as a staff surgeon, 90.4% were not confident or were neutral.

CONCLUSION

Although military surgical residents have a generally positive perception of their surgical training, they also lack confidence in their future military surgical careers. Our findings suggest that declining MTF surgical volume will likely negatively impact long-term retention of military surgeons and may negatively impact force generation for Operational Commander.

LEVEL OF EVIDENCE

Prognostic and Epidemiological, Level IV.
Identification of whole-body reaching movement phenotypes in young and older active adults: an unsupervised machine learning approach
Authors: Pfaff Michel , Casteran Matthieu
Published: July 2024

Studies reported age-related motor control modifications in whole-body movement in several aspects of spatiotemporal movement organization by comparing young and older adults. However, studies on motor control involve high complexity and high-dimensional data of different natures, in which machine learning has proved to be effective. Furthermore, conventional studies focus on comparisons of movement parameters based on a priori grouping, whereas unsupervised machine learning allows the identification of inherent groupings within the dataset. The current investigation was carried out by using the unsupervised machine learning on motor control features across age-groups. An important question was whether we could identify different movement patterns based on motor control features and whether they were age-dependent or independent. We investigated motor control parameters variations in a whole-body reaching movement across young and active older adults including woman and man (n=19). We applied the K-means clustering algorithm to segment the kinematic data (21 features) of all individuals. We propose a methodology applying the latest recommendations for clustering methods in the field of whole-body movement motor control. Analysis revealed two distinct motor control patterns which were age independent. The first pattern exhibited higher shoulder, ankle and knee angular excursions, along with a higher vertical velocity of center of mass (CoM), compared to the second pattern, which had higher hip and back angular excursions, along with a lower vertical velocity CoM. The clustering methodology demonstrated its effectiveness to identify distinct motor patterns based solely on motor control features independently of age-grouping.

Significance Statement

K-means clustering algorithm enabled us to identify two distinct age-independent motor patterns: a first pattern with high shoulder, ankle and knee angular excursions, and vertical velocity of CoM; a second pattern with high hip and back angular excursions and low vertical velocity of CoM.

Demonstrates how unsupervised machine learning can identify motor patterns and proposes a methodology to apply it in the field of whole-body movement motor control.

Proves the complementary contribution of unsupervised machine learning to conventional approach for motor control studies, which enables to process the high complexity and dimensionality of movements.

Advances understanding of motor behaviours through unsupervised machine learning analysis of whole-body reaching movements.
Tempo and mode of diversification of the red devil spiders (Araneae: Dysderidae) of the Canary Islands
Authors: Bellvert Adria , Pollock Laura , Kaliontzopoulou Antigoni , Arnedo Miquel A.
Published: July 2024

The study of adaptive radiations has shed light on our current understanding of evolution. However, previous studies examining the mode in which species diversified, how diversification rates varied, and how ecological specialization affected these processes have found few different results across different taxa and geographic and ecological systems, showing how complex this process is. To gain a more complete picture of how species evolve, additional model systems that encompass alternative ecological requirements are needed. Here, we present the results of a study aimed to unravel the diversification mode and evolutionary drivers of the spider genus Dysdera, the red devil spiders, endemic to the Canary Islands. These species exhibit remarkable phenotypic variability in their mouthparts, which has been related to different levels of specialization in the predation of isopods. We explored patterns of linage diversification and assessed the role of trophic specialization as a driver of species diversification. Additionally, we used climatic variables, occurrence data and morphological information to unravel the underlying mode of speciation by means of joint species distribution models and age-range correlation methods. Our results reveal that red devil spiders underwent an early burst of diversification, followed by a slowdown of diversification rates, which is a hallmark of adaptive radiation. We also found evidence that the trophic morphology shaped diversification, with specialist species exhibiting higher rates of diversification. Finally, our analyses suggest that speciation occurred mostly in allopatry, with subsequent secondary sympatry following range expansion.
3D Brain Vascular Niche Model Captures Invasive Behavior and Gene Signatures of Glioblastoma
Authors: Lee Vivian K. , Tejero Rut , Silvia Nathaniel , Sattiraju Anirudh , Ramakrishnan Aarthi , Shen Li , Wojcinski Alexandre , Kesari Santosh , Friedel Roland H. , Zou Hongyan , Dai Guohao
Published: July 2024

Glioblastoma (GBM) is a lethal brain cancer with no effective treatment; understanding how GBM cells respond to tumor microenvironment remains challenging as conventional cell cultures lack proper cytoarchitecture whilein vivoanimal models present complexity all at once. Developing a culture system to bridge the gap is thus crucial. Here, we employed a multicellular approach using human glia and vascular cells to optimize a 3-dimensional (3D) brain vascular niche model that enabled not only long-term culture of patient derived GBM cells but also recapitulation of key features of GBM heterogeneity, in particular invasion behavior and vascular association. Comparative transcriptomics of identical patient derived GBM cells in 3D andin vivoxenotransplants models revealed that glia-vascular contact induced genes concerning neural/glia development, synaptic regulation, as well as immune suppression. This gene signature displayed region specific enrichment in the leading edge and microvascular proliferation zones in human GBM and predicted poor prognosis. Gene variance analysis also uncovered histone demethylation and xylosyltransferase activity as main themes for gene adaption of GBM cellsin vivo. Furthermore, our 3D model also demonstrated the capacity to provide a quiescence and a protective niche against chemotherapy. In summary, an advanced 3D brain vascular model can bridge the gap between 2D cultures andin vivomodels in capturing key features of GBM heterogeneity and unveil previously unrecognized influence of glia-vascular contact for transcriptional adaption in GBM cells featuring neural/synaptic interaction and immunosuppression.
HERMES: Holographic Equivariant neuRal network model for Mutational Effect and Stability prediction
Authors: Visani Gian Marco , Pun Michael N. , Galvin William , Daniel Eric , Borisiak Kevin , Wagura Utheri , Nourmohammad Armita
Published: July 2024

Predicting the stability and fitness effects of amino-acid mutations in proteins is a cornerstone of biological discovery and engineering. Various experimental techniques have been developed to measure mutational effects, providing us with extensive datasets across a diverse range of proteins. By training on these data, machine learning approaches have advanced significantly in predicting mutational effects. Here, we introduce HERMES, a 3D rotationally equivariant structure-based neural network model for mutation effect prediction. Pre-trained to predict amino-acid propensities from their surrounding 3D structure atomic environments, HERMES can be efficiently fine-tuned to predict mutational effects, thanks to its symmetry-aware parameterization of the output space. Benchmarking against other models demonstrates that HERMES often outperforms or matches their performance in predicting mutation effects on stability, binding, and fitness, using either computationally or experimentally resolved protein structures. HERMES offers a versatile suit of tools for evaluating mutation effects and can be easily fine-tuned for specific predictive objectives using our open-source code.
Immunisation of chickens with inactivated and/or infectious H9N2 avian influenza virus leads to differential immune B cell repertoire development
Authors: Dascalu Stefan , Sealy Joshua E. , Sadeyen Jean-Remy , Flammer Patrik G. , Fiddaman Steven , Preston Stephen G. , Dixon Robert J. , Bonsall Michael B. , Smith Adrian L. , Iqbal Munir
Published: July 2024

Avian influenza viruses (AIVs) are a major economic burden to the poultry industry, and pose serious zoonotic risk, with human infections being reported every year. To date, the vaccination of birds remains the most important method for the prevention and control of AIV outbreaks. Most national vaccination strategies against AIV infection use whole-virus inactivated vaccines, which predominantly trigger a systemic antibody-mediated immune response. There are currently no studies that have examined the antibody repertoire of birds that were infected with and/or vaccinated against AIV. To this end, we evaluate the changes in the H9N2-specific IgM and IgY repertoires in chickens subjected to vaccination(s) and/or infectious challenge. We show that a large proportion of the IgM and IgY clones were shared across multiple individuals, and these public clonal responses are dependent on both the immunisation status of the birds and the specific tissue that was examined. Furthermore, analysis reveals specific clonal expansions which are restricted to particular H9N2 immunisation regimes. These results indicate that both the nature and number of immunisations are important drivers of the antibody responses and repertoire profiles in chickens following H9N2 antigenic stimulation. We discuss how the repertoire biology of avian B cell responses may affect the success of AIV vaccination in chickens, in particular the implications of public versus private clonal selection.
Unraveling the immunological roles of serum amyloid A3 in aortic immune cell subsets during atherosclerosis progression
Authors: Chou Tzu-Yin , Ye Yu-Zhen , Lin I-Jung , Lien Chia-Jung , Yang Chen-Hsuan , Chen Yen-Ting , Chao Pei-An , Lin Jian-Da
Published: July 2024

Atherosclerosis is a growing concern in developed nations, necessitating the identification of therapeutic targets for advancing personalized medicine. Serum amyloid A3 (Saa3) has been linked to accelerated plaque progression by affecting cholesterol metabolism and modulation of inflammation. We hypothesize that knocking outSaa3(Saa3-/-) could mitigate plaque development by regulating aortic immune cell subsets during atherosclerosis progression. Using a murine model, we induced atherosclerosis via a gain-of-function mutant PCSK9-encoding adeno-associated viral vector (AAVmPCSK9) in wild-type (WT) andSaa3-/-mice. Single-cell RNA sequencing revealed thatSaa3-/-mice developed smaller plaques than WT mice, with significant differences in aortic immune cell populations, particularly aortic macrophages.Saa3-/-macrophages, characterized by highGpnmb,Lpl, andSpp1expressions, predominated over the typical resident foamy macrophages in WT mice.Saa3-/-mice also showed enhanced intercellular immune communication and increased signaling interactions, suggesting a shift towards an anti-inflammatory and tissue-repairing phenotype. Our study highlights the potential ofSaa3as a therapeutic target for atherosclerosis.
Molecular profile, source and lineage restriction of stem cells in an annelid regeneration model
Authors: Stockinger Alexander W , Adelmann Leonie , Fahrenberger Martin , Ruta Christine , Ozpolat B. Duygu , Milivojev Nadja , Balavoine Guillaume , Raible Florian
Published: July 2024

Regeneration of missing body parts can be observed in diverse animal phyla, but it remains unclear to which extent these capacities rely on shared or divergent principles. Research into this question requires detailed knowledge about the involved molecular and cellular principles in suitable reference models. By combining single-cell RNA sequencing and mosaic transgenesis in the marine annelid Platynereis dumerilii, we map cellular profiles and lineage restrictions during posterior regeneration. Our data reveal cell-type specific injury responses, re-expression of positional identity factors, and the re-emergence of stem cell signatures in multiple cell populations. Epidermis and mesodermal coelomic tissue produce distinct posterior stem cells (PSCs) in the emerging blastema. A novel mosaic transgenesis strategy reveals both developmental compartments and lineage restrictions during regenerative growth. Our work supports the notion that posterior regeneration involves dedifferentiation, and reveals molecular and mechanistic parallels between annelid and vertebrate regeneration.
Reproductive fluids enabling cryptic female choice of paternity do not induce concomitant gamete-mediated paternal effects in embryos of hybridizing salmonid fishes
Authors: Lantiegne Tyler H. , Wagle Ranjan , Purchase Craig F.
Published: July 2024

Post-mating sexual selection in the form of cryptic female choice provides opportunities for females to bias paternity to favor preferred males. However, little is known regarding how cryptic female choice might affect offspring outside of paternity, via female modified changes to sperm environmental experience. Gamete-mediated paternal effects are widespread, and female alteration of sperm experience may play an unrecognized role in shaping cryptic female choice. Using hybridizing salmonid fishes that have documented female mediated conspecific sperm preference via differential upregulation of sperm swimming performance, we created artificial split-brood and split-ejaculate fertilizations to determine if sperm experience in different conditions influences offspring development. Prior to contact with eggs, sperm experienced 20s of swimming in either water, or water with the addition of conspecific ovarian fluid or heterospecific ovarian fluid. Over 186 days, we quantified hatch timing, hatchling size, and developmental stage and found that differential sperm experience created biologically irrelevant (average effect size of 1.06%) changes on offspring development, which were much smaller than the effects of hybridization itself (average effect size of 10.45% for the species of the father). Since ovarian fluid drastically changes sperm experience when compared to water, we conclude that females can use ovarian fluid to bias paternity without concomitant consequences to offspring development.
Optimization of gene knockout approaches and practical solutions to sgRNA selection challenges in hPSCs with inducible Cas9 system
Authors: Ni Jie , Gong Junhao , Ran Yuqing , Bai Rui , Huang Pufeng , Zheng Zihe , Zhou Meng , You Yi , Lan Feng , Liu Xujie
Published: July 2024

Rationale

CRISPR/Cas9 has been extensively used to knock out genes, allowing the study of genetic loss-of-function in human pluripotent stem cells (hPSCs). However, the current use of the Cas9-sgRNA plasmid or iCas9 system for gene editing in hPSCs has resulted in limited and inconsistent editing efficiency, as well as labor-intensive work. Additionally, identifying single-guide RNAs (sgRNAs) with high cleavage efficiency and distinguishing them from ineffective ones, which efficiently induce frameshift INDELs (Indels and Deletions) but fail to eliminate target proteins expression, are major challenges in gene knockout experiments.

Methods

This study addresses above issues using an optimized doxycycline-induced spCas9-expressing hPSCs (hPSCs-iCas9) system. We initially developed this system by optimizing a number of parameters to maximize INDELs introducing efficiency in hPSCs-iCas9 cells. The INDELs determined by this system were then compared to predicted scores from three cleavage efficiency scoring algorithms to validate the algorithms’ accuracy and consistency. Furthermore, we conducted gene knockout using a set of sgRNAs targeting different exons of the ACE2 gene to achieve approximately 80% INDELs for each targeting locus. Western blotting was then performed to detect ACE2 protein expression levels, enabling the identification of potentially ineffective sgRNAs.

Results

Several critical factors, including cell tolerance to nucleofection stress, sgRNA stability, nucleofection frequency, and the cell-to-sgRNA ratio, were found to have significant impact on editing efficiency in hPSCs-iCas9. Fine-tuning these parameters markedly improved this efficiency, resulting in up to 93% INDELs for single gene knockout. The three scoring algorithms exhibited significant differences or even conflicts in scoring cleavage efficiency. Through comparing experimental observations to predicted scores, we discovered that the Benchling algorithm outperformed the other two in terms of accuracy and consistency. Furthermore, a sgRNA targeting exon 2 of ACE2 gene was quickly identified as ineffective, as evidenced by the edited cells pool containing 80% INDELs while ACE2 protein expression retained unchanged detected by Western blot.

Conclusion

The findings of this study offer valuable insights into the optimal design of gene knockout experiments in hPSCs and provide practical solutions to sgRNA selection challenges for gene editing.
Multi-Model Machine Learning for Automated Identification of Rice Diseases Using Leaf Image Data
Authors: Tiwari Rovin , Patel Jaideep , Khan Nikhat Raza , Dadhich Ajay , Jain Jay Kumar
Published: July 2024

Purpose

Rice is grown almost everywhere in the world but is notably prevalent in Asian nations where it serves as the main food source for nearly half of the world’s population. Yet, enduring agricultural problems like various rice diseases have been a problem for farmers and planting specialists for ages. A fast, efficient, less expensive, and reliable approach to detecting rice diseases is urgently required in agricultural information since severe rice infections could result in no harvest of grains. Automated disease monitoring of rice plants using leaf images is critical for transitioning from labor-intensive, experience-based decision-making to an automated, data-driven strategy in agricultural production. In the modern era, Artificial Intelligence (AI) is being widely investigated in various areas of the medical and plant sciences to assess and diagnose the types of diseases.

Methods

This work proposes a hybrid deep-machine learning system for the automated detection of rice plant diseases using a leaf image dataset. Benchmarked MobileNetV2 architecture is employed to extract the deep features from the input images. Obtained features are fed as input to various machine learning classifiers with different kernel functions using a 10-fold validation strategy.

Results

The developed hybrid system attained the highest classification accuracy of 98.6%, specificity of 98.85%, and sensitivity of 97.25% using a medium neural network. The results demonstrate that the established system is computationally faster and more efficient. The proposed system is ready for testing with more databases.

Conclusions

The suggested technology accurately diagnoses various rice plant illnesses, reducing manual labor and allowing farmers to receive prompt treatment. Future research topics include incorporating cloud-based monitoring for leaf image capture in non-connected farms, as well as building mobile IoT platforms for continuous screening.