bluuebunny/crossref_metadata_2025 huggingface dataset:
Market Competition and Anemia Management in the United States Following Dialysis Payment Reform
Authors: Bhatnagar Anshul , Parvathareddy Vishnupriyadevi , Winkelmayer Wolfgang C. , Chertow Glenn M. , Erickson Kevin F.
Published: September 2023

Background:

Whether market competition influences health care provider responses to national reimbursement reforms is unknown.

Objectives:

We examined whether changes in anemia management after the expansion of Medicare’s dialysis payment bundle varied with market competition.

Research Design:

With data from the US dialysis registry, we used a difference-in-differences (DID) design to estimate the independent associations of market competition with changes in anemia management after dialysis reimbursement reform.

Subjects:

A total of 326,150 patients underwent in-center hemodialysis in 2009 and 2012, representing periods before and after reimbursement reform.

Measures:

Outcomes were erythropoiesis-stimulating agent (ESA) and intravenous iron dosage, the probability of hemoglobin <9 g/dL, hospitalizations, and mortality. We also examined serum ferritin concentration, an indicator of body iron stores. We used a dichotomous market competition index, with less competitive areas defined as effectively having <2 competing dialysis providers.

Results:

Compared with areas with more competition, patients in less competitive areas had slightly more pronounced declines in ESA dose (60% vs. 57%) following reimbursement reform (DID estimate: −3%; 95% CI, −5% to −1%) and less pronounced declines in intravenous iron dose (−14% vs. −19%; DID estimate: 5%; 95% CI, 1%–9%). The likelihoods of hemoglobin <9 g/dL, hospitalization, and mortality did not vary with market competition. Serum ferritin concentrations in 2012 were 4% (95% CI, 3%–6%) higher in less competitive areas.

Conclusions:

After the expansion of Medicare’s dialysis payment bundle, ESA use declined by more, and intravenous iron use declined by less in concentrated markets. More aggressive cost-reduction strategies may be implemented in less competitive markets.
Understanding constraints to adaptation using a community-centred toolkit
Authors: Buffa Danielle C. , Thompson Katharine E. T. , Reijerkerk Dana , Brittain Stephanie , Manahira George , Samba Roger , Lahiniriko Francois , Brenah Marius Clovis Jean , Augustin Jean Yves , Tsitohery Justome Ricky Francois , Razafy Roi Magnefa , Leonce Harison , Rasolondrainy Tanambelo , Douglass Kristina
Published: September 2023

Worldwide, marginalized and low-income communities will disproportionately suffer climate change impacts while also retaining the least political power to mitigate their consequences. To adapt to environmental shocks, communities must balance intensifying natural resource consumption with the need to ensure the sustainability of ecosystem provisioning services. Thus, scientists have long been providing policy recommendations that seek to balance humanitarian needs with the best outcomes for the conservation of ecosystems and wildlife. However, many conservation and development practitioners from biological backgrounds receive minimal training in either social research methods or participatory project design. Without a clear understanding of the sociocultural factors shaping decision-making, their initiatives may fail to meet their goals, even when communities support proposed initiatives. This paper explores the underlying assumptions of a community's agency, or its ability to develop and enact preferred resilience-enhancing adaptations. We present a context-adaptable toolkit to assess community agency, identify barriers to adaptation, and survey perceptions of behaviour change around natural resource conservation and alternative food acquisition strategies. This tool draws on public health and ecology methods to facilitate conversations between community members, practitioners and scientists. We then provide insights from the toolkit's collaborative development and pilot testing with Vezo fishing communities in southwestern Madagascar.

This article is part of the theme issue ‘Climate change adaptation needs a science of culture’.
Climate micro-mobilities as adaptation practice in the Pacific: the case of Samoa
Authors: Latai-Niusulu Anita , Tsujita Masami , Neef Andreas
Published: September 2023

Recent debates on climate mobilities have largely ignored the dynamics of mobility patterns including short-distance and short-duration circular movements to enhance adaptative capacity and resilience of households and individuals, enabling them to remain in place despite facing increasingly severe climatic risks. This paper explores Pacific Islanders' climate-related mobilities with reference to cases from Samoa. It first conceptualizes Samoan mobility, which is rooted in Samoan culture, norms and worldviews, and then uses this as a framework to examine ways in which people shift and diversify their residential locations for climate-associated reasons. The study employs a comparative case study approach using conversational (the Pacific-originated
talanoa
-style) interviews with 40 participants in two villages in Samoa—one urban and the other rural. Findings suggest that shifting spatially and temporarily between two residences (a practice called
fa'a-’āigalua
) occurs not only within the village but across villages. Thereby, villagers reduce the risk of incurring physical harm from climate-related disasters, while minimizing the risk of cultural harm from place detachment. Our study challenges the discourse of ‘vulnerable Pacific Islanders' by demonstrating the adaptability of Samoans to changing socio-ecological and climatic circumstances and their ability to develop a variety of climate resilience strategies, including micro-mobilities and circular migration.

This article is part of the theme issue ‘Climate change adaptation needs a science of culture’.
Operationalizing cultural adaptation to climate change: contemporary examples from United States agriculture
Authors: Waring Timothy M. , Niles Meredith T. , Kling Matthew M. , Miller Stephanie N. , Hébert-Dufresne Laurent , Sabzian Hossein , Gotelli Nicholas , McGill Brian J.
Published: September 2023

It has been proposed that climate adaptation research can benefit from an evolutionary approach. But related empirical research is lacking. We advance the evolutionary study of climate adaptation with two case studies from contemporary United States agriculture. First, we define ‘cultural adaptation to climate change’ as a mechanistic process of population-level cultural change. We argue this definition enables rigorous comparisons, yields testable hypotheses from mathematical theory and distinguishes adaptive change, non-adaptive change and desirable policy outcomes. Next, we develop an operational approach to identify ‘cultural adaptation to climate change’ based on established empirical criteria. We apply this approach to data on crop choices and the use of cover crops between 2008 and 2021 from the United States. We find evidence that crop choices are adapting to local trends in two separate climate variables in some regions of the USA. But evidence suggests that cover cropping may be adapting more to the economic environment than climatic conditions. Further research is needed to characterize the process of cultural adaptation, particularly the routes and mechanisms of cultural transmission. Furthermore, climate adaptation policy could benefit from research on factors that differentiate regions exhibiting adaptive trends in crop choice from those that do not.

This article is part of the theme issue ‘Climate change adaptation needs a science of culture’.
Adaptive irrigation management by Balinese farmers reduces greenhouse gas emissions and increases rice yields
Authors: Lansing J. S. , Kremer J. N. , Suryawan I. B. G. , Sathiakumar S. , Jacobs G. S. , Chung N. N. , Artha Wiguna I. Wy A.
Published: September 2023

The potential for changes in water management regimes to reduce greenhouse gases (GHG) in rice paddies has recently become a major topic of research in Asia, with implications for top-down versus bottom-up management strategies. Flooded rice paddies are a major source of anthropogenic GHG emissions and are responsible for approximately 11% of global anthropogenic methane (CH
4
) emissions. However, rice is also the most important food crop for people in low- and lower-middle-income countries. While CH
4
emissions can be reduced by lessening the time the plants are submerged, this can trigger increased emissions of nitrous oxide (N
2
O), a more potent GHG. Mitigation options for CH
4
and N
2
O are different, and minimizing one gas may increase the emission of the other. Accurate measurement of these gas emissions in rice paddies is difficult, and the results are controversial. We analysed these trade-offs using continuous high-precision measurements in a closed chamber in 2018–2020. Based on the results, we tested a bottom-up adaptive irrigation regime that improves nitrogen uptake by rice plants while reducing combined GHG emissions and nitrogen runoff from paddies to reefs in agricultural drainages. In 2023, we undertook a follow-up study in which farmers obtained higher rice yields with adaptive intermittent irrigation compared to uniformly flooded fields. These results use the polycentric, self-governing capacity of Balinese
subaks
for continuous adaptation.

This article is part of the theme issue ‘Climate change adaptation needs a science of culture’.
Climate change adaptation and the back of the invisible hand
Authors: Clark Barrett H. , Armstrong Josh
Published: September 2023

A good deal of contemporary work in cultural evolutionary theory focuses on the adaptive significance of culture. In this paper, we make the case that scientifically accurate and politically feasible responses to the climate crisis require a complex understanding of human cultural practices of niche construction that moves beyond the adaptive significance of culture. We develop this thesis in two related ways. First, we argue that cumulative cultural practices of niche construction can generate stable equilibria and runaway selection processes that result in long-term existential risks within and across cultural groups. We dub this
the back of the invisible hand
. Second, we argue that the ability of cultural groups to innovate technological solutions to environmental problems is highly constrained in ways that are exacerbated by sustained intergroup conflict, inequality and by inherently unpredictable cascades in climate change and human migration patterns. After developing these theoretical points about human cultural practices of niche construction in detail, we conclude our discussion with some tentative practical suggestions about the way that cultural evolutionary history can more fruitfully be used in efforts to remit the climate crisis and contribute to sustainable practices of human climate change adaptation.

This article is part of the theme issue ‘Climate change adaptation needs a science of culture’.
A comprehensive analysis of Transcribed Ultra Conserved Regions uncovers important regulatory functions of novel non-coding transcripts in gliomas
Authors: Gibert Myron K , Zhang Ying , Saha Shekhar , Marcinkiewicz Pawel , Dube Collin , Hudson Kadie , Sun Yunan , Bednarek Sylwia , Chagari Bilhan , Sarkar Aditya , Roig-Laboy Christian , Neace Natalie , Saoud Karim , Setiady Initha , Hanif Farina , Schiff David , Kumar Pankaj , Kefas Benjamin , Hafner Markus , Abounader Roger
Published: September 2023

Transcribed Ultra-Conserved Regions (TUCRs) represent a severely understudied class of putative non-coding RNAs (ncRNAs) that are 100% conserved across multiple species. We performed the first-ever analysis of TUCRs in glioblastoma (GBM) and low-grade gliomas (LGG). We leveraged large human datasets to identify the genomic locations, chromatin accessibility, transcription, differential expression, correlation with survival, and predicted functions of all 481 TUCRs, and identified TUCRs that are relevant to glioma biology. Of these, we investigated the expression, function, and mechanism of action of the most highly upregulated intergenic TUCR, uc.110, identifying it as a new tumor enhancer. Uc.110 was highly overexpressed in GBM and LGG, where it promoted malignancy and tumor growth. Uc.110 activated the WNT pathway by upregulating the expression of membrane frizzled-related protein (MFRP), by sponging the tumor suppressor microRNA miR-544. This pioneering study shows important roles for TUCRs in gliomas and provides an extensive database and novel methods for future TUCR research.
Machine-Learning Identifies a Strategy for Differentiation Therapy in Solid Tumors
Authors: Sinha Saptarshi , Alcantara Joshua , Perry Kevin , Castillo Vanessa , Espinoza Celia R. , Taheri Sahar , Vidales Eleadah , Tindle Courtney , Adel Adel , Amirfakhri Siamak , Sawires Joseph R. , Yang Jerry , Bouvet Michael , Sahoo Debashis , Ghosh Pradipta
Published: September 2023

Background

Although differentiation therapy can ‘cure’ some hematologic malignancies, its curative potential remains unrealized in solid tumors. This is because conventional computational approaches succumb to the thunderous noise of inter-/intratumoral heterogeneity. Using colorectal cancers (CRCs) as an example, here we outline a machine learning(ML)-based approach to track, differentiate, and selectively target cancer stem cells (CSCs).

Methods

A transcriptomic network was built and validated using healthy colon and CRC tissues in diverse gene expression datasets (∼5,000 human and >300 mouse samples). Therapeutic targets and perturbation strategies were prioritized using ML, with the goal of reinstating the expression of a transcriptional identifier of the differentiated colonocyte, CDX2, whose loss in poorly differentiated (CSC-enriched) CRCs doubles the risk of relapse/death. The top candidate target was then engaged with a clinical-grade drug and tested on 3 models: CRC linesin vitro, xenografts in mice, and in a prospective cohort of healthy (n = 3) and CRC (n = 23) patient-derived organoids (PDOs).

Results

The drug shifts the network predictably, inducesCDX2and crypt differentiation, and shows cytotoxicity in all 3 models, with a high degree of selectivity towards allCDX2-negative cell lines, xenotransplants, and PDOs. The potential for effective pairing of therapeutic efficacy (IC50) and biomarker (CDX2-low state) is confirmed in PDOs using multivariate analyses. A 50-gene signature of therapeutic response is derived and tested on 9 independent cohorts (∼1700 CRCs), revealing the impact ofCDX2-reinstatement therapy could translate into a ∼50% reduction in the risk of mortality/recurrence.

Conclusions

Findings not only validate the precision of the ML approach in targeting CSCs, and objectively assess its impact on clinical outcome, but also exemplify the use of ML in yielding clinical directive information for enhancing personalized medicine.
Motivational Interviewing Interventions for Harmful Substance Use Amongst Adults in Low- and Middle-Income Countries (LMICs): A Systematic Review
Authors: Adams Amy S. , Williams Taryn , Stein Dan J. , Sibeko Goodman , Shoptaw Steven , Rollnick Stephen
Published: September 2023

Background

Harmful substance use is a major challenge globally with far reaching detrimental effects on social, economic and health systems. This burden weighs more heavily on underdeveloped countries as they do not have the infrastructure needed to manage the consequences of substance use. In high-income countries, several evidence-based brief intervention models are used for HSU including Motivational Interviewing (MI). However, fewer studies have been conducted in low-resource settings.

Aim

In this review, we systematically reviewed studies utilising motivational interviewing as a component of interventions with adults presenting with harmful substance use in LMICs.

Methods

Adhering to Cochrane and PRISMA guidelines, we systematically searched for studies published between 2010 and 2022. The search was conducted in PubMed, EBSCOhost, Web of Science, the Cochrane Library,clinicaltrials.govand the GSK Clinical Study Register. A narrative analysis was done, and The Joanna Briggs Institute (JBI) Critical Appraisal Tools were used to assess the quality of the studies included.

Results

The search yielded 518 publications. Eleven studies from five different countries met inclusion criteria. These consisted mainly of RCTs with some employing qualitative or mixed methods approaches. The focus of the interventions varied, with most targeting alcohol use, while a few addressed opioids, and other drugs. The interventions used different strategies, including MI blended with other interventions (such as CBT, BA, and imaginal desensitization) or using MI-informed approaches. Overall, MI was shown to improve substance use outcomes in seven of the 11 studies with significant reduction in substance use based on outcomes measured.

Conclusions

This review highlights that, interventions incorporating MI demonstrated positive effects in improving substance use outcomes in the majority of the studies reviewed. Further research with larger sample sizes and more rigorous study designs is necessary to strengthen the evidence base and address potential sources of bias.
Accelerated neurodevelopment of reward anticipation processing in adolescent girls with depression
Authors: Baranger David AA , Lindenmuth Morgan , Yoon Leehyun , Guyer Amanda E. , Keenan Kate , Hipwell Alison E , Forbes Erika E
Published: September 2023

Objective

To test the hypothesis that depression is associated with differential neurodevelopment of reward circuitry in adolescence.

Methods

Adolescent girls (N=183, 58 with MDD in early or late adolescence) underwent MRI scans from ages 16-20 (1-4 scans/participant, 477 scans total) and completed a card-guessing fMRI task with monetary rewards. Mixed-effect models tested the effect of age and the moderating effect of MDD on whole-brain regional activation during reward anticipation.

Results

Eighty of 414 regions showed age effects (pFDR<0.05), consisting primarily of increasing activation with increasing age. Most significant regions were in dorsal attention, salience, and somatomotor networks, and also included the bilateral putamen, pallidum, and right nucleus accumbens. MDD moderated age effects in 40 regions (pFDR<0.05), including the right putamen, medial orbitofrontal cortex, and amygdala, and regions in control and dorsal attention networks. MDD x linear and quadratic age effects were negative, suggesting that MDD was associated with accelerated neurodevelopment.

Conclusions

Theories of reward processing’s contribution to adolescent risk for depression focus primarily on core reward regions, yet a host of regions beyond these continue to develop during late adolescence. Findings demonstrate differing regional patterns of age-related changes in relation to MDD in girls, suggesting that depression involves disruption of a wide range of regions during reward anticipation processing across adolescence. Childhood and adolescent MDD is associated with accelerated neurodevelopment of attention and cognitive control regions during reward anticipation processing, which may have consequences both for cognitive function and the emergence of reward-system-specific disruptions.
Discrimination, Smoking, and Cardiovascular Disease Risk: A Moderated Mediation Analysis with the Multi-Ethnic Study of Atherosclerosis
Authors: Cook Stephanie H. , Wood Erica P. , Stein James H. , McClelland Robyn L.
Published: September 2023

Background

Race is a social determinant of cardiovascular (CVD) risk and the American Heart Association has called for increased research to understand how this social determinants of health (SDoH) impacts CVD risk. Carotid intima-media thickness (cIMT) and carotid plaque are reliable indicators of cardiovascular risk. Further, research highlights that disparities exist in these indicators of cardiovascular risk such that racial/ethnic minorities generally exhibit greater characteristics of cardiovascular risk with respect to these indices (e.g., greater cIMT and higher carotid plaque scores) than white individuals due, in part, to exacerbated stress experienced from racial discrimination. At present, the mechanisms driving these racial/ethnic disparities is poorly understood.

Methods and Results

Data came from the baseline examination of the Multi-Ethnic Study of Atherosclerosis (MESA). 6,814 participants aged 45-84 free of clinical CVD completed assessments on health behavior, perceived discrimination, CVD-related risk factors, and sociodemographics. Four biological sex-stratified moderated mediation models were used to examine the associations between discrimination, cigarette smoking, and mean cIMT and plaque, modeled separately. We hypothesized that cigarette use would mediate the association between discrimination and carotid artery disease features and that these associations would be moderated by race/ethnicity. While results did not fully support our study hypothesis, racial/ethnic differences were observed across biological sex. Significant indirect effects of discrimination on plaque scores were observed among Hispanic females such that increased discrimination was associated with more cigarette use which, in turn, was associated with higher plaque (b=.04, CI=.01, .08). Similar findings were observed among Hispanic males in relation to mean cIMT (b=.003, CI=.00, .01) and among white (b=.04, CI=.01, .08) and Hispanic males (b=.03, CI=.004, .07) and plaque. No other racial/ethnic differences were observed.

Conclusions

Results suggest that cardiovascular risk disparities should be examined within frameworks that consider the importance of the intersection of multiple identities (e.g., race and gender). To better address the American Heart Association’s call to examine social determinants of cardiovascular health, researchers must incorporate the complexity of the intersection of various social positions in future work.
VirEvol platform : accurate prediction and visualization of SARS-CoV-2 evolutionary trajectory based on protein language model, structural information and immunological recognition mechanism
Authors: Zeng Xincheng , Zhang Linghao , Ning Zhenyu , Qiu Yusong , Dong Ruobing , Li Xiangyi , Lv Lijun , Xu Hanlin , Wang Yanjing , Ma Buyong
Published: September 2023

Predicting the mutation direction of SARS-CoV-2 using exploratory computational methods presents a challenging, yet prospective, research avenue. However, existing research methods often ignore the effects of protein structure and multi-source viral information on mutation prediction, making it difficult to accurately predict the evolutionary trend of the SARS-CoV-2 S protein receptor-binding domain (RBD). To overcome this limitation, we proposed an interpretable language model combining structural, sequence and immune information. The dual utility of this model lies in its ability to predict SARS-CoV-2’s affinity for the ACE2 receptor, and to assess its potential for immune evasion. Additionally, it explores the mutation trend of SARS-CoV-2 via a genetic algorithm-directed evolution. The model exhibits high accuracy in both regards and has displayed promising early warning capabilities, effectively identifying 13 out of 14 high-risk strains, marking a success rate of 93%.”. This study provides a novel method for discerning the molecular evolutionary pattern, as well as predicting the evolutionary trend of SARS-CoV-2 which is of great significance for vaccine design and drug development of new coronaviruses. We further developed VirEvol, a unique platform designed to visualize the evolutionary trajectories of novel SARS-CoV-2 strains, thereby facilitating real-time predictive analysis for researchers. The methodologies adopted in this work may inspire new strategies and offer technical support for addressing challenges posed by other highly mutable viruses.
Assessment of behavioral flexibility in mice with conditional deletion of metabotropic glutamate receptor 2 fromEmx1-lineage neurons
Authors: Chang Doris S. , Littlepage-Saunders Mydirah , Hochstein Michael J. , Matteo Christopher J. , Amelga Kidus , Homanics Gregg E. , Johnson Kari A.
Published: September 2023

Convergent lines of evidence from animal models suggest that disrupted metabotropic glutamate receptor 2 (mGlu2) function promotes high levels of drug consumption for a variety of psychoactive drugs including alcohol, opioids, and psychostimulants. In both rodents and humans, impaired behavioral flexibility prior to first drug use correlates with high levels of drug consumption later in life. Thus, we posited that deletion of mGlu2from brain regions that contribute to behavioral flexibility, including cortical regions, could predispose animals to high levels of drug consumption by impairing behavioral flexibility. To evaluate the role of mGlu2in behavioral flexibility, we generated mice with a floxedGrm2allele (Grm2f/f) and selectively disrupted mGlu2expression in neurons of theEmx1lineage (primarily telencephalonic projection neurons) by crossing these mice with an Emx1-IRES-Cre driver line. Behavioral flexibility, including sensitivity to change in either outcome value or action-outcome contingency, was evaluated in adult male and female mice trained to press a lever for a food reinforcer. Contrary to our hypothesis, mGlu2deletion did not facilitate habitual responding assessed by devaluation, contingency degradation, or omission tests. MaleGrm2f/f;Emx1-IRES-Cre+/-mice showed modest impairment in reversal learning compared with littermate controls. Finally, we saw a sex-specific effect of mGlu2deletion on response vigor in male mice trained on a random ratio reinforcement schedule. However, we did not find evidence of a general reduction in motivation in a progressive ratio test. These findings suggest that loss of mGlu2from cortical circuitry is unlikely to create a predisposition to inflexible behavior that facilitates excessive drug consumption.
cdsBERT - Extending Protein Language Models with Codon Awareness
Authors: Hallee Logan , Rafailidis Nikolaos , Gleghorn Jason P.
Published: September 2023

Abstract

Recent advancements in Protein Language Models (pLMs) have enabled high-throughput analysis of proteins through primary sequence alone. At the same time, newfound evidence illustrates that codon usage bias is remarkably predictive and can even change the final structure of a protein. Here, we explore these findings by extending the traditional vocabulary of pLMs from amino acids to codons to encapsulate more information inside CoDing Sequences (CDS). We build upon traditional transfer learning techniques with a novel pipeline of token embedding matrix seeding, masked language modeling, and student-teacher knowledge distillation, called MELD. This transformed the pretrained ProtBERT into cdsBERT; a pLM with a codon vocabulary trained on a massive corpus of CDS. Interestingly, cdsBERT variants produced a highly biochemically relevant latent space, outperforming their amino acid-based counterparts on enzyme commission number prediction. Further analysis revealed that synonymous codon token embeddings moved distinctly in the embedding space, showcasing unique additions of information across broad phylogeny inside these traditionally “silent” mutations. This embedding movement correlated significantly with average usage bias across phylogeny. Future fine-tuned organism-specific codon pLMs may potentially have a more significant increase in codon usage fidelity. This work enables an exciting potential in using the codon vocabulary to improve current state-of-the-art structure and function prediction that necessitates the creation of a codon pLM foundation model alongside the addition of high-quality CDS to large-scale protein databases.
Deep learning-Based Correlation Analysis of Pelvic and Spinal Sequences for Enhanced Sagittal Spinal Alignment Prediction
Authors: Song Kai , Qi Huan , Ma Chi , Chi Pengfei , Lin Junyu , Yang Qiang , Yang Cao , Wang Bing , Li Fangcai , Zhu Zezhang , Li Weishi , Zhang Jianguo , Lu William , Zheng Wang
Published: September 2023

Background

Pelvic Incidence (PI) plays a crucial role in surgical planning. However, it is insufficient for accurately predicting spinal alignment parameters, including Sacral Slope, Pelvic Tilt, and Lumbar Lordosis. We have devised an AI-based method for predicting sagittal spinal alignments with enhanced precision.

Methods

We have developed an AI-based system utilizing a Seq2Seq framework to model the spatial correlation between pelvic and spinal key points. This system was trained on a dataset of 337 cases and evaluated using 51 cases obtained from a multi-centre hospital. To address the issue of pelvic rotation, we introduced an Angle Correlation Network. We compared the performance of our AI-based system in predicting spinal alignment against the traditional PI-based method. This comparison was conducted using Mean Absolute Error (MAE) and the Correlation Coefficient (R value) as evaluation metrics.

Results

We evaluated the performance of our AI-based system for predicting Sacral Slope (SS), Pelvic Tilt (PT), and Lumbar Lordosis (LL) values. The Pearson correlation coefficient of the AI-based method surpassed that of the PI-based method (0.80 vs 0.67 for SS, 0.73 vs 0.52 for PT, and 0.76 vs 0.48 for LL), indicating a more robust linear relationship between AI predictions and actual values. Additionally, the AI-based method exhibited a lower Mean Absolute Error (MAE) compared to the PI-based method for LL (5.52 vs 6.69), signifying enhanced prediction accuracy.

Conclusions

In this study, we demonstrated the potential of an AI-based approach for predicting sagittal spinal alignments with improved precision compared to the traditional PI-based method. The AI-based system, utilizing a Seq2Seq framework and an Angle Correlation Network, exhibited a stronger linear relationship between predicted and actual values for Sacral Slope, Pelvic Tilt, and Lumbar Lordosis, as well as a reduced Mean Absolute Error for Lumbar Lordosis. These findings support the integration of AI in spinal surgery planning and personalized medicine for sagittal alignment evaluation and management.
AMYGDALA VOLUME IS ASSOCIATED WITH ADHD RISK AND SEVERITY BEYOND COMORBIDITIES IN ADOLESCENTS: CLINICAL TESTING OF BRAIN CHART REFERENCE STANDARDS
Authors: Nárai Ádám , Hermann Petra , Rádosi Alexandra , Vakli Pál , Weiss Béla , Réthelyi János M. , Bunford Nóra , Vidnyánszky Zoltán
Published: September 2023

Background.Understanding atypicalities in ADHD brain correlates is a step towards better understanding ADHD etiology. Efforts to map atypicalities at the level of brain structure have been hindered by the absence of normative reference standards. Recent publication of brain charts allows for assessment of individual variation relative to age- and sex-adjusted reference standards and thus estimation not only of case-control differences but also of intraindividual prediction.Methods.Aim was to examine, whether brain charts can be applied in a sample of adolescents (N=140, 38% female) to determine whether atypical brain subcortical and total volumes are associated with ADHD at-risk status and severity of parentrated symptoms, accounting for self-rated anxiety and depression, and parent-rated oppositional defiant disorder (ODD) as well as motion.Results.Smaller bilateral amygdala volume was associated with ADHD at-risk status, beyond effects of comorbidities and motion, and smaller bilateral amygdala volume was associated with inattention and hyperactivity/impulsivity, beyond effects of comorbidities except for ODD symptoms, and motion.Conclusions.Individual differences in amygdala volume meaningfully add to estimating ADHD risk and severity. Conceptually, amygdalar involvement is consistent with behavioral and functional imaging data on atypical reinforcement sensitivity as a marker of ADHD-related risk. Methodologically, results show that brain chart reference standards can be applied to address clinically informative, focused and specific questions.
Demographics, culture, and participatory nature of multi-marathoning, an observational study.
Authors: Lundy Leo , Reilly Richard
Published: September 2023

Abstract Objectives: Completing 100 marathons defines a multi-marathoner. The aim of this study was to document the sport of multi-marathoning and to report on the demographics, culture, and participatory nature of the sport. Methods: A survey was distributed globally to the sports participants. All the major national and international multi-marathon clubs supported the survey distribution via their closed social media and email groups. The survey was fully anonymous and online. Results: The survey attracted 830 respondents from 40 countries, with an average marathon completion count of 146 per respondent. 60% of respondents were men, with a respondent's average age of over 50 years. Social life and travel superseded competitiveness as the main motivation as participants age. 57% of respondents had at least one contravention to a pre-participation screening questionnaire and 67% took pain relief medication around events. 93% of respondents reported that multi-marathoning was good for their mental health. Discussion: Multi-marathoning facilitates the older athlete, but there is a significant gender imbalance in participation. Long-term health damage potential is significant, and health awareness requires addressing by governing bodies, event facilitators and participants alike. Multi-marathoners should use available information from modern equipment to inform their health status and to optimise training. Conclusion: Recommendations from the study include implementing women-specific enhancements to events, race directors having adequately resourced health plans at events, and participants taking accountability for their own health by including proactive regular health management before and during their participation in the sport.
Analyzing the Mechanism Behind Age-agnostic Prediction of Diastolic Dysfunction Using Echocardiography Variables in Deep Neural Networks
Authors: Jamthikar Ankush D. , Shah Rohan , Tokodi Marton , Sengupta Partho P. , Yanamala Naveena
Published: September 2023

Objective

This investigation delved into the inner workings of previously published Deep Neural Networks (DNNs) designed to detect changes in diastolic function related to age using echocardiographic parameters. The primary goal was to decipher the predictive mechanism and determine whether biological age and gender played concealed roles within the DNN model.

Methods

We conducted a secondary analysis of a previously published DNN model that was trained using data from 1,009 patients (average age: 62±17 years, 57% females) to forecast risk phenogroups based on nine echocardiographic parameters. This model was assessed on both an internal cohort (n=243, mean age = 62 ± 17 years, ∼57% females) and an external validation cohort (n=5596, mean age = 76 ± 5 years, ∼57% females). To forecast biological age and gender, we developed linear regression and classification models employing hidden layer activations from the DNN. Model performance was assessed using Pearson’s correlation for regression, accuracy, and area under the curve (AUC) metrics for classification.

Results

Upon scrutinizing the hidden layer activations, we observed that the model accurately captured biological age in both younger and older populations, particularly in low-risk phenogroups, with robust correlations for the entire population (0.94, p<0.001), males (0.90, p<0.001), and females (0.94, p<0.001). In high-risk phenogroups, the correlations were lower, standing at 0.31 (p=0.274) for the entire population, 0.76 (p=0.003) for males, and 0.11 (p=0.723) for females. Predicting gender as an underlying factor resulted in an accuracy rate of 58.02% and 52.27%, accompanied by an AUC of 0.65 for both validation cohorts.

Conclusion

This study underscores that the latent space within DNNs maintains a link with age in relation to diastolic functional parameters, offering a solution that is independent of age for predicting diastolic dysfunction. The dissection of the network can further enhance our comprehension of the information learned by DNNs, thereby providing novel pathophysiological insights for medical professionals.
Hypoxia-inducible factor-2 (HIF2) regulates alveolar regeneration after repetitive injury
Authors: McCall A. Scott , Tanjore Harikrishna , Burman Ankita , Sherrill Taylor , Chapman Micah , Calvi Carla L. , Camarata Jane , Hunt Raphael P. , Nichols David , Banovich Nicholas E. , Lawson William E. , Gokey Jason J. , Kropski Jonathan A. , Blackwell Timothy S.
Published: September 2023

Idiopathic Pulmonary Fibrosis (IPF) is a progressive and often fatal chronic respiratory disease thought to result from repetitive injury and failed repair of the lung alveoli, and recent studies have identified a number of disease-emergent intermediate/transitional cell states in the IPF lung supporting this concept. In this study, we found that persistent activation of hypoxia-inducible factor (HIF)-signaling in airway-derived, repair-associated cell types/states is a hallmark of dysfunctional epithelial repair in the IPF lung epithelium and experimental models of recurrent lung epithelial injury. Disrupting Hif-signaling attenuated experimental lung fibrosis, reduced mucous-secretory cell polarization, and promoted functional alveolar regeneration following repetitive injury. Mouse and human organoid studies demonstrated that small-molecule-based HIF2 inhibition promoted alveolar epithelial cell proliferation and maturation while preventing the emergence of maladaptive intermediate/transitional states analogous to those in IPF. Together, these studies indicate that targeted HIF2-inhibition represents a novel and effective therapeutic strategy to promote functional lung regeneration, and could be readily translated into human studies of IPF and other chronic interstitial lung diseases with disease modifying effect.

One sentence summary

Inhibiting hypoxia-inducible-factor 2 (HIF2) promotes functional lung alveolar epithelial repair following recurrent injury.
LsTT2encoding R2R3-MYB transcription factor is responsible for a shift from black to white in lettuce seed
Authors: Seki Kousuke , Komatsu Kenji , Yamaguchi Kanami , Murai Yoshinori , Nishida Keiji , Koyama Ryohei , Uno Yuichi
Published: September 2023

Prickly lettuce (Lactuca serriola), which is considered the wild ancestor of lettuce, has black seeds, whereas the major seed color of domesticated lettuce is black or white. The successfully-selected white seed trait is a key domestication trait for lettuce cultivation and breeding; however, the mechanism underlying the shift from black to white seeds remains to be clarified. We aimed to identify the gene/s responsible for white seed trait in lettuce. Genetic mapping of a candidate gene was performed with double-digest RAD sequencing using an F2population derived from a cross between ‘ShinanoPower’ (white seed) and ‘Escort’ (black seed). The white seed trait was controlled by a single recessive locus (48.055–50.197 Mbp) in linkage group 7. Narrowing down using five PCR-based markers and 84 cultivars, eight candidate genes were mapped in the locus. Only theLG7_v8_49.251Mbp_HinfImarker, which employs a single nucleotide mutation in the stop codon ofLsat_1_v5_gn_7_35020.1was completely linked to the seed color phenotype. In addition, the sequences of the coding region for candidate genes except forLsat_1_v5_gn_7_35020.1were identical in the resequence analysis of ‘ShinanoPower’ (white seed) and ‘Escort’ (black seed). Therefore, we proposedLsat_1_v5_gn_7_35020.1, a gene located in the locus, as the candidate gene and designated it asLsTT2, an ortholog encoding the R2R3 MYB transcription factor inArabidopsis. When we validated the role ofLsTT2in seed color through genome editing,LsTT2knockout mutants harboring an early termination codon showed a change in seed color from black to white. White seeds accumulated less proanthocyanidins than black seeds, which was similar to the phenotype observed inArabidopsis TRANSPARENT TESTA 2(TT2) mutants. Therefore,LsTT2was the allele responsible for the shift in seed color from black to white. The development of a robust marker for marker-assisted selection and identification of the gene responsible for white seeds has implications for future breeding technology and physiological analysis.
A novel MARV glycoprotein-specific antibody with potentials of broad-spectrum neutralization to filovirus
Authors: Zhang Yuting , Zhang Min , Wu Haiyan , Wang Xinwei , Zheng Hang , Feng Junjuan , Wang Jing , Luo Longlong , Xiao He , Qiao Chunxia , Li Xinying , Zheng Yuanqiang , Huang Weijin , Wang Youchun , Wang Yi , Shi Yanchun , Feng Jiannan , Chen Guojiang
Published: September 2023

Marburg virus (MARV) is one of the filovirus species that cause deadly hemorrhagic fever in humans, with mortality rates up to 90%. Neutralizing antibodies represent ideal candidates to prevent or treat virus disease. However, no antibody has been approved for MARV treatment to date. In this study, we identified a novel human antibody named AF-03 that targeted MARV glycoprotein (GP). AF-03 possessed a high binding affinity to MARV GP and showed neutralizing and protective activities against the pseudotyped MARV in vitro and in vivo. Epitope identification, including molecular docking and experiment-based analysis of mutated species, revealed that AF-03 recognized the Niemann-Pick C1 (NPC1) binding domain within GP1. Interestingly, we found the neutralizing activity of AF-03 to pseudotyped Ebola viruses (EBOV, SUDV, and BDBV) harboring cleaved GP instead of full-length GP. Furthermore, NPC2-fused AF-03 exhibited neutralizing activity to several filovirus species and EBOV mutants via binding to CI-MPR. In conclusion, this work demonstrates that AF-03 represents a promising therapeutic cargo for filovirus-caused disease.
The diverse evolutionary histories of domesticated metaviral capsid genes in mammals
Authors: Henriques William S. , Young Janet M. , Nemudryi Artem , Nemudraia Anna , Wiedenheft Blake , Malik Harmit S.
Published: September 2023

Selfish genetic elements and their remnants comprise at least half of the human genome. Active transposons duplicate by inserting copies at new sites in a host genome. Following insertion, transposons can acquire mutations that render them inactive; the accrual of additional mutations can render them unrecognizable over time. However, in rare instances, segments of transposons become useful for the host, in a process called gene domestication. Using the first complete human genome assembly and 25 additional vertebrate genomes, we analyzed the evolutionary trajectories and functional potential of genes domesticated from the capsid genes ofMetaviridae, a retroviral-like retrotransposon family. Our analysis reveals four families of domesticated capsid genes in placental mammals with varied evolutionary outcomes, ranging from universal retention to lineage-specific duplications or losses and from purifying selection to lineage-specific rapid evolution. The four families of domesticated capsid genes have divergent amino-terminal domains, inherited from four distinct ancestral metaviruses. Structural predictions reveal that many domesticated genes encode a previously unrecognized RNA-binding domain retained in multiple paralogs in mammalian genomes both adjacent to and independent from the capsid domain. Collectively, our study reveals diverse outcomes of domestication of diverse metaviruses, which led to structurally and evolutionarily diverse genes that encode important, but still largely-unknown functions in placental mammals.
Human adolescent brain similarity development is different for paralimbic versus neocortical zones
Authors: Dorfschmidt Lena , Váša František , White Simon R. , Romero-García Rafael , Kitzbichler Manfred G. , Alexander-Bloch Aaron , Cieslak Matthew , Mehta Kahini , Satterthwaite Theodore D. ,   the NSPN consortium, Bethlehem Richard A.I. , Seidlitz Jakob , Vértes Petra E. , Bullmore Edward T.
Published: September 2023

Adolescent development of human brain structural and functional networks is increasingly recognised as fundamental to emergence of typical and atypical adult cognitive and emotional processes. We analysed multimodal magnetic resonance imaging (MRI) data collected from N ∼ 300 healthy adolescents (51%; female; 14-26 years) each scanned repeatedly in an accelerated longitudinal design, to provide an analyzable dataset of 469 structural scans and 448 functional MRI scans. We estimated the morphometric similarity between each possible pair of 358 cortical areas on a feature vector comprising six macro- and micro-structural MRI metrics, resulting in a morphometric similarity network (MSN) for each scan. Over the course of adolescence, we found that morphometric similarity increased in paralimbic cortical areas, e.g., insula and cingulate cortex, but generally decreased in neocortical areas; and these results were replicated in an independent developmental MRI cohort (N ∼ 304). Increasing hubness of paralimbic nodes in MSNs was associated with increased strength of coupling between their morphometric similarity and functional connectivity. Decreasing hubness of neocortical nodes in MSNs was associated with reduced strength of structure-function coupling and increasingly diverse functional connections in the corresponding fMRI networks. Neocortical areas became more structurally differentiated and more functionally integrative in a metabolically expensive process linked to cortical thinning and myelination; whereas paralimbic areas specialised for affective and interoceptive functions became less differentiated, as hypothetically predicted by a developmental transition from peri-allocortical to pro-isocortical organization of cortex. Cytoarchitectonically distinct zones of human cortex undergo distinct neurodevelopmental programmes during typical adolescence.
Elevated temperature fatally disrupts nuclear divisions in the earlyDrosophilaembryo
Authors: Kale Girish , Agarwal Pratika , Diaz-Larrosa J Jaime , Lemke Steffen
Published: September 2023

Temperature variations can challenge animal survival, with different life cycle stages presenting distinct vulnerabilities to elevated temperature. Here, embryonic development is known to be especially vulnerable to elevated temperature, though the molecular mechanism remain unclear. In this context, we investigate how elevated temperature affects embryogenesis inDrosophila melanogaster, utilizing it as a model with a well-characterized genetic makeup and developmental processes.

InDrosophilaembryos, we identified the first three hours as a critical, temperature-sensitive time window. This period includes the formation of a syncytial blastoderm, which involves 4 rounds of meta-synchronous nuclear divisions at the embryo cortex, and cellularization that leads to formation of the cellular blastoderm. Embryos exposed to elevated temperature during this period showed increased lethality due to subsequent developmental defects during the gastrulation stage. We observed an increase in mitotic failures causing a loss of cortical nuclei, both, during syncytial blastoderm and cellularization stages in embryos developing at elevated temperature. Additionally, these embryos show a local crowding of nuclei and an increase in asynchrony between the nuclear cycles in the center vs. the poles. Interestingly, nuclear crowding and nuclear cycle asynchrony cooperatively amplify the frequency of mitotic failures, leading to holes in the blastoderm epithelium. We functionally tested known regulators of mitosis, to rescue these developmental defects and improve embryo survival, and asked whether existing wild populations carry signatures of adaptation in these regulators of mitosis.

Our genetic rescue experiments expose a vulnerability at elevated temperatures in the interaction between cortical F-actin and microtubules, leading to mitotic failures, which can be potentially rescued by modulating the expression of just a few factors. We propose that the expression levels of the corresponding genes could be used as indicators to predict fitness effects on insect populations that are exposed to increasing temperature variations.