bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting prognostic factors in kidney transplantation using a machine learning approach to enhance outcome predictions: a retrospective cohort study
Authors: Kim Jin-Myung , Jung HyoJe , Kwon Hye Eun , Ko Youngmin , Jung Joo Hee , Kwon Hyunwook , Kim Young Hoon , Jun Tae Joon , Hwang Sang-Hyun , Shin Sung
Published: August 2024

Background:

Accurate forecasting of clinical outcomes after kidney transplantation is essential for improving patient care and increasing the success rates of transplants. The authors’ study employs advanced machine learning (ML) algorithms to identify crucial prognostic indicators for kidney transplantation. By analyzing complex datasets with ML models, the authors aim to enhance prediction accuracy and provide valuable insights to support clinical decision-making.

Materials and methods:

Analyzing data from 4077 KT patients (June 1990–May 2015) at a single center, this research included 27 features encompassing recipient/donor traits and peri-transplant data. The dataset was divided into training (80%) and testing (20%) sets. Four ML models—eXtreme Gradient Boosting (XGBoost), Feedforward Neural Network, Logistic Regression, And Support Vector Machine—were trained on carefully selected features to predict the success of graft survival. Performance was assessed by precision, sensitivity, F1 score, area under the receiver operating characteristic (AUROC), and area under the precision-recall curve.

Results:

XGBoost emerged as the best model, with an AUROC of 0.828, identifying key survival predictors like T-cell flow crossmatch positivity, creatinine levels two years post-transplant and human leukocyte antigen mismatch. The study also examined the prognostic importance of histological features identified by the Banff criteria for renal biopsy, emphasizing the significance of intimal arteritis, interstitial inflammation, and chronic glomerulopathy.

Conclusion:

The study developed ML models that pinpoint clinical factors crucial for KT graft survival, aiding clinicians in making informed post-transplant care decisions. Incorporating these findings with the Banff classification could improve renal pathology diagnosis and treatment, offering a data-driven approach to prioritizing pathology scores.
The role of artificial intelligence measured preoperative kidney volume in predicting kidney function loss in elderly kidney donors: a multicenter cohort study
Authors: Jo Eun-Ah , Lee Juhan , Moon Seonggong , Kim Jin Sung , Han Ahram , Ha Jongwon , Kim Yong Chul , Min Sangil
Published: August 2024

Background:

The increasing use of kidneys from elderly donors raises concerns due to age-related nephron loss. Combined with nephrectomy, this loss of nephrons markedly increases the risk of developing chronic kidney disease (CKD). This study aimed to investigate the prognostic value of preoperative kidney cortex volume in predicting the loss of kidney function in elderly donors, by developing an artificial intelligence (AI)-based model for precise kidney volume measurement and applying it to living kidney donors.

Materials and methods:

A multicenter retrospective cohort study using data from living donors who underwent donor nephrectomy between January 2010 and December 2020 was conducted. An AI segmentation model was developed and validated to measure kidney cortex volume from pre-donation computer tomographic (CT) images. The association between measured preoperative kidney volumes and post-nephrectomy renal function was analyzed through a generalized additive model.

Results:

A total of 1074 living kidney donors were included in the study. Validation of the developed kidney cortex volume model showed a Dice similarity coefficient of 0.97 and a Hausdorff distance of 0.76 mm. The measured cortex volumes exhibited an age-related decrease, which correlated with declining kidney function. Elderly donors showed greater decreases in estimated glomerular filtration rates (eGFR) post-donation compared to young donors (P=0.041). Larger preoperative remnant kidney cortex volume was associated with significantly less decline of eGFR post-donation than those with smaller preoperative remnant kidney cortex volume (P<0.001).

Conclusion:

This study highlights the critical role of preoperative kidney cortex volume in the donor assessment process, particularly for elderly donors. The fully automated model for measuring kidney cortex volume provides a valuable tool for predicting post-donation renal function and holds promise for enhancing donor evaluation and safety.
Simple severity scale for perforated peptic ulcer with generalized peritonitis: a derivation and internal validation study
Authors: Yamamoto Ryo , Hirakawa Shinya , Tachimori Hisateru , Matsuoka Tadashi , Kikuchi Hirotoshi , Hasegawa Hiroshi , Shirabe Ken , Kakeji Yoshihiro , Kawakubo Hirofumi , Kitagawa Yuko , Sasaki Junichi
Published: August 2024

Background:

Perforated peptic ulcer (PPU) causes peritonitis and requires surgery based on disease severity. This study aimed to develop and validate a severity scale for PPU with generalized peritonitis.

Materials and methods:

This retrospective cohort study used a nationwide multicenter surgical database (2013–2020). Patients aged >15 years who underwent surgery for PPU with generalized peritonitis were included and categorized into the derivation (2013–2018) and two validation (2019 and 2020) cohorts. Possible severity predictors were selected via a literature review, and Lasso models were developed to predict severe postoperative adverse events with 2000 bootstrapping. Final variables for the scoring system were determined based on inclusion frequency (≥90%) in the Lasso models. Discrimination and accuracy were evaluated using C-statistics and calibration plots. Cutoff values for minimal postoperative adverse events were examined using negative predictive values.

Results:

Among 12 513 patients included (1202 underwent laparoscopic surgery), 533 (5.9%), 138 (7.6%), and 117 (6.9%) in the derivation and two validation cohorts experienced postoperative adverse events. Age, dyspnea at rest, preoperative sepsis, III/IV/V of American Society of Anesthesiologists physical status, and albumin and creatinine were selected for the final model. A 0–11 scoring system was developed with C-statistics of 0.812–0.819. Cutoff value was determined as 5, which predicted <3% probability of postoperative adverse events regardless of type of surgery.

Conclusions:

A score of <5 predicts minimal risks for postoperative adverse events and, therefore, would be clinically useful to determine the type of surgery. Further studies are needed to validate the score.
Using Structural Competencies for Faculty and Students to Integrate Principles of Social Justice and Health Equity Into a Doctor of Physical Therapy Program
Authors: Naidoo Keshrie , Karim Rania , Rimmel Lauren , Watkins Liu Callie , Washington Kamaria , Privett Rachel , Godsey Keelin , Rucker-Bussie Valerie , Plummer Laura
Published: August 2024

Background and Purpose:

Integrating principles of social justice and health equity (SJHE) into Doctor of Physical Therapy (DPT) education may be one way to confront the root causes of health inequity. The purpose of this method/model presentation is to highlight structural competencies for faculty and students to integrate SJHE into a 3-year DPT program and a professional development program designed to provide core and clinical faculty with the tools to engage in critical discussions with students and support their development as agents of change.

Method/Model Description and Evaluation:

This presentation highlights how SJHE structural competencies can be integrated into existing course content (as opposed to presented as a standalone course). Researchers interviewed 10 DPT faculty and 10 DPT students about their experience learning about SJHE. Six clinical instructors (CIs) who supervised students during a full-time clinical education experience (CEE) discussed students’ ability to apply SJHE concepts during CEEs.

Outcomes:

Faculty expressed the need for practice in low-stakes settings such as through simulation. Students valued learning about SJHE over 3 years with the opportunity to integrate content during CEEs but felt that SJHE could be better integrated in classroom content. Some peers were perceived to be resistant to SJHE. Clinical instructors described that although students were prepared to apply foundational SJHE concepts, students were surprised by the complexity of patient need.

Discussion and Conclusion:

Exploratory analysis of faculty, CI, and students’ perceptions confirm that SJHE is needed in DPT education but takes time to integrate well with a steep learning curve and additional faculty development needs that must be met.
SFPO and ESOP recommendations for the practical stability of anticancer drugs: second update
Authors: D'Huart Elise , Astier Alain , Bardin Christophe , Vigneron Jean
Published: August 2024

A second update of the recommendations for the practical stability of anticancer drugs published in 2013 has been realized by the French Society of Hospital Pharmacists (SFPO); European Society of Oncology Pharmacists (ESOP); and members of the Stabilis® database (www.stabilis.org), a stability and compatibility database of drugs. Forty-six new molecules have been included. These new data make it possible to optimize anticancer drug preparations and achieve product savings. These new recommendations have to be taken into consideration only if the preparation is made according to the Good Manufacturing Practices in classified rooms.
Analyzing the Impact of CIT on the Largest Reported Cohort of Robotic Kidney Transplantation From the Deceased Donors
Authors: Petrochenkov Egor , Bencini Giulia , Martinino Alessandro , Lian Amy , Olazar Joanna , Akshelyan Stepan , Yoshikawa Kentaro , Di Cocco Pierpaolo , Almario-Alvarez Jorge , Spaggiari Mario , Benedetti Enrico , Tzvetanov Ivo
Published: August 2024

Background.

Robotic-assisted kidney transplant (RAKT) has proven to be a successful approach for patients with morbid obesity and more centers are encouraged to apply robotic approach also for deceased donor kidney transplantation. Prolonged cold ischemia time (CIT) is accompanied by delayed graft function (DGF) and early graft loss after traditional open kidney transplant (OKT). This study examines the impact of CIT after robotic kidney transplantation on settings of deceased donation.

Methods.

We present a single-center retrospective analysis of 115 cases of RAKT and 128 cases of OKT from deceased donors performed from deceased donor from 2009 to July 2022. Cohort was divided in 3 groups based on CIT (“high” CIT > 15 h, n = 43; “medium” CIT 11–15 h, n = 38; “low” CIT< 11 h, n = 40). The subgroup analysis of DGF and CIT was performed.

Results.

The median CIT in the cohort was 13.46 (7) h, and overall rate of DGF was 30.6%. The correlation between CIT and DGF was statistically significant (P = 0.008), and DGF negatively correlated with 1-y graft survival (P = 0.04). The rate of DGF was significantly different between the groups (P = 0.05).

Conclusions.

Results from our study demonstrate that the effect of CIT on DGF in settings of RAKT follows a similar pattern as in traditional OKT.
Training the Next Generation of Transplant Surgeons With a 3-Dimensional Trainer: A Pilot Study
Authors: Sanchez-Garcia Jorge , Lopez-Verdugo Fidel , Shorti Rami , Krong Jake , Zendejas Ivan , Contreras Alan G. , Botha Jean , Rodriguez-Davalos Manuel I.
Published: August 2024

Background.

In the United States, no published guidelines promote exposure to technical variants (ie, living donor or split liver) during transplant fellowship. Simulation with hands-on liver models may improve training in transplantation. This pilot study addressed 3 overall goals (material and model creation tools, recruitment rates and assessment of workload, and protocol adherence).

Methods.

A patient-specific hands-on liver model was constructed from clinical imaging, and it needed to be resilient and realistic. Multiple types of materials were tested between January 2020 and August 2022. Participants were recruited stepwise. A left lateral segmentectomy simulation was conducted between August 2022 and December 2022 to assess protocol adherence.

Results.

Digital anatomy 3-dimensional printing was considered the best option for the hands-on liver model. The recruitment rate was 100% and 47% for junior attendings and surgical residents, respectively. Ten participants were included and completed all the required surveys. Seven (70%) and 6 (60%) participants “agreed” that the overall quality of the model and the material were acceptable for surgical simulation. Five participants (50%) “agreed” that the training improved their surgical skills. Nine participants (90%) “strongly agreed” that similar sessions should be included in surgical training programs.

Conclusions.

Three-dimensional hands-on liver models have the advantage of tactile feedback and were rated favorably as a potential training tool. Study enrollment for further studies is possible with the support of leadership. Rigorous multicenter designs should be developed to measure the actual impact of 3-dimensional hands-on liver models on surgical training.
Knowledge, Attitudes, and Beliefs Toward Organ Donation Registration Among Asian Americans: Development and Pilot-testing of Educational Intervention Video
Authors: Li Miah T. , Hillyer Grace C. , King Kristen L. , Yu Miko , Husain S. Ali , Mohan Sumit
Published: August 2024

Background.

Organ donation registration rates in the United States are lowest among Asian Americans. This study aimed to investigate the reasons for low organ donation registration rates among Asian Americans and develop educational material to help improve organ donation rates and awareness.

Methods.

We conducted a 2-phase study. In phase 1, a cross-sectional observational survey was distributed in-person on an iPad to members of the Asian community in Queens, New York, to investigate their knowledge, attitudes, and beliefs toward organ donation. Based on the results, an educational video was developed, and the efficacy of the video was assessed with an independent cohort of participants in phase 2 using a pre-/post-video comprehension assessment survey.

Results.

Among 514 Chinese or Korean Americans who participated in the phase 1 survey, 97 participants (19%) reported being registered organ donors. Registered donors were more likely to have previously discussed their organ donation wishes with their family (adjusted odds ratio [aOR], 4.77; 95% confidence interval [CI], 2.56-8.85; P < 0.01), knowledge of the different registration methods (aOR, 2.57; 95% CI, 1.24-5.31; P < 0.01), or know a registered organ donor (aOR, 2.62; 95% CI, 1.39-4.95; P < 0.01). For the educational video efficacy assessment given pre-/post-video, the majority (90%) of the respondents reported learning something new from the video. After watching the video, there was a significant improvement in the mean knowledge score regarding organ donation (63% versus 92%; P < 0.01) and an increase in intention to have discussion regarding organ donation with family.

Conclusions.

We found varies factors associated with low organ donation registration rates among Asian Americans and demonstrated the potential of our educational video to impart organ donation knowledge to viewers and instigate the intention to have family discussions regarding organ donation. Further research is needed to assess the impact of videos in motivating actual organ donation registration.
Exploring Musculoskeletal Injuries Among Informal and Formal Carers of People With Dementia
Authors: Dimakopoulou Eleni , Bampouras Theodoros M. , Katsardi Georgia , Tavoulareas Georgios , Karydaki Maria , Theodorelou Maria , Zoi Panagiota , Sakka Paraskevi
Published: August 2024

Background:

Carers of people with dementia manually handle the care recipients (eg, repetitive lifting, transferring, and pulling) as part of the care service, increasing the musculoskeletal injury risk to themselves.

Objective:

We aimed to determine the prevalence of musculoskeletal injuries among informal and formal carers of people with dementia and the perceived associated risk factors.

Methods:

Primary carers of people with dementia (26 males and 141 females) from Dementia Care Centers and Home Care programs completed a questionnaire providing information about (a) the carers’ and their care recipients’ characteristics, (b) musculoskeletal symptoms (via the Nordic Musculoskeletal Questionnaire) and related aspects, and (c) the caregiving activities exposing the carers to risk of musculoskeletal injury.

Results:

Our results showed that 69.7% of informal and 86.7% of formal carers reported having more than 1 musculoskeletal injury, while 63.1% and 61.5%, respectively, reported having a musculoskeletal injury in the last year. Lower back had the highest injury prevalence (>10% for both groups). The 2 carer groups were not different in any of the variables.

Conclusions:

Our results reinforce calls for education and support of carers, regardless of their formal status, to enable injury-free and prolonged service provision.
Reclaiming behaviour settings: reviewing empirical applications of Barker’s behaviour settings theory
Authors: Avram Christa M. , Jones Anne E. , Lucas Miranda L. , Barrett Louise
Published: August 2024

Behaviour settings theory is the product of Roger Barker and Herbert F. Wright’s decades-long Midwest Field Station research programme. The theory followed from the demonstration that the best predictor of a person’s behaviour was the setting (i.e. location, timing and activity) in which their behaviour took place, rather than any individual trait (e.g. personality). Now little known in psychology, behaviour settings theory is often further obscured by being presented as a theory only, neglecting the clear methodology Barker provided for investigating the question: ‘What do people do in everyday life?’ This literature review takes a comprehensive look at Barker’s contributions both within and outside of psychology. The corpus comprises both theoretical and empirical articles; however, our primary interest is in the empirical articles. We describe the who, when and where of behaviour settings research over the past half-century, and we identify branches and neighbours of behaviour settings research (e.g. manning theory, behaviour mapping and activity settings theory). Primarily, however, we attempt to answer the following questions: (i) Are any of Barker’s tools for studying people in everyday settings being used currently? (ii) How accurately has Barker’s theory been explained, or his methods applied? (iii) Does such work contribute to behaviour settings theory in a meaningful way?

This article is part of the theme issue ‘People, places, things and communities: expanding behaviour settings theory in the twenty-first century’.
Applying the Barker School concept of ‘behaviour settings’ to virtual contexts
Authors: Aunger Robert , Deterding Sebastian , Zhao Xiaoyang , Baxter Weston
Published: August 2024

People are spending more and more time interacting with virtual objects and environments. We argue that Roger Barker’s concept of a ‘behaviour setting’ can be usefully applied to such experiences with relatively little modification if we recognize subjective aspects of such experiences such as presence and immersion. We define virtual behaviour settings as virtual environments where the partly or fully digital milieu is synomorphic with and circumjacent to embodied behaviour, as opposed to the fragmented behaviour settings of much-mediated interaction. We present two tools that can help explain and predict the outcomes of virtual experiences—the behaviour setting canvas (BSC) and model—and demonstrate their utility through examples. We conclude that the behaviour setting concept is helpful in both designing virtual environments and understanding their impact, while virtual environments offer a powerful new methodological paradigm for studying behaviour settings.

This article is part of the theme issue ‘People, places, things, and communities: expanding behaviour settings theory in the twenty-first century’.
Resting-State Electroencephalography and Magnetoencephalography in Migraine – A Systematic Review and Meta-Analysis
Authors: Zebhauser Paul Theo , Heitmann Henrik , May Elisabeth S. , Ploner Markus
Published: August 2024

Magnetoencephalography/electroencephalography (M/EEG) can provide insights into migraine pathophysiology and help develop clinically valuable biomarkers. To integrate and summarize the existing evidence on changes in brain function in migraine, we performed a systematic review and meta-analysis (PROSPERO CRD42021272622) of resting-state M/EEG findings in migraine. We included 27 studies after searching MEDLINE, Web of Science Core Collection, and EMBASE. Risk of bias was assessed using a modified Newcastle–Ottawa Scale. Semi-quantitative analysis was conducted by vote counting, and meta-analyses of M/EEG differences between people with migraine and healthy participants were performed using random-effects models. In people with migraine during the interictal phase, meta-analysis revealed higher power of brain activity at theta frequencies (3-8 Hz) than in healthy participants. Furthermore, we found evidence for lower alpha and beta connectivity in people with migraine in the interictal phase. No associations between M/EEG features and disease severity were observed. Moreover, some evidence for higher delta and beta power in the premonitory compared to the interictal phase was found. Strongest risk of bias of included studies arose from a lack of controlling for comorbidities and non-automatized or non-blinded M/EEG assessments. These findings can guide future M/EEG studies on migraine pathophysiology and brain-based biomarkers, which should consider comorbidities and aim for standardized, collaborative approaches.
Analysis of Multiple Myeloma Drug Efficacy
Authors: Matov Alexandre
Published: August 2024

Introduction

Multiple myeloma (MM) is an incurable plasma cell neoplasm. MM-specific alterations in methylation status cause gradual epigenetic changes and lead to pre-MM disease states, such as Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering MM (SMM). The communication between MM cells and the bone marrow (BM) stromal cells serves a pivotal role in MM development by supporting transformed cell growth and proliferation. MM cells are known to modify the BM microenvironment through secretion of exosomes, which enhances disease progression by the induction of angiogenesis, immune suppression as well as drug resistance. This form of intercellular communication is thought to be mediated by several types of cargo molecules prevalent in exosomes, including microRNAs (miRs).

Methods

The main obstacle in the treatment of MM is the difficulty in eliminating the residual cancer cells. Even if there are multiple treatment options, none is curative, and remissions have an unpredictable relapse onset. We attempt to address the two hurdles in terms of the difficulty in predicting the duration of remission and the challenge, which currently remains out of reach, treatment regiments that guarantee cancer-free bone marrow and propose a computational strategy based on our analysis of patient samples and patient cultures.

Results

Our method will allow performing quantitative live-cell companion diagnostics by evaluating the relative contribution of different signaling pathways in drug resistance and response via quantitative exosome imaging, beyond MM, in primary tumor cells originating from different organs and tissues.

Conclusions

Our approach will allow us to identify putative drug targets for the treatment of refractory disease for which currently there is no known suitable treatment regimen in acute myeloid leukemia, primary pancreatic, and bone metastatic prostate tumors.
A transgene-free, human peri-gastrulation embryo model with trilaminar embryonic disc-, amnion- and yolk sac-like structures
Authors: Sun Shiyu , Zheng Yi , Kim Yung Su , Zhong Zheng , Kobayashi Norio , Xue Xufeng , Liu Yue , Zhou Zhuowei , Xu Yanhong , Zhai Jinglei , Wang Hongmei , Fu Jianping
Published: August 2024

The ultimate outcome of the gastrulation in mammalian development is a recognizable trilaminar disc structure containing organized cell lineages with spatially defined identities in an emerging coordinate system1–4. Despite its importance in human development, gastrulation remains difficult to study. Stem cell-based embryo models, including those that recapitulate different aspects of pre- and peri-gastrulation human development5–15, are emerging as promising tools for studying human embryogenesis16–18. However, it remains unclear whether existing human embryo models are capable of modeling the development of the trilaminar embryonic disc structure, a hallmark of human gastrulation. Here we report a transgene-free human embryo model derived solely from primed human pluripotent stem cells (hPSCs), which recapitulates various aspects of peri-gastrulation human development, including formation of trilaminar embryonic layers situated between dorsal amnion and ventral definitive yolk sac and primary hematopoiesis. We term this model the peri-gastrulation trilaminar embryonic disc (PTED) embryoid. The development of PTED embryoid does not follow natural developmental sequences of cell lineage diversification or spatial organization. Instead, it exploits both extrinsic control of tissue boundaries and intrinsic self-organizing properties and embryonic plasticity of the diverse peri-gastrulation-stage cell lineages, leading to the emergence ofin vivo-like tissue organization and function at a global scale. Our lineage tracing study reveals that in PTED embryoids, embryonic and extraembryonic mesoderm cells, as well as embryonic and extraembryonic endoderm cells, share common progenitors emerging during peri-gastrulation development. Active hematopoiesis and blood cell generation are evident in the yolk sac-like structure of PTED embryoids. Together, PTED embryoids provide a promising and ethically less challenging model for studying self-organizing properties of peri-gastrulation human development.
Highly Extensible Physically Crosslinked Hydrogels for High-Speed 3D Bioprinting
Authors: Song Ye Eun , Eckman Noah , Sen Samya , Jons Carolyn K. , Saouaf Olivia M. , Appel Eric A.
Published: August 2024

Hydrogels have emerged as promising materials for bioprinting and many other biomedical applications due to their high degree of biocompatibility and ability to support and/or modulate cell viability and function. Yet, many hydrogel bioinks have suffered from low efficiency due to limitations on accessible printing speeds, often limiting cell viability and/or the constructs which can be generated. In this study, we report a highly extensible bioink system created by modulating the rheology of physically crosslinked hydrogels comprising hydrophobically-modified cellulosics and either surfactants or cyclodextrins. We demonstrate that these hydrogels are highly shear-thinning with broadly tunable viscoelasticity and stress-relaxation through simple modulation of the composition. Rheological experiments demonstrate that increasing concentration of rheology-modifying additives yields hydrogel materials exhibiting extensional strain-to-break values up to 2000%, which is amongst the most extensible examples of physically crosslinked hydrogels of this type. We demonstrate the potential of these hydrogels for use as bioinks by evaluating the relationship between extensibility and printability, demonstrating that greater hydrogel extensibility enables faster print speeds and smaller print features. Our findings suggest that optimizing hydrogel extensibility can enhance high-speed 3D bioprinting capabilities, reporting over 5000-fold enhancement in speed index compared to existing works reported for hydrogel-based bioinks in extrusion-based printing.
Asymmetric genome merging leads to gene expression novelty through nucleo-cytoplasmic disruptions and transcriptomic shock inChlamydomonastriploids
Authors: Prost-Boxoen Lucas , Bafort Quinten , Van de Vloet Antoine , Almeida-Silva Fabricio , Thet Paing Yunn , Casteleyn Griet , D’hondt Sofie , De Clerck Olivier , Van de Peer Yves
Published: August 2024

Genome merging is a common phenomenon in many organisms, causing a wide range of consequences on phenotype, adaptation, and gene expression, among other effects, yet its broader implications are not well understood. Two consequences of genome merging on gene expression remain poorly understood: dosage effects and evolution of expression. In this study, we employedChlamydomonas reinhardtiias a model to investigate the effects of asymmetric genome merging by crossing a diploid with a haploid strain to create a novel triploid line. Five independent clonal lineages derived from this triploid line were evolved for 425 asexual generations in a laboratory natural selection (LNS) experiment. Utilizing fitness assays, qPCR, and RNA-Seq, we assessed the immediate consequences of genome merging and subsequent evolution over time. Our findings reveal substantial alterations in gene expression, protein homeostasis (proteostasis) and cytonuclear stoichiometry. Notably, gene expression exhibited expression level dominance and transgressivity (i.e., expression level higher or lower than either parent). Ongoing expression level dominance and a pattern of “functional dominance” from the haploid parent was observed, alongside remarkable stability in expression patterns across generations. Despite major nucleo-cytoplasmic disruptions, enhanced fitness was detected in the triploid strain. By comparing gene expression across generations, our results indicate that proteostasis restoration is a critical component of rapid adaptation following genome merging inChlamydomonas reinhardtiiand possibly other systems.
Precision cutaneous stimulation in freely moving mice
Authors: Parkes Isobel , Schorscher-Petcu Ara , Gan Qinyi , Browne Liam E.
Published: August 2024

Somatosensation connects animals to their immediate environment, shaping critical behaviors essential for adaptation, learning, and survival. Probing the relationships between somatosensory inputs and behavior in mice presents substantial challenges, primarily due to the practical difficulties of delivering stimuli to the skin in moving mice. To address this problem, we have developed a system for precise cutaneous stimulation of mice as they walk and run through environments. The system employs real-time body part tracking and targeted optical stimuli, offering precision while preserving the naturalistic context of the behaviors studied to overcome the traditional trade-offs between precision and animal behavior. We demonstrate the system across nociceptive testing conducted in standard small chambers to behavior in large complex environments, such as mazes. We observed that cutaneous inputs evoke rapid responses, which modify behavior when stimuli are applied during motion. This system provides a means to explore the diverse and integrative nature of somatosensation, from reflexes to decision-making, in naturalistic settings.
Differential Contributions of CA3 and Entorhinal Cortex Inputs to Ripple Patterns in the Hippocampus Under Cannabidiol
Authors: Aleman-Zapata Adrian , Capitan Melisa Maidana , Samanta Anumita , Özsezer Pelin , Agarwal Kopal , Adam Tugdual , Rayan Abdelrahman , Genzel Lisa
Published: August 2024

Cannabidiol (CBD), increasingly recognized for its potential to treat insomnia, notably extends NonREM sleep phases and modifies sleep-associated ripple dynamics. Utilizing a threshold-based approach, our study differentiated distinct ripple types in rats, clarifying the contributions of intra-hippocampal (CA3) and cortical (mEC) regions to these events. The findings reveal that CBD primarily influences the CA3’s input to the CA1, resulting in an increased occurrence of short ripples predominantly induced by cortical (mEC) activity and a corresponding decrease in long, intra-hippocampal sharp-wave-ripples. This study highlights the critical interplay between the CA3 and entorhinal cortex dynamics in shaping the characteristics of hippocampal ripples under the influence of CBD.
Predicting plasmodesmata-mediated interface permeability and intercellular diffusion
Authors: Liesche Johannes , Li Jiazhou , Martens Helle Jakobe , Gao Chen , Subroto Angeline Christina , Schulz Alexander , Deinum Eva
Published: August 2024

Intercellular communication is essential for plant development and responses to biotic and abiotic stress. A key pathway is diffusive exchange of signal molecules and nutrients via plasmodesmata. These cell wall channels connect the cytoplasms of most cells in land plants. Their small size, with a typical diameter of about 50 nm, and complex structure have hindered the quantification plasmodesmata-mediated intercellular diffusion. This measure is essential for disentangling the contributions of diffusive and membrane transporter-mediated movement of molecules that, together, define cell interactions within and across tissues. We compared the two most promising methods to measure plasmodesmata-mediated interface permeability, live-cell microscopy with fluorescent tracer molecules and transmission electron microscopy-based mathematical modeling, to evaluate the potential for obtaining absolute quantitative values. We applied both methods to 29 cell-cell interfaces from nine angiosperm species and found a stronger association between the modelled and experimentally determined interface permeabilities than between the experimentally-determined permeability and any single structural parameter. By feeding the values into a simulation of an artificial Arabidopsis leaf, we illustrate how interface permeabilities can help to predict diffusion patterns of defense-related molecules, such as glucosinolates and transcription factors.
Study on the phenotypic diversity and comprehensive evaluation analysis of 43 ornamental peonies of Sect.Paeonia
Authors: Cao Hui-yan , Xu Shi-yi , Liu Mei-qi , Jiang Shan , Ma Leng-leng , Wu Jian-hao , Zhang Xiao-Zhuang , Kong Ling-yang , Ren Wei-chao , Liu Zhi-yang , Chen Xi , Ma Wei , Liu Xiu-bo
Published: August 2024

The peony of Sect.Paeoniawas a perennial herbaceous plant with numerous ornamental varieties and riched diversity in flower color and shape. It has ornamental, edible, and medicinal value and a long history of cultivation in China. The study of phenotypic diversity of plants is an important foundation for plants of Sect.Paeoniabreeding. This study conducted phenotypic diversity analysis, principal component analysis, and cluster analysis on 43 varieties of Sect.Paeoniagermplasm resources. Phenotypic traits included 30 qualitative traits and 7 quantitative traits. Through genetic diversity analysis, principal component analysis, comprehensive evaluation, and cluster analysis, we ultimately concluded that plant samples had relatively rich genetic phenotype traits. In principal component analysis, the first 12 principal components have covered the vast majority of information for phenotypic traits. The comprehensive evaluation results of phenotypic traits indicate that the F values of each variety in the germplasm sample were all positive number. The degree of stamen petals played a key role in determining the phenotypic diversity of plants, and the shape of the cotyledons and leaflets may determine the plant’s stress resistance performance, which provides a reference for breeding new varieties of peonies of Sect.Paeonia.
AMPK/ULK1 activation downregulates TXNIP, Rab5, and Rab7 and inhibits endocytosis-mediated entry of human pathogenic viruses
Authors: Diesendorf Viktoria , La Rocca Veronica , Teutsch Michelle , Alattar Haisam , Obernolte Helena , Kenst Kornelia , Seibel Jens , Wörsdörfer Philipp , Sewald Katherina , Steinke Maria , Schneider-Schaulies Sibylle , Lutz Manfred B. , Munschauer Mathias , Bodem Jochen
Published: August 2024

Cellular metabolism must adapt rapidly to environmental alterations and adjust nutrient uptake. Low glucose availability activates the AMP-dependent kinase (AMPK) pathway. We demonstrate that activation of AMPK or the downstream Unc-51-like autophagy-activating kinase (ULK1) inhibits receptor-mediated endocytosis. Beyond limiting dextran-uptake, this activation prevents endocytic uptake of human pathogenic enveloped and non-enveloped, positive and negative-stranded RNA viruses, such as yellow fever, dengue, tick-borne encephalitis, chikungunya, polio, rubella, rabies lyssavirus and SARS-CoV-2 not only in mammalian and insect cells but in precision-cut lung slices and neuronal organoids. However, receptor presentation at the cytoplasmic membrane was unaffected, indicating that receptor-binding remained unaltered and later steps of endocytosis were targeted. Indeed, AMPK pathway activation reduced early endocytic factors TXNIP, Rab5 and the late endosomal marker Rab7 amounts. Furthermore, AMPK activation impaired SARS-CoV-2 late-replication steps by reducing viral RNAs and proteins and the endo-lysosomal markers LAMP1 and GRP78, suggesting a reduction of early and late endosomes and lysosomes. Inhibition of the PI3K and mTORC2 pathways, which sense amino acids and growth factor availability, promotes AMPK activity and blocks viral entry. Our results indicate that AMPK and ULK1 emerge as restriction factors of cellular endocytosis, impeding the receptor-mediated endocytic entry of enveloped and non-enveloped RNA viruses.
Enhanced translational activity is linked to lymphatic endothelial cell activation in cutaneous leishmaniasis
Authors: Fry Lucy , Roys Hayden , Bowlin Anne , Venugopal Gopinath , Bird Jordan T. , Weaver Alexx , Byrum Stephanie D. , Weinkopff Tiffany
Published: August 2024

Cutaneous leishmaniasis (CL) is a significant public health problem leading to permanently disfiguring skin lesions caused byLeishmaniaparasites. Lesion severity stems from an excessive host inflammatory response that prevents healing. Here, we characterized the transcriptional and translational responses of lymphatic endothelial cells (LECs) during murine CL using historical single-cell RNA sequencing data combined with flow cytometry and in vivo puromycin incorporation to assess translational activity. We identified upregulation of antigen presentation pathways including MHC-I, MHC-II, and immunoproteasome transcripts in dermal LECs fromLeishmania major-infected mice compared to naive controls. LECs also exhibited increased expression of guanylate binding proteins and interferon-inducible genes, indicative of immune activation. Moreover, our findings demonstrate that LECs in leishmanial lesions displayed heightened translational activity relative to LECs from uninflamed ears, and LEC translational activity was highest in activated LECs. Furthermore, LEC translational activity exceeded that of other cell types within the lesion microenvironment. Validating the transcriptomic data, LECs in lesions expressed elevated MHC-II and programmed death-ligand 1 (PDL-1), supporting their potential role in antigen presentation. Functional assays using DQ-OVA confirmed that LECs from leishmanial lesions efficiently uptake and process antigens, highlighting their capability as antigen presenting cells in the inflamed dermal microenvironment. Overall, our study reveals the activation status of LECs in leishmanial lesions, shedding light on their potential role in shaping local immunity and inflammation in a variety of skin diseases.
LitGene: a transformer-based model that uses contrastive learning to integrate textual information into gene representations
Authors: Jararweh Ala , Macaulay Oladimeji , Arredondo David , Oyebamiji Olufunmilola M , Hu Yue , Tafoya Luis , Zhang Yanfu , Virupakshappa Kushal , Sahu Avinash
Published: August 2024

Representation learning approaches leverage sequence, expression, and network data, but utilize only a fraction of the rich textual knowledge accumulated in the scientific literature. We present LitGene, an interpretable transformer-based model that refines gene representations by integrating textual information. The model is enhanced through a Contrastive Learning (CL) approach that identifies semantically similar genes sharing a Gene Ontology (GO) term. LitGene demonstrates accuracy across eight benchmark predictions of protein properties and robust zero-shot learning capabilities, enabling the prediction of new potential disease risk genes in obesity, asthma, hypertension, and schizophrenia. LitGene’s SHAP-based interpretability tool illuminates the basis for identified disease-gene associations. An automated statistical framework gauges literature support for AI biomedical predictions, providing validation and improving reliability. LitGene’s integration of textual and genetic information mitigates data biases, enhances biomedical predictions, and promotes ethical AI practices by ensuring transparent, equitable, open, and evidence-based insights. LitGene code is open source and also available for use via a public web interface atlitgene.avisahuai.com.
Forest dieback in drinking water protection areas – a hidden threat to water quality
Authors: Winter Carolin , Müller Sarina , Kattenborn Teja , Stahl Kerstin , Szillat Kathrin , Weiler Markus , Schnabel Florian
Published: August 2024

For centuries, forests have been considered a natural safeguard for drinking water quality. We challenge this view in light of the rising frequency of climate extremes, such as droughts coinciding with high temperatures, which have caused unprecedented pulses of forest dieback globally. Drought-induced forest diebacks may jeopardize the crucial role of forests in protecting water quality, potentially even turning forests into sources of contamination. To underscore the critical importance of the topic, here we provide the first comprehensive assessment of forest cover, type, and dieback (assessed as canopy cover loss) across drinking Water Protection Areas (WPAs) in Germany, one of the countries hit most severely by the unprecedented Central European drought of 2018–2020. Our findings reveal a high forest cover of 43% in WPAs, from which a substantial amount of 5% canopy cover got lost within only three years as a direct or indirect consequence of the drought. Spruce-dominated forests, constituting 28% of all forests in WPAs, were particularly susceptible, but other dominant tree species also experienced anomalously high mortality rates. Combining this assessment with exemplary records of nitrate concentrations in the groundwater of WPAs revealed that forest dieback can significantly impair drinking quality. On average, nitrate concentrations more than doubled in WPAs with severe forest dieback, whereas nitrate concentrations did not significantly change in undisturbed WPAs. However, we also found pronounced differences between WPAs affected by forest dieback, underlining the need for further data and research to derive a generalizable understanding of the underlying mechanisms and controls. Based on this assessment, we deduce critical data and knowledge gaps essential to developing well-informed prediction, adaptation, and mitigation strategies. We call for interdisciplinary research addressing the hidden threat forest dieback poses for our drinking water resources.
Adults with Severe Acute Respiratory Illness in Glasgow, 2021-22: A Prospective Cohort Study
Authors: Ho Antonia , McInnes Neil , Blunsum Andrew , Quinn Joanna , Lynagh Daniel , Murphy Michael E , Gunson Rory , MacConnachie Alisdair , Lowe David J
Published: August 2024

Objectives

We report the findings of a novel enhanced syndromic surveillance which characterised influenza- and SARS-CoV-2-associated severe acute respiratory illness (SARI) in the 2021/2022 winter season.

Methods

Prospective cohort study of adults admitted to the Queen Elizabeth University Hospital, Glasgow, with a severe acute respiratory illness. Patient demographics, clinical history, admission details, and outcome were recorded.

Results

Between November 2021 and May 2022, 1,063 hospitalised SARI episodes in 1,037 adult patients were identified. Median age was 72.0 years and 44.5% were male. Most (82.6%) SARI cases had ≥1 co-morbidity; chronic lung disease (50.0%) and malignancy (22.5%) were the most frequently reported.

Overall, 229 (22%) and 33 (3%) SARI episodes were SARS-CoV-2 and influenza A PCR positive, respectively. Overall, 74.7%, 6.5% and 43.0% SARI episodes received antibiotics, antivirals, and steroids, respectively (54.5, 11.0 and 51.3% among COVID-19 patients). 1.1% required mechanical ventilation and 7.8% died. Male sex, multimorbidity, frailty, respiratory rate >30, low GCS and chest X-ray consolidation were predictive of in-hospital mortality.

Conclusion

Our syndromic surveillance provided near real-time data on hospitalised SARI to clinicians and Public Health Scotland, and informed them of the evolving clinical epidemiology of SARS-CoV-2 and influenza as we transition from the pandemic phase.
Dense dipole-dipole-coupled two-level systems in a thermal bath
Authors: Macovei Mihai A.
Published: August 2024

The quantum dynamics of a dense and dipole-dipole-coupled ensemble of two-level emitters interacting via their environmental thermostat is investigated. The static dipole-dipole interaction strengths are being considered strong enough but smaller than the transition frequency. Therefore, the established thermal equilibrium of ensemble's quantum dynamics is described with respect to the dipole-dipole-coupling strengths. We have demonstrated the quantum nature of the spontaneously scattered light field in this process for weaker thermal baths as well as non-negligible dipole-dipole couplings compared to the emitter's transition frequency. Furthermore, the collectively emitted photon intensity suppresses or enhances depending on the environmental thermal baths' intensities.

Published by the American Physical Society
2024
In situ
observation of chemistry in Rydberg molecules within a Bose-Einstein-condensate
Authors: Engel Felix , Tiwari Shiva Kant , Pfau Tilman , Wüster Sebastian , Meinert Florian
Published: August 2024

We often infer the state of systems in nature indirectly, for example, in high-energy physics by the interaction of particles with an ambient medium. We adapt this principle to energies 9 orders of magnitude smaller, to classify the final state of exotic molecules after internal conversion of their electronic state, through their interaction with an ambient quantum fluid, a Bose-Einstein condensate (BEC). The BEC is the ground state of a million bosonic atoms near zero temperature, and a single embedded ultra-long-range Rydberg molecule can coherently excite waves in this fluid, which carry telltale signatures of its dynamics. Bond lengths exceeding a micrometer allow us to observe the molecular fingerprint on the BEC , via optical microscopy. Interpreting images in comparison with simulations strongly suggests that the molecular electronic state rapidly converts from the initially excited S and D orbitals to a much more complex molecular state (called “trilobite”), marked by a maximally localized electron. This internal conversion liberates energy, such that one expects final-state particles to move rapidly through the medium, which is however ruled out by comparing experiment and simulations. The molecule thus must strongly decelerate in the medium, for which we propose a plausible mechanism. Our experiment demonstrates a medium that facilitates and records an electronic state change of embedded exotic molecules in ultracold chemistry, with sufficient sensitivity to constrain velocities of final-state particles.

Published by the American Physical Society
2024