bluuebunny/crossref_metadata_2025 huggingface dataset:
Multimodal Outcomes of Early Open Extended Midline Strip Craniectomy With Bilateral Microbarrel Staving for Correction of Isolated Nonsyndromic Sagittal Synostosis
Authors: Plonczak Agata M. , Hennedige Anusha , Kearney Anna , Blumenow Wendy , Piggott Katie , Garvie Laura , Milligan Claudine , Duncan Christian , Parks Chris James
Published: October 2024

Aim:

Sagittal synostosis is the most common craniosynostosis. The aim of surgery is to preserve cognitive function and to correct the morphologic changes. In our unit, the authors offer strip craniectomy and microbarrel staving (SMB) performed at 16 to 22 weeks. This study aims to ascertain the 7-year outcome of scaphocephaly correction by SMB. The authors investigate whether the improvement in cranial index (CI) is sustained over time, and report speech and language and neurodevelopmental outcomes.

Methods:

All nonsyndromic patients with sagittal synostosis who underwent SMB between 2009 and 2012 were identified from a prospectively created database that recorded anthropometric measurements, quality metrics, and neurodevelopmental outcomes.

Results:

A total of 27 patients were analyzed. The mean CI preoperatively was 67.5% (±3.5), and at 7 years 78% (±4.8). Regarding neurodevelopmental outcomes at 7 years, SDQ responses did not highlight any concerns for social, emotional, or behavioral outcomes. The vast majority of those who completed a WASI-II assessment performed within the average ranges in terms of cognitive ability. In terms of speech and language 70% of subjects demonstrated receptive language within normal level (WNL). Seventy-seven percent of subjects demonstrated expressive language WNL.

Conclusions:

In conclusion, after 7 years of follow-up, early open extended SMB is a safe and effective method for correction of isolated nonsyndromic isolated sagittal synostosis. Across the neurodevelopmental measures and assessments, the children in the current study appeared to perform within expected ranges. Speech and language problems are more prevalent than in the general population.
Maxillofacial Trauma in Females: A Retrospective Study
Authors: Attyia Marwa Akram , Bede Salwan Y.
Published: October 2024

Maxillofacial trauma in females is not widely reported. This study aimed to analyze the clinical characteristics and the patterns of maxillofacial injuries in females and to determine the differences in these patterns among different causes. This retrospective study analyzed several variables, including demographic, social, injury-related, and treatment-related variables, and compared these variables in relation to the main etiologies of maxillofacial trauma. The main etiologies of maxillofacial injuries involving females were assault, followed by road traffic accidents, and falls. There were significant differences in relation to the 3 etiologies in age groups (P= 0.002) and marital status (P< 0.0001). There were significantly more soft tissue injuries in the assault group compared with the other groups (P= 0.007). Associated injuries were significantly more with injuries caused by road traffic accidents (P= 0.0009). Most females were victims of assault and violence. There were significant differences in relation to the etiology of trauma in terms of age groups, marital status, types of injury, and associated injuries. Most of the assaults were due to domestic violence.
Improving Endoscopy Nursing Staff's Patient Management Through the Implementation of an Education Initiative
Authors: Blythe Josiah C. , Smith-Steinert Rachel M. , Crouch Jordan R. , Lehman Marcus E.
Published: October 2024

Endoscopic procedure areas have high-volume, fast-paced work environments. This practice requires a diverse range of knowledge and skills that are continuously changing with the evolution of high-acuity procedures and the shift toward routine use of anesthesia services. Endoscopy nursing staff have recently shown higher levels of stress and emotional exhaustion than their colleagues in similar practice settings. Patient management and recovery from anesthesia are identified by this group of nurses as a perceived stressor with high priority for improvement in competencies. Standardized education in collaboration with anesthesia services regarding these topics does not exist. As an improvement initiative, a standardized education guide was developed and implemented in an urban endoscopy unit situated within a Level 1 trauma center to improve nursing staff's patient management, knowledge, and readiness. Nursing knowledge was evaluated before and after the delivery of an educational presentation. Results demonstrated a substantial improvement in nursing knowledge and preparedness for complex procedures and high-acuity patients. Implementation of a similar standardized endoscopy nursing education guide has the potential to positively impact endoscopy nursing staff's knowledge and preparedness related to complex endoscopy patient care delivery, possibly relieving a source of stress for endoscopy staff and improving patient safety.
Immunogenicity of virus-like particle vaccine candidates against SARS-CoV-2 infection
Authors: Nguyen Hai Trong , Garg Ravendra , Gerdts Volker , Falzarano Darryl , Liu Qiang
Published: October 2024

SARS-CoV-2 variants could become more virulent and transmissible due primarily to the mutations of the viral spike protein, rendering currently approved vaccines less effective. More effective vaccines are needed as vaccination is by far the best strategy against this virus. We have produced two SARS-CoV-2 virus-like particles (VLPs) using a baculovirus BacMam expression platform and examined their immunogenicity in mice. VLP1 contains the spike protein from the Wuhan strain whereas VLP2 contains that of an Omicron variant. Mice immunized with VLP1 and boosted with VLP2 developed significantly higher antibodies in the sera, and more IFNγ secreting cells than the control group. Furthermore, both VLPs induced virus neutralization antibodies against the ancestral Wuhan and an Omicron variant. In conclusion, our study warrants further development of VLPs as effective vaccines against emerging variants of SARS-CoV-2.
Postpartum hormonal contraceptive use and risk of depression
Authors: Larsen Søren Vinther , Ozenne Brice , Mikkelsen Anders Pretzmann , Liu Xiaoqin , Madsen Kathrine Bang , Munk-Olsen Trine , Lidegaard Øjvind , Frokjaer Vibe G
Published: October 2024

Importance

Hormonal contraceptive (HC) use is associated with depression. It is, however, unknown whether this is also true in the postpartum period where women have a heightened depression risk and are routinely offered to start HC.

Objective

To determine if HC initiation postpartum is associated with depression development within 12 months postpartum.

Design

A cohort study based on Danish register data.

Setting

Nationwide population-based.

Participants

All primiparous women in Denmark who gave birth from 1997 through 2022. Women were excluded if they had a depression within 24 months prior to delivery, had multiple birth or stillbirth, or a diagnosis of breast cancer or liver tumor.

Exposure

HC initiation within 12 months postpartum treated as a time-varying exposure. HC types were categorized as combined oral contraceptives (COCs), combined non-oral contraceptives (CNOCs), progestogen-only pills (POPs), and progestogen-only non-oral contraceptives (PNOCs).

Main Outcome and Measure

Depression defined as filling an antidepressant prescription or receiving a hospital depression diagnosis. Adjusted hazards ratios (HRs) and average absolute risks of depression within 12 months postpartum were estimated using Cox regression and a G-formula estimator.

Results

Of 610,038 first-time mothers, 41% initiated HC within 12 months postpartum (mean [SD] age; 27.6 [4.3] years for HC users vs. 29.6 [4.8] years for non-users). HC initiation was associated with subsequent depression with a HR of 1.49 (95% CI, 1.42;1.56) compared to no use resulting in an increase in the 12-month absolute risk from 1.36% (1.32;1.39) to 1.54% (1.50;1.57).The HR for COC was 1.72 (1.63;1.82); CNOC 1.97 (1.64;2.36); PNOC 1.40 (1.25;1.56). POP exposure was associated with an initially reduced instantaneous risk but it was increased late postpartum. Investigating the impact of timing of initiation showed that the earlier COC was initiated postpartum the higher the associated rate ratio of depression.

Conclusions and Relevance

HC initiation postpartum was associated with 49% higher instantaneous depression risk resulting in an increase in 12-month risk from 1.36% to 1.54% in the observed population. Such associated risk was higher the earlier it was initiated postpartum, at least for COC. This raises the question if depression incidence postpartum is inflated by routine HC initiation after childbirth.
FBXO22deficiency defines a pleiotropic syndrome of growth restriction and multi-system anomalies associated with a unique epigenetic signature
Authors: Ramakrishna Navin B. , Johmura Yoshikazu , Ali Nur Ain , Mohamad Sahari Umar Bin , Alghamdi Malak , Bauer Peter , Khan Suliman , Ordoñez Natalia , Ferreira Mariana , Pinto Basto Jorge , Alkuraya Fowzan S. , Faqeih Eissa Ali , Mori Mari , Almontashiri Naif A. M. , Al Shamsi Aisha , ElGhazali Gehad , Abu Subieh Hala , Al Ojaimi Mode , El-Hattab Ayman W. , Al-Kindi Said Ahmed Said , Alhashmi Nadia , Alhabshan Fahad , Al Saman Abdulaziz , Tfayli Hala , Arabi Mariam , Khalifeh Simone , Taylor Alan , Alfadhel Majid , Jain Ruchi , Sinha Shruti , Shenbagam Shruti , Ramachandran Revathy , Altunoğlu Umut , Jacob Anju , Thalange Nandu , Shin Jay W. , Al-Maawali Almundher , Al-Shidhani Azza , Al-Futaisi Amna , Rabea Fatma , Chekroun Ikram , Al Marri Mohamed , Ohta Tomohiko , Nakanishi Makoto , Alsheikh-Ali Alawi , Ali Fahad R. , Bertoli-Avella Aida M. , Reversade Bruno , Abou Tayoun Ahmad
Published: October 2024

FBXO22encodes an F-box protein which acts as a substrate-recognition component of the SKP1-CUL1-F-box (SCF) E3 ubiquitin ligase complex. Despite its known roles in the post-translational ubiquitination and degradation of specific substrates, including histone demethylases, the impact of FBXO22 on human development remains unknown. Here, we characterize a pleiotropic syndrome with prominent prenatal onset growth restriction and notable neurodevelopmental delay across 14 cases from 12 families. Through exome and genome sequencing, we identify three distinct homozygous loss-of-functionFBXO22variants segregating with the disease: p.(Arg53Serfs*13), p.(Pro3Leufs*3) and p.(Val240Alafs*6), all predicted to lead to premature translation termination due to frameshift effects. We confirm that patient-derived primary fibroblasts are bereft of FBXO22 and show increased levels of the known substrate histone H3K9 demethylase KDM4B. Accordingly, we delineate a unique epigenetic signature for this disease in peripheral blood. Altogether, we identify and demonstrate that FBXO22 deficiency leads to a pleiotropic syndrome in humans encompassing growth restriction and neurodevelopmental delay, the pathogenesis of which may be explained by broad chromatin alterations.
Racialised experience of detention under the Mental Health Act: a photovoice investigation of practice, policy and legislation
Authors: Bhui Kamaldeep , Mooney Roisin , Joseph Doreen , McCabe Rose , Newbigging Karen , McCrone Paul , Raghavan Ragu , Keating Frank , Husain Nusrat
Published: October 2024

Background

The rates of compulsory admission and treatment (CAT) are rising in mental health systems in the UK. These disparities are reported among migrants and black and ethnic minorities in Europe and North America. Lived experience perspectives from marginalised and multiple disadvantaged people are neglected in research yet may offer vital and novel insights into preventive opportunities to reduce coercive care

Methods

We conducted a participatory photovoice research process to assemble the life- experiences of people within two years of receiving CAT. We purposively sampled to maximise diversity by age, ethnicity, and different ‘sections’ of the Mental Health Act (England & Wales, 1983, 2007) from 8 health systems in England. The images, captions, and reflective narratives were deepened over 3 workshops before thematic analysis.

Outcomes

Forty-eight ethnically diverse people with lived experience of CAT contributed over 500 images and 30 hours of transcribed narratives. Participants lives showed significant complexity in terms of multimorbidity, adverse childhood experiences, and carer roles. The findings suggest insufficient co-ordination to prevent CAT despite early help-seeking, not being taken seriously when seeking help, hostility and dismissive responses from professionals; unnecessary police involvement which was distressing, stigmatising, and risked criminalisation. Participants wanted more advocacy given their vulnerability and inability to process information in crisis, as well as therapeutic and creative activities in inpatient environments. Participants recommended more family and carer involvement, and more appropriate, frequent and personalised information about care options, appeals processes, levels of restriction, and seclusion. A major concern was the lack of highly skilled staff, trauma-informed care, and therapies into the community.

Interpretation

We showed epistemic injustice in care processes and recommend better standards for essential skills, prevention, trauma informed care and therapies. Criminalising and coercive responses must also be reduced.

Funding

This study/project is funded by the National Institute for Health Research (NIHR) Policy Research Programme [NIHR201704]. The views expressed are those of the author and not necessarily those of the NIHR or the Department of Health and Social Care
End-to-End Machine Learning based Discrimination of Neoplastic and Non-neoplastic Intracerebral Hemorrhage on Computed Tomography
Authors: Nawabi Jawed , Schulze-Weddige Sophia , Baumgärtner Georg Lukas , Orth Tobias , Dell Orco Andrea , Morotti Andrea , Mazzacane Federico , Kniep Helge , Hanning Uta , Scheel Michael , Fiehler Jens , Penzkofer Tobias
Published: October 2024

Purpose

To develop and evaluate an automated segmentation and classification tool for the discrimination of neoplastic and non-neoplastic intracerebral hemorrhage (ICH) on admission Computed Tomography (CT) utilizing images containing hemorrhage and perihematomal edema.

Materials and Methods

The models were developed and evaluated using a retrospective dataset of patients who presented with acute ICH of unknown cause upon admission, using CT scans obtained from a single institution between January 2016 and May 2020 for both training and testing. Etiology of ICH were binarized into non-neoplastic and neoplastic ICH according to follow-up MRI results based on the ATOMIC ICH classification. Masks for ICH and PHE were manually segmented. Two separate models were trained: 1) An nnU-Net segmentation model 2) A ResNet-34 classification model. An end-to-end tool was evaluated by concatenating the two models which allowed the segmentation model to preprocess the images for the classification model. Performance enhancement was assessed by fine-tuning the model on a randomly selected, small subset of the external cohort. To assess the model’s generalizability, the performance was additionally validated on an external dataset. Evaluation metrics were accuracy (Acc), area under the curve (AUC) and corresponding sensitivities and specificities.

Results

A total of 291 patients were included of whom 116 (39.86%) presented with neoplastic and 175 (60.14%) with non-neoplastic ICH. The end-to-end classification tool achieved an Acc of 86% and an AUC of 85% with a sensitivity and specificity of 80% and 93% in the test set. On the external validation cohort (n=58), the classification pipeline achieved an AUC of 68% and Acc of 66% (sensitivity 64%; specificity 67%). Fine-tuning on a selected small subset of the external cohort enhanced performance, achieving an AUC and accuracy of 70% (sensitivity 70%; specificity 71%).

Conclusion

An end-to-end classification tool achieved a high diagnostic performance and generalizability in classifying neoplastic from non-neoplastic ICH on CT, suggesting a robust framework for a potential clinical implementation as a decision-aided tool in early ICH management.
Outcomes of endoscopic ultrasound-guided transmural drainage for postoperative peripancreatic fluid collection with an external drainage-first approach
Authors: Noda Jun , Takano Yuichi , Tamai Naoki , Yamawaki Masataka , Azami Tetsushi , Niiya Fumitaka , Nishimoto Fumiya , Nagahama Masatsugu
Published: October 2024

Objectives

Endoscopic ultrasound-guided transmural drainage (EUS-TD) is widely performed to treat postoperative peripancreatic fluid collection (POPFC). Recent reports on EUS-TD lack a consensus on stent selection. This study aimed to assess the efficacy of EUS-TD for POPFC using an external drainage-first approach.

Methods

We retrospectively examined the medical records of patients with POPFC treated with EUS-TD using external drainage between October 2016 and July 2024. Technical success was defined as successful placement of the external drainage. Clinical success was defined as the disappearance of fluid collection on follow-up computed tomography without additional intervention.

Results

This study included 14 patients. The median duration from surgery to endoscopic treatment was 13 (range: 11–26) days. The median procedural time was 26 (range: 13–35) min. The technical success rate was 100%, and 6 Fr endoscopic nasocystic drainage was performed in all patients. The clinical success rate was 64.3%, and no adverse events were observed. In 35.7% (5/14) of the patients, additional endoscopic internal drainage was required; the POPFC was successfully controlled in all patients. The reasons for conversion to internal drainage were prolonged inflammation in one patient, remaining fluid collection in one patient, and requests from surgeons in three patients.

Conclusions

EUS-TD for POPFC with external drainage proved to be safe and effective, with a short procedure time. However, in certain patients, additional internal drainage is required.
Social Determinants of Health and Functional Brain Connectivity Predict Long-Term Physical Activity in Older Adults with a New Cardiovascular Diagnosis
Authors: Thovinakere Nagashree , Ghosh Satrajit S. , Itturia-Medina Yasser , Geddes Maiya R.
Published: October 2024

Background

Physical activity is essential for preventing cognitive decline, stroke and dementia in older adults. A new cardiovascular diagnosis offers a critical window for positive lifestyle changes. However, sustaining physical activity behavior change remains challenging and the underlying mechanisms are poorly understood.

Methods

To identify the neural, behavioral and contextual predictors of successful longer-term behavior change after a new cardiovascular diagnosis, we used support vector machine learning to predict changes in moderate-to-vigorous physical activity over four years in 295 cognitively unimpaired older adults from the UK Biobank, testing three models that incorporated baseline: (i) demographic, cognitive, and contextual factors, (ii) baseline resting-state functional connectivity alone, and (iii) combined multimodal features across all predictors.

Results

The combined multi-modal model had the highest predictive power (r=0.28, p=0.001). Key predictors included greenspace access, social support, retirement status, executive function, and between-network functional connectivity within the default mode, frontoparietal control and salience/ventral attention networks.

Conclusions

These findings underscore the importance of social and structural determinants of health and uncover neural mechanisms that may support lifestyle modifications. In addition to furthering our understanding of the mechanisms underlying successful physical activity behavior change, these findings help to guide the design of interventions and health policy with the ultimate goal of preventing cardiovascular disease burden and late-life cognitive decline.
Mental Effort and Counterfactuals Modulate Language Understanding: ERP Evidence in Older Adults
Authors: Salas-Herrera José Luis , Martínez Mabel Urrutia , Hinrichs Nicolás Andrés
Published: October 2024

The relationship between language and physical effort in older adults is a field that is scarcely explored in the literature associated with embodiment. An electrophysiological experiment was conducted to explore the modulation of two linguistic contexts: factual and counter-factual, in relation to physical and mental effort using electrophysiological components. 27 older adults (M = 70.34 years, SD = 4.82, 15 women and 12 men) read sentences on a computer screen and responded to an activation test. The results indicate that the linguistic, factual, and counterfactual contexts, as well as the embodiment parameter of mental effort modulate the understanding of language and participate with variable preponderance in different time windows. Furthermore, counterfactuality seems to facilitate the processing of high mental effort, and both factual and counterfactual language elicit the N400 component. These findings contribute to the growing body of research on embodied cognition by providing novel insights into the nuances of cognitive demands involved in language processing in aging population, paving the way for developing targeted interventions aimed at improving communication and cognitive well-being in older adults.
Identification of Cellular Signatures Associated with Chinese Hamster Ovary (CHO) Cell Adaptation for Secretion of Antibodies
Authors: Bai Ying , Mercade Ivan Domenech , Elgendy Ramy , Lambiase Giulia , Peak-Chew Sew Yeu , Franco Catarina , Wingett Steven W , Stevens Tim J , Grassi Luigi , Hitchcock Noah , Ferreira Cristina Sayago , Hatton Diane , Miller Elizabeth A. , Mistry Rajesh K
Published: October 2024

The secretory capacity of Chinese hamster ovary (CHO) cells remains a fundamental bottleneck in the manufacturing of protein-based therapeutics. Unconventional biological drugs with complex structures and processing requirements are particularly problematic. Although engineered vector DNA elements can achieve rapid and high-level therapeutic protein production, a high metabolic and protein folding burden is imposed on the host cell. Cellular adaptations to these conditions include differential gene expression profiles that can in turn influence the productivity and quality control of recombinant proteins. In this study, we used quantitative transcriptomics and proteomics analyses to investigate how biological pathways change with antibody titre. Gene and protein expression profiles of CHO pools and clones producing a panel of different monoclonal and bispecific antibodies were analysed during fed-batch production. Antibody-expressing CHO pools were heterogeneous, resulting in few discernible genetic signatures. Clonal lines derived from these pools, selected for high and low production, yielded a small number of differentially expressed proteins that correlated with productivity and were shared across biotherapeutics. However, the dominant feature associated with higher protein production was transgene copy number and resulting mRNA expression level. Moreover, variability between clones suggested that the process of cellular adaptation is variable with diverse cellular changes associated with individual adaptation events.
A novel method for harmonization of PET image spatial resolution without phantoms
Authors: Carbonell Felix , Zijdenbos Alex P. , Hempel Evan , Hajós Mihály , Bedell Barry J. ,   Alzheimer’s Disease Neuroimaging Initiative
Published: October 2024

The most common approach for estimating the spatial resolution of PET images in multi-center studies typically uses Hoffman phantom data as a surrogate. Specifically, the phantom-based matching resolution approach assumes that scanned phantom PET images are well approximated by a ground truth, noise-free digital phantom convolved with a Gaussian kernel of unknown size. The size of the kernel is then estimated by an exhaustive search on the amount of blurring needed to match the smoothed digital phantom to a particular scanned phantom image. Unfortunately, Hoffman phantom images may not always be readily available, and phantom-based approaches may yield sub-optimal results. We propose a new, computational approach that allows estimation of spatial resolution directly from the PET image itself. We generalized the so-called logarithmic intensity plots method to the 3D case to perform a spatial resolution estimation in both axial and in-plane directions of the PET images. The proposed approach was applied to two different cohorts. The first cohort consisted of [18F]florbetapir amyloid PET images and matching phantoms coming from a Phase II clinical trial and includes different scanner models and/or orientation and grid reconstructions. The second cohort included β-amyloid, FDG and tau PET images from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. We obtained in-plane and axial resolution estimators that vary between 3.5 mm and 8.5 mm for both PET and matching phantom images. In both cases, we obtained small across-subject variability in groups of images sharing the same PET scanner model and reconstruction parameters. For human PET images, we also obtained a strong cross-tracer and longitudinal consistency in the spatial resolution estimators. Our novel approach does not only eliminate the need for surrogate brain phantom data, but also provides a general framework that can be applied to a wide range of tracers and other image modalities, such as SPECT.
Maintenance of neuronal TDP-43 expression requires axonal lysosome transport
Authors: Ryan Veronica H. , Lawton Sydney , Reyes Joel F. , Hawrot James , Frankenfield Ashley M. , Seddighi Sahba , Ramos Daniel M. , Faghri Faraz , Johnson Nicholas L. , Zou Jizhong , Kampmann Martin , Replogle John , Yuan Hebao , Johnson Kory R. , Maric Dragan , Hao Ling , Nalls Mike A. , Ward Michael E.
Published: October 2024

TDP-43 mislocalization and pathology occurs across a range of neurodegenerative diseases, but the pathways that modulate TDP-43 in neurons are not well understood. We generated a Halo-TDP-43 knock-in iPSC line and performed a genome-wide CRISPR interference FACS-based screen to identify modifiers of TDP-43 levels in neurons. A meta-analysis of our screen and publicly available screens identified both specific hits and pathways present across multiple screens, the latter likely responsible for generic protein level maintenance. We identified BORC, a complex required for anterograde lysosome transport, as a specific modifier of TDP-43 protein, but not mRNA, levels in neurons. BORC loss led to longer half-life of TDP-43 and other proteins, suggesting lysosome location is required for proper protein turnover. As such, lysosome location and function are crucial for maintaining TDP-43 protein levels in neurons.
Population genomics uncover loci for trait improvement in the indigenous African cereal tef (Eragrostis tef)
Authors: Jones Maximillian R. W. , Kebede Worku , Teshome Abel , Girija Aiswarya , Teshome Adanech , Girma Dejene , Brown James K. M. , Quiroz-Chavez Jesus , Jones Chris S. , Wulff Brande B. H. , Assefa Kebebew , Tadele Zerihun , Mur Luis A. J. , Chanyalew Solomon , Uauy Cristobal , Shorinola Oluwaseyi
Published: October 2024

Tef (Eragrostis tef) is an indigenous African cereal that is gaining global attention as a gluten-free “superfood” with high protein, mineral, and fibre contents. However, tef yields are limited by lodging and by losses during harvest owing its small grain size (150x lighter than wheat). Breeders must also consider a strong cultural preference for white-grained over brown-grained varieties. Tef is relatively understudied with limited “omics” resources. Here, we resequenced 220 tef accessions from an Ethiopian diversity collection and also conducted multi-locational phenotyping for 25 agronomic and grain traits. Grain metabolome profiling revealed differential accumulation of fatty acids and flavonoids between white and brown grains. We conductedk-mer and SNP-based genome wide association and uncovered novel marker-trait associations. A significant 70 kb peak for panicle morphology contained the tef orthologue of riceqSH1, a transcription factor regulating inflorescence morphology in cereals. We also observed a previously unknown relationship between grain size, colour, and fatty acids. These traits were highly associated with retrotransposon insertions in homoeologues ofTRANSPARENT TESTA 2, a known regulator of grain colour. Our study provides valuable resources for tef research and breeding, facilitating the development of improved cultivars with desirable agronomic and nutritional properties.
A newly developed whole genome sequencing protocol enables early tracking of Enterovirus D68 molecular evolution
Authors: Giardina Federica AM , Romano Greta , Ferrari Guglielmo , Pellegrinelli Laura , Seiti Arlinda , Galli Cristina , Pariani Elena , Piralla Antonio , Baldanti Fausto
Published: October 2024

Background Human enterovirus D68 (EV-D68) has been associated with an increase in mild-to-severe pediatric respiratory diseases worldwide. The rate of circulation of this virus is largely underestimated in the population and genetic evolutionary data are usually available only for partial sequences (e.g VP1 region). To achieve a timely genomic surveillance, a reliable, high-throughput EV-68 sequencing assay is required. Here we report an improved high-throughput EV-D68 whole-genome sequencing (WGS) assay performed directly on clinical samples that is suitable for short-read sequencing platforms. Between June and December 2022, a total 37 (1.9%) respiratory samples were EV-D68 positive and together with 52 additional samples with a median cycle threshold of 28.3, ranging from 18 to 36.8 were included in the validation analyses. Overall, all the primers had good performance and no mismatches were detected in more than 85% of sequences (932 WGS dataset). Using a cut-off of Cq <32 in at least 85.5% of samples a WG or PG was obtained, confirming an acceptable positive sequencing rate for the designed method. A total of 65 WGS were obtained and have a mean coverage of 98.4% across the genome, with a median depth of 6158x (range 2815x-7560x). Based on the obtained data, this method is cost effective resulting in an easy-to-perform protocol helpful for tracing the evolution of EV-D68 in protein different from VP1. EV-D68 could become a significant pathogen for public health in the next future, and thus this protocol for whole genome sequencing could help clinical and molecular virologists to be ready for molecular epidemiology surveillance.
Spatial and Spectral Changes in Cortical Surface Potentials during Pinching versus Thumb and Index Finger Flexion
Authors: Kerezoudis Panagiotis , Jensen Michael A , Huang Harvey , Ojemann Jeffrey G. , Klassen Bryan T. , Ince Nuri F. , Hermes Dora , Miller Kai J
Published: October 2024

Electrocorticographic (ECoG) signals provide high-fidelity representations of sensorimotor cortex activation during contralateral hand movements. Understanding the relationship between independent and coordinated finger movements along with their corresponding ECoG signals is crucial for precise brain mapping and neural prosthetic development. We analyzed subdural ECoG signals from three adult epilepsy patients with subdural electrode arrays implanted for seizure foci identification. Patients performed a cue-based task consisting of thumb flexion, index finger flexion or a pinching movement of both fingers together. Broadband power changes were estimated using principal component analysis of the power spectrum. All patients showed significant increases in broadband power during each movement compared to rest. We created topological maps for each movement type on brain renderings and quantified spatial overlap between movement types using a resampling metric. Pinching exhibited the highest spatial overlap with index flexion, followed by superimposed index and thumb flexion, with the least overlap observed for thumb flexion alone. This analysis provides practical insights into the complex overlap of finger representations in the motor cortex during various movement types, and may help guide more nuanced approaches to brain-computer interfaces and neural prosthetics.

SIGNIFICANCE STATEMENT

This study measured brain activity actively during finger movement and found that pinching movements show higher cortical overlap with index finger flexion and uniquely engage parietal regions, advancing our understanding of motor control hierarchy and sensorimotor integration, while suggesting improvements for more naturalistic brain-computer interfaces through prioritized index finger decoding and integration of parietal lobe measurements.
scGNN+: Adapting ChatGPT for Seamless Tutorial and Code Optimization
Authors: Jiang Yi , Wang Shuang , Feng Shaohong , Wang Cankun , Wu Weidong , Huang Xiaopei , Ma Qin , Wang Juexin , Ma Anjun
Published: October 2024

Foundation models have transformed AI by leveraging large-scale data to efficiently perform diverse tasks, and their applications in bioinformatics are primarily focused on data-centric tasks like cell type annotation and gene expression analysis. However, their potential extends beyond data analysis, offering significant opportunities in software development and optimization, such as code refinement, tutorial generation, and advanced visualization. For example, models like OpenAI Codex can suggest optimized code snippets and generate well-documented, reproducible workflows, enhancing accessibility and reducing computational complexity. Despite these advantages, the use of foundation models for improving computational tool engineering in single-cell research remains underutilized. To address this gap, we developed scGNN+, a web-based platform that combines the power of graph neural networks with the capabilities of ChatGPT to enhance reproducibility, code optimization, and visualization. scGNN+ further simplifies the process for users by generating standardized, well-annotated code, making complex procedures more accessible to non-programmers. Additionally, ChatGPT integration allows users to create high-quality, customizable visualizations through natural language prompts, improving data interpretation and presentation. Ultimately, scGNN+ offers a user-friendly, reproducible, and optimized solution for single-cell research, leveraging the full potential of foundation models in bioinformatics. scGNN+ is publicly available at https://bmblx.bmi.osumc.edu/scgnn+.
Capturing the Hierarchically Assorted Protein-protein Interaction Modules of Mammalian Cell
Authors: Dai Shuaijian , Zhang Yage , Yu Weichuan , Li Ning
Published: October 2024

Proteins are organized into modules by both functions and physical interactions within compartments of an eukaryotic cell. Thein vivochemical crosslinking mass spectrometry (XL-MS) data collected from organelles, the whole cells and tissues are able to provide unique information about both protein-protein interaction (PPI) and the intensity of PPI. In the present study, we have retrieved 55,982 crosslinked peptides (XL-peptides) from the XL-MS databases, out of which 6,356in vivoPPIs were identified. Introduction of the MONET software into analysis of 4,526 hetero PPIs revealed a total of 402 protein modules, including 15, 58 and 163 stable protein complex(s), condensate-forming protein module(s) and intrinsically disordered region (IDR)-containing protein module(s), respectively. The application of ChatGPT in analysis of these modules unexpectedly identified 4 vesicle-related modules. Together, these modules were assorted into 6 communities (module of modules) and 3 systems (module of communities) hierarchically. The bioinformatic analysis found that the three systems are corresponding to three compartments of eukaryotic cell: nuclei, mitochondria, endoplasmic reticulum (ER), respectively. This study presents a novel and comprehensive biomolecular modulome of a mammalian cell, which captures putative protein compositions of protein complexes, protein condensates and vesicles and provides a hierarchical protein organization and function within compartments of mammalian cell.
Oddball evoked deviant responses reflect complex context dependent expectations in mouse V1
Authors: Knudstrup Scott G. , Martinez Reyes Catalina , Jensen Cambria M. , Schecter Rachel W. , Frank Mac Kenzie , Gavornik Jeffrey P.
Published: October 2024

Evoked responses in the mouse primary visual cortex can be modulated by the temporal context in which visual inputs are presented. Oddball stimuli embedded in a sequence of regularly repeated visual elements have been shown to drive relatively large deviant responses, a finding that is generally consistent with the theory that cortical circuits implement a form of predictive coding. These results can be confounded by short-term adaptation effects, however, that make interpretation difficult. Here we use various forms of the oddball paradigm to disentangle temporal and ordinal components of the deviant response, showing that it is a complex phenomenon affected by temporal structure, ordinal expectation, and event frequency. Specifically, we use visually evoked potentials to show that deviant responses occur over a large range of time, lead to long-term plasticity in some cases, cannot be explained by a simple adaptation model, scale with predictability, and are modulated by violations of both first and second-order sequential expectations.

Significance Statement

Visual experience and temporal context can modulate evoked responses in mouse V1. There remains disagreement about whether this reflects predictive coding in visual circuits and if visual mismatched negativity, which has important cross-over implications for human clinical work, constitutes evidence supporting this theory or simple neural adaptation. This work strongly supports the former interpretation by demonstrating complex experience-dependent deviant responses that cannot be easily explained by a simple adaptation model. We use statistically rigorous analysis of the local field potential to show that oddball evoked deviance signals reflect relative timing, event frequency, 1stand 2ndorder sequence expectations and scale as a function of event probability.
Relating GPCR domains with functionality: receptor helix-bundle and C-terminus differentially influence GRK-specific functions and β-arrestin-mediated regulation
Authors: Matthees Edda S. F. , Haider Raphael S. , Klement Laura , Reichel Mona , Blum Nina K. , Weitzel Verena , Trüpschuch Thimea , Ziegler Carla , Drube Julia , Schulz Stefan , Hoffmann Carsten
Published: October 2024

G protein-coupled receptors (GPCRs) orchestrate diverse physiological responses via intracellular signaling through G proteins, GPCR kinases (GRKs), and arrestins. While the role of G proteins in receptor signaling is well-established, the contributions of GRKs and arrestins remain incompletely understood. Here, we investigate the influence of arrestin-interacting GPCR domains (helix-bundle/C-terminus) on β-arrestin conformations and functions using refined biosensors and advanced cellular knockout systems. By focusing on prototypical class A (b2AR) and B (V2R) receptors and their chimeras (b2V2/V2b2), we can now characterize differential β-arrestin conformational changes as primarily mediated by the receptor C-terminus or helix-bundle. Moreover, we demonstrate that some β-arrestin-supported processes are governed by distinct receptor domains, such as ERK1/2 activation (helix-bundle) and arrestin co-internalization (C-terminus), while others depend on the overall GPCR configuration, such as receptor internalization. Our findings elucidate how individual GPCR domains dictate downstream signaling events, shedding light on the structural basis of receptor-specific signaling and regulation.
Acid excretion is impaired in calcium oxalate stone formers
Authors: Imenez Silva Pedro H , Dhayat Nasser A. , Fuster Daniel G. , Seeger Harald , Ritter Alexander , Ernandez Thomas , Buchkremer Florian , Roth Beat , Bonny Olivier , Rubio-Aliaga Isabel , Wagner Carsten A.
Published: October 2024

Background

Urine pH is a key factor in kidney stone formation. We aimed to identify whether acid excretion capacity is disturbed in calcium oxalate (CaOx) or calcium phosphate (CaP) stone formers.

Method

Urinary, serum, clinical, and anthropomorphic baseline data were obtained from the Swiss Kidney Stone Cohort, a prospective, longitudinal, and multi-centric observational study. We included in this study 193 non-stone formers (NSF, confirmed by negative CT scan), and 309 CaOx and 28 CaP stone formers. Titratable acids, net acid excretion (NAE), NAE capacity (NAEC) and acid-base (AB) score were calculated. Logistic regression analyses were used to estimate the potential associations of various acid-base variables with the occurrence of CaOx kidney stones.

Results

CaOx stone formers showed a disturbed capacity to excrete acids in comparison to NSF (NAEC NSF = 3.49±12.6 mmol/24h; CaOx = −1.06±13.10; CaP = 0.97±14.70 and AB score NSF = 20.5±6.36 mmol/24h; CaOx = 17.9± 6.53; CaP = 18.8±6.10). The correlation between urine calcium and urine pH was altered in CaOx stone formers and between urine calcium and NAE was stronger in CaP stone formers. Logistic models showed that urinary ammonium was negatively associated with CaOx stone formation (unadjusted model, odds ratio 0.43[0.32-0.58], p< 0.001 for CaOx). Urine calcium was positively associated with CaOx kidney stones (2.85 [2.11-3.92], p<0.001). Similar results were obtained after adjusting for age, sex, and BMI. Replacing urine ammonium, pH, and phosphate with NAEC or ammonium and pH with AB score in our logistic regression models showed that NAEC and AB score are strongly associated with CaOx kidney stone formation.

Conclusion

Ammonium excretion, NAEC and AB score are associated with the occurrence of CaOx kidney stones suggesting a potential role of proximal tubule dysfunction in their formation. CaP stone formers exhibit a disproportionately higher calcium excretion when acid excretion increases.

Key learning points

What was known

Urine pH is a strong determinant in the formation of various urologically relevant crystals. Impaired urine acidification capacity has been observed in individuals who form calcium phosphate and uric acid stones.

This study adds

When compared to non-stone formers, calcium oxalate stone formers are marked by a reduced capacity of excreting acids when urine pH becomes more acidic.

Potential impact

The calculation of net acid excretion capacity and acid-base score are novel tools to identify those under potential higher risk of developing calcium oxalate stones.
Dissociable after-effects of prosocial acts: Effort is costly for others but valued for self
Authors: Zheng Ya , Tang Rumeng
Published: October 2024

Prosocial behavior requires effort, yet people are often reluctant to exert effort for others’ benefit. However, the manner in which effort exertion affects subsequent reward evaluation during prosocial acts remains elusive. Here, we leveraged the temporal precision of electroencephalography, along with a paradigm that independently manipulated effort and reward for self and another person, to uncover the neural mechanism underlying the reward after-effect of effort expenditure during prosocial acts. We found a dissociable reward after-effect between self-benefitting and other-benefitting effort. When the beneficiary was oneself, the reward positivity (RewP) became more positive as effort increased, indicating an effort-enhancement effect. In contrast, when the beneficiary was others, the RewP became less positive as effort increased, demonstrating an effort-discounting effect. Moreover, this dissociation occurred only when reward system was activated and was independent of performance evaluation. Our finding provides novel insights into how prior effort expenditure shape reward evaluation during prosocial behavior.
Experience shapes the transformation of olfactory representations along the cortico-hippocampal pathway
Authors: Schiltz Eleonore , Broux Martijn , Aydin Cagatay , Goncalves Pedro , Haesler Sebastian
Published: October 2024

Perception relies on the neural representation of sensory stimuli. Primary sensory cortical representations have been extensively studied, but how sensory information propagates to memory-related multisensory areas has not been well described. We studied this question in the olfactory cortico-hippocampal pathway in mice. We recorded single units in the anterior olfactory nucleus (AON), the anterior piriform cortex (aPCx), lateral entorhinal cortex (LEC), the hippocampal CA1 subfield, and the subiculum (SUB) while animals performed a non-associative learning paradigm involving novel and familiar stimuli. Novel stimuli evoked larger responses than familiar stimuli in the AON, whereas in hippocampal areas, novelty was reflected by the number of responsive neurons. In parallel, odorant selectivity increased along the pathway. While both stimulus identity and experience were thus reflected in all regions, their neural representations gradually separated. Our findings provide a potential mechanism for how sensory representations are transformed to support stimulus identification and implicit memories.
Scalable Fabrication of an Array-Type Fixed-Target Device for Automated Room Temperature X-ray Protein Crystallography
Authors: Saha Sarthak , Chen Yaozu , Russi Silvia , Marchany-Rivera Darya , Cohen Aina , Perry Sarah L.
Published: October 2024

1.

X-ray crystallography is one of the leading tools to analyze the 3-D structure, and therefore, function of proteins and other biological macromolecules. Traditional methods of mounting individual crystals for X-ray diffraction analysis can be tedious and result in damage to fragile protein crystals. Furthermore, the advent of serial crystallography methods explicitly require the mounting of large numbers of crystals. To address this need, we have developed a device that facilitates the straightforward mounting of protein crystals for diffraction analysis, and that can be easily manufactured at scale. Inspired by grid-style devices that have been reported in the literature, we have developed an X-ray compatible microfluidic device that can be used to trap protein crystals in an array configuration, while also providing excellent optical transparency, a low X-ray background, and compatibility with the robotic sample handling and environmental controls used at synchrotron macromolecular crystallography beamlines. At the Stanford Synchrotron Radiation Lightsource (SSRL), these capabilities allow for fully remote-access data collection at controlled humidity conditions. Furthermore, we have demonstrated continuous manufacturing of these devices via roll-to-roll fabrication to enable cost-effective and efficient large-scale production.