bluuebunny/crossref_metadata_2025 huggingface dataset:
Refugees in Violent Decolonizations
Authors: Nguyen Phi-Vân
Published: November 2023

Refugee flows are not only an important consequence of violent decolonizations. Population movements also affect belligerents’ access to human resources, food, or information. In the case of competing groups vying for power, the arrival or departure of the population may also reinforce or diminish their political legitimacy. In the case of the Vietnam wars, competing factions engineered population movements and instrumentalized their representations to undermine their opponent. Contrary to the idea that population movements are collateral damage, the politics of refugee protection in violent decolonization underscore their importance in sustaining an armed effort and backing the legitimacy of a nascent and oft-contested nation-state.
Evaluating the Neural Underpinnings of Motivation for Walking Exercise
Authors: Doren Sarah , Schwab Sarah M , Bigner Kaitlyn , Calvelage Jenna , Preston Katie , Laughlin Abigail , Drury Colin , Tincher Brady , Carl Daniel , Awosika Oluwole O , Boyne Pierce
Published: November 2023

Objective

Motivation is critically important for rehabilitation, exercise, and motor performance, but its neural basis is poorly understood. Recent correlational research suggests that the dorsomedial prefrontal cortex (dmPFC) may be involved in motivation for walking activity and/or descending motor output. This study experimentally evaluated brain activity changes in periods of additional motivation during walking exercise and tested how these brain activity changes relate to self-reported exercise motivation and walking speed.

Methods

Adults without disability (N = 26; 65% women; 25 [standard deviation = 5] years old) performed a vigorous exercise experiment involving 20 trials of maximal speed overground walking. Half of the trials were randomized to include “extra-motivation” stimuli (lap timer, tracked best lap time, and verbal encouragement). Wearable near-infrared spectroscopy measured oxygenated hemoglobin responses from frontal lobe regions, including the dmPFC, primary sensorimotor, dorsolateral prefrontal, anterior prefrontal, supplementary motor, and dorsal premotor cortices.

Results

Compared with standard trials, participants walked faster during extra-motivation trials (2.43 vs 2.67 m/s; P < .0001) and had higher oxygenated hemoglobin responses in all tested brain regions, including dmPFC (+842 vs +1694 μM; P < .0001). Greater dmPFC activity was correlated with more self-determined motivation for exercise between individuals (r = 0.55; P = .004) and faster walking speed between trials (r = 0.18; P = .0002). dmPFC was the only tested brain region that showed both of these associations.

Conclusion

Simple motivational stimuli during walking exercise seem to upregulate widespread brain regions. Results suggest that dmPFC may be a key brain region linking affective signaling to motor output.

Impact

These findings provide a potential biologic basis for the benefits of motivational stimuli, elicited with clinically feasible methods during walking exercise. Future clinical studies could build on this information to develop prognostic biomarkers and test novel brain stimulation targets for enhancing exercise motivation (eg, dmPFC).
Effects of Analgesics on Self-Reported Physical Function and Walking Ability in People With Hip or Knee Osteoarthritis: A Systematic Review and Meta-Analysis
Authors: Sveaas Silje H , Smedslund Geir , Walsh David A , Dagfinrud Hanne
Published: November 2023

Objective

Hip and knee osteoarthritis are among the leading causes of global disability, and one of the main aims of the management is to improve physical function. The objective of this review was to investigate the effect of analgesics on physical function (self-reported physical function and walking ability).

Methods

A systematic review and meta-analysis of the findings were performed. Randomized controlled trials investigating the effect of analgesics on self-reported physical function and walking ability were included. Analgesics were orally administered acetaminophen, nonsteroidal antiinflammatory drugs (NSAIDs), or opioids. Data were pooled in a random-effects model, and the standardized mean difference (SMD) with 95% CI was calculated (SMDs: 0.2–0.4 = small, 0.5–0.7 = medium, and ≥0.8 = large effect sizes). The quality of the evidence was evaluated according to the Grading of Recommendations Assessment, Development, and Evaluation approach.

Results

A total of 1454 studies were identified, of which 33 were included. On self-reported physical function, the results showed low- to moderate-quality evidence for a small beneficial effect of acetaminophen (SMD = −0.13 [95% CI = −0.26 to 0.00]), NSAIDs (SMD = −0.32 [95% CI = −0.37 to −0.27]), or opioids (SMD = −0.20 [95% CI = −0.32 to −0.09]). There was moderate-quality evidence for a small effect of NSAIDs on pain during walking (SMD = −0.34 [95% CI = −0.45 to −0.23]).

Conclusion

In people with hip or knee osteoarthritis, there was low- to moderate-quality evidence for small beneficial effects of analgesics on physical function and walking ability.

Impact

Analgesics may improve physical function by reducing pain during exercise and walking.
Effects of forage quality and particle size on feed intake and ruminoreticulum content of goats
Authors: Lopes Daniel Souza , Rodrigues Marcelo Teixeira , de Oliveira Tadeu Silva
Published: November 2023

The aim was to evaluate the effect of particle size and hay quality on feed intake, granulometric profile, and composition of the ruminoreticulum content in goats. We used 54 Alpine bucks in a completely randomized design with a factorial arrangement of 3 × 3. Treatments were a combination of Bermuda grass hay (Cynodon dactylon) with three quality levels: high (35 days), medium (50 days), and low (65 d) harvested at regrowth times. Were evaluated three particle sizes: small (16% ≥4.76 mm), medium (48% ≥4.76 mm), and large (75% ≥4.76 mm), which accounted for 66%, 75%, and 94% of physically effective fiber, respectively. Samples of offered diet, intake, and ruminoreticulum content were used to generate the granulometric profile. The offered diet, intake, and ruminoreticulum content presented different granulometric profiles regarding hay quality and particle size. Dry matter intake (DMI) and neutral detergent fiber intake (NDFI) increased (P < 0.05) when low-quality hay and large particles were offered. However, when particle size in low-quality hay was reduced, DMI and NDF decreased (P < 0.05). When analyzing the ruminoreticulum content (DM, NDF, peNDF, and indigestible DM), we did not observe any effect (P > 0.05) of hay quality or particle size on the variables. Thus, reducing hay quality and increasing particle size increase dry matter and fiber intake, presenting an interaction between forage quality and particle size. Forage quality and particle size promote intense selective behavior and chewing, which leads to a homogeneous content of particle profile in ruminoreticulum and a uniform average retention time.
Is Nothing Sacrum? Identification and Treatment of Sacral Insufficiency Fractures
Authors: Monsma Nicholaus , Le Rebecca , Brooks Robert , Basha Evan , Schneider Garrett
Published: November 2023

Sacral insufficiency fractures are an overlooked etiology of back pain that can also be difficult to diagnose radiographically. Advanced imaging, including MR and scintigraphy, are useful modalities for diagnosis, as these fractures are frequently missed on plain films. Management is often conservative to avoid surgical fixation, a rarely performed surgery due to its high morbidity. Radiologists are also able to provide symptomatic relief via sacroplasty, a minimally invasive, percutaneous, image-guided procedure first described in 2002. The most common sites of pelvic insufficiency fractures include the sacral ala and parasymphyseal region of the os pubis. The butterfly or “H-shaped” pattern is a classic sign of this fracture on scintigraphy, best appreciated posteriorly. MR is considered the gold standard in diagnosing insufficiency fractures and is characterized by low T1 band-like signal intensity with corresponding high T2/T2 short-tau inversion recovery (STIR) signal intensity. Such fractures can be treated via sacroplasty by carefully injecting polymethylmethacrylate bone cement via one or more trocar needles. Knowledge of sacral anatomy is critical during the procedure to not violate specific sacral zones or traverse any of the neural foramina.
Evaluation of a Pressure Injury Prevention Care Bundle in an ICU in Turkey
Authors: Altaş Gülnaz , Çelik Selda
Published: November 2023

OBJECTIVE

To evaluate a pressure injury (PI) prevention care bundle in ICU patients diagnosed with internal diseases.

METHODS

The study had a quasi-experimental design and included 98 patients who were diagnosed with internal diseases and hospitalized in the ICU. Patients in the control group (n = 49) received routine clinical care, whereas those in the intervention group (n = 49) received the PI prevention care bundle. Data were collected using a patient information form and the Braden Scale.

RESULTS

All patients in the control group and 61.2% of the patients in the intervention group developed PIs. Those in the intervention group who developed PIs did so later on average in comparison with the control group. Patient risk of PI development increased with advanced age, low oxygen saturation, low prealbumin values, and low Braden Scale scores. Fewer PIs developed in the patients in the intervention group despite their longer duration of hospitalization and high glucose levels.

CONCLUSIONS

The PI prevention care bundle may help prevent the development of PI.
Clear-Cell Dermal Duct Tumor: Case Report and Literature Review
Authors: Urso Carmelo
Published: November 2023

Clear-cell dermal duct tumor is a benign adnexal neoplasm composed of dermal multiple solid islands of clear cells, displaying ductal differentiation. Histopathologically, lesions can be subdivided into 2 distinct subgroups: (1) “pure” clear-cell dermal duct tumors, entirely composed of clear cells, and (2) “mixed” clear-cell dermal duct tumors, showing an associated conventional poroid component. Such a subclassification may be significant for the differential diagnosis: the less frequent “mixed” variant may be more easily recognized because of the presence of poroid and cuticular cells and the more frequent “pure” variant is to be distinguished from many other benign and malignant dermal clear-cell epithelial tumors.
Radioactive iodine treatment for Graves’ hyperthyroidism: incidence of Graves orbitopathy
Authors: Quah Nicole Q.X. , Sobti Manvi M. , Wren Alison M. , Scawn Richard , Kalogianni Eleni , Cleland James , Maenhout Annelies
Published: November 2023

Purpose

There are limited recent data on the effect of radioactive iodine (RAI) for Graves’ disease on Graves’ orbitopathy (GO) development or reactivation. This audit investigates the GO incidence in patients with Graves’ disease after RAI treatment, and explores risk factors present, and steroid prophylaxis use.

Methods

A retrospective audit of Graves’ disease patients treated with RAI over a 5-year period. Data collected: smoking status, thyroid-stimulating hormone receptor antibody (TRAb) status, GO history, Graves’ disease duration, eye features pre- and post-treatment, prophylactic corticosteroids, RAI dose given, post-RAI thyroid status, duration until hypothyroid.

Results

One hundred one patients were included, with a median Graves’ disease duration 36 months. 34/101 (33.7%) were active/ex-smokers, 86/101 (85.1%) were TRAb-positive, 11/101 (10.9%) had a GO history; 32 (31.7%) had eye features present. Median RAI dose given was 596MBq. 8/101 (7.9%) patients received prophylactic corticosteroid; 89/101 (88.1%) achieved hypothyroid state in the year after RAI. GO developed in 5/101 (5.0%), of which 4/5 (80%) were de novo in high-risk individuals who did not receive steroids. One was a GO reactivation despite steroids. Two required intravenous steroids with/without orbital radiotherapy, one completed oral steroid taper; the remainder were treated conservatively.

Conclusion

Our cohort had a lower GO incidence in patients with Graves’ disease receiving RAI, with majority arising de novo. It is essential that all patients are assessed for Graves orbitopathy risk factors and counselled adequately prior to RAI. The decision to initiate steroids should be undertaken in a multi-disciplinary setting involving endocrinologists and ophthalmologists.
Effects of pharmacogenetic profiles on pediatric pain relief and adverse events with ibuprofen and oxycodone
Authors: Ali Samina , Yukseloglu Aran , Ross Colin J. , Rosychuk Rhonda J. , Drendel Amy L. , Manaloor Robin , Johnson David W. , Le May Sylvie , Carleton Bruce
Published: November 2023

Introduction:

Individual genetic variation may influence clinical effects for pain medications. Effects of CYP2C9, CYP3A4, and CYP2D6 polymorphisms on clinical effectiveness and safety for ibuprofen and oxycodone were studied.

Objective:

Primary objectives were to AU2 evaluate if allelic variations would affect clinical effectiveness and adverse events (AEs) occurrence.

Methods:

This pragmatic prospective, observational cohort included children aged 4 to 16 years who were seen in a pediatric emergency department with an acute fracture and prescribed ibuprofen or oxycodone for at-home pain management. Saliva samples were obtained for genotyping of allelic variants, and daily telephone follow-up was conducted for 3 days. Pain was measured using the Faces Pain Scale-Revised.

Results:

We included 210 children (n = 140 ibuprofen and n = 70 oxycodone); mean age was 11.1 (±SD 3.5) years, 33.8% were female. Median pain reduction on day 1 was similar between groups [ibuprofen 4 (IQR 2,4) and oxycodone 4 (IQR 2,6), P = 0.69]. Over the 3 days, the oxycodone group experienced more AE than the ibuprofen group (78.3% vs 53.2%, P < 0.001). Those with a CYP2C9*2 reduced function allele experienced less adverse events with ibuprofen compared with those with a normal functioning allele CYP2C9*1 (P = 0.003). Neither CYP3A4 variants nor CYP2D6 phenotype classification affected clinical effect or AE.

Conclusion:

Although pain relief was similar, children receiving oxycodone experienced more AE, overall, than those receiving ibuprofen. For children receiving ibuprofen or oxycodone, pain relief was not affected by genetic variations in CYP2C9 or CYP3A4/CYP2D6, respectively. For children receiving ibuprofen, the presence of CYP2C9*2 was associated with less adverse events.
Identification and immunological characterization of cuproptosis-related molecular clusters in ischemic stroke
Authors: Liu Chunhua , Wu Binbin , Tao Yongjun , Liu Xiang , Lou Xiqiang , Wang Zhen , Guo Zhaofu , Tang Dongmei
Published: November 2023

The present study elucidated cuproptosis-related molecular clusters involved in ischemic stroke and developed predictive models. Transcriptomic and immunological profiles of ischemic stroke-related datasets were extracted from the Gene Expression Omnibus database. Next, we conducted weighted gene co-expression network analysis to determine cluster-specific differentially expressed genes (DEGs). Models such as random forest and eXtreme gradient boosting (XGB) were evaluated to select the best prediction performance model. Subsequently, we validated the model’s predictive efficiency by using nomograms, decision curve analysis, calibration curves, and receiver operating characteristic curve analysis with an external dataset. We identified two cuproptosis-related clusters involved in ischemic stroke. The DEGs in Cluster 2 were closely associated with amino acid metabolism, various immune responses, and cell proliferation pathways. The XGB model showed lower residuals, a smaller root mean square error, and a greater area under the curve value (AUC = 0.923), thus exhibiting the best discriminative performance. The AUC value for the external validation dataset was 0.921, thus confirming the high performance of the model. NFE2L2, NLRP3, GLS, LIPT1, and MTF1 were identified as potential cuproptosis predictors, thus shedding new light on ischemic stroke pathogenesis and heterogeneity.
Semantic segmentation of defects based on DCNN and its application on fatigue lifetime prediction for SLM Ti-6Al-4V alloy
Authors: Pan Jinchao , Hu Dianyin , Zhou Liucheng , Huang Di , Wang Ying , Wang Rongqiao
Published: November 2023

Inevitable defects have an important impact on the fatigue lifetime of additive manufacturing materials. Therefore, it is critical to thoroughly characterize the characteristics of the defects, which requires effective semantic segmentation of the imaged defects. In this paper, a defect dataset for SLM Ti-6Al-4V alloy was obtained by synchrotron radiation computed tomography. Then a semantic segmentation method was developed based on the DeepLabV3 + network to automatically extract defects. Cropping and undersampling were introduced in the dataset pre-processing. A weighted scheme based on the ratio between the number of defect and matrix pixels was applied in the classification layer, and morphological operations were employed in image post-processing to improve the accuracy of identifying small-target defect. Finally, the above method was applied to segment the X-ray computed tomography data for two batches of SLM Ti-6Al-4V materials, and the defect segmentation results were used to predict the fatigue lifetime. The semantic segmentation method performs well with a pixel recognition accuracy of 98.2% for the test dataset, and the error in the predicted fatigue lifetime lies within the scatter band of ±2.2.

This article is part of the theme issue 'Physics-informed machine learning and its structural integrity applications (Part 2)'.
Spot the Difference: Can ChatGPT4-Vision Transform Radiology Artificial Intelligence?
Authors: Kelly Brendan S , Duignan Sophie , Mathur Prateek , Dillon Henry , Lee Edward H , Yeom Kristen W , Keane Pearse , Lawlor Aonghus , Killeen Ronan P
Published: November 2023

OpenAI’s flagship Large Language Model ChatGPT can now accept image input (GPT4V). “Spot the Difference” and “Medical” have been suggested as emerging applications. The interpretation of medical images is a dynamic process not a static task. Diagnosis and treatment of Multiple Sclerosis is dependent on identification of radiologic change. We aimed to compare the zero-shot performance of GPT4V to a trained U-Net and Vision Transformer (ViT) for the identification of progression of MS on MRI.

170 patients were included. 100 unseen paired images were randomly used for testing. Both U-Net and ViT had 94% accuracy while GPT4V had 85%. GPT4V gave overly cautious non-answers in 6 cases. GPT4V had a precision, recall and F1 score of 0.896, 0.915, 0.905 compared to 1.0, 0.88 and 0.936 for U-Net and 0.94, 0.94, 0.94 for ViT.

The impressive performance compared to trained models and a no-code drag and drop interface suggest GPT4V has the potential to disrupt AI radiology research. However misclassified cases, hallucinations and overly cautious non-answers confirm that it is not ready for clinical use. GPT4V’s widespread availability and relatively high error rate highlight the need for caution and education for lay-users, especially those with limited access to expert healthcare.

Key points

Even without fine tuning and without the need for prior coding experience or additional hardware, GPT4V can perform a zero-shot radiologic change detection task with reasonable accuracy.

We find GPT4V does not match the performance of established state of the art computer vision models. GPT4V’s performance metrics are more similar to the vision transformers than the convolutional neural networks, giving some possible insight into its underlying architecture.

This is an exploratory experimental study and GPT4V is not intended for use as a medical device.

Summary statement

GPT4V can identify radiologic progression of Multiple Sclerosis in a simplified experimental setting. However GPT4V is not a medical device and its widespread availability and relatively high error rate highlight the need for caution and education for lay-users, especially those with limited access to expert healthcare.
Exploring Emotions in EEG: Deep Learning Approach with Feature Fusion
Authors: Tasaouf Mridula Danastan , Ferdaus Abu Ahmed , Pias Tanmoy Sarkar
Published: November 2023

Emotion is an intricate physiological response that plays a crucial role in how we respond and cooperate with others in our daily affairs. Numerous experiments have been evolved to recognize emotion, however still require exploration to intensify the performance. To enhance the performance of effective emotion recognition, this study proposes a subject-dependent robust end-to-end emotion recognition system based on a 1D convolutional neural network (1D-CNN). We evaluate the SJTU1Emotion EEG Dataset SEED-V with five emotions (happy, sad, neural, fear, and disgust). To begin with, we utilize the Fast Fourier Transform (FFT) to decompose the raw EEG signals into six frequency bands and extract the power spectrum feature from the frequency bands. After that, we combine the extracted power spectrum feature with eye movement and differential entropy (DE) features. Finally, for classification, we apply the combined data to our proposed system. Consequently, it attains 99.80% accuracy which surpasses each prior state-of-the-art system.
Demographic and health characteristics associated with fish and n-3 fatty acid supplement intake during pregnancy: results from pregnancy cohorts in the ECHO program
Authors: Oken Emily , Musci Rashelle J. , Westlake Matthew , Gachigi Kennedy , Aschner Judy L. , Barnes Kathrine L. , Bastain Theresa M. , Buss Claudia , Camargo Carlos A. , Cordero Jose F. , Dabelea Dana , Dunlop Anne L. , Ghassabian Akhgar , Hipwell Alison E. , Hockett Christine W. , Karagas Margaret R. , Lugo-Candelas Claudia , Margolis Amy E. , O’Connor Thomas G. , Shuster Coral L. , Straughen Jennifer K. , Lyall Kristen
Published: November 2023

Objective

Omega-3 (n-3) fatty acid consumption during pregnancy is recommended for optimal pregnancy outcomes and offspring health. We examined characteristics associated with self-reported fish or omega-3 supplement intake.

Design

Pooled pregnancy cohort studies.

Setting

Cohorts participating in the Environmental influences on Child Health Outcomes (ECHO) consortium with births from 1999-2020.

Participants

A total of 10,800 pregnant people in 23 cohorts with food frequency data on fish consumption; 12,646 from 35 cohorts with information on supplement use.

Results

Overall, 24.6% reported consuming fish never or less than once per month, 40.1% less than once a week, 22.1% 1-2 times per week, and 13.2% more than twice per week. The relative risk (RR) of ever (vs. never) consuming fish was higher in participants who were older (1.14, 95% CI: 1.10, 1.18 for 35-40 vs. <29 years), were other than non-Hispanic White (1.13, 95% CI: 1.08, 1.18 for non-Hispanic Black; 1.05, 95% CI: 1.01, 1.10 for non-Hispanic Asian; 1.06, 95% CI: 1.02, 1.10 for Hispanic), or used tobacco (1.04, 95% CI: 1.01, 1.08). The RR was lower in those with overweight vs. healthy weight (0.97, 95% CI: 0.95, 1.0). Only 16.2% reported omega-3 supplement use, which was more common among individuals with a higher age and education, a lower BMI, and fish consumption (RR 1.5, 95% CI: 1.23, 1.82 for twice-weekly vs. never).

Conclusions

One-quarter of participants in this large nationwide dataset rarely or never consumed fish during pregnancy, and omega-3 supplement use was uncommon, even among those who did not consume fish.
Antibody response to symptomatic infection with SARS-CoV-2 Omicron variant viruses, December 2021—June 2022
Authors: Sandford Ryan , Yadav Ruchi , Noble Emma K. , Sumner Kelsey , Joshi Devyani , Tartof Sara Y. , Wernli Karen J. , Martin Emily T. , Gaglani Manjusha , Zimmerman Richard K. , Talbot H. Keipp , Grijalva Carlos G. , Belongia Edward A. , Carlson Christina , Coughlin Melissa , Flannery Brendan , Pearce Brad , Rogier Eric
Published: November 2023

To describe humoral immune responses to symptomatic SARS-CoV-2 infection, we assessed immunoglobulin G binding antibody levels using a commercial multiplex bead assay against SARS-CoV-2 ancestral spike protein receptor binding domain (RBD) and nucleocapsid protein (N). We measured binding antibody units per mL (BAU/mL) during acute illness within 5 days of illness onset and during convalescence in 105 ambulatory patients with laboratory-confirmed SARS-CoV-2 infection with Omicron variant viruses. Comparing acute- to convalescent phase antibody concentrations, geometric mean anti-N antibody concentrations increased 47-fold from 5.5 to 259 BAU/mL. Anti-RBD antibody concentrations increased 2.5-fold from 1258 to 3189 BAU/mL.
A Formal Model for the Representation of Binary Temporal Relations in Healthcare Applications and an Efficient Algorithm for Logic-Based Temporal Subsumption Testing and Pattern Matching
Authors: Sujansky Walter , Campbell Keith E.
Published: November 2023

Objectives

Important temporal relationships exist among pairs of medically relevant events stored in electronic health records (EHRs), such as “the infection began within two weeks after surgery”. Queries for specific temporal patterns also appear in decision-support rules and data-analysis programs. The accurate matching of such patterns to the patient data in EHRs is critical to the effective performance of decision-support systems, statistical analysis programs, data-abstraction processes, digital phenotyping for machine-learning, and other applications. The correct classification of temporally-qualified concepts in biomedical terminologies and ontologies, such as SNOMED-CT, is also important to ensure the accuracy and completeness of these knowledge-based resources.

Methods

In this paper, we describe an expressive model to formally represent temporal relationships between pairs of events, including “Before”, “During”, “Withinndays after”, and “Withinnhours before ormhours after, but not during”. We also describe a novel logic-based algorithm to deduce whether one such relationship temporally matches (i.e., is subsumed by) another such relationship, which enables the querying of structured time-stamped patient data, the querying of semi-structured narrative patient data, and the classification of logically defined medical concepts. Our model assumes an interval-based notion of time and our algorithm implements a logic-based definition of subsumption.

Results

We formally prove the correctness of the algorithm based on the properties of temporal intervals and the axioms of propositional logic. We also prove that the algorithm has computational complexity of constant-time (i.e., O(1)) with respect to the size of the database being queried or the knowledge base being classified.

Conclusion

The novel model and algorithm described here for temporal representation and reasoning are sound and have the potential to facilitate temporal subsumption testing and pattern matching in a number of medical application domains. Empirical testing is needed to establish the full scope of useful applicability.
Misexpression of inactive genes in whole blood is associated with nearby rare structural variants
Authors: Vanderstichele Thomas , Burnham Katie L , de Klein Niek , Tardaguila Manuel , Howell Brittany , Walter Klaudia , Kundu Kousik , Koeppel Jonas , Lee Wanseon , Tokolyi Alex , Persyn Elodie , Nath Artika P , Marten Jonathan , Petrovski Slavé , Roberts David J , Di Angelantonio Emanuele , Danesh John , Berton Alix , Platt Adam , Butterworth Adam S , Soranzo Nicole , Parts Leopold , Inouye Michael , Paul Dirk S , Davenport Emma E
Published: November 2023

Gene misexpression is the aberrant transcription of a gene in a context where it is usually inactive. Despite its known pathological consequences in specific rare diseases, we have a limited understanding of its wider prevalence and mechanisms in humans. To address this, we analyzed gene misexpression in 4,568 whole blood bulk RNA sequencing samples from INTERVAL study blood donors. We found that while individual misexpression events occur rarely, in aggregate they were found in almost all samples and over half of inactive genes. Using 2,821 paired whole genome and RNA sequencing samples, we identified that misexpression events are enriched incisfor rare structural variants. We established putative mechanisms through which a subset of SVs lead to gene misexpression, including transcriptional readthrough, transcript fusions and gene inversion. Overall, we develop misexpression as a novel type of transcriptomic outlier analysis and extend our understanding of the variety of mechanisms by which genetic variants can influence gene expression.
Role of desmoplakin in supporting neuronal activity, neurogenic processes, and emotional-related behaviors in the dentate gyrus
Authors: Otsubo Keisuke , Sakashita Naoko , Nishimoto Yuki , Sato Yo , Tsutsui Takehisa , Kobayashi Katsunori , Suzuki Kanzo , Segi-Nishida Eri
Published: November 2023

Desmoplakin (Dsp) is a component of desmosomal cell-cell junctions that interacts with the cadherin complex and cytoskeletal intermediate filaments. In addition to its function as an adhesion component, Dsp is involved in various biological processes, such as gene expression, differentiation, and migration. Dsp is specifically expressed in the hippocampal dentate gyrus (DG) in the central nervous system. However, it is unclear how Dsp impacts hippocampal function and its related behaviors. Using an adeno-associated virus knockdown system in mice, we provide evidence that Dsp in the DG maintains hippocampal functions, including neuronal activity and adult neurogenesis, and contributes to anxiolytic-like effects. Dsp protein is mostly localized in mature granule cells in the adult DG. Dsp knockdown in the DG resulted in a lowered expression of an activity-dependent transcription factor FosB, and an increased expression of mature neuronal markers, such as calbindin. In addition, the suppression of Dsp decreases serotonin responsiveness at the DG output mossy fiber synapses and alters adult neurogenic processes in the subgranular zone of the DG. Moreover, DG- specific Dsp knockdown mice showed an increase in anxiety-like behaviors. Taken together, this research uncovers an unexplored function for Dsp in the central nervous system and suggests that Dsp in the DG may function as a regulator to maintain proper neuronal activation and adult neurogenesis, and contribute to the adaptation of emotion-related behavior.
BFCI at #SMM4H 2023: Integration of Machine Learning and TF-IDF for Covid-19 Tweets Analysis
Authors: Nayel Hamada , Ashraf Nsrin , Aldawsari Mohamed
Published: November 2023

Extracting information from texts generated by users of social media platforms becomes a crucial task. In this paper, we describe the systems submitted to the SMM4H shared tasks 1 and 2. The aims of these two tasks are binary and multi-class classification of English tweets. We developed a machine learning-based model integrated with TF-IDF as a feature extraction approach. Four classification algorithms have been implemented namely, support vector machines, passive-aggressive classifier, multi-layer perceptron and random forest. For task 1, the passive-aggressive classifier reported f1-score of 63.7%. For task 2, multi-layer perceptron reported f1-score of 71.4%.
Shape variation and sexual dimorphism of the adult human mandible evaluated by geometric morphometrics
Authors: Chalazoniti Aspasia , Lattanzi Wanda , Halazonetis Demetrios J.
Published: November 2023

Mandibular shape variability and effects of age and sex were explored in an adult human sample using dense landmarking and geometric morphometrics. We segmented 50 male and 50 female mandibular surfaces from CBCT images (age range: 18.9 to 73.7 years). Nine fixed landmarks and 496 sliding semilandmarks were digitized on the mandibular surface, and then slid by minimizing bending energy against the average shape. Principal component analysis extracted the main patterns of shape variation. Sexes were compared with permutation tests and allometry was assessed by regressing on the log of the centroid size. Almost 49 percent of shape variation was described by the first three principal components. Shape variation was related to width, height and length proportions, variation of the angle between ramus and corpus, height of the coronoid process and inclination of the symphysis. Significant sexual dimorphism was detected, both in size and shape. Males were larger than females, had a higher ramus, more pronounced gonial angle, larger inter-gonial width, and more distinct antegonial notch. Accuracy of sexing based on the first two principal components in form space was 91 percent. The degree of edentulism was weakly related to mandibular shape. Age effects were not significant.
Social contact patterns during the early COVID-19 pandemic in Norway: insights from a panel study, April to September 2020
Authors: Veneti Lamprini , Robberstad Bjarne , Steens Anneke , Forland Frode , Winje Brita A. , Vestrheim Didrik F. , Jarvis Christopher I , Gimma Amy , John Edmunds W. , Zandvoort Kevin Van , de Blasio Birgitte Freiesleben
Published: November 2023

Background

During the COVID-19 pandemic, many countries adopted social distance measures and lockdowns of varying strictness. Social contact patterns are essential in driving the spread of respiratory infections, and country-specific measurements are needed. This study aimed to gain insights into changes in social contacts and behaviour during the early pandemic phase in Norway.

Methods

We conducted an online survey among a nationally representative sample of Norwegian adults, including six data collections/waves between April and September 2020, and used survey data from 2017 as baseline. We calculated mean daily contacts, and estimated age-stratified contact matrices that were used to estimate reproduction numbers during the study period.

Results

The mean daily number of contacts varied between 3.2 (95% CI 3.0-3.4) to 3.9 (95% CI 3.6-4.2) across waves, representing a 67-73% decline compared to pre-pandemic levels. Fewer contacts in the community setting largely drove the reduction; the drop was most prominent among younger adults. Despite gradual easing of social distance measures during the survey period, population contact matrices remained relatively stable and displayed more inter-age group mixing than at baseline. Contacts within households and the community outside schools and workplaces contributed most to social encounters.

Conclusion

Social contacts experienced a significant decline during the months following the March 2020 lockdown in Norway, aligning with the implementation of stringent social distancing measures. The findings contribute valuable empirical information into the social behaviour of the Norwegian population during the early pandemic, which can be used to enhance policy-relevant models for addressing future crises when mitigation measures might be implemented.
DormantMycobacterium tuberculosisreactivatesex vivoin blood from HIV infected individuals
Authors: Kalyan Madhur , Agarwal Stuti , Sharma Aman , Verma Indu
Published: November 2023

Reports of tuberculosis in Human Immunodeficiency Virus infected patients despite high CD4+T-cell counts suggest different mechanisms of reactivation.In vitrodeveloped dormantMycobacterium tuberculosisH37Rv were cultured in HIV blood and normal blood. Colony forming units analysis was performed and expression of mycobacterial Resuscitation Promomoting Factor genes was analyzed by qRT-PCR. Thein vitrodeveloped dormantM. tbresuscitated in HIV blood as evident from increase in CFUs and up-regulation in the expression of mycobacterialrpfgenes. Reactivation of dormant tubercle bacilli following HIV infection in spite of high CD4+T-cell counts could be due to some viral or host factors which needs further studies.
Robust and time-resolved estimation of cardiac sympathetic and parasympathetic indices
Authors: Candia-Rivera Diego , de Vico Fallani Fabrizio , Chavez Mario
Published: November 2023

The time-resolved analysis of heart rate (HR) and heart rate variability (HRV) is crucial for the evaluation of the dynamic changes of autonomic activity under different clinical and behavioral conditions. Standard HRV analysis is performed in the frequency domain because the sympathetic activations tend to increase low-frequency HRV oscillations, while the parasympathetic ones increase high-frequency HRV oscillations. However, a strict separation of HRV in frequency bands may cause biased estimations, especially in the low frequency range. To overcome this limitation, we propose a robust estimator that combines HR and HRV dynamics, based on the correlation of the Poincaré plot descriptors of interbeat intervals from the electrocardiogram. To validate our method, we used electrocardiograms gathered from open databases where standardized paradigms were applied to elicit changes in autonomic activity. Our proposal outperforms the standard spectral approach for the estimation of low- and high-frequency fluctuations in HRV, and its performance is comparable to newer methods. Our method constitutes a valuable, robust, time-resolved, and cost-effective tool for a better understanding of autonomic activity through HR and HRV in healthy state and potentially for pathological conditions.
Guanylate cyclase activity of TIR1/AFB auxin receptors in rapid auxin responses
Authors: Qi Linlin , Kwiatkowski Mateusz , Kulich Ivan , Chen Huihuang , Gao Yongqiang , Yun Ping , Li Lanxin , Shabala Sergey , Farmer Edward E. , Jaworski Krzysztof , Friml Jiří
Published: November 2023

The major developmental signal in plants, auxin is perceived by TIR1/AFB receptors. It triggers transcriptional reprogramming via well-established canonical mechanism but also elusive rapid, non-transcriptional responses. Here we demonstrate that TIR1/AFB receptors have, next to recently identified adenylate cyclase, also guanylate cyclase activity. Auxin perception activates independently the cAMP and cGMP production by TIR1/AFBsin vitroand increases cAMP and cGMP levelsin plantawith a slow and fast dynamics, respectively. Exogenous cGMP but not cAMP application induces rapid cytosolic Ca2+transients and root growth inhibition, suggesting that TIR1/AFB-derived cGMP mediates rapid auxin responses. This unprecedented combination of adenylate and guanylate cyclase activities in a hormone receptor provides a new paradigm for how a single perception mechanism can mediate a multitude of diverse downstream responses.

One-Sentence Summary

TIR1/AFB auxin receptors have guanylate cyclase activity, whose product, cGMP mediates rapid non-transcriptional auxin responses.
Hierarchical motion perception as causal inference
Authors: Shivkumar Sabyasachi , DeAngelis Gregory C. , Haefner Ralf M.
Published: November 2023

Since motion can only be defined relative to a reference frame, which reference frame guides perception? A century of psychophysical studies has produced conflicting evidence: retinotopic, egocentric, world-centric, or even object-centric. We introduce a hierarchical Bayesian model mapping retinal velocities to perceived velocities. Our model mirrors the structure in the world, in which visual elements move within causally connected reference frames. Friction renders velocities in these reference frames mostly stationary, formalized by an additional delta component (at zero) in the prior. Inverting this model automatically segments visual inputs into groups, groups into supergroups, etc. and “perceives” motion in the appropriate reference frame. Critical model predictions are supported by two new experiments, and fitting our model to the data allows us to infer the subjective set of reference frames used by individual observers. Our model provides a quantitative normative justification for key Gestalt principles providing inspiration for building better models of visual processing in general.
Control of Biofilm Formation by anAgrobacterium tumefaciensPterin-Binding Periplasmic Protein Conserved Among Pathogenic Bacteria
Authors: Greenwich Jennifer L. , Eagan Justin L. , Feirer Nathan , Boswinkle Kaleb , Minasov George , Shuvalova Ludmilla , Inniss Nicole L. , Raghavaiah Jakka , Ghosh Arun K. , Satchell Karla J.F. , Allen Kylie D. , Fuqua Clay
Published: November 2023

Biofilm formation and surface attachment in multiple Alphaproteobacteria is driven by unipolar polysaccharide (UPP) adhesins. The pathogenAgrobacterium tumefaciensproduces a UPP adhesin, which is regulated by the intracellular second messenger cyclic diguanylate monophosphate (cdGMP). Prior studies revealed that DcpA, a diguanylate cyclase-phosphodiesterase (DGC-PDE), is crucial in control of UPP production and surface attachment. DcpA is regulated by PruR, a protein with distant similarity to enzymatic domains known to coordinate the molybdopterin cofactor (MoCo). Pterins are bicyclic nitrogen-rich compounds, several of which are formed via a non-essential branch of the folate biosynthesis pathway, distinct from MoCo. The pterin-binding protein PruR controls DcpA activity, fostering cdGMP breakdown and dampening its synthesis. Pterins are excreted and we report here that PruR associates with these metabolites in the periplasm, promoting interaction with the DcpA periplasmic domain. The pteridine reductase PruA, which reduces specific dihydro-pterin molecules to their tetrahydro forms, imparts control over DcpA activity through PruR. Tetrahydromonapterin preferentially associates with PruR relative to other related pterins, and the PruR-DcpA interaction is decreased in apruAmutant. PruR and DcpA are encoded in an operon that is conserved amongst multiple Proteobacteria including mammalian pathogens. Crystal structures reveal that PruR and several orthologs adopt a conserved fold, with a pterin-specific binding cleft that coordinates the bicyclic pterin ring. These findings define a new pterin-responsive regulatory mechanism that controls biofilm formation and related cdGMP-dependent phenotypes inA. tumefaciensand is found in multiple additional bacterial pathogens.

SIGNIFICANCE

Biofilms are bacterial communities attached to surfaces, physiologically distinct from free-living cells, and a common cause of persistent infections. Here we define the mechanism of a novel biofilm regulatory system based on excreted metabolites called pterins, that is conserved within a wide range of Gram-negative bacteria, including multiple pathogens of animals and plants. The molecular mechanism of pterin-dependent regulation is reported including structural determination of several members of a new family of pterin-binding proteins. Pterins are produced across all domains of life and mechanistic insights into this regulatory circuit could lead to new advances in antibiofilm treatments.
Lymphatic muscle cells are unique cells that undergo aging induced changes
Authors: Lei Pin-Ji , Ruscic Katarina J. , Roh Kangsan , Rajotte Johanna J. , O’Melia Meghan J. , Bouta Echoe M. , Marquez Marla , Pereira Ethel R. , Kumar Ashwin S. , Arroyo-Ataz Guillermo , Razavi Mohammad S. , Zhou Hengbo , Menzel Lutz , Kumra Heena , Duquette Mark , Huang Peigen , Baish James W. , Munn Lance L. , Ubellacker Jessalyn M. , Jones Dennis , Padera Timothy P.
Published: November 2023

Lymphatic muscle cells (LMCs) within the wall of collecting lymphatic vessels exhibit tonic and autonomous phasic contractions, which drive active lymph transport to maintain tissue-fluid homeostasis and support immune surveillance. Damage to LMCs disrupts lymphatic function and is related to various diseases. Despite their importance, knowledge of the transcriptional signatures in LMCs and how they relate to lymphatic function in normal and disease contexts is largely missing. We have generated a comprehensive transcriptional single-cell atlas—including LMCs—of collecting lymphatic vessels in mouse dermis at various ages. We identified genes that distinguish LMCs from other types of muscle cells, characterized the phenotypical and transcriptomic changes in LMCs in aged vessels, and uncovered a pro-inflammatory microenvironment that suppresses the contractile apparatus in advanced-aged LMCs. Our findings provide a valuable resource to accelerate future research for the identification of potential drug targets on LMCs to preserve lymphatic vessel function as well as supporting studies to identify genetic causes of primary lymphedema currently with unknown molecular explanation.
Evolution is All You Need in Promoter Design and Optimization
Authors: Ren Ruohan , Yu Hongyu , Teng Jiahao , Mao Sihui , Bian Zixuan , Tao Yangtianze , Yau Stephen S.-T.
Published: November 2023

Predicting the strength of promoters and guiding their directed evolution is a crucial task in synthetic biology. This approach significantly reduces the experimental costs in conventional promoter engineering. Previous studies employing machine learning or deep learning methods have shown some success in this task, but their outcomes were not satisfactory enough, primarily due to the neglect of evolutionary information. In this paper, we introduce the Chaos-Attention net for Promoter Evolution (CAPE) to address the limitations of existing methods. We comprehensively extract evolutionary information within promoters using chaos game representation and process the overall information with DenseNet and Transformer. Our model achieves state-of-the-art results on two kinds of distinct tasks. The incorporation of evolutionary information enhances the model’s accuracy, with transfer learning further extending its adaptability. Furthermore, experimental results confirm CAPE’s efficacy in simulating in silico directed evolution of promoters, marking a significant advancement in predictive modeling for prokaryotic promoter strength. Our paper also presents a user-friendly website for the practical implementation of in silico directed evolution on promoters.
Design and Mathematical Analysis of Synthetic Inhibitory Circuits that Program Self-Organizing Multicellular Structures
Authors: Lam Calvin
Published: November 2023

Bottom-up approaches are becoming increasingly popular for studying multicellular self-organization and development. In contrast to the classic top-down approach, where parts of the organization/developmental process are broken to understand the process, the goal is to build the process to understand it. For example, synthetic circuits have been built to understand how cell-cell communication and differential adhesion can drive multicellular development. The majority of current bottom-up efforts focus on using activatory circuits to engineer and understand development, but efforts with inhibitory circuits have been minimal. Yet, inhibitory circuits are ubiquitous and vital to native developmental processes. Thus, inhibitory circuits are a crucial yet poorly studied facet of bottom-up multicellular development. To demonstrate the potential of inhibitory circuits for building and developing multicellular structures, I designed several synthetic inhibitory circuits that combine engineered cell-cell communication and differential adhesion. Using a previously validatedin silicoframework, I examine the capability of these circuits for synthetic development. I show that the designed inhibitory circuits can build a variety of patterned, self-organized structures and even morphological oscillations. These results support that inhibitory circuits can be powerful tools for building, studying, and understanding developmental processes.

Graphical Abstract