bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arthroscopic Discectomy Technique: A Beneficial Approach for Managing Disk Perforations in the Temporomandibular Joint
Authors: Jerez Daniel , Laissle German , Díaz-Báez David , Martin-Granizo López Rafael , Vicente González Luis 
Published: August 2024

Abstract
Disk perforation can result in degenerative changes within the joint structures. While discectomy has demonstrated enduring benefits, it has traditionally been described using an open approach, with the disadvantages inherent to this method. This study aims to present a series of patients who underwent arthroscopic discectomy technique and to report the outcomes.

Methods
Patients diagnosed with internal disorders of the temporomandibular joint underwent arthroscopic arthroscopic discectomy technique. Surgical outcomes were assessed by changes in pain using a visual analog scale and the maximum incisal opening.

Results
One hundred seventy-eight joints from 106 patients who underwent arthroscopic surgery were included. Discectomy was performed on 22 joints. Prior to surgery, patients reported an average visual analog scale pain score of 6.5, which decreased to an average of 0.5 at 6 months postsurgery (P<0.001). Before surgery, the average maximum incisal opening was 30 mm, which increased to 41 mm at 6 months postsurgery (P<0.001).

Conclusions
The described technique represents an excellent alternative for managing patients with disk perforations.
Obesity is a predictor of abdominal computed tomography imaging in pediatric trauma patients
Authors: Colosimo Christina , Otaibi Banan , Bhogadi Sai Krishna , Nelson Adam , Spencer Audrey L. , Anand Tanya , Stewart Collin , Magnotti Louis J. , Joseph Bellal 
Published: August 2024

BACKGROUND
Computed tomography (CT) has helped to reduce the morbidity due to missed injuries. However, CT imaging is associated with radiation exposure and thus has limited indications in pediatric patients. In this study, we aimed to identify the association between obesity and abdominal CT imaging in pediatric trauma patients.

METHODS
We performed a 4-year retrospective analysis of the American College of Surgeons Trauma Quality Improvement 2017–2020. We identified all pediatric trauma patients aged between 7 and 17 years presenting with isolated abdominal trauma (nonabdominal Abbreviated Injury Scale score, 0). We excluded patients undergoing hemorrhage control surgeries and those with missing information in height and weight. Patients were stratified by body mass index into four groups (underweight, normal, overweight, and obese [body mass index, ≥30 kg/m2]). Outcomes were predictors of undergoing CT imaging of the abdomen. Descriptive statistics and multivariable logistic regression analyses were performed.

RESULTS
We identified a total of 10,204 pediatric trauma patients. The mean age was 13 years, 68% were male, and 77% were White. The median abdominal Abbreviated Injury Scale score in all the four groups was 2. On univariate analysis, underweight patients had lowest rates (25%), whereas obese patients had highest rates of CT imaging (38%) (p < 0.001). On multivariable regression analysis, increasing age (adjusted odds ratio [aOR], 1.08; 95% confidence interval [CI], 1.06–1.10; p < 0.001), male sex (aOR, 1.14; 95% CI, 1.03–1.26; p = 0.009), White race (aOR, 0.84; 95% CI, 0.76–0.92; p < 0.011), penetrating injury (aOR, 1.16; 95% CI, 1.03–1.32; p = 0.017), obesity (aOR, 1.30; 95% CI, 1.07–1.57; p = 0.008), and management at American College of Surgeons level II (aOR, 1.63; 95% CI, 1.44–1.85; p < 0.001) and level III or lower centers (aOR, 1.17; 95% CI, 1.06–1.26; p = 0.002) were identified as independent predictors of receiving CT imaging.

CONCLUSION
Obesity is associated with increased odds of undergoing CT imaging in pediatric trauma patients independent of injury characteristics. Future efforts to define the appropriate indications for CT imaging in pediatric trauma patients are warranted to reduce the adverse effects of CT radiation.

LEVEL OF EVIDENCE
Prognostic and Epidemiological; Level III.
Substantial role of rare inherited variation in individuals with developmental disorders
Authors: Samocha Kaitlin E. , Kartik Chundru V. , Fu Jack M. , Gardner Eugene J. , Danecek Petr , Wigdor Emilie M. , Malawsky Daniel S. , Lindsay Sarah J. , Campbell Patrick , Singh Tarjinder , Eberhardt Ruth Y. , Gallone Giuseppe , Wright Caroline F. , Martin Hilary C. , Firth Helen V. , Hurles Matthew E. 
Published: August 2024

AbstractWhile the role ofde novoand recessively-inherited coding variation in risk for rare developmental disorders (DDs) has been well established, the contribution of damaging variation dominantly-inherited from parents is less explored. Here, we investigated the contribution of rare coding variants to DDs by analyzing 13,452 individuals with DDs, 18,613 of their family members, and 3,943 controls using a combination of family-based and case/control analyses. In line with previous studies of other neuropsychiatric traits, we found a significant burden of rare (allele frequency < 1×10-5) predicted loss-of-function (pLoF) and damaging missense variants, the vast majority of which are inherited from apparently unaffected parents. These predominantly inherited burdens are strongest in DD-associated genes or those intolerant of pLoF variation in the general population, however we estimate that ∼10% of the excess of these variants in DD cases is found within the DD-associated genes, implying many more risk loci are yet to be identified. We found similar, but attenuated, burdens when comparing the unaffected parents of individuals with DDs to controls, indicating that parents have elevated risk of DDs due to these rare variants, which are overtransmitted to their affected children. We estimate that 6-8.5% of the population attributable risk for DDs are due to rare pLoF variants in those genes intolerant of pLoF variation in the general population. Finally, we apply a Bayesian framework to combine evidence from these analyses of rare, mostly-inherited variants with priorde novomutation burden analyses to highlight an additional 25 candidate DD- associated genes for further follow up.
Monitoring seizure cycles with seizure diaries
Authors: Reynolds Ashley , Stirling Rachel E. , Håkansson Samuel , Karoly Philippa , Lai Alan , Grayden David B. , Cook Mark J. , Nurse Ewan , Peterson Andre 
Published: August 2024

AbstractObjectiveThe periodicity of seizures, ranging from circadian to circannual cycles, is increasingly recognized as a significant opportunity to advance epilepsy management. Current methods for detecting seizure cycles rely on intrusive techniques or specialised biomarkers, limiting their accessibility. This study evaluates a non-invasive seizure cycle detection method using seizure diaries and compares its accuracy with cycles identified from intracranial electroencephalography (iEEG) seizures and interictal epileptiform discharges (IEDs).ApproachUsing data from a previously published first in-human iEEG device trial (n=10), we analysed seizure cycles identified through diary reports, iEEG seizures and IEDs. Cycle similarities across diary reports, iEEG seizures and iEDs were evaluated at periods of 1 to 45 days using spectral coherence, accuracy, precision and recall scores.Main resultsSpectral coherence of the raw signals averaged over frequencies and participants indicated moderately similar frequency components between diary seizures/day and iEEG seizures/day (Median=0.43, IQR=0.68). In contrast, there was low coherence between diary seizures/day and IEDs/day (Median=0.11, IQR=0.18) and iEEG seizures/day and IEDs/day (Median=0.12, IQR=0.19). Mean accuracy, precision and recall of iEEG seizure cycles from diary seizure cycles was significantly higher than chance across all participants (Accuracy: Mean=0.95, SD=0.02; Precision: Mean=0.56, SD=0.19; Recall: Mean=0.56, SD=0.19). Accuracy, precision and recall scores between seizures cycles using diary or iEEG compared to IED cycles did not perform above chance, on average. Recall scores were compared across good diary reporters, under-reporters and over-reporters, with recall scores generally performing better in good reporters and under-reporters (Mean=0.74, SD=0.02) compared to over-reporters (Mean=0.37, SD=0.06).SignificanceThese findings suggest that iEEG seizure cycles can be identified with diary reports, even in both under- and over-reporters. This approach offers a practical, accessible alternative for monitoring seizure cycles compared to more invasive methods.Key pointsSeizure cycles identified from seizure diaries can identify the same cycle periods to those detected by intracranial electroencephalography with high accuracy.Seizure under and overreporting reduces the accuracy of seizure cycle detection from diaries.
Maternal humoral factors modulate offspring gut immune homeostasis to mitigate diabetes development
Authors: Strachan Erin , Pessoa-Soares Luisa , Ju Tingting , Schcolnik-Cabrera Alejandro , Wang Henry , Akbari Masoud , Basso Paulo Jose , Winer Daniel A. , Huang Carol , Julien Olivier , Willing Benjamin P. , Clemente-Casares Xavier , Tsai Sue 
Published: August 2024

AbstractEnvironmental risk factors possess the potential to modulate the pathogenesis of type I diabetes (T1D). Foremost among these factors are early life influences impacting the gastrointestinal (GI) tract. During infancy, both the microbiota and immune system are influenced by maternal factors contributing to key events in the neonatal GI tract. Despite the well-known importance of maternal factors on infant immune development, whether maternal immune dysregulation and dysbiosis can perpetuate the same in offspring remains largely unknown. To explore how these maternal factors impact offspring disease development, we used IgA-deficiency induced maternal dysbiosis in Non-Obese Diabetic (NOD) dams to study T1D development in their progeny. We found that maternal dysbiosis led to changes in IgA-sufficient offspring immune development resulting in heightened GI immune activity. Maternal dysbiosis also contributed to altered microbiome establishment in progeny, such that pups exhibited reduced colonic abundance ofAkkermansia muciniphilaandClostridoides difficile. In adulthood, these mice exhibited a lowered incidence of T1D. This protection was replicated by fostering high incidence offspring to dysbiotic dams, prompting us to propose that altered breast milk composition in dysbiotic dams can influence immune development and microbiome establishment in offspring, contributing to T1D resistance.
A two-dose regimen of Qβ virus-like particle-based vaccines elicit protective antibodies against heroin and fentanyl
Authors: Romano Isabella G. , Johnson-Weaver Brandi , Core Susan B. , Jamus Andzoa N. , Brackeen Marcus , Blough Bruce , Dey Subhakar , Huang Yumei , Staats Herman , Wetsel William C. , Chackerian Bryce , Frietze Kathryn M. 
Published: August 2024

ABSTRACTOpioid overdoses and the growing rate of opioid use disorder (OUD) are major public health concerns, particularly in the United States. Current treatment approaches for OUD have failed to slow the growth of the opioid crisis. Opioid vaccines have shown pre-clinical success in targeting multiple different opioid drugs. However, the need for many immunizations can limit their clinical implementation. In this study, we investigate the development of novel opioid vaccines by independently targeting fentanyl and the active metabolites of heroin using a bacteriophage virus-like particle (VLP) vaccine platform. We establish the successful conjugation of haptens to bacteriophage Qβ VLPs and demonstrate immunogenicity of Qβ-fentanyl, Qβ-morphine, and Qβ-6-acetylmorphine in animal models after one or two immunizations. We show that in independently or in combination, these vaccines elicit high-titer, high-avidity, and durable antibody responses. Moreover, we reveal their protective capacities against heroin or fentanyl challenge after two immunizations. Overall, these findings establish Qβ-VLP conjugated vaccines for heroin and fentanyl as very promising opioid vaccine candidates.
State-Threatened Gopher Tortoise (Gopherus polyphemus) Gut Microbiome Analysis Reveals Health Insights into Southeastern Florida Population
Authors: Giakoumas Dimitrios S. , Moore Jon , Stamper Ericca , Bernot Kelsie M. , Mincer Tracy J. 
Published: August 2024

AbstractThe gopher tortoise (Gopherus polyphemus), endemic to the southeastern part of the United States, is a keystone species that provides ecological support to over 350 species. Deforestation, urbanization, road mortality, and disease, over the past 100 years, have caused population decline by over 80%, causing Florida to declare the gopher tortoise a threatened species. Little is known about the gopher tortoise gut microbiome, which could play a major role in tortoise health. This study aimed to better understand the health and biology of this threatened keystone species through the characterization and analysis of their gut microbiomes in the Abacoa Greenway of Southeastern Florida using next-generation sequencing to survey the gut microbiome. Major findings include: high levels of alpha diversity; lack of significant difference of male and female alpha diversity and taxonomic composition profiles and, counterintuitively, male beta diversity was less disparate than female beta diversity; phyla associated with fiber fermentation short-chain fatty acid metabolism, Firmicutes and Bacteroidetes, predominated all samples. Notable probiotic taxa present included: Lachnospiraceae andClostridium butyricum. Potentially pathogenic taxa included:Helicobactersp. and Mollicutes sp. Pathogenetic taxa undetected: gopher tortoiseHelicobacter, andMycoplasmaspp. These results add to the understudied reptiles and tortoise gut microbiome.
Structural and systems characterization of phosphorylation on metabolic enzymes identifies sex-specific metabolic reprogramming in obesity
Authors: Tamir Tigist Y , Chaudhary Shreya , Li Annie X , Trojan Sonia E , Flower Cameron T , Vo Paula , Cui Yufei , Davis Jeffrey C , Mukkamala Rachit S , Venditti Francesca N , Hillis Alissandra L , Toker Alex , Vander Heiden Matthew G , Spinelli Jessica B , Kennedy Norman J , Davis Roger J , White Forest M 
Published: August 2024

AbstractCoordination of adaptive metabolism through cellular signaling networks and metabolic response is essential for balanced flow of energy and homeostasis. Post-translational modifications such as phosphorylation offer a rapid, efficient, and dynamic mechanism to regulate metabolic networks. Although numerous phosphorylation sites have been identified on metabolic enzymes, much remains unknown about their contribution to enzyme function and systemic metabolism. In this study, we stratify phosphorylation sites on metabolic enzymes based on their location with respect to functional and dimerization domains. Our analysis reveals that the majority of published phosphosites are on oxidoreductases, with particular enrichment of phosphotyrosine (pY) sites in proximity to binding domains for substrates, cofactors, active sites, or dimer interfaces. We identify phosphosites altered in obesity using a high fat diet (HFD) induced obesity model coupled to multiomics, and interrogate the functional impact of pY on hepatic metabolism. HFD induced dysregulation of redox homeostasis and reductive metabolism at the phosphoproteome and metabolome level in a sex-specific manner, which was reversed by supplementing with the antioxidant butylated hydroxyanisole (BHA). Partial least squares regression (PLSR) analysis identified pY sites that predict HFD or BHA induced changes of redox metabolites. We characterize predictive pY sites on glutathione S-transferase pi 1 (GSTP1), isocitrate dehydrogenase 1 (IDH1), and uridine monophosphate synthase (UMPS) using CRISPRi-rescue and stable isotope tracing. Our analysis revealed that sites on GSTP1 and UMPS inhibit enzyme activity while the pY site on IDH1 induces activity to promote reductive carboxylation. Overall, our approach provides insight into the convergence points where cellular signaling fine-tunes metabolism.Summary StatementBy employing a multi-disciplinary approach we stratify structural features of phosphorylation sites on metabolic enzymes, map the systems level changes induced by obesity, identify key pathways with sex specific phosphoproteomic responses, and validate the functional role of phosphorylation sites for select enzymes.
Extinction burst could be explained by curiosity-driven reinforcement learning
Authors: Yamada Kota , Matsui Hiroshi , Toda Koji 
Published: August 2024

AbstractCuriosity encourages agents to explore their environment, leading to learning opportunities. Although psychology and neurobiology have tackled how external rewards control behavior, how intrinsic factors control behavior remains unclear. An extinction burst is a behavioral phenomenon in which a sudden increase in the frequency of a behavior immediately follows the omission of a reward. Although the extinction burst is textbook knowledge in psychology, there is little empirical evidence of it in experimental situations. In this study, we show that the extinction burst can be explained by curiosity by combining computational modeling of behavior and empirical demonstrations in mice. First, we built a reinforcement learning model incorporating curiosity, defined as expected reward prediction errors, and the model additively controlled the agent’s behavior to the primary reward. Simulations revealed that the curiosity-driven reinforcement learning model produced an extinction burst and burst intensity depended on the reward probability. Second, we established a behavioral procedure that captured extinction bursts in an experimental setup using mice. We conducted an operant conditioning task with head-fixed mice, in which the reward followed after pressing a lever at a given probability. After the training sessions, we occasionally withheld the reward delivery when the mice performed the task. We found that phasic bursts of responses occurred immediately after reward omission when responses were rewarded with a high probability, suggesting that the magnitude of reward prediction errors controlled the burst. These results provide theoretical and experimental evidence that intrinsic factors control behavior in adapting to an ever-changing environment.Significance statementIn theories of learning and behavior, primary rewards such as food, water, and sex occupy a dominant position as factors controlling behavior. However, primary rewards are scarce. Experimental investigations in psychology, neuroscience, ethology, and economics have revealed that novelty, uncertainty, and unpredictability drive behavior. How these intrinsic factors affect behavior is essential for a comprehensive understanding of the principles of learning and behavior. This study provides theoretical and experimental evidence that operant responses in mice are directly controlled by external rewards and intrinsic factors such as curiosity. Our study provides a robust example of curiosity-driven behavior and paves the way for understanding the mechanism of curiosity.
Dissociation of putative open loop circuit from ventral putamen to motor cortical areas in humans I: high-resolution connectomics
Authors: Rizor Elizabeth , Dundon Neil M. , Wang Jingyi , Stasiak Joanne , Li Taylor , Bostan Andreea C. , Lapate Regina C. , Grafton Scott T. 
Published: August 2024

AbstractHuman movement is partly organized and executed by cortico-basal ganglia-thalamic closed-loop circuits (CLCs), wherein motor cortical areas both send inputs to and receive feedback from the basal ganglia, particularly the dorsal putamen (PUTd). These networks are compromised in Parkinson’s disease (PD) due to neurodegeneration of dopaminergic inputs primarily to PUTd. Yet, fluid movement in PD can sporadically occur, especially when induced by emotionally arousing events. Rabies virus tracing in non-human primates has identified a potential alternative motor pathway, wherein the ventral putamen (PUTv) receives inputs from subcortical limbic areas (such as amygdala nuclei) and sends outputs to motor cortical areas putatively via the nucleus basalis of Meynert (NBM). We hypothesize that this separable open loop circuit (OLC) may exist in humans and explain the preservation of movement after CLC degradation. Here, we provide evidence for the normal human OLC with ultra-high field (7T), multi-echo functional magnetic resonance imaging. We acquired resting-state functional connectivity (FC) scans from 21 healthy adults (avg. age = 29, 12M/9F, all right-handed) and mapped left-hemisphere seed-to-voxel connectivity to assess PUTv FC with putative subcortical nodes and motor cortical areas. We found that putative OLC node (basolateral amygdala, NBM) FC was greater with PUTv (p < 0.05), while CLC subcortical seed (ventrolateral nucleus of thalamus) FC was greater with PUTd (p<0.01). Striatal FC patterns varied across cortical motor areas, with cingulate (p < 0.0001) and supplementary (p < 0.0001) motor areas showing greater FC with PUTv vs. nucleus accumbens. SMA had greater FC with PUTd vs. PUTv (p < 0.0001), while cingulate and primary motor areas showed no significant differences in FC between PUTd and PUTv (p > 0.1). Collectively, these results suggest that PUTv is functionally connected to motor cortical areas and may be integrated into a separable motor OLC with subcortical limbic inputs.
DAMP-inducing Peptide Nanofibers and PAMP Combination Adjuvants Boost Functional Lung Tissue-resident Memory CD4+T Cell Responses
Authors: Files Megan A. , Das Anirban , Kim Darren , Buck Jeremy , Endsley Janice J. , Rudra Jai S. 
Published: August 2024

ABSTRACTVaccine adjuvants are typically composed of pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) that activate innate immune cells. Advances in basic immunology have demonstrated the need for various ‘types’ of protective immunity, which are difficult to achieve with a single adjuvant. The FDA approval of multiple PAMP-DAMP combinations for clinical use has led to an increased momentum in the area in recent years. Here we report the use of DAMP-inducing peptide nanofibers (PNFs) and CL429 (PAMP) combinations as subunit boosters for Bacille Calmette-Guérin (BCG). We demonstrate that pulmonary boosting with PNFs and CL429 enhances the lung-resident memory phenotype, effector cytokine profiles, and transcription factor bias of antigen-specific CD4+T cell populations compared to PNFs alone. Importantly, the combination significantly improved the frequency of tissue-resident memory T (TRM) cells which, have been shown to provide superior protection compared to circulating memory T cells. Interestingly, the T helper (Th) subset profile was driven in part driven by the route of vaccination resulting in a Th17 bias via a mucosal route or a Th1 bias when delivered intravenously. We show that following pulmonary administration, lung-resident antigen presenting cells (APCs) efficiently internalize PNFs and upregulate important co-stimulatory markers that drive T cell priming and activation. Our findings suggest that heterologous booster vaccines composed of DAMP-inducing PNFs and PAMP combinations can engage innate and adaptive immunity for generating TRMcells that protect against TB and potentially other respiratory diseases.