bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive Potential of Artificial Intelligence for Predicting PD-L1 Expression and EGFR Mutations in Lung Cancer: A Systematic Review and Meta-Analysis
Authors: Wu Linyong , Wei Dayou , Chen Wubiao , Wu Chaojun , Lu Zhendong , Li Songhua , Liu Wenci 
Published: August 2024

Objective
To evaluate the methodological quality and the predictive performance of artificial intelligence (AI) for predicting programmed death ligand 1 (PD-L1) expression and epidermal growth factor receptors (EGFR) mutations in lung cancer (LC) based on systematic review and meta-analysis.

Methods
AI studies based on PET/CT, CT, PET, and immunohistochemistry (IHC)–whole-slide image (WSI) were included to predict PD-L1 expression or EGFR mutations in LC. The modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool was used to evaluate the methodological quality. A comprehensive meta-analysis was conducted to analyze the overall area under the curve (AUC). The Cochrane diagnostic test and I
2 statistics were used to assess the heterogeneity of the meta-analysis.

Results
A total of 45 AI studies were included, of which 10 were used to predict PD-L1 expression and 35 were used to predict EGFR mutations. Based on the analysis using the QUADAS-2 tool, 37 studies achieved a high-quality score of 7. In the meta-analysis of PD-L1 expression levels, the overall AUCs for PET/CT, CT, and IHC-WSI were 0.80 (95% confidence interval [CI], 0.77–0.84), 0.74 (95% CI, 0.69–0.77), and 0.95 (95% CI, 0.93–0.97), respectively. For EGFR mutation status, the overall AUCs for PET/CT, CT, and PET were 0.85 (95% CI, 0.81–0.88), 0.83 (95% CI, 0.80–0.86), and 0.75 (95% CI, 0.71–0.79), respectively. The Cochrane Diagnostic Test revealed an I
2 value exceeding 50%, indicating substantial heterogeneity in the PD-L1 and EGFR meta-analyses. When AI was combined with clinicopathological features, the enhancement in predicting PD-L1 expression was not substantial, whereas the prediction of EGFR mutations showed improvement compared to the CT and PET models, albeit not significantly so compared to the PET/CT models.

Conclusions
The overall performance of AI in predicting PD-L1 expression and EGFR mutations in LC has promising clinical implications.
Speech Acoustic Analysis in Adult Patients With Cleft Palate After Cleft Palate Repair and Speech Therapy
Authors: Lou Qun , Wang Xudong , Wan Teng , Wang Bixia 
Published: August 2024

Objective:
This study aims to evaluate the enhancement of speech functionality in adult patients with cleft palate through acoustic analysis, assessing pronunciation level improvements before and after palatopharyngoplasty and speech treatment. The findings aim to provide an objective assessment of the treatment efficacy for older patients with cleft palate.

Participants and Intervention:
The study involved acoustic comparisons encompassing vowel formants, voice onset time (VOT) of consonant syllables, syllable duration, and voice characteristic analysis. Speech functionality in each adult cleft palate patient was evaluated thrice: before palatopharyngoplasty, after palatopharyngoplasty, and following speech therapy, using a self-comparative analysis method to discern phonological differences.

Results:
No significant alteration in vowel formants was observed in adult cleft palate patients pre-palatopharyngoplasty and post-palatopharyngoplasty. Post-speech treatment, the F2 and F3 values for the anterior high vowel /i/ significantly improved, aligning closely with those of the normal adult group. Similarly, while consonant parameters (VOT value and syllable duration) remained unchanged post-surgery, both metrics showed significant improvement after speech therapy. Except for the prolonged syllable duration of /s/ compared with normal adults, other indicators were not significantly different. Voice parameter analysis revealed no significant change post-operation; however, both HNR and CPPS values post-speech treatment notably increased, matching those of normal adults.

Conclusion:
Surgical intervention addresses the physical closure of the cleft palate and reconstructs the resonator’s structure. Conversely, consonant improvement predominantly occurs through targeted speech therapy aimed at rectifying pronunciation habits and tutoring patients on the effective utilization of repaired articulatory organs. The combined intervention of cleft palate surgery and speech therapy plays a complementary role in speech restoration for cleft palate patients.
Influence of Socioeconomic Deprivation on Surgical Outcomes for Patients With Sigmoid Diverticulitis in France
Authors: Alves Arnaud , Sabbagh Charles , Ouaissi Mehdi , Zerbib Philippe , Bridoux Valérie , Manceau Gilles , Panis Yves , Buscail Etienne , Venara Aurélien , Khaoudy Iman , Gaillard Martin , Viennet Manon , Thobie Alexandre , Menahem Benjamin , Eveno Clarisse , Bonnel Catherine , Mabrut Jean-Yves , Badic Bogdan , Godet Camille , Eid Yassine , Duchalais Emilie , Lakkis Zaher , Cotte Eddy , Laforest Anaïs , Defourneaux Véronique , Maggiori Léon , Rebibo Lionel , Christou Niki , Talal Ali , Mege Diane , Bonnamy Cécile , Germain Adeline , Mauvais François , Tresallet Christophe , Roudie Jean , Laurent Alexis , Trilling Bertrand , Bertrand Martin , Massalou Damien , Romain Benoit , Tranchart Hadrien , Pellegrin Alexandra , Beyer-Berjot Laura , Dejardin Olivier ,   on behalf of the French Surgical AssociationΦ
Published: August 2024

Objectives:
To evaluate the relationship between socioeconomic deprivation and postoperative outcomes in patients who underwent colonic resection for sigmoid diverticulitis (SD).

Background:
The potential impact of socioeconomic inequalities on the management of SD has been scarcely studied in the literature. Considering other gastrointestinal pathologies for which lesser access to optimal treatment and poorer survival have been shown, we hypothesize that deprivation could be associated with outcomes for SD.

Methods:
This multicenter retrospective study was conducted at 41 French hospitals between January 1, 2010, and August 31, 2021. The main outcome was the occurrence of severe postoperative complications on postoperative day 90, according to the Clavien-Dindo scale (≥3). The European Deprivation Index was used to approximate deprivation for each patient. Multiple imputations by a chained equation were performed to consider the influence of missing data on the results.

Results:
Twenty percent of the 6415 patients operated on had severe postoperative complications at 90 days. In the multivariate regression analysis, increasing age, male sex, American Society of Anesthesiologists score ≥3, conversion to laparotomy or upfront open approach, surgical procedures, and perioperative transfusion were independent risk factors for severe postoperative complications. After adjusting for age, sex, body mass index, American Society of Anesthesiologists score, emergent setting, blood transfusion, indications for surgery, surgical approach, and procedures, the probability of severe postoperative complications increased with socioeconomic deprivation (P=0.026) by day 90.

Conclusions:
This study highlights the potential influence of socioeconomic deprivation on the surgical outcomes of SD. Socioeconomic deprivation should be considered as a risk factor for severe postoperative complications during the preoperative assessment of the patient’s medical conditions.
Dominant Malignant Clones Leverage Lineage Restricted Epigenomic Programs to Drive Ependymoma Development
Authors: Kardian Alisha , Sun Hua , Ippagunta Siri , Laboe Nicholas , Chen Hsiao-Chi , Emanus Erik , Varadharajan Srinidhi , Zheng Tuyu , Holcomb Blake , Connelly Patrick , Connelly Jon P. , Wang Michael , Lowe Kimberley , Pruett-Miller Shondra M. , Bertrand Kelsey C. , Deneen Benjamin , Mack Stephen C. 
Published: August 2024

ABSTRACTZFTA-RELA is the most recurrent genetic alteration seen in pediatric supratentorial ependymoma (EPN) and is sufficient to initiate tumors in mice. Despite ZFTA-RELA’s potent oncogenic potential,ZFTA-RELAgene fusions are observed exclusively in childhood EPN, with tumors located distinctly in the supratentorial region of the central nervous system (CNS). We hypothesized that specific chromatin modules accessible during brain development would render distinct cell lineage programs at direct risk of transformation by ZFTA-RELA. To this end, we performed combined single cell ATAC and RNA-seq analysis (scMultiome) of the developing mouse forebrain as compared to ZR-driven mouse and human EPN. We demonstrate that specific developmental lineage programs present in radial glial cells and regulated by Plagl family transcription factors are at risk of neoplastic transformation. Binding of this chromatin network byZFTA-RELAor other PLAGL family motif targeting fusion proteins leads to persistent chromatin accessibility at oncogenic loci and oncogene expression. Cross-species analysis of mouse and human EPN reveals significant cell type heterogeneity mirroring incomplete neurogenic and gliogenic differentiation, with a small percentage of cycling intermediate progenitor-like cells that establish a putative tumor cell hierarchy.In vivolineage tracing studies reveal single neoplastic clones that aggressively dominate tumor growth and establish the entire EPN cellular hierarchy. These findings unravel developmental epigenomic states critical for fusion oncoprotein driven transformation and elucidate how these states continue to shape tumor progression.HIGHLIGHTS1. Specific chromatin modules accessible during brain development render distinct cell lineage programs at risk of transformation by pediatric fusion oncoproteins.2. Cross-species single cell ATAC and RNA (scMultiome) of mouse and human ependymoma (EPN) reveals diverse patterns of lineage differentiation programs that restrain oncogenic transformation.3. Early intermediate progenitor-like EPN cells establish a tumor cell hierarchy that mirrors neural differentiation programs.4. ZFTA-RELA transformation is compatible with distinct developmental epigenetic states requiring precise ‘goldilocks’ levels of fusion oncoprotein expression.5. Dominant tumor clones establish the entire EPN cellular hierarchy that reflects normal gliogenic and neurogenic differentiation programs.
Changes in Proteome Profiles Linked to Hormonal Contraceptive Use Among African American Women with untreated high blood pressure
Authors: DeRoo Lisa , Abbas Malak , Goodney Gabriel , Gaye Amadou 
Published: August 2024

ABSTRACTBackgroundThe use of oral contraceptives among women with pre-existing cardiometabolic risk factors has been associated with increased risk of cardiovascular events but the underlying mechanisms are not well understood. Analyzing the proteome enables the identification and quantification of proteins involved in various cellular processes, including those affected by oral contraceptives.ObjectiveThe objective of this study was to investigate if current oral contraceptive use was associated with alterations in the plasma proteome among pre-menopausal African American women with hypertension in the Genomics, Environmental Factors, and the Social Determinants of Cardiovascular Disease in African Americans Study (GENE-FORECAST).Study DesignWe evaluated 2,941 serum proteins measured on the Olink platform to assess the associations between oral contraception use and protein levels among 51 pre-menopausal women with untreated Stage 2 hypertension (13 oral contraception users and 38 non-users). A generalized linear model was fitted for each protein, adjusting for age, body mass index, alcohol consumption, level of education, and physical activity. Pathway enrichment analysis was carried out to identify common pathways among the proteins associated with oral contraceptive use. Gene Ontology enrichment analysis was conducted to gain insight into the functional characteristics of the proteins and the underlying biology.ResultsWe identified 44 proteins significantly associated with oral contraceptive use. Among those, 31 showed decreased levels among oral contraceptive users, while 13 exhibited an increase in users. Fourteen proteins were enriched in potentially relevant pathways for the pathogenesis of cardiovascular disease including complement and coagulation cascades, cholesterol metabolism and Notch signaling. There were 25 enriched Gene Ontology terms encompassing 39 of the 44 proteins linked to oral contraceptive use; several of these are involved in peptidase inhibitor activity.ConclusionsThis study provides novel insights into the proteomic landscape associated with oral contraceptive use among African American women with uncontrolled hypertension.
Graphical Representation of Landscape Heterogeneity Identification through Unsupervised Acoustic Analysis
Authors: Guerrero Maria J. , Sánchez-Giraldo Camilo , Uribe Cesar A. , Martínez Victor , Isaza Claudia 
Published: August 2024

AbstractChanges in land use and global warming pose an increasing threat to global biodiversity and ecosystems, calling for the urgent development of effective conservation strategies. Recognizing landscape heterogeneity, which refers to the variation in natural features within an area, is crucial for these strategies. While remote sensing images quantify landscape heterogeneity, they might fail to detect ecological patterns in moderately disturbed areas, particularly at minor spatial scales. This is partly because satellite imagery may not effectively capture undergrowth conditions due to its resolution constraints. In contrast, soundscape analysis, which studies environmental acoustic signals, emerges as a novel tool for understanding ecological patterns, providing reliable information on habitat conditions and landscape heterogeneity in complex environments across diverse scales and serving as a complement to remote sensing methods.We propose an unsupervised approach using passive acoustic monitoring data and network inference methods to analyze acoustic heterogeneity patterns based on biophony composition and richness. This method uses sonotypes, unique acoustic entities characterized by their specific time-frequency spaces, to establish the acoustic structure of a site through sonotype occurrences, focusing on general biophony rather than specific species and providing information on the acoustic footprint of a site. From a sonotype composition matrix, we use the Graphical Lasso method, a sparse Gaussian graphical model, to identify acoustic similarities across sites, map ecological complexity relationships through the nodes (sites) and edges (similarities) and transform acoustic data into a graphical representation of ecological interactions and landscape acoustic diversity.We implemented the proposed method across 17 sites within an oil palm plantation in Santander, Colombia. The resulting inferred graphs visualize the acoustic similarities among sites, reflecting the biophony achieved by characterizing the landscape through its acoustic structures. Correlating our findings with ecological metrics like the Bray-Curtis dissimilarity index and satellite imagery indices reveals significant insights into landscape heterogeneity.This unsupervised approach offers a new perspective on understanding ecological and biological interactions and advances soundscape analysis. The soundscape decomposition into sonotypes underscores the method’s advantage, offering the possibility to associate sonotypes with species and identify their contribution to the similarity proposed by the graph.
Male and female mice respectively form stronger social aversive memories with same and different sex conspecifics
Authors: Beaver Jasmin N. , Nicodemus Marissa M. , Spalding Isabella R. , Dutta Sohini , Jasnow Aaron M. , Gilman T. Lee 
Published: August 2024

AbstractMice offer a wealth of opportunities for investigating brain circuits regulating multiple behaviors, largely due to their genetic tractability. Social behaviors are of translational relevance, considering both mice and humans are highly social mammals, and disruptions in human social behavior are key symptoms of myriad neuropsychiatric disorders. Stresses related to social experiences are particularly influential in the severity and maintenance of neuropsychiatric disorders like anxiety disorders, and trauma and stressor-related disorders. Yet, induction and study of social stress in mice is disproportionately focused on males, influenced heavily by their natural territorial nature. Conspecific-elicited stress (i.e., defeat), while ethologically relevant, is quite variable and predominantly specific to males, making rigorous and sex-inclusive studies challenging. In pursuit of a controllable, consistent, high throughput, and sex-inclusive paradigm for eliciting social stress, we have discovered intriguing sex-specific social aversions that are dependent upon the sex of both experimental and conspecific mice. Specifically, we trained male and female F1 129S1/SvlmJ × C57BL/6J mice to associate (via classical conditioning) same or different sex C57BL/6J conspecifics with a mild, aversive stimulus. Upon subsequent testing for social interaction 24 h later, we found that males socially conditioned better to male conspecifics by exhibiting reduced social interaction, whereas females socially conditioned better to male conspecifics. Serum corticosterone levels inversely corresponded to social avoidance after different sex, but not same sex, conditioning, suggesting corticosterone-mediated arousal could influence cross sex interactions. While our paradigm has further optimization ahead, these current findings reveal why past pursuits to develop same sex female social stress paradigms may have met with limited success. Future research should expand investigation of utilizing male mouse conspecifics to instigate social stress across sexes.
Protamine protects against Vancomycin Induced Kidney Injury
Authors: Shiau Justin , Engel Patti , Olsen Mark , Pais Gwendolyn , Chang Jack , Scheetz Marc H. 
Published: August 2024

ABSTRACTIntroductionVancomycin causes kidney injury by accumulating in the proximal tubule, likely mediated by megalin uptake. Protamine is a putative megalin inhibitor that shares binding sites with heparin and is approved for heparin overdose in patients.MethodsWe employed a well characterized Sprague Dawley rat model to assess kidney injury and function in animals that received vancomycin, protamine alone, or vancomycin plus protamine over 5 days. Urinary KIM-1 was used as the primary measure for kidney injury while iohexol clearance was calculated to assess kidney function. Animals had samples drawn pre-treatment to serve as their own controls. Additionally, since protamine is not a known nephrotoxin, the protamine group also served as a control. Cellular inhibition studies were performed to assess the ability of protamine to inhibit OAT1, OAT3, and OCT2.ResultsRats that received vancomycin had significantly increased urinary KIM-1 on day 2 (24.9 ng/24h, 95% CI 1.87 to 48.0) compared to the protamine alone group. By day 4, animals that received protamine with vancomycin had urinary KIM-1 amounts that were elevated compared to protamine alone (KIM-1 29.0 ng/24h, 95% CI 5.0 to 53.0). No statistically significant differences were identified for iohexol clearance changes between drug groups or when comparing clearance change from baseline (P>0.05). No substantial inhibition of OAT1, OAT3, or OCT2 was observed with protamine. IC50values for protamine were 1e-4 M for OAT1 and OAT3 and 4.3e-5 M for OCT2.ConclusionProtamine, when added to vancomycin therapy, delays vancomycin induced kidney injury as defined by urinary KIM-1 in the rat model by one to three days. Protamine putatively acts through blockade of megalin and does not appear to have significant inhibition on OAT1, OAT3, or OCT2. Since protamine is an approved FDA medication, it has clinical potential as a therapeutic to reduce vancomycin related kidney injury; however, greater utility may be found by pursuing compounds with fewer adverse event liabilities.
Variable responses of alpine-plant communities to warming and loss of dominant species
Authors: Marraffini ML , Sanders NJ , Sundquist MK , Classen AT , Deslippe JR , He JS , McLaren JR , Rixen C , Wipf S , Chisholm C , Giejsztowt J , Prager C , Stouffer DB 
Published: August 2024

AbstractResponses of ecological communities to perturbations are inherently variable because responses of their constituent populations also vary. Species within a single community may show combinations of no response, positive responses, and negative responses to any given perturbation often canceling each other out resulting in small or no signal that the community level. Here we explore the impacts of warming and loss of the dominant species on alpine ecosystems in a global study. We investigate warming and species-loss treatments on population- and community-level dynamics across alpine-plant communities at two elevations in five globally-distributed mountain locations. Communities showed varied responses to treatments; no community showed strong responses to a single treatment. Rather, most sites were influenced by both perturbations. Populations within these communities responded idiosyncratically, suggesting that constituent species are not all equally robust to perturbations even when community-level effects appear weak. Our results highlight the challenge of making general predictions about population- and community-level responses of alpine ecosystems in the face of present and future perturbations.
Iron homeostasis in the annual and perennial stem zones ofArabis alpina
Authors: Sergeeva Anna , Mai Hans-Jörg , Bauer Petra 
Published: August 2024

AbstractPlants serve as reservoirs for vital micronutrients, including iron, which they store in bioavailable forms to support growth in subsequent seasons. The perennial life style is preponderant in nature. Annual species allocate iron towards their seeds. However, our understanding of iron homeostasis in perennial plants remains limited.Arabis alpinais a perennial model organism. Its perenniating branches undergo secondary growth where they store carbon-rich macromolecules.In this study, we investigated iron homeostasis in the perennial and annual stem zones (PZ, AZ) ofA. alpina. We found that both, the wild-type Pajares (Paj) andperpetual flowering 1mutant accumulated iron at various developmental stages in the PZ as well as in the AZ. Notably, iron levels in the PZ were found to be approximately two-fold higher than those in the AZ, underscoring the PZ’s enhanced capacity for iron storage, irrespective of flowering status. Iron was predominantly located within plastid-bound ferritin, providing insight into its storage mechanism. Furthermore, gene expression analyses supported the significance of ferritin and demonstrated an enrichment of transcripts related to iron homeostasis within the stems. Distinct patterns of expression among iron homeostasis genes were observed in relation to iron contents in the PZ and AZ, indicating tissue-specific regulatory mechanisms governing iron accumulation.These findings collectively emphasize the critical function of secondary growth and the PZ as an important site for iron storage in perennial plants, suggesting thatfuture research should further explore the nuances of iron homeostasis signaling in perennial plants.Highlight‐ Iron accumulates in the perennial stem zone, and ferritin is a storage form for iron there.‐ Transcripts of iron homeostasis genes are enriched among genes expressed in the annual and perennial stem zones, yet iron accumulation correlates with different gene expression patterns.