bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Resurgence of Lymphogranuloma Venereum: Changing Presentation of Lymphogranuloma Venereum in the Era of HIV Preexposure Prophylaxis, 2004 to 2022
Authors: Gupta Amit K. , Lyons Brody , Hunter Ian , Arnold Barbra , Gilbert Mark , Hoang Linda , Malleson Sarah , Ryan Venessa , Romney Marc G. , Severini Alberto , Wong Jason , Grennan Troy 
Published: February 2024

BackgroundBefore the early 2000s, the sexually transmitted infection lymphogranuloma venereum (LGV) was rare in high-income countries. Initially, most cases in these countries were among symptomatic men who have sex with men (MSM) living with HIV. In the context of widespread HIV preexposure prophylaxis (PrEP), LGV's epidemiology may be changing. We aimed to characterize the epidemiology and clinical presentation of LGV in the PrEP era.MethodsA retrospective chart review was performed on all LGV cases occurring between November 2004 to October 2022 in British Columbia (BC), Canada. Cases were stratified by having occurred before (2004–2017) or after widespread PrEP availability in BC (2018–2022). Annual rates and test positivity percentages were calculated. Bivariate logistic regression was performed to identify drivers of asymptomatic infection in the PrEP era.ResultsAmong 545 cases identified, 205 (37.6%) occurred pre-PrEP and 340 (62.4%) occurred during the PrEP era. Most cases were among MSM (97.2%). The estimated rate of LGV has doubled from 2018 to 2022, reaching 1535.2 cases per 100,000 PrEP users. Most PrEP-era cases were among HIV-negative individuals (65.3%), particularly those on PrEP (72.6%). Cases in the PrEP era were often asymptomatic compared with pre-PrEP (38.6% vs. 19.3%;P< 0.001). Users of PrEP were more likely to experience asymptomatic infection compared with HIV-negative PrEP nonusers (odds ratio, 2.07; 95% confidence interval, 1.07–3.99).ConclusionsIn the context of increased asymptomatic testing, LGV may be increasing in BC. Most infections now occur among HIV-negative MSM. A high proportion of infections are asymptomatic.
Use of Banked Fibula for Improved Nasal Reconstruction Following Free Fibula Midface Reconstruction
Authors: Bernstein Jaime L. , Reeve Gwendolyn , Kutler David I. , Spector Jason A. 
Published: February 2024

Objective:
Anterior maxillary deficiency caused by trauma or oncologic resection presents a complex reconstructive challenge. The authors present a technique for 2-stage midface reconstruction utilizing a vascularized free fibula flap for maxillary reconstruction, followed by nasal reconstruction at a second stage utilizing a banked fibula graft.

Methods:
This case series utilizes a 2-stage technique for midface reconstruction. In the first stage, a fibula-free flap was used to reconstruct the maxilla with the excess banked in the abdomen. In the second stage, this bone graft was used to restore the nasal dorsum.

Results:
Two patients were included in this series. Patient 1 was a 28-year-old man who presented after a remote gunshot wound to his face, resulting in complete loss of his anterior maxilla and nasal support with midface collapse. Patient 2 was a 65-year-old man who presented with squamous cell carcinoma of the hard palate with extension into the maxilla and nasal septum. In both cases, the flaps healed without complication, providing midface restoration. Placement of the banked fibula graft in a second stage resulted in restoration of dorsal nasal projection.

Conclusion:
The authors describe the use of “spare” fibula parts for nasal reconstruction after loss of the maxilla and cartilaginous septum. The use of the fibula bone as a graft to restore the nasal dorsum in a delayed manner allows for a better assessment of the esthetic needs after the massive swelling from the initial surgery has abated. Further, this approach eliminates the need for a second donor site for nasal reconstruction.
Prevalence of Craniofacial Injuries in the Elderly Population
Authors: Chepyala Pranav , Stead Thor S. , Mangal Rohan K. , Ganti Latha 
Published: February 2024

Introduction:
Recognizing and understanding risk factors for craniofacial injury in the elderly is of paramount importance in prevention. This research aims to investigate the prevalence of craniofacial injuries in connection with extrinsic preventable factors, particularly identifying common household products that pose the greatest risk for such injuries.

Materials and Methods:
This study was done with the utilization of the 2013 to 2022 National Electronic Injury Surveillance System (NEISS). Data gathered included patient age, injury type, cause of injury, and year of incidence. “Elderly” was defined as an individual of 65 years of age or older.

Results:
There was a total of 9,703,688 estimated national cases of elderly craniofacial injury from 2013 to 2022. In all, 5,888,112 (60.68%) of these occurred in females. In descending order, the 5 most common items responsible for craniofacial injury in the elderly are floors/flooring Materials (3,741,706, 30.92%), beds/bed frames (1,250,396, 10.33%), stairs/steps (907,92, 7.50%), chairs (546,697, 4.52%), and tables (453,989, 3.75%). These top 5 account for roughly 57% of all cases. The 5 most common presenting diagnoses were internal injury (2,957,095, 40.21%), lacerations (1,435,926, 19.53%), ABR (1,191,008, 16.20%), fracture (568,842, 7.74%), and hematoma (355,871, 4.84%).

Conclusions:
Out of the roughly 10 million cases of craniofacial injury in the last decade, ~three-fifths have happened to women. The majority of injuries occur in a home setting. The overwhelming majority of cases were related to the product code 1807-floors or flooring materials, and the largest diagnosis was internal injury by a wide margin. Evidently, there is a large population of elderly patients who suffer from craniofacial injuries related to objects and items that permeate within their living residences. The elimination of excess elderly craniofacial injury can be achieved by reducing fall risk factors in the immediate vicinity of the elderly.
Effect of Therapeutic Radiation on Polycaprolactone/Hydroxyapatite Biomaterials in a Calvarial Model
Authors: Park Hojin , Jeong Woo Shik , Choi Jong Woo 
Published: February 2024

Bone defects caused by cancer resection often require postoperative radiotherapy. Although various synthetic polymers have been introduced as graft materials, their biological behavior after radiation exposure remains unclear. Here, we investigated how polycaprolactone/hydroxyapatite (PCL/HA) implants respond to therapeutic radiation exposure (in terms of volume and bone regeneration). Four 8 mm diameter calvaria defects were surgically created on the parietal bone of 6 rabbits. PCL/HA implants made of porous, solid, and hybrid polymers were grafted by random placement in each defect. The fourth defect was left untreated. Four weeks after surgery, radiation exposure was conducted weekly for 6 weeks (total: 48 Gy). Micro-computed tomography and histologic analysis were performed at 3 and 6 months, and 6 months postradiation, respectively. The total augmented volumes of all implants showed no significant differences between 3- and 6-months postradiation computed tomography images. In histologic analysis, new bone areas were 0.45±0.11 mm2, 2.02±0.34 mm2, and 3.60±0.77 mm2 in solid, hybrid, and porous polymer grafts, respectively. Bone regeneration was limited to the periphery of the defect in the hybrid and porous polymer grafts, whereas new bone formed inside the porous implant. The total augmented volume of the defect was maintained without significant absorption even after radiation exposure. The PCL/HA implant maintained its structure despite radiation exposure. The porous PCL/HA implant demonstrated excellent bone regeneration, followed by the hybrid and solid implants. The PCL/HA implant is a promising candidate for bone defect reconstruction.
Prevalence of co-infection between high-risk human papillomavirus and common sexually transmitted infections in cervical specimens
Authors: Kostera Joshua , Tursunovic Almedina , Botts Paige , Galloway Regina , Davis April , Yang Tong 
Published: February 2024

AbstractObjectivesEvidence suggests that co-infection with sexually transmitted infection (STI) pathogens may support HPV infection persistence and cervical disease progression and neoplasia. We examined the prevalence of HPV and co-infection with other common STI pathogens in liquid-based cytology (LBC) cervical specimens, and their association with cervical disease by cytology.MethodsIn this retrospective, cross-sectional study, 149 randomly selected remnant cervical specimens, collected in LBC as part of routine cervical cancer screening in a large urban academic healthcare system, were tested on the Alinity m HR HPV assay and Alinity m STI assay. All specimens were processed for cytology and graded as negative for intraepithelial lesions or malignancy (NILM), atypical squamous cells of undetermined significance (ASC-US) or having any atypical cytology beyond ASC-US (≥LSIL).Results62.4% (n=93/149) of specimens had abnormal (≥ASC-US) cytology and the remaining 37.6% (n=56/149) had NILM cytology. HR HPV was detected in 62.4% (93/149) of specimens and a single STI pathogen was detected in 11.4% (17/149) of specimens. Most specimens with a positive HPV result (73.1%; n=68/93) or positive STI result (94.1%; n=16/17) had ≥ASC-US cytology. Compared to HPV infection alone, co-infection with HPV and STI was associated with an increased prevalence of ASC-US (39.8% vs. 50.0%) and ≥LSIL cytology (33.3% vs. 41.7%). Having ≥LSIL cytology (OR= 4.1667; 95%CI: 1.6110;10.7763) or a positive STI result (OR= 1.5111; 95%CI: 0.5027;4.5420) were predictive of a positive Alinity m HR HPV assay result.ConclusionsOur study confirmed an association between co-infection with HPV and STI pathogens and abnormal cytology in cervical specimens. HPV and STI co-testing may provide granular analyses of the risk of cervical disease associated with co-infections by specific HPV genotypes and STI pathogens.KEY MESSAGESWhat is already known on this topicRecent studies have suggested a possible link between HPV and STI co-infection, HPV persistence in the reproductive tract, and cervical neoplasia.What this study addsCompared to cervical specimens positive for HPV infection alone, specimens with HPV/STI co-infection had a higher prevalence of abnormal cytology.Having abnormal cytology or a positive Alinity m STI assay result were predictive of a positive Alinity m HR HPV assay result.How this study might affect research, practice, or policyMolecular testing for high-risk HPV and common STI pathogens may reveal additional insight for predictors of cervical disease.
De novo HDAC3variants leading to epigenetic machinery dysfunction are associated with a neurodevelopmental disorder
Authors: Yoon Jihoon G. , Lim Seong-Kyun , Seo Hoseok , Lee Seungbok , Cho Jaeso , Kim Soo Yeon , Koh Hyun Yong , Poduri Annapurna H. ,   Deciphering Developmental Disorders Study, Ko Jung Min , Han Dohyun , Chae Jong-Hee , Lee Chul-Hwan 
Published: February 2024

AbstractHistone deacetylase 3 (HDAC3) is a crucial epigenetic modulator essential for brain development. Although its dysfunction is increasingly recognized in various neurodevelopmental disorders, there have been no reports of human diseases related to HDAC3 dysfunction in Online Mendelian Inheritance in Man (OMIM). This study establishes a novel link between heterozygousde novovariants inHDAC3and a distinct neurodevelopmental syndrome, characterized by intellectual disability, developmental delays, and other variable manifestations such as musculoskeletal anomalies and congenital heart defects. In a cohort of six individuals, we identifiedde novomissenseHDAC3variants (D93N, A110T, P201S, L266S, G267S, and R359C), all located in evolutionarily conserved sites. Using trio exome sequencing and extensive phenotypic analysis, we correlated these genetic alterations with the observed clinical spectrum. Our investigations using HDAC assays and western blot analyses identified reduced deacetylation activity in the L266S and G267S variants, positioned near the enzymatic pocket. Additionally, proteomic analysis employing co-immunoprecipitation revealed that disrupted interactions with key multi-protein complexes, particularly CoREST and NCoR in the A110T variant, suggesting a critical pathogenic mechanism. Moreover, immunofluorescence analysis revealed diminished fluorescence intensity (nuclear to cytoplasmic ratio) in the A110T, G267S, and R359C variants, indicating impaired nuclear localization. This study highlights thatde novo HDAC3variants are associated with a novel neurodevelopmental syndrome, emphasizing the importance of histone deacetylase activity, multi-protein complex interactions, and nuclear localization for normal cellular function of HDAC3. These insights open new possibilities for understanding the molecular mechanisms of this uncharacterized neurodevelopmental disorder and may inform future therapeutic approaches.Graphical abstractThis study identifiesde novo HDAC3variants in patients with neurodevelopmental disorders, characterized by intellectual disability, developmental delays, and other variable manifestations. We demonstrate that these variants result in reduced HDAC activity, compromised interactions with multi-protein complexes, and improper nuclear localization of the HDAC3 protein. This provides a novel gene-disease association and offers insights into the molecular underpinnings of this disorder.
Effects of Maize Development and Phenology on the Field Infestation Dynamics of the European Corn Borer (Lepidoptera: Crambidae)
Authors: Revillon Sacha , Dillmann Christine , Galic Nathalie , Bauland Cyril , Palaffre Carine , Malvar Rosa Ana , Butron Ana , Rebaudo François , Legrand Judith 
Published: February 2024

AbstractPhenological match/mismatch between cultivated plants and their pest could impact pest infestastion dynamics in the field. To explore how such match/mismatch of plant and pest phenologies may interact with plant defense dynamics, we studied the infestation dynamics of maize by one of its main pests in Europe, the European Corn Borer (Ostrinia nubilalis; Lepidoptera: Crambidae). A two-year field experiment was carried out on a collection of 23 maize inbred lines contrasted for their earliness. Each inbred line was sown at three different dates in order to expose different developmental stages of maize to natural European corn borer infestation. The effect of the sowing date depended on the inbred line, the pest generation and the year. In 2021, the final pest incidence ranged from 36% to 91% depending on inbred lines and sowing date. In 2022, it ranged from 2% to 77%. This variability in final pest incidence can be related to variations in plant development during plant exposure to pest infestation. However, this relationship was not straightforward. Indeed, the shape and intensity of the relationship depended on the timing of the onset of the pest infestation. When infestation occurred while plants were in a vegetative stage, a non-linear relationship between development and pest incidence was observed with the least and most developed plants being the most infested. When infestation occurred when all plants were in the mature phase, the most developed plants were the least infested. Our results highlight the effect of plant-pest phenological match/mismatch on pest infestation dynamics and underline the importance of taking plant-pest interactions into account to propose relevant control strategies.
Long G4-rich enhancer physically interacts with EXOC3 promoter via a G4:G4 DNA-based mechanism
Authors: DeMeis Jeffrey D , Roberts Justin T , Delcher Haley A , Godang Noel L , Coley Alexander B , Brown Cana L , Shaw Michael H , Naaz Sayema , Alsatari Enas S , Dahal Ayush , Alqudah Shahem Y , Nguyen Kevin N , Nguyen Anita D , Paudel Sunita S , Dang Hong , O’Neal Wanda K. , Knowles Michael R. , Houserova Dominika , Gillespie Mark N , Borchert Glen M 
Published: February 2024

Enhancers are genomic sequences that function as regulatory elements capable of increasing the transcription of a given gene often located at a considerable distance. The broadly accepted model of enhancer activation involves bringing an enhancer-bound activator protein complex into close spatial proximity to its target promoter through chromatin looping. Equally relevant to the work described herein, roles for guanine (G) rich sequences in transcriptional regulation are now widely accepted. Non-coding G-rich sequences are commonly found in gene promoters and enhancers, and various studies have described specific instances where G-rich sequences regulate gene expression via their capacity to form G-quadruplex (G4) structures under physiological conditions. In light of this, our group previously performed a search for long human genomic stretches significantly enriched for minimal G4 motifs (referred to as LG4s herein) leading to the identification of 301 LG4 loci with a density of at least 80 GGG repeats / 1,000 basepairs (bp) and averaging 1,843 bp in length. Further, in agreement with previous reports indicating that minimal G4s are highly enriched in promoters and enhancers, we found 217/301 LG4 sequences overlap a GeneHancer annotated enhancer, and the gene promoters regulated by these LG4 enhancers were found to be similarly, markedly enriched with G4-capable sequences. Importantly, while the generally accepted model for enhancer:promoter specificity maintains that interactions are dictated by enhancer- and promoter-bound transcriptional activator proteins, the current study was designed to test an alternative hypothesis: that LG4 enhancers physically interact with their cognate promoters via a direct G4:G4 DNA-based mechanism. As such, this work employs a combination of informatic mining and locus-specific immunoprecipitation strategies to establish the spatial proximity of enhancer:promoter pairs within the nucleus then biochemically confirms the ability of individual LG4 ssDNAs to directly and specifically interact with DNA sequences found in their target promoters. In addition, we also identify four single nucleotide polymorphisms (SNPs), occurring within a LG4 enhancer on human chromosome 5, significantly associated with Cystic Fibrosis (CF) lung disease severity (avg. p value = 2.83E-9), presumably due to their effects on the expressions of CF-relevant genes directly regulated by this LG4 enhancer (e.g., EXOC3 and CEP72).Graphical AbstractIn brief: LG4 enhancers physically interact with gene promoters by forming composite G4 structures where both the LG4 and cognate promoter contribute half of the necessary sequence for G4 formation.
The mitochondrial thiolase ACAT1 regulates monocyte/macrophage type I interferonviaepigenetic control
Authors: Wu Jing , Singh Komudi , Shing Vivian , Gupta Anand K. , Huffstutler Rebecca D. , Lee Duck-Yeon , Sack Michael N. 
Published: February 2024

ABSTRACTLipid-derived acetyl-CoA is shown to be the major carbon source for histone acetylation. However, there is no direct evidence demonstrating lipid metabolic pathway contribututions to this process. Mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1) catalyzes the final step of ß-oxidation, the aerobic process catabolizing fatty acids (FA) into acetyl-CoA. To investigate this in the context of immunometabolism, we generated macrophage cell line lacking ACAT1.13C-carbon tracing combined with mass spectrometry confirmed incorporation of FA-derived carbons into histone H3 and this incorporation was reduced in ACAT1 KO macrophage cells. RNA-seq identified a subset of genes downregulated in ACAT1 KO cells including STAT1/2 and interferon stimulated genes (ISGs). CHIP analysis demonstrated reduced acetyl-H3 binding to STAT1 promoter/enhancer regions. Increasing histone acetylation rescued STAT1/2 expression in ACAT1 KO cells. Concomitantly, ligand triggered IFNβ release was blunted in ACAT1 KO cells and rescued by reconstitution of ACAT1. Furthermore, ACAT1 promotes FA-mediated histone acetylation in an acetylcarnitine shuttle-dependent manner. In patients with obesity, levels of ACAT1 and histone acetylation are abnormally elevated. Thus, our study identified a novel link between ACAT1 mediated FA metabolism and epigenetic modification on STAT1/2 that uncovers a regulatory role of lipid metabolism in innate immune signaling and opens novel avenues for interventions in human diseases such as obesity.
Recurrent drought increases grassland community seasonal synchrony
Authors: Müller Lena M. , Bahn Michael , Weidle Maximillian , Leitinger Georg , in ‘t Zandt Dina 
Published: February 2024

Abstract1. Climate change increases the frequency and severity of drought events with strong repercussions on grassland ecosystems. While the effects of single drought events on ecosystem structure and functioning are well understood, it is largely unknown whether and how drought frequency modifies ecosystem responses to drought.2. Here, we assessed how the increase in frequency of severe, annual summer drought impacted grassland communities. We examined these effects in a species-rich sub-alpine mountain meadow with a drought frequency of one, three, and 13 years, as well as ambient conditions.3. We found that high drought frequency increased seasonal plant community synchrony through a reduction in species richness, a shift of plant functional groups, a loss of early-seasonal plant species, and the constrained establishment of seedlings throughout the growing season. These changes were associated with a decreased fraction of biomass as drought frequency increased.4. Furthermore, we show that negative drought effects were enhanced with an increasing drought frequency, and that negative drought effects on plant communities outweighed the weak adaptive effects of species.5. Synthesis. We conclude that single and low-frequency drought studies may not adequately predict longer-term changes in our rapidly shifting climate. With the ongoing increase in drought frequency due to climate change, we predict that grassland plant communities will increase in seasonal synchrony. We suggest that this increase in synchrony will leave ecosystems highly vulnerable to future disturbances, because asynchrony is a critical component of stability. Moreover, given the weak adaptive effects of plant species to long-term recurrent drought, we conclude that plant communities are unlikely to be able to adapt to the rapid increase in recurrent drought events.
More than a token photo: humanizing scientists enhances student engagement
Authors: Costello Robin A. , Driessen Emily P. , Kjelvik Melissa K. , Schultheis Elizabeth H. , Youngblood Rachel M. , Zemenick Ash T. , Weber Marjorie G. , Ballen Cissy J. 
Published: February 2024

AbstractHighlighting scientists from historically excluded groups in educational materials increases student engagement in STEM. However, which specific elements of these educational materials maximize their impact remains untested, leaving educators guessing how to best highlight counter-stereotypical scientists in their classrooms. We tested the effects of including visual and humanizing descriptions of scientists featured in quantitative biology activities on over 3,700 students across 36 undergraduate institutions. We found that including humanizing information about counter-stereotypical scientists increased the extent to which students related to those scientists, which in turn translated to higher student engagement. Students who shared one or more excluded identity(s) with the featured scientists related most strongly. Our findings demonstrate the importance of humanizing counter-stereotypical scientists in classrooms, beyond simply adding a photo to increase representation.