bluuebunny/crossref_metadata_2025 huggingface dataset:
The toxicological effects ofEryngium foetidumextracts on zebrafish embryos and larvae depend on the type of extract, dose, and exposure time.
Authors: Castro Tassia Flavia Dias , Carneiro William Franco , Reichel Tharyn , Fabem Sarah Lacerda , Machado Mônica Rodrigues Ferreira , de Souza Krisnanda Kelly Castro , Resende Luciane Vilela , Murgas Luis David Solis
Published: October 2022

Eryngium foetidum is a herbaceous plant found in tropical and subtropical regions. In vivo pharmacological parameters show that leaf extracts of this plant have antioxidant, anti-inflammatory, antidiabetic, and antimicrobial activities due to their bioactive compounds such as flavonoids and phenols. Despite the evidence for several bioactivities of E. foetidum, information on its safety and tolerability is limited. The objective of this study was to assess the effect and concentration of different extracts of E. foetidum on the development of zebrafish (Danio rerio) embryos. To study the impact of aqueous (AE), ethanolic (EE), and methanolic (ME) extracts, the embryos were exposed to 0.625, 1.25, 2.5, 5, and 10 mg mL−1 for up to 120-h postfertilization to assess embryonic developmental toxicity and then to 0.039, 0.078, 0.156, 0.312, and 0.625 mg mL−1 to assess the antioxidant responses of the enzymes superoxide dismutase catalase, glutathione S-transferase (GST), and cell apoptosis. The results showed that, depending on the extraction solvent, concentration used, and exposure time, E. foetidum extracts caused mortality, altered the hatching time, and promoted changes in enzymatic activities. Delays in development and increased GST activity were found in all treatments. Apoptosis was not observed in any of the treatments. In conclusion, AE, EE, and ME concentrations above 0.625 mg mL−1 can cause adverse effects on the early stages of zebrafish development.
Comparative Transcriptomic Analysis of MAPK-Mediated Regulation of Pathogenicity, Stress Responses, and Development in Cytospora chrysosperma
Authors: Yu Lu , Wen Dasen , Yang Yuchen , Qiu Xiaolin , Xiong Dianguang , Tian Chengming
Published: October 2022

Mitogen-activated protein kinase (MAPK) cascades are highly conserved signal transduction pathways that mediate cellular responses to various biotic and abiotic signals in plant-pathogenic fungi. Generally, there are three MAPKs in filamentous pathogenic fungi: Pmk1/Fus3/Kss1, Hog1, and Stl2. Our previous studies have shown that CcPmk1 is a core regulator of fungal pathogenicity in Cytospora chrysosperma, the causal agent of canker disease in a wide range of woody plants. Here, we identified and functionally characterized the other two MAPK genes ( CcHog1 and CcSlt2) and then compared the transcriptional differences among these three MAPKs in C. chrysosperma. We found that the MAPKs shared convergent and distinct roles in fungal development, stress responses, and virulence. For example, CcHog1, CcSlt2, and CcPmk1 were all involved in conidiation and response to stresses, including hyperosmotic pressure, cell wall inhibition agents, and H2O2, but only CcPmk1 and CcSlt2 were required for hyphal growth and fungal pathogenicity. Transcriptomic analysis showed that numerous hyperosmosis- and cell wall-related genes significantly reduced their expression levels in Δ CcHog1 and Δ CcSlt2, respectively. Interestingly, RNA- and ribosome-related processes were significantly enriched in the upregulated genes of Δ CcSlt2, whereas they were significantly enriched in the downregulated genes of Δ CcPmk1. Moreover, two secondary metabolite gene clusters were significantly downregulated in Δ CcPmk1, Δ CcSlt2, and/or Δ CcHog1. Importantly, some virulence-associated genes were significantly downregulated in Δ CcPmk1 and/or Δ CcSlt2, such as candidate effector genes. Collectively, these results suggest that the similar and distinct phenotypes of each MAPK deletion mutant may result from the transcriptional regulation of a series of common or specific downstream genes, which provides a better understanding of the regulation network of MAPKs in C. chrysosperma.
A novel BRET‐Based GAP assay reveals phosphorylation‐dependent regulation of the RAC‐specific GTPase activating protein ARHGAP25
Authors: Wisniewski Éva , Czárán Domonkos , Kovács Fanni , Bahurek Enikő , Németh Afrodité , Sasvári Péter , Szanda Gergő , Pettkó‐Szandtner Aladár , Klement Eva , Ligeti Erzsébet , Csépányi‐Kömi Roland
Published: October 2022

ARHGAP25, a RAC‐specific GTPase activating protein (GAP), is an essential regulator of phagocyte effector functions such as phagocytosis, superoxide production, and transendothelial migration. Furthermore, its complex role in tumor behavior has recently been recognized. We previously demonstrated that phosphorylation of serine 363 in ARHGAP25 regulates hematopoietic stem cells and progenitor cells in mouse bone marrow. However, the significance of other potential phosphorylation sites of ARHGAP25 remained unknown. Now, we developed a novel, real‐time bioluminescence resonance energy transfer (BRET) assay to monitor the GAP activity of ARHGAP25 in vitro. Using this approach, we revealed that phosphorylation of S363 and S488, but not that of S379‐380, controls ARHGAP25's RACGAP activity. On the other hand, we found in granulocyte‐differentiated human PLB‐985 cells that superoxide production and actin depolymerization are regulated by residues S363 and S379‐380. The present data demonstrate the value of our BRET‐GAP assay and show that different phosphorylation patterns regulate ARHGAP25's GAP activity and its effect on superoxide production and phagocytosis.
Thirty-day Unplanned Reoperations After Posterior Surgery for Thoracic Spinal Stenosis: A Single-center Study Based on 1948 Patients
Authors: Hu Yuanyu , Ouyang Hanqiang , Ye Kaifeng , Qi Junbo , Dong Yanlei , Peng Xianlong , Zhang Xin , Dong Shu , Chen Zhongqiang , Liu Zhongjun , Liu Xiaoguang , Sun Chuiguo , Li Weishi , Tian Yun
Published: October 2022

Study Design.

A retrospective study.

Objective.

The purpose of this study is to identify the incidences, causes, and risk factors of 30-day unplanned reoperation of posterior surgery for thoracic spinal stenosis (TSS) based on 1948 patients in a single center.

Summary of Background Data.

Unplanned reoperation is suggested to be a useful quality indicator for spine surgery. However, the incidences, causes, and risk factors of 30-day unplanned reoperation in patients who underwent posterior spinal surgery for TSS have not been well-established.

Materials and Methods.

We retrospectively analyzed the clinical data of patients who underwent posterior spinal surgery for TSS from January 2011 to December 2021. Statistical methods including univariate and multivariate analyses were performed to assess the incidences, causes, and risk factors.

Results.

A total of 1948 patients who underwent posterior spinal surgery for TSS in our institution were reviewed, and 77 (3.95%) required unplanned reoperations within 30 days because of epidural hematoma (1.64%), wound-related complications (1.02%), inadequate decompression (0.41%), and implant malposition or failure (0.36%), neurological deficit (0.26%), and other causes (0.26%). After univariate analysis, seven clinical factors were associated with unplanned reoperation (P<0.05). Multivariate logistic regression analysis showed that upper thoracic spine surgery (P=0.010), thoracic kyphosis ≥45° (P=0.039), and intraoperative dural injury (P=0.047) were independent risk factors for 30-day unplanned reoperation of posterior surgery for TSS.

Conclusions.

The incidence of 30-day unplanned reoperations after posterior surgical treatment for TSS was 3.95%. The most common causes were epidural hematoma, wound-related complications, inadequate decompression, and implant malposition or failure. Upper thoracic spine surgery, thoracic kyphosis ≥45°, and intraoperative dural injury led to an increased risk of unplanned reoperation within 30 days after posterior spinal surgery for TSS.

Level of Evidence.

4.
Feasibility and Surgical Effect of Annulus Sparing in Consecutive Patients with Tetralogy of Fallot: A Retrospective Cohort Study
Authors: Lv Lizhi , Liu Jinyang , Jiang Xianchao , Liu Yang , Tian Yanjin , Cao Hong , Liu Zhimin , Wang Qiang
Published: October 2022

Objective:

Annulus-sparing (AS) repair for tetralogy of Fallot (TOF) with a dysplastic pulmonary valve annulus (PVA) is a challenging procedure and is controversial. This study aimed to assess the feasibility and surgical effect of AS repair versus transannular patch enlargement (TAPE) repair, especially in individuals with dysplastic pulmonary valves.

Methods:

This retrospective cohort study included 375 pediatric patients with a primary diagnosis of TOF in the Center for Pediatric Cardiac Surgery of Fuwai hospital from January 2014 to June 2017. Among them, 60 consecutive and nonselective patients underwent 1-stage repair of TOF with aggressive PVA-preserving strategies performed by a single surgeon were enrolled in AS cohort. In AS cohort, patients were divided into AS, PVA z-score ≥−2 group (33 patients) and AS, PVA z-score <−2 group (27 patients). During the same period, 315 patients underwent TAPE repair by other surgeons were enrolled as TAPE cohort, of these, 87 patients with PVA z-score ≥−2 were excluded. From the 228 patients in the TAPE group, 27 cases were selected as TAPE, PVA z-score <−2 group according to the propensity score and 1:1 ratio with AS, PVA z-score <−2 group. The primary outcome was a composite of reintervention, significant pulmonary regurgitation, and significant annular peak gradient (APG). Kaplan-Meier curve was plotted to show the survival rate of severe pulmonary regurgitation.

Results:

One death occurred after the TAPE operation in TAPE group, and 1 patient in the AS z ≥−2 group needed reintervention with a balloon. After a median follow-up of (30.3 ± 11.6) months, compared with AS z ≥−2 group, there was no difference in the technical performance score for severe pulmonary stenosis (APGs > 20 mmHg) in the AS z <−2 group. Compared with TAPE, AS repair was often accompanied by a postoperative APGs over 20 mmHg (P = 0.001). More patients underwent TAPE suffered from moderate or severe pulmonary regurgitation than those who received AS repair (20 (74.1%) vs. 7 (26.0%), P < 0.001). AS repair was associated with a shorter duration of mechanical ventilation (20 vs. 29 hours, P = 0.039), faster discharge from the intensive care unit (2.0 vs. 4.0 days, P = 0.022) and shorter postoperative hospitalization (8.0 vs. 11.0 days, P = 0.008) compared with TAPE.

Conclusions:

APG demonstrated an upward trend in the TAPE group and a downtrend in the AS group after discharge from hospital. AS repair had an acceptable surgical effect in TOF patients, even in those with a dysplastic PVA. A higher APG remained upon hospital discharge in dysplastic patients with AS, but a downward trend was observed over time.
Epigenome-wide association of neonatal methylation and trimester-specific prenatal PM2.5 exposure
Authors: Parikh Milan N. , Brokamp Cole , Rasnick Erika , Ding Lili , Mersha Tesfaye B. , Bowers Katherine , Folger Alonzo T.
Published: October 2022

Background:

Exposure to particulate matter with an aerodynamic diameter smaller than 2.5 microns (PM2.5) can affect birth outcomes through physiological pathways such as inflammation. One potential way PM2.5 affects physiology could be through altering DNA methylation (DNAm). Considering that exposures during specific windows of gestation may have unique effects on DNAm, we hypothesized a timing-specific association between PM2.5 exposure during pregnancy and DNAm in the neonatal epithelial-cell epigenome.

Methods:

After collecting salivary samples from a cohort of 91 neonates, DNAm was assessed at over 850,000 cytosine-guanine dinucleotide (CpG) methylation sites on the epigenome using the MethylationEPIC array. Daily ambient PM2.5 concentrations were estimated based on the mother’s address of primary residence during pregnancy. PM2.5 was averaged over the first two trimesters, separately and combined, and tested for association with DNAm through an epigenome-wide association (EWA) analysis. For each EWA, false discovery rate (FDR)-corrected P < 0.05 constituted a significant finding and every CpG site with uncorrected P < 0.0001 was selected to undergo pathway and network analysis to identify molecular functions enriched by them.

Results:

Our analysis showed that cg18705808 was associated with the combined average of PM2.5. Pathway and network analysis revealed little similarity between the first two trimesters. Previous studies reported that TMEM184A, the gene regulated by cg18705808, has a putative role in inflammatory pathways.

Conclusions:

The differences in pathway and network analyses could potentially indicate trimester-specific effects of PM2.5 on DNAm. Further analysis with greater temporal resolution would be valuable to fully characterize the effect of PM2.5 on DNAm and child development.
Artificial intelligence-based opportunistic screening for the detection of arterial hypertension through ECG signals
Authors: Angelaki Eleni , Barmparis Georgios D. , Kochiadakis George , Maragkoudakis Spyros , Savva Eirini , Kampanieris Emmanuel , Kassotakis Spyros , Kalomoirakis Petros , Vardas Panos , Tsironis Giorgos P. , Marketou Maria E.
Published: October 2022

Objectives:

Hypertension is a major risk factor for cardiovascular disease (CVD), which often escapes the diagnosis or should be confirmed by several office visits. The ECG is one of the most widely used diagnostic tools and could be of paramount importance in patients’ initial evaluation.

Methods:

We used machine learning techniques based on clinical parameters and features derived from the ECG, to detect hypertension in a population without CVD. We enrolled 1091 individuals who were classified as hypertensive or normotensive, and trained a Random Forest model, to detect the existence of hypertension. We then calculated the values for the Shapley additive explanations (SHAP), a sophisticated feature importance analysis, to interpret each feature's role in the Random Forest's results.

Results:

Our Random Forest model was able to distinguish hypertensive from normotensive patients with accuracy 84.2%, specificity 78.0%, sensitivity 84.0% and area under the receiver-operating curve 0.89, using a decision threshold of 0.6. Age, BMI, BMI-adjusted Cornell criteria (BMI multiplied by RaVL+SV3), R wave amplitude in aVL and BMI-modified Sokolow-Lyon voltage (BMI divided by SV1+RV5), were the most important anthropometric and ECG-derived features in terms of the success of our model.

Conclusion:

Our machine learning algorithm is effective in the detection of hypertension in patients using ECG-derived and basic anthropometric criteria. Our findings open new horizon in the detection of many undiagnosed hypertensive individuals who have an increased CVD risk.
Periocular Granuloma Annulare: A Case Report of a Rare Childhood Disease in an Adult
Authors: Kanavati Sam , Munthali Lamios , Rajak Saul
Published: October 2022

A 21-year-old female presented to the oculoplastic clinic with a 2-year history of raised lesions in the right upper eyelid and lateral canthus area. Due to their unusual appearance, the patient underwent an excisional biopsy of the lateral canthus lesion. A diagnosis of granuloma annulare was made after histopathology demonstrated palisading epithelioid granulomas with central fibrinoid necrosis and Alician blue positive acid mucin. Granuloma annulare is a benign inflammatory skin condition characterized by firm discolored papules or nodules classically arranged in an annular pattern. Periocular involvement is extremely rare in adults and may pose a diagnostic challenge to ophthalmologists unfamiliar with its presentation and management.
Residual Apical Lamina Papyracea as a Cause for Persistent Dysthyroid Optic Neuropathy After Orbital Decompression
Authors: Gupta Ankur , Garcia Maria D. , North Victoria , Kazim Michael , Rose Geoffrey E.
Published: October 2022

Two patients had persistent compressive dysthyroid optic neuropathy after decompression of the medial orbital wall and floor. In both cases, there was ~3 mm of unresected lamina papyracea anterior to the Annulus of Zinn, and removal of this residual bone led to resolution of the neuropathy. These illustrative cases suggest that, in some patients, even small amounts of residual crowding at the orbital apex can critically embarrass optic nerve perfusion, with resulting continued ischemic optic neuropathy.
Assessing Patient Barriers to Cochlear Implantation
Authors: Mangan Andrew R. , Davis Kyle P. , Anzalone C. Lane , Saadi Robert A. , Dornhoffer John L. , King Deanne L.
Published: October 2022

Objective

Evaluate barriers that deter adult patients from following through with cochlear implantation.

Study Design

Retrospective chart review and phone survey.

Setting

Single tertiary referral center.

Patients

Between January 2019 and August 2021, 113 patients, without a previous cochlear implant (CI), were determined to be candidates for cochlear implantation. Thirty-eight (33.6%) patients deferred cochlear implantation. Survey response rate was 61.1% (22/36).

Intervention

None.

Main Outcome Measures

Demographic, socioeconomic, otologic history, and comorbidity factors associated with deferment of cochlear implantation. Patient survey assessment of factors that had the greatest impact, rated on a scale of 1 to 10 (10 being the most impactful), on their decision to defer a CI.

Results

Out of the 113 patients who met inclusion criteria, 75 (66.3%) underwent cochlear implantation and 38 (33.6%) patients deferred. Comparing implanted versus deferred groups, there was no statistical difference in age (67.1 y versus 68.5 y; p = 0.690) or male sex (53.3% versus 57.9%; p = 0.692). The deferred group had higher mean neighborhood disadvantage state decile (5.3 versus 4.3; p = 0.064) and national percentile (73.0 versus 66.2; p = 0.106) scores, although neither were statistically significant. A greater proportion of the deferred group were not living independently at time of CI evaluation (13.2 versus 2.7%; p = 0.017). Fear of losing residual hearing was rated the highest among the survey respondents (mean rating of 5.1), followed by general medical health (4.9) and cost and financial concerns (3.6).

Conclusion

The greatest concern among the patients was the fear of losing residual hearing. Spending greater time educating patients about the success and failure rates of cochlear implantation may reduce patient hesitancy with implantation.
The Frailty Phenotype in Older Adults Undergoing Cochlear Implantation
Authors: Kay-Rivest Emily , Friedmann David R. , McMenomey Sean O. , Jethanamest Daniel , Thomas Roland J. , Waltzman Susan B.
Published: October 2022

Objective

To prospectively evaluate the frailty phenotype in a population of older adults and determine its association with 1) perioperative complications, 2) need for vestibular rehabilitation after surgery, and 3) early speech perception outcomes.

Study Design

Prospective cohort study.

Setting

Tertiary care hospital.

Patients

Adults older than 65 years undergoing cochlear implantation.

Interventions

The Fried Frailty Index was used to classify patients as frail, prefrail, or not frail based on five criteria: 1) gait speed, 2) grip strength, 3) unintentional weight loss, 4) weekly physical activity, and 5) self-reported exhaustion.

Main Outcomes Measures

Rates of intraoperative and postoperative complications, postoperative falls, need for vestibular rehabilitation, and early speech perception outcomes.

Results

Forty-six patients were enrolled in this study. Five patients (10.8%) were categorized as frail and 10 (21.7%) as prefrail. The mean ages of frail, prefrail, and not frail patients were 80.9, 78.8, and 77.5, respectively. There were no intraoperative complications among all groups. Three patients required postoperative vestibular rehabilitation; all were not frail. One postoperative fall occurred in a nonfrail individual. Mean (standard deviation) device use times at 3 months in frail, prefrail, and not frail patients were 7.6 (3.5), 11.1 (3.6), and 11.6 (2.9) hours per day, respectively. Consonant–nucleus–consonant word scores 3 months after surgery in frail, prefrail, and not frail patients were 13% (12.2), 44% (19.7), and 51% (22.4), respectively. The median (range) number of missed follow-up visits (surgeon, audiologist, speech language pathologist combined) was 7 (1–10) in frail patients, compared with a median of 3 (0–4) and 2 (0–5) in prefrail and not frail patients.

Conclusions

Frail patients did not have increased rates of surgical complications, need for vestibular rehabilitation, or postoperative falls. However, frail patients experienced challenges in accessing postoperative care, which may be addressed by using remote programming and rehabilitation.
Clinical Impact of Genetic Diagnosis of Sensorineural Hearing Loss in Adults
Authors: Corriols-Noval Patricia , López Simón Eugenia Carmela , Cadiñanos Juan , Diñeiro Marta , Capín Raquel , González Aguado Rocío , Costales Marcos María , Morales Angulo Carmelo , Cabanillas Farpón Rubén
Published: October 2022

Hypothesis

Adult genetic sensorineural hearing loss (SNHL) may be underestimated.

Background

The diagnosis of genetic hearing loss is challenging, given its extreme genetic and phenotypic heterogeneity, particularly in adulthood. This study evaluated the utility of next-generation sequencing (NGS) in the etiological diagnosis of adult-onset SNHL.

Materials and Methods

Adults (>16 yr old) with SNHL were recruited at the Otolaryngology Department at Marqués de Valdecilla University Hospital (Spain). Environmental factors, acoustic trauma, endolymphatic hydrops, and age-related hearing loss were excluding criteria. An NGS gene panel was used, including 196 genes (OTOgenics v3) or 229 genes (OTOgenics v4) related to syndromic and nonsyndromic hearing loss.

Results

Sixty-five patients were included in the study (average age at the onset of SNHL, 41 yr). Fifteen pathogenic/likely pathogenic variants considered to be causative were found in 15 patients (23% diagnostic yield) in TECTA (4), KCNQ4 (3), GJB2 (2), ACTG1 (1), COL2A1 (1), COCH (1), COCH/COL2A1 (1), STRC (1), and ABHD12 (1). Three patients had syndromic associations (20% of patients with genetic diagnosis) that had not been previously diagnosed (two Stickler type I and one polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, cataract syndrome). Seven variants of unknown significance were found in COL11A1 (1), GSMDE (2), DNTM1 (1), SOX10 (1), EYA4 (1), and TECTA (1).

Conclusion

NGS gene panels can provide diagnostic yields greater than 20% for adult SNHL, with a significant proportion of variant of unknown significance that could potentially contribute to increasing diagnostic output. Identifying a genetic cause enables genetic counseling, provides prognostic information and can reveal unrecognized syndromes contributing to an accurate management of their associated manifestations.
The Relationship Between Defenses and Learning
Authors: Patra Vlachopanou , Evangelia Karagiannopoulou , Georgios Ntritsos
Published: October 2022

This study investigates the relationship among defense styles and learning through academic procrastination and psychological well-being. The sample comprises 628 social science students from a Greek university. Path analysis is used to explore associations and interactions among the variables. The results show that academic procrastination and psychological well-being mediate the relationship between defense styles and approaches to learning, indicating the expected direct and indirect effects. Defense styles are directly related to approaches to learning. Mature defense styles are associated with learning through psychological well-being in a positive way, and immature defense styles are associated with learning through academic procrastination in a negative way. This study supports the current line of research in associations between defense styles and learning and the importance of linking mental health variables with learning.
The Relationship Among Autistic Traits, Impulsivity, and Functionality in Patients With Obsessive-Compulsive Disorder
Authors: Namli Zeynep , Tamam Lut , Demirkol Mehmet Emin , Karaytuğ Mahmut Onur , Sun Tunahan
Published: October 2022

Obsessive-compulsive disorder (OCD) is a chronic mental disorder that causes disabilities. This study investigated the relationship among impulsivity, autistic traits, and disabilities in patients with OCD. We included 88 patients with OCD and 90 healthy volunteers without any mental disorders. The participants were evaluated using the Yale-Brown Obsessive-Compulsive Scale, Autism Spectrum Quotient (AQ), Barratt Impulsiveness Scale-11 (BIS-11), and World Health Organization Disability Assessment Schedule (WHODAS 2.0). Regression analyses revealed that AQ-attention switching and BIS-attentional subscale scores were associated with WHODAS-overall score in the OCD group (p = 0.017 and p = 0.034, respectively). In the OCD group, AQ total, social skills, and communication subdomain scores partially mediated the relationship between impulsivity and disability. BIS total, attentional, and nonplanning subscale scores partially mediated the relationship between autistic traits and disability. Developing new treatment strategies for cognitive recovery, in addition to traditional treatment approaches in patients with OCD, may help increase functionality in patients with OCD.
3-Dimensional Morphometric Outcomes After Endoscopic Strip Craniectomy for Unicoronal Synostosis
Authors: Elawadly Ahmed , Smith Luke , Borghi Alessandro , Nouby Radwan , Silva Adikarige H.D. , Dunaway David J. , Jeelani Noor ul O. , Ong Juling , James Greg
Published: October 2022

Background:

Endoscopic strip craniectomy with postoperative helmeting (ESCH) for unicoronal synostosis has shown to be a less morbid procedure when compared with fronto-orbital remodeling (FOR). We aim in this pilot study to report objective methods and quantitative morphologic outcomes of endoscopically treated unicoronal synostosis using 3-dimensional surface scans.

Methods:

Our electronic records were reviewed for ophthalmological, neurodevelopmental outcomes, and helmet-related complications. For morphologic outcomes, the following parameters were used: Cranial Index, Cranial Vault Asymmetry Index, Anterior Symmetry Ratio (ASR), and Root Mean Square between the normal and synostotic sides of the head. Three-dimensional stereophotogrammetry scans were evaluated at 3 time points preoperative, 6 months post-op, and at the end of the treatment, which was compared with age-matched scans of normal controls and FOR patients. Nonparametric tests were used for statistical analysis.

Results:

None of the ESCH cases developed strabismus, major neurodevelopmental delay, or helmet complications. All morphologic parameters improved significantly at 6 months post-op except for the Cranial Vault Asymmetry Index. The ASR was the only parameter to change significantly between 6 months post-op and final scans. At end of helmet treatment, ASR and Root Mean Square differed significantly between the ESCH and both FOR and control groups.

Conclusions:

Endoscopic strip craniectomy with postoperative helmeting for single unicoronal synostosis had excellent clinical outcomes. Most of the improvement in head morphology occurred in the first 6 months of treatment. Despite the normalization of the overall head shape, there was residual asymmetry in the frontal and temporal regions of the head.
Met and Unmet Needs of Older Adults With Cognitive Impairment, and Burden and Benefits of Their Family Caregivers
Authors: Sung Pildoo , Hashim Nawal , Malhotra Rahul , Chan Angelique
Published: October 2022

Objectives:

This study examined the association between met and unmet needs of older adults with cognitive impairment living in the community and unique types of caregiving experience, each comprising different levels of caregiving burden and benefits.

Methods:

Latent class analysis and multivariable regression were applied to data on 266 caregivers of community-dwelling Singaporean older adults, aged 60 years and above, with cognitive impairment who participated in a community-based dementia care study in 2018.

Results:

Three unique types of caregiving experience were identified: satisfied (low burden and high benefits; 54% of caregivers), dissatisfied (low burden and low benefits; 35%), and intensive (high burden and high benefits; 11%). Met needs were positively associated with satisfied caregiving experience (vs. dissatisfied caregiving experience), and both met and unmet needs were positively associated with intensive caregiving experience (vs. dissatisfied caregiving experience). Specifically, caregivers tended to have satisfied caregiving experience if older adults’ care needs in daytime activities or mobility were met.

Discussion:

Fulfillment of unmet needs of older adults with cognitive impairment is associated with a satisfied caregiver experience characterized by lower caregiver burden and greater caregiver benefits. Identification of and tailored interventions for unmet care needs of older adults will likely promote satisfied caregiving experience.
Evolution of the cardiac dyad
Authors: Mackrill John James
Published: October 2022

Cardiac dyads are the site of communication between the sarcoplasmic reticulum (SR) and infoldings of the sarcolemma called transverse-tubules (TT). During heart excitation–contraction coupling, Ca2+-influx through L-type Ca2+channels in the TT is amplified by release of Ca2+-from the SR via type 2 ryanodine receptors, activating the contractile apparatus. Key proteins involved in cardiac dyad function are bridging integrator 1 (BIN1), junctophilin 2 and caveolin 3. The work presented here aims to reconstruct the evolutionary history of the cardiac dyad, by surveying the scientific literature for ultrastructural evidence of these junctions across all animal taxa; phylogenetically reconstructing the evolutionary history of BIN1; and by comparing peptide motifs involved in TT formation by this protein across metazoans. Key findings are that cardiac dyads have been identified in mammals, arthropods and molluscs, but not in other animals. Vertebrate BIN1 does not group with members of this protein family from other taxa, suggesting that invertebrate BINs are paralogues rather orthologues of this gene. Comparisons of BIN1 peptide sequences of mammals with those of other vertebrates reveals novel features that might contribute to TT and dyad formation. The analyses presented here suggest that the cardiac dyad evolved independently several times during metazoan evolution: an unexpected observation given the diversity of heart structure and function between different animal taxa.

This article is part of the theme issue ‘The cardiomyocyte: new revelations on the interplay between architecture and function in growth, health, and disease’.
Lamin A precursor localizes to the Z-disc of sarcomeres in the heart and is dynamically regulated in muscle cell differentiation
Authors: Brayson Daniel , Shanahan Catherine M.
Published: October 2022

The lamin A precursor, prelamin A, requires extensive processing to yield mature lamin A and effect its primary function as a structural filament of the nucleoskeleton. When processing is perturbed, nuclear accumulation of prelamin A is toxic and causes laminopathic diseases such as Hutchinson–Gilford progeria syndrome and cardiomyopathy. However, the physiological role of prelamin A is largely unknown and we sought to identify novel insights about this. Using rodent heart tissue, primary cells and the C2C12 model of myofibrillogenesis, we investigated the expression and localization patterns of prelamin A in heart and skeletal muscle cells. We found that endogenous prelamin A was detectable in mouse heart localized to the sarcomere in both adult mouse heart and isolated neonatal rat cardiomyocytes. We investigated the regulation of prelamin A in C2C12 myofibrillogenesis and found it was dynamically regulated and organized into striations upon myofibril formation, colocalizing with the Z-disc protein α-actinin. These data provide evidence that prelamin A is a component of the sarcomere, underpinning a physiological purpose for unprocessed prelamin A.

This article is part of the theme issue ‘The cardiomyocyte: new revelations on the interplay between architecture and function in growth, health, and disease’.
Anaeromyxobacter oryzae sp. nov., Anaeromyxobacter diazotrophicus sp. nov. and Anaeromyxobacter paludicola sp. nov., isolated from paddy soils
Authors: Itoh Hideomi , Xu Zhenxing , Mise Kazumori , Masuda Yoko , Ushijima Natsumi , Hayakawa Chie , Shiratori Yutaka , Senoo Keishi
Published: October 2022

Three bacterial strains (Red232T, Red267T and Red630T) were isolated from paddy soils sampled in Japan. Cells of these strains were Gram-stain-negative, facultative anaerobic, long rod-shaped with monotrichous flagella or pilus-like structures for motility, and formed red colonies on agar plates. Phylogenetic trees based on 16S rRNA gene and multiple single-copy gene sequences showed that the three strains formed a cluster with the type strains of

Anaeromyxobacter

species, independent from any other strain genera. Similarity values of the 16S rRNA gene sequences and genomes among the three isolated strains and the type strain of

Anaeromyxobacter

,

Anaeromyxobacter dehalogenans

2CP-1T, were 95.4–97.4% for 16S rRNA gene sequence, 75.3–79.5% for average nucleotide identity, 19.6–21.7% for digital DNA–DNA hybridization and 64.1–72.6% for average amino acid identity, all of which are below the species delineation thresholds. Nitrogenase genes were observed in the genomes of the three novel strains, but not in

A. dehalogenans

2CP-1T. Moreover, multiple genomic, physiological and chemotaxonomic features supported the discrimination between these three strains. Based on the evidence in this study, the three isolates represent three novel independent species for which the following names are proposed: Anaeromyxobacter oryzae sp. nov., Anaeromyxobacter diazotrophicus sp. nov. and Anaeromyxobacter paludicola sp. nov. The type strains are Red232T (=NBRC 114074T=MCCC 1K03954T), Red267T (=NBRC 114075T=MCCC 1K04211T), and Red630T (=NBRC 114076T=MCCC 1K03957T), respectively.
Exploration of the presence and abundance of multidrug resistance efflux genes in oil and gas environments
Authors: Brown Damon C. , Aggarwal Naomi , Turner Raymond J.
Published: October 2022

As sequencing technology improves and the cost of metagenome sequencing decreases, the number of sequenced environments increases. These metagenomes provide a wealth of data in the form of annotated and unannotated genes. The role of multidrug resistance efflux pumps (MDREPs) is the removal of antibiotics, biocides and toxic metabolites created during aromatic hydrocarbon metabolism. Due to their naturally occurring role in hydrocarbon metabolism and their role in biocide tolerance, MDREP genes are of particular importance for the protection of pipeline assets. However, the heterogeneity of MDREP genes creates a challenge during annotation and detection. Here we use a selection of primers designed to target MDREPs in six pure species and apply them to publicly available metagenomes associated with oil and gas environments. Using in silico PCR with relaxed primer binding conditions we probed the metagenomes of a shale reservoir, a heavy oil tailings pond, a civil wastewater treatment, two marine sediments exposed to hydrocarbons following the Deepwater Horizon oil spill and a non-exposed marine sediment to assess the presence and abundance of MDREP genes. Through relaxed primer binding conditions during in silico PCR, the prevalence of MDREPs was determined. The percentage of nucleotide sequences identified by the MDREP primers was partially augmented by exposure to hydrocarbons in marine sediment and in shale reservoir compared to hydrocarbon-free marine sediments while tailings ponds and wastewater had the highest percentages. We believe this approach lays the groundwork for a supervised method of identifying poorly conserved genes within metagenomes.
Maternal dietary deficiencies in folates or choline during pregnancy and lactation worsen stroke outcome in 3-month-old male and female mouse offspring
Authors: Clementson McCoy , Hurley Lauren , Coonrod Sarah , Bennett Calli , Marella Purvaja , Pascual Agnes S. , Pull Kasey , Wasek Brandi , Bottiglieri Teodoro , Malysheva Olga , Ca udill Marie A. , Jadavji Nafisa M.
Published: October 2022

Maternal one-carbon (1C) metabolism plays an important role in early life programming. There is a well-established connection between the fetal environment and the health status of the offspring. However, there is a knowledge gap on how maternal nutrition impacts stroke outcome in offspring. The aim of our study was to investigate the role of maternal dietary deficiencies in folic acid or choline on stroke outcome in 3-month-old offspring. Adult female mice were fed a folic acid deficient diet (FADD), choline deficient diet (ChDD), or control diet (CD) prior to pregnancy. They were continued on diets during pregnancy and lactation. Male and female offspring were weaned onto a CD and at 2 months of age were subject to ischemic stroke within the sensorimotor cortex via photothrombosis damage. At 3-months-of-age, motor function was measured in offspring and tissue was collected for analysis. Mothers maintained on either a FADD or ChDD had reduced levels of S-adenosylmethionine in liver and S-adenosylhomocysteine in plasma. After ischemic stroke, motor function was impaired in 3-month-old offspring from deficient mothers compared to CD animals. In brain tissue, there was no difference in ischemic damage volume. When protein levels were assessed in brain tissue, there were lower levels of neurodegeneration in males compared to females and betaine levels were reduced in offspring from ChDD mothers. Our results demonstrate that a deficient maternal diet during critical timepoints in neurodevelopment results in worse stroke outcomes. This study emphasizes the importance of maternal diet and the impact it can have on offspring health.
Photoacoustic imaging reveals transient decrease of oxygenation in murine blood due to monoclonal IgG4 antibody
Authors: Khadria Anjul , Paavola Chad D. , Maslov Konstantin , Brown-Augsburger Patricia L. , Grealish Patrick F. , Lozano Emmanuel , Blankenship Ross L. , Cao Rui , Shi Junhui , Beals John M. , Oladipupo Sunday S , Wang Lihong V.
Published: October 2022

Over 100 monoclonal antibodies have been approved by the FDA for clinical use; however, a paucity of knowledge exists regarding the injection site behavior of these formulated therapeutics, i.e., the effect of antibody and formulation on the tissue around the injection site and vice versa. In this report, we injected a near-infrared dye-labeled IgG4 isotope control antibody into the subcutaneous space in mouse ears to analyze the injection site dynamics, including quantifying molecular movement. Surprisingly, we discovered that the antibody reduces the local blood oxygen saturation levels in mice after prolonged anesthesia without affecting the total hemoglobin content and oxygen extraction fraction. The local oxygen saturation results open a new pathway to study the functional effects of monoclonal antibodies.
We the Hunted
Authors: Martin Jesse M. , Leece A.B. , Herries Andy I.R. , Baker Stephanie E. , Strait David S.
Published: October 2022

Classic depictions of human evolutionary ecology castHomoas predator and other hominins, includingParanthropus robustus,as prey. Such hypotheses rest on a small number of fossils that exhibit evidence of carnivore predation, including the iconic SK 54 cranium from Swartkrans in South Africa. Here we demonstrate that the SK 54 cranium shares its closest affinities withH. erectusrather thanP. robustus.Demonstrating thatHomowas prey for leopards at Swartkrans weakens the historically significant hypothesis thatHomowas better able to avoid predation because of being behaviourally and technologically advanced compared toParanthropus. Subsequent ideas about hominin paleobiology derived from this hypothesis warrant reconsideration.
Cardiac MAO-A inhibition protects against catecholamine-induced ventricular arrhythmias via enhanced diastolic calcium control
Authors: Shi Qian , Malik Hamza , Streeter Jennifer , Wang Jinxi , Huo Ran , Crawford Rachel M. , Shih Jean C. , Chen Biyi , Hall Duane , Abel E. Dale , Song Long-Sheng , Anderson Ethan J.
Published: October 2022

Background

People with clinical depression exhibit increased risk for cardiac arrhythmias that could be related to differences in catecholamine metabolism. Emerging studies have implicated a pathophysiologic role for monoamine oxidase (MAO-A), which catalyzes catecholamine metabolism in the heart. MAO-A is the pharmacological target of some classes of anti-depressants. Here, we investigated the relationship between MAO-A activity and arrhythmogenesis.

Methods & Results

TriNetX database analysis of adult patients with depression (n=11,533) revealed that MAO inhibitor (MAOI) treatment is associated with significantly lower risk of arrhythmias compared with selective serotonin reuptake inhibitor (SSRI) treatment (16.7% vs 18.6%, p=0.0002). To determine a mechanistic link between MAO activity and arrhythmia, we utilized a genetically modified mouse model with cardiomyocyte-specific MAO-A deficiency (cMAO-Adef). Compared with wild-type (WT) mice, cMAO-Adefmice had a significant reduction in the incidence (38.9% vs. 77.8%, p=0.0409) and duration (55.33 ± 26.21s vs.163.1 ± 56.38s, p=0.0360) of catecholamine stress-induced ventricular tachyarrhythmias (VT). Reduced VT risk and duration were associated with altered cardiomyocyte Ca2+handling in the cMAO-Adefhearts, including a marked increase in Ca2+reuptake rate, decreased diastolic Ca2+levels, decreased SR Ca2+load and reduced Ca2+spark activity following catecholamine stimulation relative to WT. Further analysis of molecular mechanisms revealed that altered Ca2+handling in the cMAO-Adefhearts was related to decreased catecholamine-induced phosphorylation of Ca2+/calmodulin-dependent kinase II (CaMKII) and ryanodine receptor 2 (RyR2), and increased phosphorylation of phospholamban (PLB).

Conclusions

These findings suggest that MAO-A inhibition in cardiomyocytes mitigates arrhythmogenesis via enhanced Ca2+reuptake that lowers diastolic Ca2+levels thereby diminishing arrhythmic triggers following catecholamine stimulation. Thus, cardiac MAO-A represents a potential target for antiarrhythmic therapy.
Early categorization of social affordances during the visual encoding of bodily stimuli.
Authors: Moreau Q. , Parrotta E. , Pesci U.G. , Era V. , Candidi M
Published: October 2022

Interpersonal interactions rely on various communication channels, both verbal and non-verbal, through which information regarding one’s intentions and emotions are perceived. Here, we investigated the neural correlates underlying the visual processing of hand postures conveying social affordances (i.e., hand-shaking), compared to control stimuli such as hands performing non-social actions (i.e., grasping) or showing no movement at all. Combining univariate and multivariate analysis on electroencephalography (EEG) data, our results indicate that occipito-temporal electrodes show early differential processing of stimuli conveying social information compared to non-social ones. First, the amplitude of the Early Posterior Negativity (EPN, an Event-Related Potential related to the perception of body parts) is modulated differently during the perception of social and non-social content carried by hands. Moreover, our multivariate classification analysis (MultiVariate Pattern Analysis - MVPA) expanded the univariate results by revealing early (<200ms) categorization of social affordances over occipito-parietal sites. In conclusion, we provide new evidence suggesting that the encoding of socially relevant hand gestures is categorized in the early stages of visual processing.
Xanomeline restores endogenous nicotinic acetylcholine receptor signaling in mouse prefrontal cortex
Authors: Power Saige K. , Venkatesan Sridevi , Lambe Evelyn K.
Published: October 2022

Cholinergic synapses in prefrontal cortex are vital for attention, but this modulatory system undergoes substantial pre- and post-synaptic alterations during adulthood. To examine the integrated impact of these changes, we optophysiologically probe cholinergic synapsesex vivo, revealing a clear decline in neurotransmission in middle adulthood. Pharmacological dissection of synaptic components reveals a selective reduction in postsynaptic nicotinic receptor currents. Other components of cholinergic synapses appear stable, by contrast, including acetylcholine autoinhibition, metabolism, and excitation of postsynaptic muscarinic receptors. Pursuing strategies to strengthen cholinergic neurotransmission, we find that positive allosteric modulation of nicotinic receptors with NS9283 is effective in young adults but wanes with age. To boost nicotinic receptor availability, we harness the second messenger pathways of the preserved excitatory muscarinic receptors with xanomeline. This muscarinic agonist and cognitive-enhancer restores nicotinic signaling in older mice significantly, in a muscarinic- and PKC-dependent manner. The rescued nicotinic component regains youthful sensitivity to allosteric enhancement: treatment with xanomeline and NS9283 restores cholinergic synapses in older mice to the strength, speed, and receptor mechanism of young adults. Our results reveal a new and efficient strategy to rescue age-related nicotinic signaling deficits, demonstrating a novel pathway for xanomeline to restore cognitively-essential endogenous cholinergic neurotransmission.
Contrast-free Super-resolution Doppler (CS Doppler) based on Deep Generative Neural Networks
Authors: You Qi , Lowerison Matthew R. , Shin YiRang , Chen Xi , Chandra Sekaran Nathiya Vaithiyalingam , Dong Zhijie , Llano Daniel A. , Anastasio Mark A. , Song Pengfei
Published: October 2022

Super-resolution ultrasound microvessel imaging based on ultrasound localization microscopy (ULM) is an emerging imaging modality that is capable of resolving micron-scaled vessels deep into tissue. In practice, ULM is limited by the need for contrast injection, long data acquisition, and computationally expensive post-processing times. In this study, we present a contrast-free super-resolution Doppler (CS Doppler) technique that uses deep generative networks to achieve super-resolution with short data acquisition. The training dataset is comprised of spatiotemporal ultrafast ultrasound signals acquired from in vivo mouse brains, while the testing dataset includes in vivo mouse brain, chicken embryo chorioallantoic membrane (CAM), and healthy human subjects. The in vivo mouse imaging studies demonstrate that CS Doppler could achieve an approximate 2-fold improvement in spatial resolution when compared with conventional power Doppler. In addition, the microvascular images generated by CS Doppler showed good agreement with the corresponding ULM images as indicated by a structural similarity index of 0.7837 and a peak signal-to-noise ratio of 25.52. Moreover, CS Doppler was able to preserve the temporal profile of the blood flow (e.g., pulsatility) that is similar to conventional power Doppler. Finally, the generalizability of CS Doppler was demonstrated on testing data of different tissues using different imaging settings. The fast inference time of the proposed deep generative network also allows CS Doppler to be implemented for real-time imaging. These features of CS Doppler offer a practical, fast, and robust microvascular imaging solution for many preclinical and clinical applications of Doppler ultrasound.