bluuebunny/crossref_metadata_2025 huggingface dataset:
The Association of Interlimb Coordination and Temporal Symmetry With Walking Function and Motor Impairment After Stroke
Authors: Cleland Brice Thomas , Madhavan Sangeetha
Published: May 2024

Objective

Interlimb coordination during walking is impaired after stroke, with unknown effects on walking function. This cross-sectional study determined associations of interlimb coordination and temporal symmetry with walking function and motor impairment.

Design

During walking, participants wore wireless sensors to detect heel strikes. We calculated interlimb coordination as the phase coordination index and temporal symmetry as the ratio of contralesional (i.e., paretic) to ipsilesional (i.e., nonparetic) stance times. Associations with walking speed (10-meter walk test), walking endurance (6-min walk test), dynamic balance (Mini-Balance Evaluation Systems Test), and motor impairment (Fugl-Meyer Lower Extremity assessment) were assessed.

Results

Fifty-six individuals with chronic stroke were tested. Worse interlimb coordination was correlated with slower comfortable (R = −0.38, P = 0.004) and maximal (R = −0.36, P = 0.006) walking speed and worse motor function (R = −0.45, P = 0.001). Worse temporal symmetry was correlated with worse motor function (R = 0.39, P = 0.004). Interlimb coordination had stronger associations than temporal symmetry with comfortable (R = −0.38 vs. 0.08) and maximal walking speeds (R = −0.36 vs. 0.12).

Conclusions

Poor interlimb coordination was associated with slow walking and motor impairment and had stronger associations with walking speeds than temporal symmetry did. Interlimb coordination may provide unique insights into walking function and a target for walking rehabilitation after stroke.
COVID-19 Incidence, Risk Factors, Impact, and Related Stigma Among a Cohort of Persons With HIV in Washington, DC
Authors: Barth Shannon K. , Monroe Anne K. , Houston Patricia , Benator Debra , Horberg Michael , Castel Amanda D. ,   on behalf of the DC Cohort Executive Committee
Published: May 2024

Background:

Studies on the incidence of COVID-19 among persons with HIV (PWHs) present varied results. Few studies have investigated the impact of COVID-19 infection on health and socioeconomic factors or COVID-19 stigma. We sought to measure the incidence and severity of COVID-19 infection among a cohort of PWHs, characterize associated risk factors and impact, and document perceptions of COVID-19-related stigma.

Methods:

Data for this cross-sectional study come from the COVID-19 survey of participants in the DC Cohort longitudinal study from October 30, 2020, through December 31, 2022. Survey results were linked to electronic health records, including HIV laboratory test results and COVID test results. We conducted analyses comparing demographic, socioeconomic, HIV measures, and stigma among those with and without self-reported COVID-19.

Results:

Of 1972 survey respondents, 17% self-reported COVID-19 infection, with the greatest incidence in the Omicron wave of the pandemic. We found statistically significant differences by age, employment status, essential worker status, education, and household income. Longer duration of HIV diagnosis was associated with greater incidence of COVID-19. PWHs who were overweight or obese had a greater incidence of COVID-19 compared with those who were not. Over 40% of PWHs with COVID-19 reported experiencing at least 1 form of COVID-19-related stigma.

Conclusion:

We observed a high incidence of COVID-19 infection among PWHs in DC. Furthermore, a substantial proportion of PWHs with COVID-19 reported experiencing COVID-19-related stigma. These findings add to the existing literature on COVID-19 coinfection among PWHs and highlight the need for awareness and support for those experiencing COVID-19 stigma.
Measurement of Nasal Skin Thickness and Body Mass Index in Preoperative Rhinoplasty Patients Utilizing Computed Tomography Scanning and Ultrasound Techniques: A Prospective Comparative Study
Authors: Assiri Hassan , Abdelkader Waleed , Alfallaj Rayan , Alanazi Hani , AlEnazi Abdulaziz Saud , AlDosari Badi
Published: May 2024

One of the most important indicators of rhinoplasty success is nasal skin thickness. Nasal thickness can lead to irregularities over the osseocartilaginous framework among patients with thin nasal skin and difficulty making tip work changes in patients with thick nasal skin. This study aimed to compare different objective methods. These include computed tomography (CT) and ultrasound (US) techniques, and report the relationship between nasal skin thickness and body mass index (BMI). A prospective cross-sectional study that included all patients at the rhinoplasty clinic (King Abdul-Aziz University Hospital), Riyadh, Saudi Arabia, between December 2022 and March 2023. Age, sex, and Fitzpatrick skin type were collected from the patients’ histories and physical examinations. Body mass index was calculated for the subjects. The study sample included 29 patients. The median age of the patients was 25 years (interquartile range: 20–32 y). Most of the included patients were Saudi (89.7%, n = 26). Females represented 62.1% of the study sample. The average BMI was 25.6 ± 4.95 kg/m2. The highest correlation was observed between the US and CT tip (r = 0.544, P < 0.01) and rhinion (r = 0.525, P < 0.01) measurements. Body mass index was not associated with any US or CT measurements when BMI was used as a continuous or ordinal variable. The correlation between the US and CT measurements was highest for rhinoin and tip measurements, whereas supratip measurements were not correlated (r = -0.029, P = 0.88). The correlation between mid-dorsum and nasion measurements was low (~0.3). The correlation between nasal skin thickness using CT and US varies depending on the nasal point and location. Body mass index was not associated with nasal skin thickness.
BiZact-Assisted Endoscopic Resection of a Sinonasal Tumor
Authors: Kwon Kyung Won , Kim Joo Yeon , Kwon Jae Hwan
Published: May 2024

The BiZact device, a bipolar electrosurgical scissor designed for tonsillectomy, minimizes thermal tissue damage and seals blood vessels <3 mm in diameter while dividing the soft tissue. This study describes the authors’ experience with sinonasal tumor surgery using a BiZact and discusses its clinical utility and advantages. The authors analyzed BiZact-assisted endoscopic sinonasal tumor surgery cases between January 2021 and May 2023. Data were collected on patients’ demographics, histopathology, extent of tumor involvement, surgical records, and postoperative medical records. Clinical utility was assessed using the success rate of complete tumor excision, estimated blood loss during surgery, device-related complications, and operation time. A survey of the surgeons’ BiZact experience was also conducted. The diagnoses of the 20 patients in this study included squamous cell carcinoma (n = 2), malignant melanoma (n = 1), sarcoma (n = 1), natural killer cell lymphoma (n = 1), inverted papilloma (n = 12), angiofibroma (n = 2), and schwannoma (n = 1). This pilot study demonstrated a shortened operative time, with a median of 0.8 hours and <100 mL of intraoperative blood loss. In addition, no BiZact-related complications were observed. The BiZact device allows efficient sinonasal surgery because it has the unique advantage of one-step sealing and cutting. BiZact-assisted endoscopic sinonasal tumor surgery is a beneficial and safe procedure that reduces blood loss during surgery, shortens the operative time, and minimizes postoperative complications.
Predictors of Plastic Surgery Applicant Success: An Analysis of the Texas STAR Database
Authors: Hallman Taylor G. , Qureshi Umer , Soltani Hannah , Gutowski Kristof S. , Arcelona Christian , Donaldson Rachel , Mihalic Angela P. , Gosain Arun K.
Published: May 2024

Introduction:

Integrated plastic surgery residency is one of the most competitive medical specialties. Although previous studies have surveyed integrated plastic surgery residency program directors regarding desired applicant characteristics, there is a paucity of literature assessing detailed application characteristics and reported match outcomes from applicants in recent application cycles. This study examines application characteristics associated with matching into integrated plastic surgery residency from 2017 to 2023.

Methods:

The authors accessed the Texas Seeking Transparency in Application to Residency database, which contains survey information from graduating medical students nationwide regarding residency application characteristics and specialties/programs to which applications were submitted. Characteristics of matched versus unmatched applicants between 2017 and 2023 were compared using χ2 and 2-sided, independent t tests. Univariate logistic regression models were used to assess predictors of a successful match.

Results:

A total of 381 integrated plastic surgery residency applicants responded to the Texas Seeking Transparency in Application to Residency survey from 2017 to 2023. Mean United States Medical Licensing Exam Step 2 CK scores; the number of away rotations, interview offers, and honored clerkships; and Alpha Omega Alpha membership rate were significantly associated with and predictive of matching. Preference signaling of programs was associated with an increased interview offer rate.

Conclusions:

Higher board examination scores, increasing numbers of honored clerkships, away rotations, and Alpha Omega Alpha membership were identified as statistically significant predictors of matching into integrated plastic surgery residency. Prospective applicants should use this information to help guide their efforts in these areas that appear to be associated with a successful transition to residency.
Clinical Experience With Acute Phase Repair of Facial Nerve Dissections
Authors: Wang Weihao , Kong Lingxu , Zhang Wanqi , Shao Ying
Published: May 2024

The purpose of this study was to evaluate the facial nerve recovery of patients with traumatic facial nerve transections after tension-free end-to-end nerve epineural anastomosis during the acute phase. A total of 11 patients with traumatic facial nerve transections during the acute phase were surgically treated in the authors’ department from November 2016 to August 2022. The case data and imaging data were collected from the patients, and the House-Brackman evaluation system of the facial nerve was applied to assess the recovery of facial nerve function, and the higher the grade, the worse the facial nerve function. Of the patients, 90.9% recovered to H-B grade II or below, and there were differences in the degree of recovery of the facial nerve function among the branches, and the ones that recovered to H-B grade II or below after surgery were 100% of the zygomatic branch, of which 80% were H-B grade I, 100% of the buccal branch, of which 44.4% were H-B grade I, 88.9% of the marginal mandibular branch, and 66.7% of the temporal branch. The study showed that the recovery rate of young patients was better than that of middle-aged and old people, and the best recovery of each branch of the facial nerve was the zygomatic branch, followed by the buccal branch, the marginal mandibular branch, and the worse was the temporal branch.
The Top 100 Most-Cited Publications in Clinical Craniofacial Research
Authors: Braud Savannah C. , Treger Dylan , Lizardi Juan J. , Boghosian Tanya , El Abd Rawan , Arakelians Aris , Jabori Sinan K. , Thaller Seth R.
Published: May 2024

Introduction:

Craniosynostosis is a birth defect defined as premature closure of sutures leading to possible neurological deficits and cosmetic deformities. Most of the current literature to date focuses on craniosynostosis etiology by analyzing genetics. This paper is a bibliometric analysis of the most influential works related to the clinical management of craniosynostosis to help guide clinicians in their decision-making.

Methods and Materials:

Clarivate Web of Science database was used to identify the top 100 most-cited articles addressing the clinical management of craniosynostosis. A bibliometric review was performed to analyze publication metrics and track research trends.

Results:

The 100 most-cited publications pertaining to craniosynostosis management were cited a cumulative 12,779 times. The highest cited article was Shillito and colleagues’ “Craniosynostosis: A Review Of 519 Surgical Patients” with 352 citations. The oldest clinical craniosynostosis article dates back to 1948, and the most recent was published in 2016. The year with the most clinical-focused publications was 2011. The most prolific author was Renier, D. The United States produced 56 of the 100 articles. Most articles (n=52) were level 3 evidence.

Discussion:

This bibliometric evaluation of craniosynostosis provides insight into the most impactful literature on this topic. The highest cited articles retrospectively analyze large sample sizes, outline proper evaluation, discuss intervention timelines, and highlight specific treatment plans for this birth defect. By filtering through existing literature, this analysis can guide clinicians on the management of craniosynostosis to maximize patient outcomes.
Nasal Airway Volumes are More Asymmetric in Skeletally Mature Patients With Cleft lip and Palate Than Controls on 3-Dimensional Analysis
Authors: Romeo Dominic J. , Oral Kaan T. , Massenburg Benjamin B. , Ng Jinggang J. , Wu Meagan , Sussman Jonathan H. , Du Steven , Bartlett Scott P. , Swanson Jordan W. , Taylor Jesse A.
Published: May 2024

Background:

This study assesses nasal airway volumes in skeletally mature patients with CLP and healthy controls and examines the relationship among nasal volumes, cleft laterality, and facial asymmetry.

Methods:

Computed tomography images from patients with CLP and controls were analyzed using Mimics Version 23.0 (Materialise, Leuven, Belgium). Relationships among nasal airway volume, cleft laterality, and facial asymmetry were compared.

Results:

The 89 patients in this study included 66 (74%) CLP and 23 (17%) controls. Nasal airway volumes in CLP were more asymmetric than controls (26.8±17.5% vs. 17.2±14.4%; P=0.015). In UCLP, the smaller nasal airway was on the cleft side 81% of the time (P<0.001). Maximum airway stenosis was on the cleft side 79% of the time (P<0.001), and maximum stenosis was on the same side as the smaller airway 89% of the time (P<0.001). There was a mild linear relationship between nasal airway asymmetry and maximum stenosis (r=0.247, P=0.023). On 3-dimensional image reconstruction, the septum often bowed convexly into the cleft-sided nasal airway with a caudal deviation towards the noncleft side. Nasal airway asymmetry was not associated with facial midline asymmetry (P>0.05).

Conclusion:

The nasal airway is more asymmetric in patients with cleft lip and palate compared with the general population, with the area of maximum stenosis usually occurring on the cleft-sided airway. In patients with unilateral cleft lip and palate, the septum often bows into the cleft side, reducing the size of that nasal airway. Nasal airway asymmetry did not correlate with facial asymmetry.
A New Multiplane Dissection Method for Frontotemporal Lift and Fixation
Authors: Şirinoglu Hakan , Güvercin Emre , Tatar Burak E.
Published: May 2024

Lifting procedures of the upper face have gained significant popularity, and various methods and dissection planes have been described. The deep temporalis fascia (DTF) is a crucial structure for securing lifting sutures and allowing horizontal tissue vectorization. However, achieving vertical eyebrow lifting often requires bone maneuvers and introduces potential complications. This letter proposes a novel multiplanar dissection method for the temporal and forehead regions, obviating the need for bone maneuvers in lifting suture fixations. The presence of the subgaleal fascia in the temporal region has been identified, in addition to the DTF and superficial temporal fascia. Furthermore the superficial temporal fascia is divided into 3 layers, with attention paid to their medial connection with the structures of the forehead. Surgical techniques involve meticulous dissection down to the DTF and identification of the subgaleal fascia for lateral temporal dissection or transition to the subplane of the epicranial aponeurosis for forehead lifting. By leaving a thick layer, the subplane of the epicranial aponeurosis during forehead lifting eliminates the need for drilling and reduces the risk of relapse. The described multiplanar dissection method enhances the safety and effectiveness of forehead lift procedures, offers a viable alternative to bone drilling, minimizes flap-related complications, and provides valuable insights for facial rejuvenation surgery.
Palatal Stent Following Tumor Ablative Surgery
Authors: Sousa Rafael Aguiar de , Figueiredo Pedro Henrique Almeida , Aguiar Maria Cássia Ferreira de , Jardilino Francisca Daniele Moreira , Rocha Amanda Leal
Published: May 2024

Mucoepidermoid carcinoma is one of the most prevalent malignant tumors of the salivary glands. Resection of this tumor can result in postsurgical morbidity, affecting the patient’s quality of life and normal oral functioning. This study aimed to present a successful case of postsurgical rehabilitation following mucoepidermoid carcinoma resection in the palate. Following tumor ablative surgery, the 32-year-old patient experienced impairments in both speech and feeding due to the surgical wound. A protective stent that covered the entire extent of the palate and teeth was made. This esthetic device was fabricated in a single session and provided sealing and protection of the surgical site, ensuring comfort, functionality, and, consequently, a higher quality of life during the postoperative period. The simplicity and low cost of the custom palatal stent make it applicable for use in a diverse range of postsurgical oncology patients, providing protection for surgical wounds and reducing postoperative morbidity.
Bilateral Subcutaneous Pedicled Nasolabial Island Flap for Total Reconstruction of the Lower Lip
Authors: Moreno Torres Andrey , Cuesta Antonio J. , Erazo Davila Luis A. , Galviz Tabares Brandon
Published: May 2024

Squamous cell carcinomas are the most common cancer of the lower lip. In most cases, the tumor is small and occupies less than a third of the lower lip, so the defect created can be closed with a primary suture without altering the esthetics and function of the lower lip. However, there is a percentage of large tumors that affect more than two thirds of the lower lip, in which the primary suture is insufficient to correct the defect created by resection of the tumor. Therefore, these cases require more complex reconstructions using facial locoregional flaps. Hence, in this article, the authors present a total reconstruction of the lower lip with a bilateral subcutaneous pedicled nasolabial island flap after complete resection of a squamous cell carcinoma with involvement of the entire lower lip.
Comparison of the Diagnosis and Treatment of Nasal Bone Fracture by Physicians in China With Different Levels of Experience
Authors: Jian Feitong , Wu Shuo
Published: May 2024

Objective:

This study aimed to investigate the conflicts in the diagnosis and treatment of nasal bone fracture by Chinese otolaryngologists to improve the diagnosis and treatment accuracy of junior otolaryngologists and emergency physicians.

Methods:

A questionnaire was designed and filled out by otolaryngologists in large general hospitals. The questions included how to choose an auxiliary examination to diagnose nasal bone fracture, whether tamponade is required after closed reduction, the selection of packing materials, the timing of an operation, and the evaluation of postoperative effect. The questionnaire results were divided into 3 groups according to the experience levels of experienced of physicians.

Results:

A total of 151 otolaryngologists with different levels of experience from 26 provinces in China completed the questionnaire. 90.73% of physicians thought that nasal bone computed tomography was the most important auxiliary examination to diagnose a nasal bone fracture. 52.32% of them compared photos before and after the operation to evaluate postoperative effects. About 53% of physicians thought that 7 to 10 days after reducing local swelling is the optimal time for closed reduction.

Conclusions:

There is no obvious difference in the diagnosis and treatment of nasal bone fracture among otolaryngologists with different levels of experience in Chinese otolaryngologists with different levels. Most physicians choose nasal bone computed tomography for diagnosis, perform surgery at 7 to 10 days after injury, and compare photos from before and after the operation to evaluate the postoperative effect.
Detection of Language Lateralization Using Spectral Analysis of EEG
Authors: Nix Kerry C. , Oh Ahyuda , Goad Beattie S. , Wu Wei , Lucas Molly V. , Baumer Fiona M.
Published: May 2024

Purpose:

Language lateralization relies on expensive equipment and can be difficult to tolerate. We assessed if lateralized brain responses to a language task can be detected with spectral analysis of electroencephalography (EEG).

Methods:

Twenty right-handed, neurotypical adults (28 ± 10 years; five males) performed a verb generation task and two control tasks (word listening and repetition). We measured changes in EEG activity elicited by tasks (the event-related spectral perturbation [ERSP]) in the theta, alpha, beta, and gamma frequency bands in two language (superior temporal and inferior frontal [ST and IF]) and one control (occipital [Occ]) region bilaterally. We tested whether language tasks elicited (1) changes in spectral power from baseline (significant ERSP) at any region or (2) asymmetric ERSPs between matched left and right regions.

Results:

Left IF beta power (−0.37±0.53, t = −3.12, P = 0.006) and gamma power in all regions decreased during verb generation. Asymmetric ERSPs (right > left) occurred between the (1) IF regions in the beta band (right vs. left difference of 0.23±0.37, t(19) = -2.80, P = 0.0114) and (2) ST regions in the alpha band (right vs. left difference of 0.48±0.63, t(19) = -3.36, P = 0.003). No changes from baseline or hemispheric asymmetries were noted in language regions during control tasks. On the individual level, 16 (80%) participants showed decreased left IF beta power from baseline, and 16 showed ST alpha asymmetry. Eighteen participants (90%) showed one of these two findings.

Conclusions:

Spectral EEG analysis detects lateralized responses during language tasks in frontal and temporal regions. Spectral EEG analysis could be developed into a readily available language lateralization modality.
Endothelial ERG programs neutrophil transcriptome for sustained anti-inflammatory vascular niche
Authors: Vellingiri Vigneshwaran , Balaji Ragunathrao Vijay Avin , Joshi Jagdish Chandra , Akhter Md Zahid , Anwar Mumtaz , Banerjee Somenath , Dudek Steven , Tsukasaki Yoshikazu , Pinho Sandra , Mehta Dolly
Published: May 2024

Neutrophils (PMNs) reside as a marginated pool within the vasculature, ready for deployment during infection. However, how endothelial cells (ECs) control PMN extravasation and activation to strengthen tissue homeostasis remains ill-defined. Here, we found that the vascular ETS-related gene (ERG) is a generalized mechanism regulating PMN activity in preclinical tissue injury models and human patients. We show that ERG loss in ECs rewired PMN-transcriptome, enriched for genes associated with the CXCR2-CXCR4 signaling. Rewired PMNs compromise mice survival after pneumonia and induced lung vascular inflammatory injury following adoptive transfer into naïve mice, indicating their longevity and inflammatory activity memory. Mechanistically, EC-ERG restricted PMN extravasation and activation by upregulating the deubiquitinase A20 and downregulating the NFκB-IL8 cascade. Rescuing A20 inEC-Erg-/-endothelium or suppressing PMN-CXCR2 signaling rescued EC control of PMN activation. Findings deepen our understanding of EC control of PMN-mediated inflammation, offering potential avenues for targeting various inflammatory diseases.

Highlights

ERG regulates trans-endothelial neutrophil (PMN) extravasation, retention, and activation

Loss of endothelial (EC) ERG rewires PMN-transcriptome

Adopted transfer of rewired PMNs causes inflammation in a naïve mouse

ERG transcribesA20and suppresses CXCR2 function to inactivate PMNs

In brief/blurb

The authors investigated how vascular endothelial cells (EC) control polymorphonuclear neutrophil (PMN) extravasation, retention, and activation to strengthen tissue homeostasis. They showed that EC-ERG controls PMN transcriptome into an anti-adhesive and anti-inflammatory lineage by synthesizingA20and suppressing PMNs-CXCR2 signaling, defining EC-ERG as a target for preventing neutrophilic inflammatory injury.
Effects of Classical Psychedelics on Implicit and Explicit Emotional Empathy and Cognitive Empathy: A Meta-analysis of MET task
Authors: Olami Amit , Peled-Avron Leehe
Published: May 2024

This meta-analysis investigates the effect of classic psychedelic drugs on empathy and focuses on cognitive and emotional empathy measured using the Multifaceted Empathy Test (MET). Empathy entails the ability to understand and share the feelings of another and is a significant component of social interaction. Several studies have examined the effects of psychedelic drugs such as LSD, psilocybin and ayahuasca on empathy, yet their overall effect has not been studied so far. In this meta analysis, we reviewed data from studies up to November 2023 with the aim of examining the effects of various psychedelic drugs on empathic abilities broadly. Our findings suggest that classical psychedelics significantly enhance explicit and implicit emotional empathy without affecting measures of cognitive empathy. The results emphasize the need to continue testing the therapeutic potential of classic psychedelic drugs.
IRF7 from the black flying fox induces a STAT1-independent ISG response in unstimulated cell lines that protects against diverse RNA viruses
Authors: Cruz-Rivera Pamela C. De La , Eitson Jennifer L. , Schoggins John W.
Published: May 2024

Bats are considered unique in their ability to harbor large numbers of viruses and serve as reservoirs for zoonotic viruses that have the potential to spill over into humans. However, these animals appear relatively resistant to the pathogenic effects of many viruses. Mounting evidence suggests that bats may tolerate viral infections due to unique immune features. These include evolutionary innovations in inflammatory pathways and in the molecules involved in viral sensing, interferon induction, and downstream interferon-induced antiviral effectors. We sought to determine whether interferon-stimulated genes (ISGs) from the black flying fox (Pteropus alecto) encoded proteins with unique antiviral activity relative to their human orthologs. Accordingly, we compared the antiviral activity of over 50 ISG human-bat ortholog pairs to identify differences in individual effector functions. We identified IRF7 fromPteropus alecto(Pa.IRF7) as a potent and broad-acting antiviral molecule that provides robust antiviral protection without prior activation. We show that Pa.IRF7 uniquely induces a subset of protective ISGs independent of canonical IFN signaling, which leads to protection from alphaviruses, a flavivirus, a rhabdovirus, and a paramyxovirus. In uninfected cells, Pa.IRF7 partially localizes to the nucleus and can directly bind interferon-sensitive regulatory elements (ISREs). Compared to human IRF7, Pa.IRF7 also has additional serines in its C terminal domain that contribute to antiviral activity and may serve as unique phosphorylation hubs for activation. These properties constitute major differences between bat and human IRF7 that offer additional insight into the potential uniqueness of the black flying fox immune system.
Highly Effective Batch Effect Correction Method for RNA-seq Count Data
Authors: Zhang Xiaoyu
Published: May 2024

RNA sequencing (RNA-seq) has become a cornerstone in transcriptomics, offering detailed insights into gene expression across diverse biological conditions and sample types. However, RNA-seq data often suffer from batch effects, which are systematic non-biological differences that compromise data reliability and obscure true biological variation. To address these challenges, we introduce ComBat-ref, a refined method of batch effect correction that enhances the statistical power and reliability of differential expression analysis in RNA-seq data. Building on the foundations of ComBat-seq, ComBat-ref employs a negative binomial model to adjust count data but innovates by using a pooled dispersion parameter for entire batches and preserving count data for the reference batch. Our method demonstrated superior performance in both simulated environments and real datasets, such as the growth factor receptor network (GFRN) data and NASA GeneLab transcriptomic datasets, significantly improving sensitivity and specificity over existing methods. By effectively mitigating batch effects while maintaining high detection power, ComBat-ref proves to be a robust tool for enhancing the accuracy and interpretability of RNA-seq data analyses.
Unraveling the proteome landscape of mouse hematopoietic stem and progenitor compartment with high sensitivity low-input proteomics
Authors: Üresin Nil , Petrosius Valdemaras , Aragon-Fernandez Pedro , Furtwängler Benjamin , Schoof Erwin M. , Porse Bo T.
Published: May 2024

Proteins play a key role in defining cellular phenotypes, yet comprehensive proteomic analysis often requires substantial input material, posing challenges in studying rare populations in complex cell systems. Here, we present an accessible, label-free low-input proteomics workflow that allows for comprehensive proteome coverage reminiscent of classical bulk samples from only 500 cells and showcase its application in murine hematopoiesis. With this approach, we construct a proteomic map of hematopoietic stem and progenitor cell (HSPC) populations isolated by fluorescence-activated cell sorting (FACS) from the bone marrow of a single mouse, identifying approximately 7,000 proteins per cell population. Our study recapitulates the differentiation trajectories along the megakaryocytic-erythroid and granulocytic-monocytic lineages. We specifically focus on the dynamics of transcriptional regulators and provide insights into both known and novel population-specific factors. Furthermore, we extend our exploration to the most primitive stem and progenitor compartment, and identify ADP-Ribosyltransferase ART4 (CD297) as a novel cell surface marker that can potentially be used to enrich for long-term hematopoietic stem cells (LT-HSC). The low-input proteomics workflow presented here holds promise for overcoming the challenges associated with analyzing proteomes of rare cell populations, thereby paving the way for broader applications in biomedical research.
Protection of savings by reducing the salience of opposing errors
Authors: Javidialsaadi Mousa , Albert Scott T. , Al Mutairi Badr Moufarrej S , Wang Jinsung
Published: May 2024

When humans encounter the same disturbance twice, they adapt to it faster during the second exposure. To examine how subconscious learning systems contribute to this savings process, previous studies have suppressed explicit awareness of the perturbation by gradually increasing its magnitude during initial learning. This has produced mixed effects, with some studies demonstrating faster relearning, and others observing no acceleration during relearning. Here we examined whether these differences might be due to the nature of a de-adaptation period that separates two learning periods. To test this idea, we manipulated the magnitude of washout errors by de-adapting participants abruptly, gradually, or by removing feedback entirely. Empirical analyses indicated that the different classes of washout errors had a profound effect on savings: large washout errors nullified the ability to save, whereas small errors or the absence of error protected savings. Model-based analyses suggested that changes in learning rates were mediated by an increase in sensitivity to error that could be reversed by experience with oppositely-oriented washout errors. This suggests that the experience of error produces both a facilitation of learning for similar errors and a reduction in learning for dissimilar errors. The latter can abolish the expression of savings following gradual adaptation.
Mechanical Analysis of Cell Migration Using Hybrid Structural Optimization
Authors: Havenhill Eric , Ghosh Soham
Published: May 2024

Cell migration requires the dynamic formation and dissolution of mechanical structures inside the cytoplasm. Stress fibers are made of F-actin during cell migration driven by the strategic localization of focal adhesion complexes at the cell-substrate interface. The nucleus is also strategically positioned in the cell during the migration and the stress fibers wrap around the nucleus possibly to carry the nucleus with the cell. Cell migration is energetically demanding and should require strategic utilization of resources such as the F-actin stress fiber formation at specific locations so that they generate enough force by actomyosin contraction at the cell-matrix adhesion sites for a directed movement. In this work we propose a structural optimization based biophysical model to predict the strategic localization and sizes of F-actin fibers that supports the nucleus and the cytoplasm during migration. With the use of a nonlinear controller via a Newton-Euler-based model of the generated design, we further quantified the force in the stress fibers during migration, with results close to those obtained through experimental methods such as traction force microscopy. The predicted force decreases for a cell that migrates slowly due to a pharmacological perturbation. Such quantification of forces only require the information of the trajectory of the cell that can be readily obtained from time lapse microscopy. With novel microscopy techniques emerging, such biophysical model framework can be combined with traction force microscopy data to achieve unprecedented mechanical information inside and outside cells during migration, which is otherwise not possible by experiments only.

SIGNIFICANCE

Cell migration plays a critical role in biological functions. It requires the strategic formation of F-actin stress fibers at specific locations, to generate forces by actomyosin contraction for cells to migrate in a directed manner. The present study predicts the localization and force generated by stress fibers based on the trajectory of the cell, which can be obtained via time lapse microscopy. The technique can complement other techniques such as traction force microscopy to provide mechanical information inside and outside cells during cell migration.
Protein interactions, calcium, phosphorylation, and cholesterol modulate CFTR cluster formation on membranes
Authors: Wan Yimei , Hudson Rhea , Smith Jordyn , Forman-Kay Julie D. , Ditlev Jonathon A.
Published: May 2024

The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a chloride channel whose dysfunction leads to intracellular accumulation of chloride ions, dehydration of cell surfaces, and subsequent damage to airway and ductal organs. Beyond its function as a chloride channel, interactions between CFTR, ENaC, and SLC transporter family membrane proteins and cytoplasmic proteins, including calmodulin and NHERF-1, co-regulate ion homeostasis. CFTR has also been observed to form mesoscale membrane clusters. However, the biophysical mechanisms that regulate the formation of CFTR clusters are unknown. Using a combination of computational modeling and complex biochemical reconstitution assays, we demonstrate that multivalent protein-protein interactions with CFTR binding partners, calcium, and membrane cholesterol can induce CFTR cluster formation on model membranes. Phosphorylation of the intracellular domains of CFTR also promotes cluster formation in the absence of calcium, indicating that multiple mechanisms can regulate CFTR cluster formation. Our findings reveal that coupling of multivalent protein and lipid interactions promote CFTR cluster formation consistent with membrane-associated biological phase separation.

SIGNIFICANCE STATEMENT

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) membrane protein underlie cystic fibrosis. It is thought that molecular “hubs” of CFTR and its binding partners co-regulate ion homeostasis and that disruption of these clusters can result in disease. However, the physical basis for molecular hub formation is unclear. In this study, we present evidence that multivalent protein and lipid interactions drive the formation of mesoscale CFTR-containing clusters or “hubs” on model membranes in a manner consistent with biological phase separation. These data provide important insights into physical mechanisms that modulate CFTR membrane organization and offer a new lens for the development of corrective therapeutics.
DeepLeMiN: Deep-learning-empowered Physics-aware Lensless Miniscope
Authors: Tian Feng , Mattison Ben , Yang Weijian
Published: May 2024

Mask-based lensless fluorescence microscopy is a compact, portable imaging technique promising for biomedical research. It forms images through a thin optical mask near the camera without bulky optics, enabling snapshot three-dimensional imaging and a scalable field of view (FOV) without increasing device thickness. Lensless microscopy relies on computational algorithms to solve the inverse problem of object reconstruction. However, there has been a lack of efficient reconstruction algorithms for large-scale data. Furthermore, the entire FOV is typically reconstructed as a whole, which demands substantial computational resources and limits the scalability of the FOV. Here, we developed DeepLeMiN, a lensless microscope with a custom designed optical mask and a multi-stage physics-informed deep learning model. This not only enables the reconstruction of localized FOVs, but also significantly reduces the computational resource demands and facilitates real-time reconstruction. Our deep learning algorithm can reconstruct object volumes over 4×6×0.6 mm3, achieving lateral and axial resolution of ∼10 µm and ∼50 µm respectively. We demonstrated significant improvement in both reconstruction quality and speed compared to traditional methods, across various fluorescent samples with dense structures. Notably, we achieved high-quality reconstruction of 3D motion of hydra and the neuronal activity with cellular resolution in awake mouse cortex. DeepLeMiN holds great promise for scalable, large FOV, real-time, 3D imaging applications with compact device footprint.
The effect ofCitrus reticulatapeel extract containing hesperidin on inhibition of SARS-CoV-2 infection based on pseudovirus entry assays
Authors: Septisetyani Endah Puji , Harsan Hayfa Salsabila , Kumara Dennaya , Prasetyaningrum Pekik Wiji , Paramitasari Komang Alit , Cahyani Anisa Devi , Anam Khairul , Kastian Ria Fajarwati , Santoso Adi , Ikawati Muthi , Meiyanto Edy
Published: May 2024

Orange (Citrus reticulataBlanco) peel contains a flavonoid glycoside hesperidin (HSD) as the primary component. HSD, upon enzymatic hydrolysis, forms hesperetin (HST) aglycone derivate. These two flavonoids have been predicted to havein-silicoaffinities for ACE2 and SARS-CoV-2 spike, crucial proteins in SARS-CoV-2 infection mechanisms. However,in vitroantiviral testing of orange peel extract, HSD, and HST has not been reported. This study presents for the first time a pseudovirus entry assay approach to test the anti-SARS-CoV-2 effect of HSD, HST, and orange peel extract prepared by hydrodynamic cavitation (HCV). We used a non-virulent pseudovirus model as an alternative to the original virus to target the entry point and enable research to be conducted outside the BSL-3 facility. Based on HPLC analysis, the test results showed that HCV contained HSD at about 4% w/w. Moreover, HSD 1 and 10 μM, HST 10 μM, and HCV 1 μg/ml showed inhibition of pseudovirus entry in 293/hACE2 cells with percentages inhibition 25.92, 37.40, 27.32, and 38.97 %, respectively. Despite HCV 1 μg/ml showing about 6 % lower inhibitory activity than HSD 1 μM in pseudovirus entry assay, it holds potential as a supplement or source of raw material for HSD as a SARS-CoV-2 antiviral.
Structural Basis for Intermodular Communication in Assembly-Line Polyketide Biosynthesis
Authors: Cogan Dillon P. , Soohoo Alexander M. , Chen Muyuan , Liu Yan , Brodsky Krystal L. , Khosla Chaitan
Published: May 2024

Assembly-line polyketide synthases are large multienzyme systems with considerable potential for genetic reprogramming. To investigate the mechanisms by which reactive biosynthetic intermediates are directionally channeled across a defined sequence of active sites in a naturally occurring assembly line, we employed a bifunctional reagent to crosslink transient domain-domain interfaces of the 6-deoxyerythronolide B synthase. Structural resolution of these crosslinked states by single-particle cryogenic electron microscopy (cryo-EM) together with statistical per-particle image analysis of cryo-EM data revealed ketosynthase – acyl carrier protein (KS-ACP) interactions that discriminate between intra- and inter-modular communication, while reinforcing the relevance of asymmetric conformations during the catalytic cycle. Our findings provide a new foundation for the structure-based design of hybrid polyketide synthases comprised of biosynthetic modules from different assembly lines.
KAP1 negatively regulates RNA polymerase II elongation kinetics to activate signal-induced transcription
Authors: Hyder Usman , Challa Ashwini , Thornton Micah , Nandu Tulip , Kraus W. Lee , D’Orso Iván
Published: May 2024

Signal-induced transcriptional programs regulate critical biological processes through the precise spatiotemporal activation of Immediate Early Genes (IEGs); however, the mechanisms of transcription induction remain poorly understood. By combining an acute depletion system with high resolution genomics approaches to interrogate synchronized, temporal transcription, we reveal that KAP1/TRIM28 is a first responder that fulfills the temporal and heightened transcriptional demand of IEGs. Unexpectedly, acute KAP1 loss triggers an increase in RNA polymerase II elongation kinetics during early stimulation time points. This elongation defect derails the normal progression through the transcriptional cycle during late stimulation time points, ultimately leading to decreased recruitment of the transcription apparatus for re-initiation thereby dampening IEGs transcriptional output. Collectively, KAP1 plays a counterintuitive role by negatively regulating transcription elongation to support full activation across multiple transcription cycles of genes critical for cell physiology and organismal functions.
TrAQ: a novel, versatile, semi-automated, two-dimensional motor behavioural tracking software
Authors: Di Censo Davide , Rosa Ilaria , Ranieri Brigida , Di Lorenzo Tiziana , Alecci Marcello , Florio Tiziana M. , Galante Angelo
Published: May 2024

We present TrAQ, a new MATLAB-based two-dimensional tracking software for Open Field video analysis of unmarked single animal, featuring minimum user intervention. We developed TrAQ with the purpose to automatically count the in-plane rotations, an important parameter in the 6-hydroxydopamine hemiparkinsonian rat model and in many rodent models of neurodegenerative diseases, a very time-consuming manual task for highly trained human operators. In addition, TrAQ allows automatic recognition of the animal within a user defined arena providing a quantitative measurement of the body centroid and the two extremities positions. A full range of quantitative kinematic behavioral parameters are automatically calculated, and the optional shape erosion feature adds usage flexibility. TrAQ, free and non-species-specific application, was quantitively tested with rodents and on a qualitative basis with zebrafish, and invertebrate animal models. Quantitative results were successfully validated against a commercial software (for tracking) and manual annotation (for rotations in an hemiparkinsonian rat model). This is a widely used model in preclinical research to study postural instability and motor asymmetry. TrAQ allows the characterization of motor asymmetry using non-invasive tools, thus appreciating the spontaneous Open Field behaviour of unmarked single animal, with minimum user intervention.
Subunit positioning and diversity of the nematode levamisole-sensitive acetylcholine receptor
Authors: Noonan JD , Duguet TB , Handy-Hart CJ , Beech RN
Published: May 2024

The helminth levamisole-sensitive acetylcholine receptor (L-AChR) is a historically significant drug target. This heteromeric receptor belongs to the larger class of pentameric ligand-gated ion channels that has recently expanded within the nematodes and therefore provides the opportunity to study specific examples of how worm receptors evolve. TheCaenorhabditis elegansL-AChR can exist in two forms. The first contains three alpha subunits: ACR-13, UNC-38, and UNC-63, and two non-alpha subunits UNC-29 and LEV-1. The second can be formed by replacing ACR-13 with its paralog ACR-8, from eitherC. elegansor the closely relatedHaemonchus contortus.This form no longer requires LEV-1, demonstrating an evolved functional difference between ACR-8 and ACR-13. Since the properties of a channel depend on its composition and organization, knowing the underlying mechanisms regulating this would provide valuable insight into one of the least understood aspects of this important drug target. The goal of this study was to identify the subunit stoichiometry of the L-AChR and further elucidate the functional divergence of alpha subunits ACR-8 and ACR-13. Using a series of subunit concatemers, we determined the arrangement of threeC. elegansL-AChR subunits in the following N- to C-terminal order; UNC-38 – LEV-1 – UNC-63. We were unable to order the ACR-13 and UNC-29 subunits unambiguously. Additionally, our concatemers provide support for the sequential model of subunit assembly whereby a trimer is formed first, consisting of UNC-38 – LEV-1 – UNC-63, followed by individual addition of the remaining two subunits ACR-13 and UNC-29. UsingC. elegansandH. contortussubunit admixtures, we show that replacing ACR-13 with ACR-8 alleviates the requirement for five distinct subunits, as a functional receptor can be measured in the absence of non-alpha LEV-1. We confirm that UNC-29 can replace LEV-1 and that the intracellular loop determines this positional plasticity. This work provides the first evidence of the quaternary structure of the L-AChR which is necessary for future studies on this drug target. It also confirms that subunit arrangement is determined first during receptor heteromerization, followed by functional fine-tuning once subunit types have defined positions.
Fuzzy gauge theory for quantum computers
Authors: Alexandru Andrei , Bedaque Paulo F. , Carosso Andrea , Cervia Michael J. , Murairi Edison M. , Sheng Andy
Published: May 2024

Continuous gauge theories, because of their bosonic degrees of freedom, have an infinite-dimensional local Hilbert space. Encoding these degrees of freedom on qubit-based hardware demands some sort of “qubitization” scheme, where one approximates the behavior of a theory while using only finitely many degrees of freedom. We propose a novel qubitization strategy for gauge theories, called “fuzzy gauge theory,” building on the success of the fuzzy σ-model in earlier work. We provide arguments that the fuzzy gauge theory lies in the same universality class as regular gauge theory, in which case its use would obviate the need of any further limit besides the usual spatial continuum limit. Furthermore, we demonstrate that these models are relatively resource-efficient for quantum simulations.

Published by the American Physical Society
2024