bluuebunny/crossref_metadata_2025 huggingface dataset:
Complex Attention-Deficit Hyperactivity Disorder in a 4-Year-Old With Repaired Critical Congenital Heart Disease and Autism Spectrum Disorder
Authors: Campbell Kathleen , Wallis Kate E. , El-Messidi Hampton Lyla , Burnham Alisa , Mercer-Rosa Laura , Miller Olivia , Mazza Laura , Diekroger Elizabeth , Fogler Jason
Published: November 2024

Background:

Congenital heart disease (CHD) is a risk factor for developmental delay and for attention-deficit hyperactivity disorder (ADHD). The Cardiac Neurodevelopmental Outcome Collaborative has developed recommendations for ongoing monitoring of this at-risk population to be able to detect developmental, learning, and behavioral concerns, as they become apparent as a child ages.

Case Presentation:

A 4-year-old boy with tetralogy of Fallot with a ventricular septal defect repaired in infancy was followed periodically in the cardiac neurodevelopmental follow-up clinic and diagnosed with autism spectrum disorder as well as additional developmental and medical issues. He received early childhood special education and therapeutic interventions as well as social skills training and applied behavior analysis. At age 4 years, Alex presented with symptoms of hyperactivity, inattention, impulsivity, and immediate safety concerns for elopement. The clinician diagnosed him with ADHD-combined type. He was recommended to start medication in addition to behavioral and developmental supports. Managing medications in a child with CHD and ADHD presents unique challenges, and medication decisions were carefully made in collaboration with the child’s cardiologist. After some medication adjustments and ongoing behavioral therapy to address behaviors associated with ADHD and autism spectrum disorder, the child is doing well academically and socially.

Conclusion:

Attention-deficit hyperactivity disorder medications can be safely prescribed in patients with CHD. However, pharmacotherapy for co-occurring ADHD and CHD needs an additional level of oversight and collaboration between cardiology and prescribing clinicians. Behavioral therapies can be transdiagnostic and address challenges associated with autism and symptoms related to ADHD.
Utilization of Injectable and Device-Based Treatments in Medical Dermatology: A Survey on Demographics, Conditions, and Resident Involvement
Authors: Fathizadeh Sam , Richmond Alexandra , Almukhtar Rawaa
Published: November 2024

BACKGROUND

Injectable and device-based treatments are used for medical dermatologic conditions, but understanding dermatologists' practices remains limited.

OBJECTIVE

This study examines injectable and device-based treatments for medical dermatologic conditions to identify patterns and potential improvements.

MATERIALS AND METHODS

A survey was distributed to Association of Academic Cosmetic Dermatology members, covering practice settings, conditions treated, pricing, and resident involvement.

RESULTS

Thirty-four of 40 (85%) respondents practiced in academic teaching hospitals, primarily in urban settings. Conditions treated included acne vulgaris, alopecia, skin cancers, disorders of pigmentation, follicular disorders, gender-affirming care, birthmarks, oncodermatology, rosacea, scars, tattoos, and vascular lesions. Treatments were offered at various prices, with clinical trials and insurance used in some cases. Resident involvement ranged from 72% to 94% of cases. Respondents also reported laser usage, with 100% using lasers for treating scars, 98% for treating vascular lesions, 98% for treating rosacea, and 88% for treating disorders of pigmentation. For acne vulgaris and associated scarring, the top treatments were chemical peels (86%), lasers (83%), and mechanical modalities (48%). With gender-affirming care, respondents used lasers (100%), filler (55%), and neurotoxins (48%).

CONCLUSION

Academic dermatologists treat medical dermatologic conditions and involve residents.
Influenza Activity and Preterm Birth in the Atlanta Metropolitan Area: A Time-Series Analysis from 2010 to 2017
Authors: Zheng Xiaping , Wang Tingyu , Hao Hua , D’Souza Rohan R. , Strickland Matthew J. , Warren Joshua L. , Darrow Lyndsey A. , Chang Howard H.
Published: November 2024

Background:

Annual influenza epidemics lead to a substantial public health burden, and pregnant people are vulnerable to severe outcomes. Influenza during pregnancy is hypothesized to increase the risk of adverse birth outcomes, but population-based epidemiologic evidence remains limited and inconsistent.

Methods:

We conducted a time-series analysis to estimate short-term associations between community-level seasonal influenza activity and daily counts of preterm births in Atlanta, United States from October 17, 2010 to July 10, 2017. We defined weekly influenza exposures four ways: (1) percent test-positive from virologic surveillance, (2) percent of patients with symptoms of influenza-like illness (ILI) in outpatient settings, (3) a composite measure of percent test-positive and ILI, and (4) influenza hospitalization rates. We used Poisson log-linear models to estimate associations, adjusting for time-varying confounders and ongoing at-risk pregnancies. We further examined associations by influenza type and exposure lags and effect modification by maternal characteristics.

Results:

We studied a total of 316,253 births. We found consistent positive associations between influenza activity and preterm birth across different exposure measures and exposure lags. An interquartile range increase in a composite measure of ILI activity and percent test-positive was associated with a 1.014 (95% confidence interval: 1.001–1.027) increase in preterm birth during the same week. In stratified analyses, associations were more pronounced among married, non-Black, and Hispanic pregnant people.

Conclusion:

Periods of high influenza activity were associated with an increased risk of preterm birth.
Critical Assessment of Fellowship Director Gender and Ethnic Diversity across the Five Major Plastic Surgery Fellowships
Authors: Boroumand Sam , Stogniy Sasha , Katsnelson Beatrice , Allam Omar , Zahedi Vafa Aliyar , Sullivan Janessa , Pomahac Bohdan , Haykal Siba , Butler Paris D.
Published: November 2024

Background:

Subspecialty fellowship directors are essential to the selection and mentorship of trainees. The purpose of this study is to evaluate the gender and racial/ethnic diversity of fellowship directors across fellowship programs in plastic and reconstructive surgery (PRS).

Methods:

In December 2023, listings of fellowship programs/directors were surveyed from respective professional society websites across the 5 primary PRS fellowships: hand (American Society for Surgery of the Hand), craniofacial (American Society of Craniofacial Surgeons), microsurgery (American Society for Reconstructive Microsurgery), aesthetic (The Aesthetic Society), and burn (American Burn Association). Fellowship director demographics from each program were researched and identified.

Results:

In total, 248 fellowship directors were identified: 94 hand, 34 craniofacial, 62 microsurgery, 38 aesthetic, and 20 burn. There was a significantly greater percentage of male versus female directors across all fellowships (87.5% versus 12.5%; P < 0.01). Men were noted to have a significantly higher average h-index score (20.4 versus 15.0; P = 0.045) but constituted a lower proportion of assistant professorships (32.3% versus 12.9%; P < 0.01). Relative to directors from racial/ethnic minority backgrounds, White directors constituted a significantly greater percentage of fellowship directors (72.9% versus 27.1%; P < 0.01) and had a greater number of years passed since completing their most recent training (21.7 versus 17.1; P = 0.030).

Conclusions:

Across PRS fellowship programs, women and racial/ethnic minorities are disproportionately underrepresented in leadership. Targeted initiatives to promote diversity in PRS fellowship directors should be considered as medicine works toward a surgical workforce more reflective of the patient population.
Acute physical exercise and ambulatory blood pressure in resistant hypertension
Authors: Saco-Ledo Gonzalo , Valenzuela Pedro L. , Almazán-Polo Jaime , Plaza-Florido Abel , Alejo Lidia B. , Bustos Asunción , Río-García Antía , Gálvez Beatriz G. , Rubio-González Esther , Fiuza-Luces Carmen , León-Sanz Miguel , Boraita Araceli , Santos-Lozano Alejandro , Ruilope Luis M. , Lucia Alejandro
Published: November 2024

Objectives:

The effects of acute physical exercise in patients with resistant hypertension remain largely unexplored compared with hypertensive patients in general. We assessed the short-term effects of acute moderate-intensity (MICE) and high-intensity interval exercise (HIIE) on the clinic (BP) and 24-h ambulatory blood pressure (ABP) of patients with resistant hypertension.

Methods:

Using a crossover randomized controlled design, 10 participants (56 ± 7 years) with resistant hypertension performed three experimental sessions: MICE, HIIE, and control. MICE consisted of continuous treadmill exercise at an intensity of 3–4 metabolic equivalents of energy (METs) until completing 3 kcal/kg and was energy-matched to HIIE (which included six to eight intervals of 3 min duration at 6–7 METs interspersed with 1.5-min rests at 3 METs). In the control session, participants remained seated for 50 min. Flow-mediated vasodilation, autonomic nervous system balance (heart rate variability), exerkines [interleukin (IL)-6, IL-8, IL-15, vascular endothelial growth factor A, irisin, adiponectin, and angiopoietin] and 71 inflammatory-related proteins were also measured.

Results:

Compared with baseline, HIIE and MICE reduced clinic SBP immediately (P < 0.001 for both) and 90 min (P = 0.001 and P = 0.041, respectively) postexercise. HIIE and MICE also reduced clinic DBP immediately postexercise (P = 0.003 and P = 0.025). By contrast, no changes were found in the control session. On the other hand, no significant effects were noted for 24 h ABP measures or for the rest of variables.

Conclusion:

Although in patients with resistant hypertension, acute aerobic exercise induces short-term reductions in clinic BP, this stimulus does not suffice to reduce 24 h ABP or to impact on potential biological mechanisms.
Sedentary behavior modified the association between depression and risk of all-cause deaths in hypertensive population
Authors: Wang Haixu , Zhou Zeming , Zhang Lihua , Yu Fang , Li Jingkuo , Lei Lubi , Zhao Zhenyan , Zhao Jie
Published: November 2024

Objective:

The pathogenic mechanism of depression involves chronic inflammation, which can be affected by sedentary behavior. This study aimed to determine whether sedentary behavior modified the association between depression and risk of death in the hypertensive population.

Methods:

Data from the National Health and Nutrition Examination Survey (2007–2018) was analyzed. Depression was assessed through the Health Questionnaire-9, and sedentary behavior was evaluated using self-reported sitting hours in a day. Deaths were ascertained through the National Death Index until 31 December 2019. The interaction effect was evaluated through multivariable Cox regression analysis.

Results:

Eight thousand one hundred and twenty-four patients with hypertension were involved in the study. During a median follow-up of 7.3 years, we confirmed 1384 all-cause and 373 cardiovascular deaths. Separate analyses revealed that both depression and sitting for 6 h per day or more were correlated with increased risks of all-cause and cardiovascular deaths. Of note, we found that sitting time modified the link between depression and the risk of all-cause death (P for interaction: 0.02). Compared with the nondepression group, the depression group was correlated with an elevated risk of all-cause death among participants with sitting time of more than 6 h/day [hazard ratio 1.52, 95% confidence interval (CI) 1.22–1.91, P < 0.001], but not among participants with sitting time of less than 6 h/day (hazard ratio 0.95, 95% CI 0.65–1.39, P = 0.76).

Conclusion:

Sedentary behavior modified the link between depression and the risk of all-cause death. Reducing sedentary time might attenuate the detrimental effects of depression on survival in the hypertensive population.
Participation interest and completion of home blood pressure measurements with mailed devices in adults with and without hypertension
Authors: Weihrauch Tim , Lemcke Johannes , Büschges Julia Charlotte , Allen Jennifer , Schmich Patrick , Kintscher Ulrich , Maier Birga , Neuhauser Hannelore
Published: November 2024

Objectives:

Home blood pressure monitoring (HBPM) is valuable for the detection and monitoring of hypertension. Despite logistical advantages, HBPM has not yet been used in national blood pressure (BP) surveys. We investigated randomly selected adults’ willingness to participate in an HBPM study (attitude survey) and piloted this approach (feasibility study).

Methods:

The attitude survey, part of the 2020 population representative cross-sectional telephone interview survey, German Health Update (GEDA), assessed willingness to self-measure BP on three days in the morning and evening in 6517 participants. Descriptive analyses and weighted log-binomial regression were used to examine associations between willingness to participate in HBPM and sociodemographic and health factors. The feasibility study piloted self-measurements with mailed devices, video instructions, and before and after online interviews with 258 commercial panel volunteers.

Results:

In the attitude survey, 38% of randomly selected adults expressed willingness to participate in the HBPM study. Willingness to participate was associated with higher education [risk ratio (RR) 1.63, 95% confidence interval (CI) 1.37–1.94] and medium education (RR 1.30, 95% CI 1.09–1.56) compared to low education, ages 18–39 (RR 1.69, 95% CI 1.45–1.97) and 40–59 (RR 1.37, 95% CI 1.20–1.58) compared to participants from age 60s, and self-reported hypertension (RR 1.19, 95% CI 1.04–1.36). In the feasibility study, 43% (n = 110) of those receiving a device completed the study.

Conclusion:

Our findings suggest that national BP studies cannot rely solely on HBPM because selective participation would yield biased results. However, HBPM may be used in other epidemiological studies, such as longitudinal studies.
A case study of hypophosphatasia: An underdiagnosed bone disorder characterized by low alkaline phosphatase
Authors: Moro Leslie
Published: November 2024

Hypophosphatasia (HPP) is a rare genetic metabolic bone disorder that is underdiagnosed. Although there are many forms of this disease, based on age of onset, symptoms, and severity, HPP is characterized by low serum alkaline phosphatase levels, bone fractures, and dental complications. Diagnosis of HPP is made from clinical, laboratory, and radiologic findings. Genetic testing for an ALPL gene variant responsible for causing HPP confirms a molecular diagnosis. Distinguishing HPP from other more common bone disorders, such as osteoporosis, is important as the treatment for these diseases differs greatly. Although there is no known cure for HPP, treatment should be holistic and multidisciplinary.
Plasma Concentration as a Proxy for Perilymph Drug Levels: Preclinical and Clinical Dexamethasone Measures with a Long-Acting Formulation for Precise Delivery to the Round Window Membrane
Authors: Jung Benson T. , Kuthubutheen Jafri , Sharon Jeffrey D. , Foster Alan C. , Erickson Signe , Peris Hugo , De Juan Eugene , Limb Charles J. , Farinas Kathleen Cogan , Turner Jeremy , Henton Amanda , Salt Alec
Published: November 2024

Objective

To use animal pharmacokinetic data and FluidSIM modeling to estimate human dexamethasone perilymph concentrations from plasma concentration measurements over time following a single intratympanic administration of SPT-2101.

Study Design

Perilymph and plasma dexamethasone concentrations were measured in guinea pigs and African green monkeys over 3 to 6 weeks post-intratympanic administration of SPT-2101. Plasma concentrations of dexamethasone were measured in Ménière’s disease patients post-intratympanic administration of SPT-2101. FluidSIM was trained on the correlations of animal plasma and animal perilymph levels, allowing the human perilymph drug time course for SPT-2101 to be predicted from measured human plasma dexamethasone concentrations.

Setting

Tertiary care neurotology clinic in Perth, Australia.

Patients

Nine adults with unilateral definite Ménière’s disease per Barany Society criteria.

Intervention

Intratympanic SPT-2101, a single injection of a long-acting gel formulation of dexamethasone precisely delivered at the round window.

Main Outcome Measure

Estimated dexamethasone levels in human perilymph following a single administration of SPT-2101 at the round window over time.

Results

Perilymph dexamethasone concentrations were above estimated therapeutic levels for up to 35 days in guinea pigs and at least 21 days in African green monkeys. In human subjects, plasma dexamethasone concentrations were detected for 2 weeks post-administration. Animal middle ear, plasma and perilymph drug interrelationships were compared to FluidSIM simulations, providing rationale for correlating dexamethasone concentrations in the respective compartments. Comparable simulations of human plasma concentrations predicted perilymph dexamethasone therapeutic levels in humans for 23–55 days.

Conclusions

Sustained release dexamethasone from SPT-2101 precisely delivered at the round window provides prolonged and durable estimated perilymph concentrations in clinical subjects.
Endoplasmic reticulum stress-related signatures: a game-changer in prognostic stratification for hepatocellular carcinoma
Authors: Li Hongxuan , Zhang Lei , Shu Bin , Wang Xiaojuan , Yang Shizhong
Published: November 2024

Background

Hepatocellular carcinoma (HCC) has limited therapeutic options and a poor prognosis. The endoplasmic reticulum (ER) plays a crucial role in tumor progression and response to stress, making it a promising target for HCC stratification. This study aimed to develop a risk stratification model using ER stress-related signatures.

Methods

We utilized transcriptome data from The Cancer Genome Atlas and Gene Expression Omnibus, which encompass whole-genome expression profiles and clinical annotations. Machine learning algorithms, including the least absolute shrinkage and selection operator, random forest, and support vector machine recursive feature elimination, were applied to the key genes associated with HCC prognosis. A prognostic system was developed using univariate Cox hazard analysis and least absolute shrinkage and selection operator Cox regression, followed by validation using Kaplan–Meier analysis and receiver operating characteristic curves. Tumor immune dysfunction and exclusion tools were used to predict immunotherapy responsiveness.

Results

Two distinct clusters associated with ER stress were identified in HCC, each exhibiting unique clinical and biological features. Using a computational approach, a prognostic risk model, namely the ER stress-related signature, was formulated, demonstrating enhanced predictive accuracy compared with that of existing prognostic models. An effective clinical nomogram was established by integrating the risk model with clinicopathological factors. Patients with lower risk scores exhibited improved responsiveness to various chemotherapeutic, targeted, and immunotherapeutic agents.

Conclusion

The critical role of ER stress in HCC is highlighted. The ER stress-related signature developed in this study is a powerful tool to assess the risk and clinical treatment of HCC.
Cartilage Forming Tumors of the Skeleton
Authors: Diaz-Perez Julio A. , Rosenberg Andrew E.
Published: November 2024

Cartilage-forming tumors are a broad and diverse group of neoplasms frequently affecting the skeleton. Distinguishing between the members of this group is important because of significant differences in treatment and prognosis. Accurate diagnosis can be challenging because of similarities in their clinical, radiographic, and pathologic features. Immunohistochemistry and molecular tools are helpful in select instances. Therefore, careful evaluation and correlation of these features are essential in arriving at the correct diagnosis and appropriate patient management. This review provides an overview of the current literature, emphasizing helpful features in diagnosis.
Transformation of the HIV treatment cascade for people who inject drugs in Ukraine
Authors: Bromberg Daniel J. , Rhoades Delaney , Madden Lynn M. , Ivasiy Roman , Meteliuk Anna , Pykalo Iryna , Filippovych Myroslava , Nikitin Benjamin M. , Farnum Scott O. , Fomenko Tetiana , Dvoriak Sergii , Altice Frederick L. ,   the ExMAT Consortium
Published: November 2024

Background:

Ukraine's HIV epidemic, the second-largest in Europe, is concentrated among people who inject drugs (PWID), primarily opioids. Between 2014 and 2021, Ukraine has scaled up opioid agonist therapies (OAT) considerably.

Methods:

We conducted a large cross-sectional biobehavioral survey of PWID in 2020–2021 to compare to an equivalent survey from 2014 to 2015 using representative sampling approaches including random sampling and RDS of PWID with opioid dependence, recruiting those who were: currently on OAT; previously on OAT; and never on OAT. Only PWID who tested positive for HIV were assessed for the proportion linked to care, prescribed antiretroviral therapy (ART), and adherent to ART.

Results:

Comparing samples from 2021 (N = 2027) to 2014 (N = 1613), there were differences in HIV diagnosis (92.6 vs. 90%), linkage to care (86.5 vs. 85.3%), prescription of ART (95.8 vs. 78.9%), and adherence to ART (93.6 vs. 85.7%), for those patients who had previously been on OAT. In a subanalysis from the 2020 to 2021 sample, having ever touched the OAT treatment system (currently or previously on OAT) had significantly better outcomes at each step of the cascade relative to those who had never been on OAT.

Interpretation:

Although OAT had previously been demonstrated to improve HIV treatment outcomes along the HIV care cascade, findings here suggest that OAT has scaled-up along with higher levels of engagement in the HIV care cascade over time. Importantly, but not previously described, is the finding that touching the OAT treatment system, irrespective of retention on treatment contributes to improved HIV treatment outcomes for each step of the cascade.
Impact of Specimen Extraction Site and Gallstone Size on Early Postoperative Pain Following Laparoscopic Cholecystectomy: A Prospective Randomized Controlled Study
Authors: Akgul Nedim , Turan Mehmet I. , Dincer Aydin , Ozyurt Erhan
Published: November 2024

Background:

Laparoscopic cholecystectomy (LC) is widely performed with generally favorable outcomes, but postoperative pain remains a significant issue, influenced by various factors including the specimen extraction site and gallstone size.

Methods:

A prospective randomized controlled study was conducted on 100 patients undergoing LC. Participants were randomized to have the specimen removed through either the epigastric or umbilical trocar. Postoperative pain was assessed using the visual analog scale (VAS) on postoperative days 1, 3, and 7. Statistical analyses were performed to evaluate the impact of trocar site and gallstone size on pain levels.

Results:

Patients whose specimens were extracted through the umbilical trocar experienced significantly less pain on postoperative days 1 and 3 (P=0.006 and 0.014, respectively) than those with epigastric trocar extraction. In addition, patients with gallstones larger than 10 mm reported higher pain levels on day 3 (P=0.001) irrespective of the extraction site.

Conclusions:

The umbilical trocar site for specimen extraction and smaller gallstone size is associated with reduced early postoperative pain following LC. These findings suggest the importance of considering extraction site and gallstone size in managing postoperative pain in LC patients.
Leaving Slings and Other Transfer Devices Under Patients
Authors: Bradley Sarah E. , Chavez Margeaux , Barrett Blake , Lind Jason , Cowan Linda , Broderick Vianna , Bulat Tatjana
Published: November 2024

PURPOSE:

The purpose of this quality improvement project was to develop guidance for safe patient handling and mobility efforts to prevent pressure injuries (PIs) within the Veterans Health Administration (VHA) when slings and other transfer devices are left under patients.

PARTICIPANTS AND SETTING:

Health care staff (n = 112) in patient safety and nursing at 77 unique VHA facilities responded to surveys between November and December 2019. Interviews (n = 24) were conducted using purposive sampling with VHA staff at facilities with highest and lowest PI rates (n = 9) between January and March 2021.

APPROACH:

Feedback on practices and perceptions related to leaving slings and other transfer devices were evaluated using online cross-sectional surveys and interviews with VHA staff. Secondary data for VHA inpatient rates of PIs were used to examine associations with staff-reported sling and other transfer device practices.

OUTCOMES:

Leaving slings under patients was associated with higher proportion of patients developing PIs in intensive care units (ICUs, P = .042) and medical-surgical care units (P = .025). In addition, use of sliding boards for seated transfer among short-stay residents in Community Living Centers was associated with higher PI occurrences (P = .017). Qualitative interviews found perceptions and guidance about PI risk related to slings and other transfer devices varied among staff who consider many factors when determining risk.

IMPLICATIONS FOR PRACTICE:

There are perceived benefits and risks of leaving slings and other transfer devices under patients and limited knowledge of PI occurrences associated with this practice. Clinical decision support can help staff determine safe sling use. More work is needed to test the safety of common sling and transfer device practices and define best practices for communicating PI risk related to sling and transfer device use across the care continuum.
Dysregulated airway epithelial antiviral immunity in Down Syndrome impairs type III IFN response and amplifies airway inflammation during RSV infection
Authors: Chorvinsky Elizabeth , Bhattacharya Surajit , Bera Betelehem Solomon , Welham Allison , Ismat Karim , Lawlor Claire M , Preciado Diego , Gomez Jose L , Morizono Hiroki , Pillai Dinesh K , Gutierrez Maria J. , Jaiswal Jyoti K , Nino Gustavo
Published: November 2024

Trisomy 21 (TS21), also known as Down syndrome (DS), increases pediatric mortality risk from respiratory syncytial virus (RSV) by nine-fold, yet its underlying immunological basis remains unclear. Here, we investigated RSV-induced immunological responses in TS21 airway epithelial cells (AECs), the primary site of respiratory virus entry and host defense. TS21 AECs exhibit hyperactive interferon (IFN) signaling and reduced RSV infectivity, but they also show impaired type-III IFN responses during viral infection. Furthermore, TS21 AECs demonstrate heightened production of proinflammatory mediators CXCL5 and CXCL10 both before and after RSV exposure. Infants with DS suffering from severe viral bronchiolitis demonstrate dysregulated airway immune responses in vivo, characterized by diminished type-III IFN levels and increased CXCL5/CXCL10 secretion. Our results indicate that RSV severity in DS is not due to impaired viral control but to dysregulated airway proinflammatory responses, offering new therapeutic opportunities to mitigate the severity of RSV infection in children with DS.
Evolvability through segmental duplication follows species-specific dynamics
Authors: Islam Saiful , Aqil Alber , Hach Faraz , Numanagić Ibrahim , Masuda Naoki , Gokcumen Omer
Published: November 2024

Evolvability, the capacity of populations to respond to selection, is influenced by genomic structural properties such as segmental duplications. These duplications establish redundancy, creating adaptive potential by co-opting duplicated elements for new functions. Here, we identify segmental duplications in 117 vertebrate species and the starfish outgroup using long-read genome assemblies. We constructed independent segmental duplication networks for each species to represent the landscape of segmental duplications therein. We quantified the duplication landscapes across species using 13 network properties and tested three hypotheses for their evolution: 1) selective constraint, 2) phylogenetic drift, and 3) species-specific dynamics. Our results show that segmental duplication profiles across vertebrates are shaped by fast-evolving, species-specific dynamics, driving unique adaptive potentials. One notable exception of lineage-specific evolution is observed within mammals, where monotremes (platypus and echidna) exhibit distinct genomic structural features, characterized by elevated insertion and deletion rates compared to therian mammals. Analysis of genome size variation in vertebrates revealed no significant correlation with segmental duplication metrics. However, in ray-finned fish, lineage-specific events such as whole-genome duplications in some species (e.g., sterlet sturgeon and brown trout) influence genome size. These findings highlight the role of segmental duplications in species-specific adaptive potential and demonstrate the utility of network-based methods in genomic research. Our dataset and framework provide a valuable resource for understanding genomic evolvability, underscoring the integration of evolutionary biology and network analysis in studying genome evolution.
Fish MicroRNA Responses to Thermal Stress: Insights and Implications for Aquaculture and Conservation Amid Global Warming
Authors: Lin Ting , Meegaskumbura Madhava
Published: November 2024

Under the backdrop of global warming, heat tolerance emerges as an important physiological trait governing the distribution and survival of fish species worldwide. While knowledge on fish heat tolerance and stress has progressed from behavioral studies to transcriptomic analyses, our understanding at the transcriptomic level remains limited. Recently, the highly conserved nature of microRNAs (miRNAs) has introduced new ways of explaining molecular mechanisms of heat stress in fish. Here, we systematically review current research across three main reference databases to explain the universal responses and mechanisms of fish miRNAs to heat stress. An initial screen of 569 articles yielded 13 target papers for comprehensive analysis. Among these, at least 214 differentially expressed genes (DEGs) were identified, with 15 DEGs recurring in at least two studies (12 upregulated, 13 downregulated). The 15 recurrent DEGs were subjected to DIANA mirPath v.3 utilizing the microT-CDS v5.0 database to identify potential target genes. The results indicate that multiple miRNAs target genes, forming a complex network to regulate glucose and energy balance metabolism, maintain homeostasis, and modulate inflammation and immune disorders. Notably,miR-1,miR-122,let-7a, andmiR-30bare identified as potential biomarkers of heat stress in fish. Due to their high conservation across species, these miRNAs could be used to monitor the health of wild fish populations, improve selective breeding programs in aquaculture, and guide conservation strategies for species that are vulnerable to climate change. This review provides a framework for further investigation into the molecular mechanisms of fish heat tolerance.
Pseudomonas aeruginosa-mediated cardiac dysfunction is driven by extracellular vesicles released during infection
Authors: Kumar Naresh , Mattoo Sameer Salam , Sanghvi Shridhar , Ellendula Maneeth P. , Mahajan Sahil , Planner Clara , Bednash Joseph S. , Khan Mahmood , Ganesan Latha P. , Singh Harpreet , Lafuse William P. , Wozniak Daniel J. , Rajaram Murugesan V.S.
Published: November 2024

Pseudomonas aeruginosa (P.a.)is a gram-negative, opportunistic bacterium abundantly present in the environment. OftenP.a.infections cause severe pneumonia, if left untreated. Surprisingly, up to 30% of patients admitted to the hospital for community- acquired pneumonia develop adverse cardiovascular complications such as myocardial infarction, arrhythmia, left ventricular dysfunction, and heart failure. However, the underlying mechanism of infection-mediated cardiac dysfunction is not yet known. Recently, we demonstrated thatP.a.infection of the lungs led to severe cardiac electrical abnormalities and left ventricular dysfunction with limitedP.a.dissemination to the heart tissue. To understand the mechanism of cardiac dysfunction duringP.a.infection, we utilized bothin vitroandin vivomodels. Our results revealed that inflammatory cytokines contribute but are not solely responsible for severe contractile dysfunction in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Instead, exposure of hiPSC-CMs with conditioned media fromP.a.infected human monocyte-derived macrophages (hMDMs) was sufficient to cause severe contractile dysfunction and arrhythmia in hiPSC-CMs. Specifically, exosomes released from infected hMDMs and bacterial outer membrane vesicles (OMVs) are the major drivers of cardiomyocyte contractile dysfunction. By using LC-MS/MS, we identified bacterial proteins, including toxins that are packaged in the exosomes and OMVs, which are responsible for contractile dysfunction. Furthermore, we demonstrated that systemic delivery of bacterial OMVs to mice caused severe cardiac dysfunction, mimicking the natural bacterial infection. In summary, we conclude that OMVs released during infection enter circulation and drive cardiac dysfunction.
Resolving the Taxonomic Status of the Marbled Toad (Bufonidae:Incilius marmoreus): 2RAD-based Phylogeography Including an Isolated Population in Veracruz, Mexico
Authors: Wang Kenneth , Pierson Todd W. , Mendelson Joseph R.
Published: November 2024

Inhabiting an extensive range along the Pacific Coast of Mexico and a smaller allopatric region in the State of Veracruz,Incilius marmoreushas an unusual distribution amongst herpetofauna. Günther (1901) considered the Pacific coastal toadsBufo argillaceusandBufo lateralisto be conspecific withIncilius [Bufo] marmoreus,for which the type locality is in Veracruz. Here, we adopt an integrative approach to reevaluate the phylogeography and taxonomy ofI. marmoreusby gathering and analyzing morphological data and conducting phylogenetic and population genetic analyses from genome-wide SNP data. Our results uphold the current taxonomy by concurring with Günther (1901). Our phylogenetic and population genetic analyses suggest thatI. marmoreusfrom Veracruz are closely related to those from Oaxaca, and our coalescent analyses recovered a north–south split along the Pacific Coast estimated to have occurred ∼1.29 Mya followed by a shallow east–west split in the southern lineage that separates the Pacific coastal populations and the allopatric population in Veracruz ∼0.46 Mya. Present gene flow throughout the western range is evident, and the species displays a marked amount of morphological and genetic diversity throughout its range. The events that led to the formation of the population isolated on the coast of Veracruz remain uncertain, but we hypothesize that climatic and vegetation changes in the Late Pleistocene may have played a role.
Diet and trophic niche partitioning of three aerial hawking bat species in the Venezuelan Llanos
Authors: Azofeifa Romero Yara , Nassar Jafet M , Mavárez Jesús
Published: November 2024

Since Neotropical insectivorous bats (IB) share feeding sites and prey, their coexistence must depend on processes promoting divergence at trophic niches. We conducted diet and activity time analyses of three coexisting IB species in Venezuelan paddies,Molossus molossus, Eptesicus furinalis, andMyotis nigricans, to understand their trophic niche partitioning. We used statistical models to understand: (1) the dietary and activity time overlap among IB species, and (2) the relationship of IB species’ morphology and hunting strategies with prey’s hardness and flight speed. We found high prey richness forM. molossus(32 families),M. nigricans(19 families), andE. furinalis(13 families). Bats exhibited differences in prey richness, proportions, types consumed, as well as in their activity periods. As expected from its larger size and fast flight,M. molossusprefers larger, fast-flying, and medium-to-high sclerotized preys such as Coleoptera and Lepidoptera, with hunting activities starting and peaking significantly earlier than the other two bat species. On the other hand, also consistent with its size and flight type,M. nigricansexhibits a significant preference for small, slow-flying, and weekly sclerotized preys such as Diptera, although with relatively high dietary and temporal overlaps withE. furinalis.Thus, in concordance with niche theory predictions, the coexistence between these bats, particularly betweenM. molossusand the other two species, seems enhanced by reduced competition driven by divergence at trophic niche dimensions.
Naturally occurring N-terminal mutations in SARS-CoV-2 nsp1 impact innate immune modulation but do not affect virus virulence
Authors: Rani Ruchi , Nooruzzaman Mohammed , Caserta Leonardo C. , Diel Diego G.
Published: November 2024

The non-structural protein 1 (nsp1) of SARS-CoV-2 plays a key role in host innate immune evasion. We identified two deletion variants (Δ82-85 and Δ83-86) in the N-terminal region of the nsp1 of a SARS-CoV-2 BA.5.2.1 variant recovered from a human patient. Analysis of the sequence databases revealed a frequency of 0.5% of these mutations amongst available SARS-CoV-2 sequences. Structural analysis of the deletion mutant nsp1Δ82-85 and nsp1Δ83-86 revealed a distortion in the protein pocket when compared to the wild-type nsp1 which may affect protein function. To evaluate the functional relevance of these mutations, we cloned the mutant BA.5.2.1 nsp1Δ82-85 and nsp1Δ83-86 and wild-type nsp1 proteins in expression plasmids and performed luciferase reporter-based assays to assess activation of the interferon and nuclear factor kappa B (NF-κB) signalling pathways. Both nsp1Δ82-85 and nsp1Δ83-86 mutants showed marked decreased ability to inhibit the interferon beta (IFN-β) and NF-κB pathway activation. To assess the relevance of these deletions in the context of SARS-CoV-2 infection, we generated recombinant viruses carrying the wild type BA.5.2.1 nsp1 or the BA.5.2.1 nsp1Δ82-85 and nsp1Δ83-86 deletions in the backbone of WA1 strain.In vitrocharacterization of the recombinant SARS-CoV-2 viruses revealed that the recombinant viruses containing the nsp1Δ82-85 and nsp1Δ83-86 deletions presented similar plaque size and morphology to those produced by the wild-type rWA1-BA.5.2.1-nsp1 virus, indicating a similar ability of the mutant viruses to spread from cell to cell. Importantly, pathogenesis studies revealed that these mutations did not affect virus virulence and pathogenesis in a hamster model of SARS-CoV-2 infection.
Secretory leukocyte protease inhibitor influences periarticular joint inflammation in B. burgdorferi-infected mice
Authors: Yu Qian , Tang Xiaotian , Hart Thomas , Homer Robert , Belperron Alexia A. , Bockenstedt Linda , Ring Aaron , Nakamura Akira , Fikrig Erol
Published: November 2024

Lyme disease, caused byBorrelia burgdorferi, is the most common tick-borne infection in the United States. Arthritis is a major clinical manifestation of infection, and synovial tissue damage has been attributed to the excessive pro-inflammatory responses. The secretory leukocyte protease inhibitor (SLPI) promotes tissue repair and exerts anti-inflammatory effects. The role of SLPI in the development of Lyme arthritis in C57BL/6 mice, which can be infected withB. burgdorferi, but only develop mild joint inflammation, was therefore examined.SLPI-deficient C57BL/6 mice challenged withB. burgdorferihad a higher infection load in the tibiotarsal joints and marked periarticular swelling, compared to infected wild type control mice. The ankle joint tissues ofB. burgdorferi-infectedSLPI-deficient mice contained significantly higher percentages of infiltrating neutrophils and macrophages.B. burgdorferi-infectedSLPI-deficient mice also exhibited elevated serum levels of IL-6, neutrophil elastase, and MMP-8. Moreover, using a recently developed BASEHIT (BActerial Selection to Elucidate Host-microbe Interactions in high Throughput) library, we found that SLPI directly interacts withB. burgdorferi. These data demonstrate the importance of SLPI in suppressing periarticular joint inflammation in Lyme disease.
Residual flexibility in the topologically constrained multivalent complex between the GKAP scaffold and LC8 hub proteins
Authors: Nagy-Kanta Eszter , Kálmán Zsófia E. , Tossavainen Helena , Juhász Tünde , Farkas Fanni , Hegedüs József , Keresztes Melinda , Beke-Somfai Tamás , Gáspári Zoltán , Permi Perttu , Péterfia Bálint
Published: November 2024

Guanylate kinase-associated protein (GKAP) is a large postsynaptic scaffold protein bearing two closely spaced noncanonical binding sites for the bivalent dynein light chain LC8 hub protein. This might allow the formation of heterogeneous complexes with different sizes and topologies. Here, we show that a well-defined hexameric complex is formed, composed of 2 GKAP molecules and 2 LC8 dimers. Using NMR spectroscopy, we demonstrate that the LC8-binding segment of GKAP is intrinsically disordered and the flexibility of the linker region is largely retained even in the complex form. Molecular dynamics calculations suggest that besides the tightly bound residues, the hexamer also exhibits several dynamically interchanging interactions. The flanking regions of the two binding sites on GKAP exhibit different interaction patterns, hinting at additional contacts that might explain the fixed stoichiometry of the assembly. Our results demonstrate that constrained stoichiometry can coexist with substantial flexibility in a multivalent system.
CRISPRi Screen Uncovers lncRNA Regulators of Human Monocyte Growth
Authors: Flores-Arena Cristina , Malekos Eric , Covarrubias Sergio , Sudek Lisa , Montano Christy , Dempsey Valory , Hyunh Vuky , Katzman Sol , Carpenter Susan
Published: November 2024

Long noncoding RNAs are emerging as critical regulators of biological processes. While there are over 20,000 lncRNAs annotated in the human genome we do not know the function for the majority. Here we performed a high-throughput CRISPRi screen to identify those lncRNAs that are important in viability in human monocytes using the cell line THP1. We identified a total of 38 hits from the screen and validated and characterized two of the top intergenic hits. The first is a lncRNA neighboring the macrophage viability transcription factor IRF8 (RP11-542M13.2hereafter referred to as long noncoding RNA regulator of monocyte proliferation,LNCRMP) and the second is a lncRNA calledOLMALINC(oligodendrocyte maturation-associated long intervening non-coding RNA) that was previously found to be important in oligodendrocyte maturation. Transcriptional repression ofLNCRMP and OLMALINCfrom monocytes severely limited their proliferation capabilities. RNA-seq analysis of knockdown lines showed thatLNCRMPregulated proapoptotic pathways while knockdown ofOLMALINCimpacted genes associated with the cell cycle. Data supports bothLNCRMPandOLMALINCfunctioningin cisto regulate their neighboring proteins that are also essential for THP1 cell growth. This research highlights the importance of high-throughput screening as a powerful tool for quickly discovering functional long non-coding RNAs (lncRNAs) that play a vital role in regulating monocyte viability.
Conspecific sociability is regulated by associative learning circuits
Authors: Lobato-Rios Victor , Lam Thomas Ka Chung , Ramdya Pavan
Published: November 2024

Sociability, an animal’s ease and propensity to interact with members of its own species, is a prerequisite for many important social interactions including courtship, mating, brood rearing, and collective behavior. Despite its fundamental nature, the manner through which sociability arises—whether it is innate or acquired and its neural mechanisms— remains unknown. Here, we found that the fly,Drosophila melanogaster, produces a constellation of fearful reactions when it encounters another fly for the first time. However, these animals become sociable following several hours of exposure to conspecific (but not heterospecific) odors. Two large-scale neural silencing screens of 188 brain cell types revealed that both initial fearful reactions and learned sociability depend upon overlapping networks including circuits in the mushroom body, the principal center for associative learning and memory in the insect brain. Functional recordings of key mushroom body output neurons (MBONs) from this network over two hours of social interactions support a mechanistic model whereby fly odors modulate social valence by rebalancing MBON population activity, biasing action selection, and thereby driving sociable rather than fearful responses towards other flies. Thus, a center for learning and memory plays a fundamental role in establishing the basis for most social interactions.
A versatile mouse model to advance human microglia transplantation research in neurodegenerative diseases
Authors: Serneels Lutgarde , Sierksma Annerieke , Pasciuto Emanuela , Geric Ivana , Nair Arya , Martinez-Muriana Anna , Snellinx An , Strooper Bart De
Published: November 2024

Background

Recent studies highlight the critical role of microglia in neurodegenerative disorders, and emphasize the need for humanized models to accurately study microglial responses. Human-mouse microglia xenotransplantation models are a valuable platform for functional studies and for testing therapeutic approaches, yet currently those models are only available for academic research. This hampers their implementation for the development and testing of medication that targets human microglia.

Methods

We developed thehCSF1Bdesmouse line suitable as new transplantation model available to be crossed to any disease model of interest. ThehCSF1Bdesmodel created by CRISPR gene editing is RAG2 deficient and expresses human CSF1. Additional we crossed this model with two humanizedAppKI mice, theAppHuand theAppSAA. Flow cytometry, immunohistochemistry and bulk sequencing was used to study the response of microglia in the context of Alzheimer’s disease.

Results

Our results demonstrate the successful transplantation of iPSC-derived human microglia into the brains of hCSF1Bdesmice without triggering a NK-driven immune response. Furthermore we confirmed the multipronged response of microglia in the context of Alzheimer’s disease. ThehCSF1Bdesand the crosses with the Alzheimer’s disease knock-in modelAppSAAand the humanizedApp knock-incontrol mice,AppHuare deposited with EMMA and fully accessible to the research community.

Conclusion

the hCSF1Bdesmouse is available for both non-profit and for-profit organisations, facilitating the use of the xenotransplantation paradigm for human microglia to study complex human disease.
Correlated evolution of multiple traits gives butterflies a false head
Authors: Yumnam Tarunkishwor , Kodandaramaiah Ullasa
Published: November 2024

Many butterflies possess a combination of characters at the posterior hindwing end, superficially resembling their head. This‘false head’has been hypothesised to deflect predator attacks towards the false head area. A clear understanding of the diversity and evolution of false head traits across butterflies is lacking. Here, we tested whether false head traits evolved from simple to complex in order to achieve a greater resemblance to a head. We also tested if false head traits formed an adaptive constellation and, thus, evolved correlatedly. Using a phylogenetic framework with 944 lycaenid species, our results illustrate evolutionary patterns of five false traits - (i) false antennae, (ii) spot, (iii) conspicuous colouration in the false head area, (iv) false head contour in the false head area, and (v) convergent lines. We found that false traits (i)–(iv) evolved in a correlated fashion across the phylogeny, likely driven by a common selective pressure. Our findings support the idea that false head functions as an adaptive constellation for predator attack deflection.