bluuebunny/crossref_metadata_2025 huggingface dataset:
Defining Spatial Epidemiology: A Systematic Review and Re-orientation
Authors: Morrison Christopher N. , Mair Christina F. , Bates Lisa , Duncan Dustin T. , Branas Charles C. , Bushover Brady R. , Mehranbod Christina A. , Gobaud Ariana N. , Uong Stephen , Forrest Sarah , Roberts Leah , Rundle Andrew G.
Published: March 2024

Background:

Spatial epidemiology has emerged as an important subfield of epidemiology over the past quarter century. We trace the origins of spatial epidemiology and note that its emergence coincided with technological developments in spatial statistics and geography. We hypothesize that spatial epidemiology makes important contributions to descriptive epidemiology and analytic risk-factor studies but is not yet aligned with epidemiology’s current focus on causal inference and intervention.

Methods:

We conducted a systematic review of studies indexed in PubMed that used the term “spatial epidemiolog*” in the title, abstract, or keywords. Excluded articles were not written in English, examined disease in animals, or reported biologic pathogen distribution only. We coded the included papers into five categories (review, demonstration of method, descriptive, analytic, and intervention) and recorded the unit of analysis (i.e., individual vs. ecological). We additionally examined articles coded as analytic ecologic studies using scales for lexical content.

Results:

A total of 482 articles met the inclusion criteria, including 76 reviews, 117 demonstrations of methods, 122 descriptive studies, 167 analytic studies, and 0 intervention studies. Demonstration studies were most common from 2006 to 2014, and analytic studies were most common after 2015. Among the analytic ecologic studies, those published in later years used more terms relevant to spatial statistics (incidence rate ratio =1.3; 95% confidence interval [CI] = 1.1, 1.5) and causal inference (incidence rate ratio =1.1; 95% CI = 1.1, 1.2).

Conclusions:

Spatial epidemiology is an important and growing subfield of epidemiology. We suggest a re-orientation to help align its practice with the goals of contemporary epidemiology.
Genetic variation in severe cystic fibrosis liver disease is associated with novel mechanisms for disease pathogenesis
Authors: Stonebraker Jaclyn R. , Pace Rhonda G. , Gallins Paul J. , Dang Hong , Aksit Melis A. , Faino Anna V. , Gordon William W. , MacParland Sonya , Bamshad Michael J. , Gibson Ronald L. , Cutting Garry R. , Durie Peter R. , Wright Fred A. , Zhou Yi-Hui , Blackman Scott M. , O’Neal Wanda K. , Ling Simon C. , Knowles Michael R.
Published: March 2024

Background and Aims:

It is not known why severe cystic fibrosis (CF) liver disease (CFLD) with portal hypertension occurs in only ~7% of people with CF. We aimed to identify genetic modifiers for severe CFLD to improve understanding of disease mechanisms.

Approach and Results:

Whole-genome sequencing was available in 4082 people with CF with pancreatic insufficiency (n = 516 with severe CFLD; n = 3566 without CFLD). We tested ~15.9 million single nucleotide polymorphisms (SNPs) for association with severe CFLD versus no-CFLD, using pre-modulator clinical phenotypes including (1) genetic variant (SERPINA1; Z allele) previously associated with severe CFLD; (2) candidate SNPs (n = 205) associated with non-CF liver diseases; (3) genome-wide association study of common/rare SNPs; (4) transcriptome-wide association; and (5) gene-level and pathway analyses. The Z allele was significantly associated with severe CFLD (p = 1.1 × 10−4). No significant candidate SNPs were identified. A genome-wide association study identified genome-wide significant SNPs in 2 loci and 2 suggestive loci. These 4 loci contained genes [significant, PKD1 (p = 8.05 × 10−10) and FNBP1 (p = 4.74 × 10−9); suggestive, DUSP6 (p = 1.51 × 10−7) and ANKUB1 (p = 4.69 × 10−7)] relevant to severe CFLD pathophysiology. The transcriptome-wide association identified 3 genes [CXCR1 (p = 1.01 × 10−6), AAMP (p = 1.07 × 10−6), and TRBV24 (p = 1.23 × 10−5)] involved in hepatic inflammation and innate immunity. Gene-ranked analyses identified pathways enriched in genes linked to multiple liver pathologies.

Conclusion:

These results identify loci/genes associated with severe CFLD that point to disease mechanisms involving hepatic fibrosis, inflammation, innate immune function, vascular pathology, intracellular signaling, actin cytoskeleton and tight junction integrity and mechanisms of hepatic steatosis and insulin resistance. These discoveries will facilitate mechanistic studies and the development of therapeutics for severe CFLD.
Obstacles to Screening Today
Authors: Quigley Harry A.
Published: March 2024

Purpose:

To introduce a discussion of glaucoma screening.

Methods/Results:

Glaucoma screening faces challenges, including not satisfying important ethical principles for medical screening.

Conclusions:

Approaches that would better provide care for glaucoma patients include eliminating the loss of follow-up and identifying glaucoma among family members of known glaucoma patients.
A Phase Three Study of the Safety and Immunogenicity of a Four-dose Series of 20-Valent Pneumococcal Conjugate Vaccine in Healthy Infants
Authors: Senders Shelly , Klein Nicola P. , Tamimi Noor , Thompson Allison , Baugher Gary , Trammel James , Peng Yahong , Giardina Peter , Scully Ingrid L. , Pride Michael , Center Kimberly J. , Gruber William C. , Scott Daniel A. , Watson Wendy
Published: March 2024

Background:

The 20-valent pneumococcal conjugate vaccine (PCV20) was developed to extend pneumococcal disease protection beyond 13-valent PCV (PCV13).

Methods:

This phase 3, double-blind study conducted in the United States/Puerto Rico evaluated PCV20 safety and immunogenicity. Healthy infants were randomized to receive a 4-dose series of PCV20 or PCV13 at 2, 4, 6 and 12–15 months old. Objectives included demonstrating noninferiority (NI) of PCV20 to PCV13 immunoglobulin G (IgG) geometric mean concentrations after doses 3 and 4 and percentages of participants with predefined IgG concentrations after dose 3, with 7 additional PCV20 serotypes compared with the lowest result among vaccine serotypes in the PCV13 group. Safety assessments included local reactions, systemic events, adverse events, serious adverse events and newly diagnosed chronic medical conditions.

Results:

Overall, 1991 participants were vaccinated (PCV20, n = 1001; PCV13, n = 990). For IgG geometric mean concentrations 1 month after both doses 3 and 4, all 20 serotypes met NI criteria (geometric mean ratio lower 2-sided 95% confidence interval > 0.5). For percentages of participants with predefined IgG concentrations after dose 3, NI (percentage differences lower 2-sided 95% confidence interval > –10%) was met for 8/13 matched serotypes and 6/7 additional serotypes; 4 serotypes missed the statistical NI criterion by small margins. PCV20 also elicited functional and boosting responses to all 20 serotypes. The safety profile of PCV20 was similar to PCV13.

Conclusion:

A 4-dose series of PVC20 was well tolerated and elicited robust serotype-specific immune responses expected to help protect infants and young children against pneumococcal disease due to the 20 vaccine serotypes. Clinical trial registration: NCT04382326.
Clinical Evaluation and Surgical Management of Ocular Malakoplakia of the Caruncle and Periorbital Region: A Report of Two Case and Literature Review
Authors: Thrishulamurthy Chinmayee J. , Ahmed H Shafeeq , Sohail J Mohammed , Biligi Dayananda S.
Published: March 2024

Ocular malakoplakia, a rare inflammatory disorder characterized by Michaelis-Gutmann bodies, is presented in 2 unique cases involving uncommon anatomical sites—the orbit and caruncle. The first case describes a 10-year-old girl with localized subconjunctival swelling near the caruncle, prompting surgical excision, and revealing characteristic malakoplakia features. Despite medical management, surgical intervention provided symptom relief. The second case involves a painless swelling below the lower lid in a 23-year-old female, initially suggestive of lymphoma. Excision biopsy confirmed malakoplakia, emphasizing the potential for clinical misdiagnosis. Histopathological examination showcased Michaelis-Gutmann bodies, von Hansemann cells, and chronic inflammation, confirming the ocular malakoplakia diagnosis. These cases underscore the rarity of ocular malakoplakia, particularly in pediatric patients, and highlight the importance of accurate diagnosis and appropriate management.
Successful Treatment of Refractory Orbital Plasmacytoma with Chimeric Antigen Receptor T Cell Therapy: A Case Report and Review of the Literature
Authors: Lin Rebecca Z. , Lu Tracy , Homer Natalie , Men Clara J.
Published: March 2024

Orbital plasmacytoma is a rare plasma cell tumor that may arise as an aggressive form of extramedullary multiple myeloma. Treatment modalities include surgical excision, radiation, and chemotherapy. Chimeric antigen receptor T cell therapy is currently reserved for refractory disease. The authors present a case of a 69-year-old woman with an extensive orbital plasmacytoma refractory to multimodal therapy who was treated with idecabtagene vicleucel chimeric antigen receptor T cell therapy. Four days after infusion, the patient exhibited grade 1 cytokine release syndrome, which resolved with tocilizumab. The orbital plasmacytoma significantly decreased in size 1 month after treatment and demonstrated complete serological response and sustained tumor burden reduction at 10-month follow-up. This case highlights the efficacy of chimeric antigen receptor T cell therapy for refractory orbital plasmacytoma and calls attention to potential inflammatory toxicities.
The Covid-19 Pandemic and The Future of Work
Authors: Ezeilo Chidimma Ogechukwu , Green-McKenzie Judith
Published: March 2024

Introduction

The “future of work” refers to workplace modifications projected to occur following large scale events impacting workforce health and safety such as pandemics, technological advancements, or economic shifts. This paper examines the influence of the COVID-19 pandemic on the future of work.

Methods

The electronic databases PubMed, Google Scholar, and Scopus were explored using search terms such as “post-pandemic,” “working force,” and “future of work” to retrieve papers published between 2000 and 2023.

Results

The main characteristics of the future of work modification revealed are blurring of work-home boundaries, increase in telework and the gig economy, demand for artificial intelligence, smart working, quiet hiring, diversity and inclusion, and algocratic governance. Needed skills include virtual collaboration capability, cross-cultural competency, computational thinking, news media literacy, transdisciplinarity, sense making, and focusing on mental health and well-being.

Conclusions

Organizations are remodeling workforces to meet employee, employer, regulatory, and market expectations to adapt to future workplace needs.
Restoring Trust for People With Psychosis Through Psychotherapy
Authors: Ridenour Jeremy M. , Hamm Jay A. , Wiesepape Courtney N. , Buck Benjamin
Published: March 2024

Mistrust is a significant problem for people with psychosis and can interfere with their capacity to engage in psychosocial treatment. In this article, the developmental trajectory of mistrust is outlined, including the impact that attachment disruption, childhood trauma, attributional biases, internalized stigma, and discrimination can have on the person's capacity to form trusting bonds with others. After this review, three elements are described that may allow for the restoration of trust: the therapist's openness to understanding the patient's experience and agenda for therapy, the therapist's effort to honestly disclose their thoughts to encourage dialogue and mutual reflection, and therapist's attempt to promote metacognition through helping the patient develop more complex representations of the minds of others. These elements are framed in the context of metacognitive reflection and insight therapy, an integrative therapy that is well suited to address mistrust through its explicit focus on metacognition and intersubjectivity.
Locked plate constructs are not necessarily stiffer than nonlocked constructs: A biomechanical investigation of locked versus nonlocked diaphyseal fixation in a human cadaveric model of nonosteoporotic and osteoporotic distal femoral fractures
Authors: Ricci William M. , Dvorzhinskiy Aleksey , Zheng Yanming , Walker Zakiyyah , Anthony Mary , Holbrook Jeffrey , Jones Bob , Cartner Jacob , Tornetta Paul
Published: March 2024

Objectives:

The objective of this study was to compare the biomechanical properties of locked and nonlocked diaphyseal fixation in a model of distal femur fractures using osteoporotic and nonosteoporotic human cadaveric bone.

Methods:

A supracondylar osteotomy was created to mimic a fracture (OTA/AO 33A3) in osteoporotic (n = 4) and nonosteoporotic (n = 5) cadaveric distal femurs. The left and right femurs of each pair were instrumented with a distal femoral locking plate and randomly assigned to have diaphyseal fixation with either locked or nonlocked screws. The construct was cyclically axially loaded, and construct stiffness and load to failure were evaluated.

Results:

In osteoporotic bone, locked constructs were more stiff than nonlocked constructs (mean 143 vs. 98 N/mm when all time points combined, P < 0.001). However, in nonosteoporotic bone, locked constructs were less stiff than nonlocked constructs (mean 155 N/mm vs. 185 N/mm when all time points combined, P < 0.001). In osteoporotic bone, the average load to failure was greater in the locked group than in the nonlocked group (mean 1159 vs. 991 N, P = 0.01). In nonosteoporotic bone, the average load to failure was greater for the nonlocked group (mean 1348 N vs. 1214 N, P = 0.02). Bone mineral density was highly correlated with maximal load to failure (R2 = 0.92, P = 0.001) and stiffness (R2 = 0.78, P = 0.002) in nonlocked constructs but not in locked constructs.

Conclusions:

Contrary to popular belief, locked plating constructs are not necessarily stiffer than nonlocked constructs. In healthy nonosteoporotic bone, locked diaphyseal fixation does not provide a stiffer construct than nonlocked fixation. Bone quality has a profound influence on the stiffness of nonlocked (but not locked) constructs in distal femur fractures.
Hospital Inpatient Nutrition Service Errors and Patient Safety Interventions: A Scoping Review
Authors: Austria Davis , McConnell Chelsea , Pope Charlene
Published: March 2024

Objectives

Food service errors are prevalent in healthcare hospital inpatient settings. Like medication administration errors, these mistakes can result in disastrous consequences. This scoping review aimed to identify the evidence describing hospitals’ nutrition department service errors and subsequent patient safety interventions.

Methods

The review was conducted on four electronic databases, OVID MedlinePlus, PubMed, Scopus, and CINAHL, to search for articles reporting hospital food-related errors. All studies and reports on parenteral nutrition were excluded, and errors reported by departments other than nutrition services were excluded. A total of 245 studies published from 1984 to 2022 were identified. After removing duplicates, 98 abstracts were evaluated, with particular attention given to dietary errors, meal accuracy, and interventions.

Results

Twenty-nine articles were selected, and 14 (n = 14) were considered relevant to the review after a full-text review. More than half of the studies (n = 8) were conducted outside the United States. Eight studies (n = 8) were descriptive, retrospective, and observational; 3 were mixed-method studies (n = 3), 2 (n = 2) were quality improvement projects, and 1 was an implementation study (n = 1). Four (n = 4) studies were published before the year 2000.

Conclusions

Various types of nutrition service inaccuracies were identified. The severity, causes, and stages of food service provision where errors occur were also documented. These errors were used as the basis for interventions to improve patient safety, justify implementing computerized dietary services systems, or add resources to augment dietary department service offerings. This review also generated valuable recommendations to promote patient safety by mitigating food service errors.
Contributions of cerebral white matter hyperintensities, age, and pedal perception to postural sway in people with HIV
Authors: Sullivan Edith V. , Zahr Natalie M. , Zhao Qingyu , Pohl Kilian M. , Sassoon Stephanie A. , Pfefferbaum Adolf
Published: March 2024

Objective:

With aging, people with HIV (PWH) have diminishing postural stability that increases liability for falls. Factors and neuromechanisms contributing to instability are incompletely known. Brain white matter abnormalities seen as hyperintense (WMH) signals have been considered to underlie instability in normal aging and PWH. We questioned whether sway-WMH relations endured after accounting for potentially relevant demographic, physiological, and HIV-related variables.

Design:

Mixed cross-sectional/longitudinal data were acquired over 15 years in 141 PWH and 102 age-range matched controls, 25–80 years old.

Methods:

Multimodal structural MRI data were quantified for seven total and regional WMH volumes. Static posturography acquired with a force platform measured sway path length separately with eyes closed and eyes open. Statistical analyses used multiple regression with mixed modeling to test contributions from non-MRI and nonpath data on sway path-WMH relations.

Results:

In simple correlations, longer sway paths were associated with larger WMH volumes in PWH and controls. When demographic, physiological, and HIV-related variables were entered into multiple regressions, the sway-WMH relations under both vision conditions in the controls were attenuated when accounting for age and two-point pedal discrimination. Although the sway-WMH relations in PWH were influenced by age, 2-point pedal discrimination, and years with HIV infection, the sway-WMH relations endured for five of the seven regions in the eyes-open condition.

Conclusion:

The constellation of age-related increasing instability while standing, degradation of brain white matter integrity, and peripheral pedal neuropathy is indicative of advancing fraility and liability for falls as people age with HIV infection.
CDC-Funded HIV Testing and Undiagnosed HIV Infection in Ending the HIV Epidemic in the U.S. Jurisdictions
Authors: Patel Deesha , Williams Weston O. , Wright Carolyn , Essuon Aba , Wang Guoshen , Mulatu Mesfin S.
Published: March 2024

Background:

Approximately 13% of persons with HIV (PWH) are unaware of their status. To help end HIV, it is important to understand the relationship between the rates of HIV testing and undiagnosed HIV infection.

Setting:

Ending the HIV in the U.S. (EHE) jurisdictions

Methods:

Using 2021 data from the National HIV Surveillance System and the National HIV Prevention Program Monitoring and Evaluation system, we calculated estimated rates of undiagnosed HIV infections per 100,000 population and rates of CDC-funded HIV tests per 1,000 population. We assessed the association between the two rates using Spearman’s rank correlation. We also calculated a rank difference between the two rates for each EHE jurisdiction to help identify jurisdictions with greater unfilled needs for HIV testing.

Results:

Overall, CDC-funded HIV tests per 1,000 population were positively associated with estimated rate of undiagnosed HIV infection per 100,000 population (rho=0.55, p<0.001). EHE jurisdictions with the greatest magnitude of negative rank differences (i.e., higher undiagnosed HIV infection per 100,000 population and lower CDC-funded HIV tests per 1,000 population) were Prince George’s County, MD; Mecklenburg County, NC; Hudson County, NJ; Bronx County, NY, and Hamilton County, OH.

Conclusions:

In general, CDC-funded HIV testing is being conducted in jurisdictions with the greatest needs. However, we also found large discrepancies between CDC-funded HIV testing and undiagnosed HIV infection rates for some jurisdictions. These jurisdictions may want to identify barriers to their HIV testing services and expand their programs to ensure that all PWH in their jurisdictions are diagnosed.
Unusual Metastasis of Signet-Ring Cell Gastric Cancer That Could Not Be Detected With 18F-FDG PET But With 68Ga-FAPI PET/CT
Authors: Kiran Murat Yilmaz , Ercan Leman Damla , Karatay Ecem , Has Simsek Duygu , Sanli Yasemin
Published: March 2024

A 70-year-old man who was scheduled for surgery because of the recurrence of gastric cancer was referred to our clinic preoperatively. The patient underwent a comprehensive evaluation through 18F-FDG and 68Ga-FAPI (68Ga-labeled FAP inhibitors) PET/CT scans. The 68Ga-FAPI PET/CT scan was particularly valuable in this case because of its ability to detect recurrent mass lesions and identify unusual metastatic sites compared with the 18F-FDG PET/CT scan.
Complete Resolution of Locally Advanced Prostate Cancer After Molecular Endoradiotherapy With 177Lu-PSMA
Authors: Beheshti Mohsen , Vali Reza , Zarehparvar Moghadam Soroush , Amini HamidReza , Hakiminejad Masoumeh , Divband GhasemAli
Published: March 2024

A 76-year-old man with castration-resistant prostate cancer underwent 68Ga–prostate-specific membrane antigen (PSMA) PET/CT for restaging. A large PSMA-avid tumor with invasion to adjacent organs was noted causing gross hematuria and symptomatic anemia. Two cycles of 177Lu-PSMA were administered, and the patient showed significant reduction of hematuria as well as declining in PSA levels. 177Lu-PSMA therapy can be a good treatment option in patients with locally invasive tumors.
Incidental Detection of Synchronous Benign Hepatic and Splenic Hemangiomas on 18F-PSMA PET/CT
Authors: Alsaleh Mohammed Hussain , Alkhars Ali Saleh , Albensaad Mohammed , Alsharif Abedallatif
Published: March 2024

A 51-year-old man with biochemical failure after brachytherapy for prostatic adenocarcinoma (PSA 5 μg/L rising to 6.45 μg/L) underwent a PSMA PET/CT scan. The scan revealed focal 18F-PSMA activity at the right apex suggestive of local residual or recurrent disease. In addition, 18F-PSMA images demonstrated 2 focal 18F-PSMA–avid liver and spleen lesions; both lesions were further evaluated by abdominal MRI, and the final radiological diagnosis was synchronous hepatic and splenic hemangiomas.
Intense PSMA Uptake in Solitary Fibrous Tumor of the Seminal Vesicle
Authors: Zhao Qian , Dong Aisheng , Ye Huamao , Zuo Changjing
Published: March 2024

Solitary fibrous tumor arising from the seminal vesicle is very rare. We describe 18F-PSMA-1007 PET/CT findings in a case of prostate adenocarcinoma with a solitary fibrous tumor of the left seminal vesicle. The solitary fibrous tumor showed intense 18F-PSMA-1007 uptake mimicking metastatic prostate adenocarcinoma. This case indicates that solitary fibrous tumor may cause false-positive result when using PSMA PET in staging of prostate cancer.
68Ga-DOTA-IBA Uptake in Breast cancer
Authors: Xiang Feifan , Liu Huipan , Tan Xiaoqi , Chen Yue
Published: March 2024

A 77-year-old woman with recently diagnosed breast cancer underwent 68Ga-labeled DOTA-ibandronic acid (68Ga-DOTA-IBA) PET/CT scan for the evaluation of bone metastases. The examination revealed increased tracer uptake, indicating that the cervical vertebrae presented osteoblastic metastasis. Interestingly, the breast cancer also showed enhanced activity of 68Ga-DOTA-IBA.
The Association Between Physical Activity and Cognition in a Racially/Ethnically Diverse Cohort of Older Adults
Authors: Almeida Mariana L. , Pederson Anna M. , Zimmerman Scott C. , Chen Ruijia , Ackley Sarah , Riley Alicia , Eng Chloe W. , Whitmer Rachel A. , George Kristen M. , Peterson Rachel L. , Mayeda Elizabeth Rose , Gilsanz Paola , Mungas Dan M. , Farias Sarah Tomaszewski , Glymour M. Maria
Published: March 2024

Objective:

Most prior research on physical activity (PA) and cognition is based on predominantly white cohorts and focused on associations of PA with mean (average) cognition versus the distribution of cognition. Quantile regression offers a novel way to quantify how PA affects cognition across the entire distribution.

Methods:

The Kaiser Healthy Aging and Diverse Life Experiences study includes 30% white, 19% black, 25% Asian, and 26% Latinx adults age 65+ living in Northern California (n = 1600). The frequency of light or heavy PA was summarized as 2 continuous variables. Outcomes were z-scored executive function, semantic memory, and verbal episodic memory. We tested associations of PA with mean cognition using linear regression and used quantile regression to estimate the association of PA with the 10th-90th percentiles of cognitive scores.

Results:

Higher levels of PA were associated with higher mean semantic memory (b = 0.10; 95% CI: 0.06, 0.14) and executive function (b = 0.05; 95% CI: 0.01, 0.09). Associations of PA across all 3 cognitive domains were stronger at low quantiles of cognition.

Conclusion:

PA is associated with cognition in this racially/ethnically diverse sample and may have larger benefits for individuals with low cognitive scores, who are most vulnerable to dementia.
The tolerance of a keystone ecosystem engineer to extreme heat stress is hampered by microplastic leachates
Authors: Uguen Marine , Gaudron Sylvie M. , Nicastro Katy R. , Zardi Gerardo I. , Spilmont Nicolas , Henry Solène , Seuront Laurent
Published: March 2024

Plastic pollution and ongoing climatic changes exert considerable pressure on coastal ecosystems. Unravelling the combined effects of these two threats is essential to management and conservation actions to reduce the overall environmental risks. We assessed the capacity of a coastal ecosystem engineer, the blue musselMytilus edulis, to cope with various levels of aerial heat stress (20, 25, 30 and 35°C) after an exposure to substances leached from beached and virgin low-density polyethylene pellets. Our results revealed a significant interaction between temperature and plastic leachates on mussel survival rates. Specifically, microplastic leachates had no effect on mussel survival at 20, 25 and 30°C. In turn, mussel survival rates significantly decreased at 35°C, and this decrease was even more significant following an exposure to leachates from beached pellets; these pellets had a higher concentration of additives compared to the virgin ones, potentially causing a bioenergetic imbalance. Our results stress the importance of adopting integrated approaches combining the effects of multiple environmental threats on key marine species to understand and mitigate their potential synergistic effects on ecosystem dynamics and resilience in the face of the changing environment.
Post-Cambrian survival of the tubicolous scalidophoran
Selkirkia
Authors: Nanglu Karma , Ortega-Hernández Javier
Published: March 2024

Scalidophoran worms represent common infaunal components of early and middle Cambrian Burgess Shale-type fossil biotas. Early scalidophorans resemble extant priapulids based on overall morphology, but the genus
Selkirkia
represents the earliest record of tube dwelling for the group. Despite its ubiquitous presence in exceptional marine deposits, whether the exclusively Cambrian occurrence of
Selkirkia
reflects its entire evolutionary history or is affected by taphonomic biases remains unresolved. Here, we demonstrate the post-Cambrian survival of
Selkirkia
based on new material from the Lower Ordovician Fezouata Shale biota of Morocco. The discovery of
Selkirkia
in the Fezouata Shale extends the biostratigraphic range of the genus by 25 million years and its palaeobiogeographic occurrence to the high latitudes of Gondwana, strengthens the evolutionary links between Cambrian and Ordovician Burgess Shale-type biotas and increases scalidophoran diversity for the Fezouata Shale biota otherwise consisting exclusively of the palaeoscolecid
Palaeoscolex? tenensis
. The tube of
Selkirkia
underwent negligible external change for over 40 million years, indicating a high degree of morphological stasis during the Early Palaeozoic. A tubicolous mode of life is rare among extant priapulids and expressed only in
Maccabeus
, which forms a delicate tube from agglutinated plant debris, unlike the macroscopic secreted cuticular tube of
Selkirkia
.
Functionally mediated cranial allometry evidenced in a genus of rock-wallabies
Authors: Mitchell D. Rex , Potter Sally , Eldridge Mark D. B. , Martin Meg , Weisbecker Vera
Published: March 2024

In assessments of skeletal variation, allometry (disproportionate change of shape with size) is often corrected to examine size-independent variation for hypotheses relating to function. However, size-related trade-offs in functional demands may themselves be an underestimated driver of mammalian cranial diversity. Here, we use geometric morphometrics alongside dental measurements to assess craniodental allometry in the rock-wallaby genus
Petrogale
(all 17 species, 370 individuals). We identified functional aspects of evolutionary allometry that can be both extensions of, and correlated negatively with, static or ontogenetic allometric patterns. Regarding constraints, larger species tended to have relatively smaller braincases and more posterior orbits, the former of which might represent a constraint on jaw muscle anatomy. However, they also tended to have more anterior dentition and smaller posterior zygomatic arches, both of which support the hypothesis of relaxed bite force demands and accommodation of different selective pressures that favour facial elongation. By contrast, two dwarf species had stouter crania with divergent dental adaptations that together suggest increased relative bite force capacity. This likely allows them to feed on forage that is mechanically similar to that consumed by larger relatives. Our results highlight a need for nuanced considerations of allometric patterns in future research of mammalian cranial diversity.
Analysis of collision avoidance in honeybee flight
Authors: Singh Shreyansh , Garratt Matthew , Srinivasan Mandyam , Ravi Sridhar
Published: March 2024

Insects are excellent at flying in dense vegetation and navigating through other complex spatial environments. This study investigates the strategies used by honeybees (
Apis mellifera
) to avoid collisions with an obstacle encountered frontally during flight. Bees were trained to fly through a tunnel that contained a solitary vertically oriented cylindrical obstacle placed along the midline. Flight trajectories of bees were recorded for six conditions in which the diameter of the obstructing cylinder was systematically varied from 25 mm to 160 mm. Analysis of salient events during the bees' flight, such as the deceleration before the obstacle, and the initiation of the deviation in flight path to avoid collisions, revealed a strategy for obstacle avoidance that is based on the relative retinal expansion velocity generated by the obstacle when the bee is on a collision course. We find that a quantitative model, featuring a controller that extracts specific visual cues from the frontal visual field, provides an accurate characterization of the geometry and the dynamics of the manoeuvres adopted by honeybees to avoid collisions. This study paves the way for the design of unmanned aerial systems, by identifying the visual cues that are used by honeybees for performing robust obstacle avoidance flight.
Robot motor learning shows emergence of frequency-modulated, robust swimming with an invariant Strouhal number
Authors: Deng Hankun , Li Donghao , Nitroy Colin , Wertz Andrew , Priya Shashank , Cheng Bo
Published: March 2024

Fish locomotion emerges from diverse interactions among deformable structures, surrounding fluids and neuromuscular activations, i.e. fluid–structure interactions (FSI) controlled by fish's motor systems. Previous studies suggested that such motor-controlled FSI may possess embodied traits. However, their implications in motor learning, neuromuscular control, gait generation, and swimming performance remain to be uncovered. Using robot models, we studied the embodied traits in fish-inspired swimming. We developed modular robots with various designs and used central pattern generators (CPGs) to control the torque acting on robot body. We used reinforcement learning to learn CPG parameters for maximizing the swimming speed. The results showed that motor frequency converged faster than other parameters, and the emergent swimming gaits were robust against disruptions applied to motor control. For all robots and frequencies tested, swimming speed was proportional to the mean undulation velocity of body and caudal-fin combined, yielding an invariant, undulation-based Strouhal number. The Strouhal number also revealed two fundamental classes of undulatory swimming in both biological and robotic fishes. The robot actuators were also demonstrated to function as motors, virtual springs and virtual masses. These results provide novel insights in understanding fish-inspired locomotion.
The subapical labial sensory organ of spotted lanternfly
Lycorma delicatula
Authors: Dweck Hany K. M. , Rutledge Claire E.
Published: March 2024

Deciphering how spotted lanternfly (SLF), an invasive polyphagous planthopper in North America, engages with its environment is a pressing issue with fundamental biological significance and economic importance. This interaction primarily depends on olfaction. However, the cellular basis of olfaction in SLF remains elusive. Here we investigate the neuronal and functional organization of the subapical labial sensory organ using scanning electron microscopy and electrophysiological recordings. This organ is believed to supply planthoppers with crucial sensory information that influences their subsequent feeding behaviour. We find in SLF that this organ comprises two identical placoid sensilla, each housing two distinct neurons. The A neuron displays a remarkable sensitivity to changes in airflow speed. Importantly, the same neuron also exhibits robust excitatory responses exclusively to three aldehydes out of a diverse pool of 85 tested odorants and inhibitory responses to 62 other odorants. By contrast, the B neuron solely serves as an olfactory detector, showing strong excitatory responses to 17 odorants and inhibitory responses to only three. The results provide a potential cellular basis for the behavioural responses of SLF to its ecologically relevant stimuli. Our study also identifies new odorants that may be useful for managing this serious pest.
Personality heterophily and friendship as drivers for successful cooperation
Authors: Bhattacharjee Debottam , Waasdorp Sophie , Middelburg Esmee , Sterck Elisabeth H.M. , Massen Jorg J. M.
Published: March 2024

Cooperation is widespread and arguably a pivotal evolutionary force in maintaining animal societies. Yet, proximately, what underlying motivators drive individuals to cooperate remains relatively unclear. Since ‘free-riders’ can exploit the benefits by cheating, selecting the right partner is paramount. Such decision rules need not be based on complex calculations and can be driven by cognitively less-demanding mechanisms, like social relationships (e.g. kinship, non-kin friendships, dyadic tolerance), social status (e.g. dominance hierarchies) and personalities (social and non-social traits); however, holistic evidence related to those mechanisms is scarce. Using the classical ‘loose-string paradigm’, we tested cooperative tendencies of a hierarchical primate, the long-tailed macaque (
Macaca fascicularis
). We studied three groups (
n
= 21) in their social settings, allowing partner choice. We supplemented cooperation with observational and experimental data on social relationships, dominance hierarchies and personality. Friendship and dissimilarities in non-social ‘exploration’ and ‘activity–sociability’ personality traits predicted the likelihood of cooperative dyad formation. Furthermore, the magnitude of cooperative success was positively associated with friendship, low rank-distance and dissimilarity in the activity–sociability trait. Kinship did not affect cooperation. While some findings align with prior studies, the evidence of (non-social) personality heterophily promoting cooperation may deepen our understanding of the proximate mechanisms and, broadly, the evolution of cooperation.
Pichia kurtzmaniana f.a. sp. nov., with the transfer of eight Candida species to Pichia
Authors: Zhu Hai-Yan , Guo Liang-Chen , Hu Shuang , Wei Yu-Hua , Hui Feng-Li , Liu Xin-Zhan , Bai Feng-Yan
Published: March 2024

Three yeast strains belonging to the ascomycetous yeast genus Pichia were isolated from two soil samples from Yunnan and Guizhou provinces and a marine water sample from Liaoning province, PR China. Phylogenetic analyses based on the sequences of the D1/D2 domains of the large subunit(LSU) rRNA gene and the internal transcribed spacer (ITS) region indicate that these three strains, together with 12 additional strains isolated from various substrates collected in different regions or countries of the world, represent a novel species of the genus Pichia, for which the name Pichia kurtzmaniana sp. nov. (holotype: strain CGMCC 2.7213) is proposed. The novel species differs from its close relatives Candida californica by eight (1.5 %) and 26 (11.1 %) mismatches in the D1/D2 domains and the ITS region, respectively; and from Pichia chibodasensis by 11 (2.1 %) and 20 (8.7 %) mismatches in the D1/D2 domains and the ITS region, respectively. In addition, eight Candida species which belong to the Pichia clade are transferred to the genus Pichia, resulting in the proposal of the following new combinations: Pichia cabralensis comb. nov., Pichia californica comb. nov., Pichia ethanolica comb. nov., Pichia inconspicua comb. nov., Pichia phayaonensis comb. nov., Pichia pseudolambica comb. nov., Pichia rugopelliculosa comb. nov., and Pichia thaimueangensis comb. nov.
Marker selection strategies for circulating tumor DNA guided by phylogenetic inference
Authors: Fu Xuecong , Luo Zhicheng , Deng Yueqian , LaFramboise William , Bartlett David , Schwartz Russell
Published: March 2024

Motivation

Blood-based profiling of tumor DNA (“liquid biopsy”) has offered great prospects for non-invasive early cancer diagnosis, treatment monitoring, and clinical guidance, but require further advances in computational methods to become a robust quantitative assay of tumor clonal evolution. We propose new methods to better characterize tumor clonal dynamics from circulating tumor DNA (ctDNA), through application to two specific questions: 1) How to apply longitudinal ctDNA data to refine phylogeny models of clonal evolution, and 2) how to quantify changes in clonal frequencies that may be indicative of treatment response or tumor progression. We pose these questions through a probabilistic framework for optimally identifying maximum likelihood markers and applying them to characterizing clonal evolution.

Results

We first estimate a distribution over plausible clonal lineage models, using bootstrap samples over pre-treatment tissue-based sequence data. We then refine these lineage models and the clonal frequencies they imply over successive longitudinal samples. We use the resulting framework for modeling and refining tree distributions to pose a set of optimization problems to select ctDNA markers to maximize measures of utility capturing ability to solve the two questions of reducing uncertain in phylogeny models or quantifying clonal frequencies given the models. We tested our methods on synthetic data and showed them to be effective at refining distributions of tree models and clonal frequencies so as to minimize measures of tree distance relative to the ground truth. Application of the tree refinement methods to real tumor data further demonstrated their effectiveness in refining a clonal lineage model and assessing its clonal frequencies. The work shows the power of computational methods to improve marker selection, clonal lineage reconstruction, and clonal dynamics profiling for more precise and quantitative assays of tumor progression.

Availability

https://github.com/CMUSchwartzLab/Mase-phi.git.

Contact

russells@andrew.cmu.edu
BLOC1S1 control of vacuolar organelle fidelity modulates TH2 cell immunity and allergy susceptibility
Authors: Sharma Rahul , Wu Kaiyuan , Han Kim , Russo Anna Chiara , Dagur Pradeep K. , Combs Christian A. , Sack Michael N.
Published: March 2024

The levels of biogenesis of lysosome organelles complex 1 subunit 1 (BLOC1S1) control mitochondrial and endolysosome organelle homeostasis and function. Reduced fidelity of these vacuolar organelles is increasingly being recognized as important in instigating cell-autonomous immune cell activation. We reasoned that exploring the role of BLOC1S1 in CD4+T cells, may further advance our understanding of regulatory events linked to mitochondrial and/or endolysosomal function in adaptive immunity. Transcript levels of the canonical transcription factors driving CD4+T cell polarization in response to activation showed that, the TH2 regulator GATA3 and phosphorylated STAT6 were preferentially induced in BLOC1S1 depleted primary CD4+T (TKO) cells. In parallel, in response to both T cell receptor activation and in response to TH2 polarization the levels of IL-4, IL-5 and IL-13 were markedly induced in the absence of BLOC1S1. At the organelle level, mitochondrial DNA leakage evoked cGAS-STING and NF-kB pathway activation with subsequent TH2 polarization. The induction of autophagy with rapamycin reduced cytosolic mtDNA and reverses these TH2 signatures. Furthermore, genetic knockdown of STING and STING and NF-κB inhibition ameliorated this immune regulatory cascade in TKO cells. Finally, at a functional level, TKO mice displayed increased susceptible to allergic conditions including atopic dermatitis and allergic asthma. In conclusion, BLOC1S1 depletion mediated disruption of mitochondrial integrity to initiate a predominant TH2 responsive phenotype via STING-NF-κB driven signaling of the canonical TH2 regulatory program.
Estimating Organ-to-Plasma Ratios in physiologically based PK modeling: a simplified approach for early drug discovery
Authors: Broccatelli Fabio , Ramakrishnan Radha
Published: March 2024

Physiologically based pharmacokinetics (PBPK) modeling is a valuable tool in drug development and candidate selection. However, its widespread adoption in early stages of drug discovery remains limited. This study proposes a novel simplified approach to estimate organ-to-plasma ratio (Kp) values based on measured or estimated volume of distribution (VDss) to eliminate the reliance on additional in vitro data such as blood to plasma partition, LogP and pKa, which may not be available for newly synthesized molecules. The study includes 11 simulations across 4 compounds and 5 species. When simulations were based on ideal VDssand clearance (CL) values determined through non-compartmental analysis (NCA), the observed average absolute fold error (AAFE) aligned with experimental variability in the in vivo experiments (AAFE=1.3). However, when in vitro to in vivo correlation approaches were used to predict VDssand CL starting from in vitro intrinsic CL, plasma protein binding and microsomal binding, the AAFE increased to 1.7, reflecting the additional error introduced by the use of in vitro data to determine PK properties. Overall, this work provides a starting point for the facile implementation of PBPK models to meet the needs of early drug discovery projects.
Distinct and Asymmetric Neuronal Responses to Pitch- and Roll-Axis Vestibular Stimulation in larval zebrafish
Authors: Migault Geoffrey , Beiza-Canelo Natalia , Chatterjee Sharbatanu , Debrégeas Georges , Bormuth Volker
Published: March 2024

The vestibular apparatus plays a pivotal role in maintaining postural equilibrium and processing movement signals, underscoring its importance in the study of certain neurological disorders. Here, we present a rotating light-sheet microscope, enabling brain-wide functional recordings during dynamic vestibular stimulation along both the roll and pitch axes in head-restrained zebrafish larvae. The system incorporates a double galvanometer mirror configuration, is amenable to 3D printing, and enhances scanning efficiency. Employing this apparatus, we have successfully conducted the first comprehensive mapping of zebrafish brain responses to dynamic pitch-tilt vestibular stimulation. Through Fourier and regression analyses, we report an asymmetry in neuronal recruitment during nose-up versus nose-down pitch tilts within critical regions including the cerebellum, oculomotor nucleus, caudal hindbrain, and vestibular nucleus, highlighting physiological adaptations to downward motion. We identified specific brain regions, notably the cerebellum and medial-rostral rhombencephalon, that exclusively respond to rollbut not pitch-tilt vestibular stimuli. Furthermore, we have identified a transgenic line that closely correlates with our functional mappings and demonstrates a significant response to vestibular stimulation. The elucidation of brain-wide neuronal circuits involved in vestibular processing establishes a foundational framework for subsequent detailed investigations into the molecular and genetic mechanisms underlying postural control and motion perception.
Multidimensional analysis of cortical interneuron synaptic features reveals underlying synaptic heterogeneity
Authors: Dummer Patrick D. , Lee Dylan I. , Hossain Sakib , Wang Runsheng , Evard Andre , Newman Gabriel , Ho Claire , Schneider-Mizell Casey M. , Menon Vilas , Au Edmund
Published: March 2024

Cortical interneurons represent a diverse set of neuronal subtypes characterized in part by their striking degree of synaptic specificity. However, little is known about the extent of synaptic diversity because of the lack of unbiased methods to extract synaptic features among interneuron subtypes. Here, we develop an approach to aggregate image features from fluorescent confocal images of interneuron synapses and their post-synaptic targets, in order to characterize the heterogeneity of synapses at fine scale. We started by training a model that recognizes pre- and post-synaptic compartments and then determines the target of each genetically-identified interneuron synapse in vitro and in vivo. Our model extracts hundreds of spatial and intensity features from each analyzed synapse, constructing a multidimensional data set, consisting of millions of synapses, which allowed us to perform an unsupervised analysis on this dataset, uncovering novel synaptic subgroups. The subgroups were spatially distributed in a highly structured manner that revealed the local underlying topology of the postsynaptic environment. Dendrite-targeting subgroups were clustered onto subdomains of the dendrite along the proximal to distal axis. Soma-targeting subgroups were enriched onto different postsynaptic cell types. We also find that the two main subclasses of interneurons, basket cells and somatostatin interneurons, utilize distinct strategies to enact inhibitory coverage. Thus, our analysis of multidimensional synaptic features establishes a conceptual framework for studying interneuron synaptic diversity.