bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk of Obstructive Sleep Apnea, Chronic Dizziness, and Sleep Duration
Authors: Kim Eunjin , Lee Minjae , Park Inkyung
Published: March 2024

Background

Although it is recommended that obstructive sleep apnea (OSA) be screened for using a validated self-report questionnaire in patients experiencing dizziness, there is still a lack of research on the relationship between high risk of OSA and chronic dizziness.

Objectives

The study aimed to examine the relationship between the high risk of OSA and chronic dizziness and investigate how this relationship is affected by sleep duration.

Methods

This cross-sectional study used data from the 8th Korea National Health and Nutrition Examination Survey (2019–2021). Adults aged 40 years or older were included and divided into two groups using the STOP–Bang questionnaire (SBQ): a high-risk group for OSA or not. Complex samples logistic regression analyses were performed to examine the odds ratios of chronic dizziness based on the national population estimates.

Results

Our findings showed that individuals in the high-risk group for OSA were significantly more likely to experience chronic dizziness. Specifically, among subgroups based on sleep duration, the high-risk group for OSA with a short sleep duration of ≤5 hr demonstrated the highest odds of chronic dizziness, showing a significantly 2.48-fold increased likelihood compared to the non-high-risk for OSA with a sleep duration of 5–9 hr.

Discussion

The SBQ can be beneficial when other causes do not explain chronic dizziness, helping to rule in the possibility of OSA. Educating individuals suspected of having OSA or who have been diagnosed with OSA about the importance of adequate sleep duration may help reduce the risk of chronic dizziness.
Brain Autopsy Findings in a Patient Who Received Lipid Emulsion Therapy for Suspected Drug Intoxication
Authors: Cutshall Hannah , Gokden Murat
Published: March 2024

Lipid emulsion therapy (LET) is the intravenous administration of lipid solution for parenteral alimentation, especially in preterm infants and adults with debilitating illnesses. It has also been used in attempts of detoxification in suspected cases of drug overdose. Whether this interferes with circulation and/or perfusion is debatable, and it is suggested that it may interfere with coagulation process. The emulsifying agent has been identified microscopically mainly in the lungs of these patients, with rare reports in adults and even more rare ones in the brain; however, although it is rarely reported in other organs, to our knowledge, no reports of gross autopsy findings in the brain are available in the English literature, nor are there reports of pathologic findings after lipid emulsion therapy administration for drug toxicity. Although it is also debated in the literature whether this material forms as an artifact or represents the actual agent, here we report the gross and microscopic autopsy findings in the brain of a patient who received LET for suspected beta-blocker intoxication. It will be beneficial for pathologists who perform autopsies in the forensic or medical settings to be aware of these findings, along with the uses and potential complications of LET.
Characterization of a Molecularly Distinct Subset of Oncocytic Pleomorphic Adenomas/Myoepitheliomas Harboring Recurrent ZBTB47-AS1::PLAG1 Gene Fusion
Authors: Alsugair Ziyad , Perrot Jimmy , Descotes Françoise , Lopez Jonathan , Champagnac Anne , Pissaloux Daniel , Castain Claire , Onea Mihaela , Céruse Philippe , Philouze Pierre , Lépine Charles , Lanic Marie-Delphine , Laé Marick , Costes-Martineau Valérie , Benzerdjeb Nazim ,   and REFCOR Members
Published: March 2024

Recurrent gene fusions are common in salivary gland tumors including benign tumors, such as pleomorphic adenoma (PA) and myoepithelioma (ME). In cases where chromosomal rearrangement is identified in the pleomorphic adenoma gene 1 (
PLAG1) gene, different gene partners are found. Oncocytic metaplasia, characterized by oncocytes with abundant eosinophilic granular cytoplasm and hyperchromatic nuclei, is a well-known phenomenon in salivary gland neoplasms. However, the pure oncocytic variant of PA/ME showed PLAG1 gene rearrangements involving various gene partners at the molecular level, without any recurrent fusion being found. Our study includes 20 cases of PA/ME, with 11 females and 9 males. The age of patients ranged from 37 to 96 years, with a median age of 62.8 years. Most tumors originate from the parotid gland. The median size of the tumor was 26.5 mm (range: 13 to 60 mm). Among the 20 cases, 14 were a pure oncocytic variant of PA/ME, whereas 6 cases showed focal oncocytic or oncocytic-like aspects. Molecular studies on 20 cases of PA/ME were conducted. A novel recurrent ZBTB47-AS1::PLAG1 fusion was identified in 6 of 12 cases with pure oncocytic metaplasia, whereas the other cases had PLAG1 gene fusion with different gene partners. The transcriptomic analysis of the cases harboring ZBTB47-AS1::PLAG1 fusion demonstrated that these tumors have a distinct molecular profile from conventional PA/ME. This study reveals a unique subset in the oncocytic PA/ME spectrum characterized by pure oncocytic morphology with larger oncocytic cells and recurrent ZBTB47-AS1::PLAG1 fusion. It also highlights the transcriptomic distinctness of salivary gland adenomas with pure oncocytic metaplasia in the spectrum of salivary gland neoplasms. Further studies are needed to better understand the oncocytic variant of PA/ME and to determine the true nature of oncocytic cells in PA/ME.
Molecular Point-of-Care Testing in the Emergency Department for Group A Streptococcus Pharyngitis
Authors: Gill Carson , Chui Clement , Goldfarb David M. , Meckler Garth , Doan Quynh
Published: March 2024

Objectives

To compare clinical and health systems outcomes of rapid molecular testing versus throat culture recovery for the management of group A Streptococcus (GAS) pharyngitis in a pediatric emergency department (PED).

Methods

We conducted a single-center randomized trial of children (3–17 years) presenting to a PED with suspected GAS pharyngitis. A single dual-headed throat swab was collected, and participants were randomized to 1 of 2 parallel treatment groups with 1:1 allocation: point-of-care (POC) nucleic acid amplification testing or standard throat culture. The primary outcomes were time to throat pain +/− fever resolution. Secondary outcomes included absenteeism, length of stay, return visits to care, and antibiotic prescriptions and utilization.

Results

A total of 227 children were randomly assigned to culture (n = 115) or POC (n = 112) testing. Antibiotics were initiated earlier in the POC group by approximately 1 day (95% confidence interval, −0.40 to −1.58). No associated difference in time to throat pain or fever resolution was observed between groups. There was a decrease in the proportion of prescribed antibiotics in the POC group (0.35) compared with the culture group (0.79; P < 0.001). Otherwise, no significant differences in secondary outcomes were observed.

Conclusions

Establishing a POC nucleic acid amplification testing program for GAS in a PED facilitates earlier treatment and fewer antibiotic prescriptions. Although this did not translate to improved clinical and health systems outcomes in our study, it may serve as an important tool amid evolving pediatric febrile illnesses and growing antimicrobial resistance patterns.
Emergency Decompression of Orbital Emphysema, a Sight-Saving Tool in a Patient With Precious Eye
Authors: Abdelazeem Mohamed Hazem , Barhoma Mohamed Gamal , Samir Hussein Ahmed
Published: March 2024

A woman, 19 years old, with a history of falling from a height with resulting zygomatico-maxillar complex fracture on the right side, a mandibular fracture on the left side for which she underwent repair with plate insertion, and traumatic optic atrophy in her right eye, presented 9 months later with eye facial swelling, proptosis, and acute rapid loss of vision in the left eye. The diagnosis was done immediately aided by radiology assistance and a decision was taken to admit the patient to undergo urgent decompression to save the vision and the patient did recover well. This case presented here and the associated literature review focus on severe orbital emphysema with compressive optic neuropathy and orbital compartment syndrome as a morbidity that can exist with delayed presentation after trauma and not elicited by sneezing or forced blowing, as well as the drastic importance of brisk intervention, to save vision and prevent visual complications if left untreated.
A pilot project of a Post Discharge Care Team for firearm injury survivors decreases emergency department utilization, hospital readmission days, and cost
Authors: Biesboer Elise A. , Brandolino Amber , Servi Ashley , Laszkiewicz Rebecca , Herbst Liza , Cronn Susan , Cadman Jennifer , Trevino Colleen , deRoon-Cassini Terri , Schroeder Mary E.
Published: March 2024

BACKGROUND

Persons of low socioeconomic status are overrepresented in the firearm injury patient population and may experience challenges in accessing complex outpatient health systems. Consequently, outpatient care for these patients is plagued by poor follow-up and increased emergency department (ED) utilization. We developed a Post Discharge Care Team (PDCT) consisting of a dedicated trauma nurse navigator and medical social worker to bridge the gap between hospital discharge and outpatient care to improve recovery.

METHODS

Adult firearm injury survivors admitted to the trauma service were randomized 1:1 to receive either PDCT services or standard of care (SOC) workflows. The PDCT nurse provided education and set expectations regarding injuries, wound care, and outpatient follow-up. The PDCT social worker performed a comprehensive assessment to identify concerns including housing and financial instability, food insecurity, or transportation issues. The primary outcome was ED utilization, with secondary outcomes including readmissions and overall health care costs compared between groups.

RESULTS

In the first 6 months of the study, a total of 44 patients were randomized to PDCT and 47 to SOC. There were 10 patients who visited the ED in the PDCT group compared with 16 in the SOC group (p = 0.23) for a total of 14 and 23 ED visits, respectively. There were 14 patients in the PDCT and 11 patients in the SOC groups who were readmitted (p = 0.31), but the PDCT group was readmitted for 27.9 fewer hospital days. After accounting for programmatic costs, the PDCT had a hospital savings of $34,542.71.

CONCLUSION

A collaborative, specialized PDCT for firearm injury survivors consisting of a dedicated trauma nurse navigator and medical social worker decreased outpatient ED utilization, readmission days, and was cost effective. Trauma centers with high volumes of penetrating trauma should consider a similar model to improve outpatient care for firearm injury survivors.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level III.
Prevalence and outcomes of high versus low ratio plasma to red blood cell resuscitation in a multi-institutional cohort of severely injured children
Authors: Mehl Steven C. , Vogel Adam M. , Glasgow Amy E. , Moody Suzanne , Kotagal Meera , Williams Regan F. , Kayton Mark L. , Alberto Emily C. , Burd Randall S. , Schroeppel Thomas J. , Baerg Joanne E. , Munoz Amanda , Rothstein William B. , Boomer Laura A. , Campion Eric M. , Robinson Caitlin , Nygaard Rachel M. , Richardson Chad J. , Garcia Denise I. , Streck Christian J. , Gaffley Michaela , Petty John K. , Greenwell Cynthia , Pandya Samir , Waters Alicia M. , Russell Robert T. , Yorkgitis Brian K. , Mull Jennifer , Pence Jeffrey , Santore Matthew T. , MacArthur Taleen A. , Klinkner Denise B. , Safford Shawn D. , Trevilian Tanya , Cunningham Megan , Black Christa , Rea Jessica , Spurrier Ryan G. , Jensen Aaron R. , Farr Bethany J. , Mooney David P. , Ketha Bavana , Dassinger Melvin S. , Goldenberg-Sandau Anna , Roman Janika San , Jenkins Todd M. , Falcone Richard A. , Polites Stephanie
Published: March 2024

BACKGROUND

The benefit of targeting high ratio fresh frozen plasma (FFP)/red blood cell (RBC) transfusion in pediatric trauma resuscitation is unclear as existing studies are limited to patients who retrospectively met criteria for massive transfusion. The purpose of this study is to evaluate the use of high ratio FFP/RBC transfusion and the association with outcomes in children presenting in shock.

METHODS

A post hoc analysis of a 24-institution prospective observational study (April 2018 to September 2019) of injured children younger than 18 years with elevated age-adjusted shock index was performed. Patients transfused within 24 hours were stratified into cohorts of low (<1:2) or high (≥1:2) ratio FFP/RBC. Nonparametric Kruskal-Wallis and χ2 were used to compare characteristics and mortality. Competing risks analysis was used to compare extended (≥75th percentile) ventilator, intensive care, and hospital days while accounting for early deaths.

RESULTS

Of 135 children with median (interquartile range) age 10 (5–14) years and weight 40 (20–64) kg, 85 (63%) received low ratio transfusion and 50 (37%) high ratio despite similar activation of institutional massive transfusion protocols (low–38%, high–46%, p = 0.34). Most patients sustained blunt injuries (70%). Median injury severity score was greater in high ratio patients (low–25, high–33, p = 0.01); however, hospital mortality was similar (low–24%, high–20%, p = 0.65) as was the risk of extended ventilator, intensive care unit, and hospital days (all p > 0.05).

CONCLUSION

Despite increased injury severity, patients who received a high ratio of FFP/RBC had comparable rates of mortality. These data suggest high ratio FFP/RBC resuscitation is not associated with worst outcomes in children who present in shock. Massive transfusion protocol activation was not associated with receipt of high ratio transfusion, suggesting variability in MTP between centers.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level III.
What Is Hot and New in Basic and Translational Science in Liver Transplantation in 2023? Report of the Basic and Translational Research Committee of the International Liver Transplantation Society
Authors: Bonaccorsi-Riani Eliano , Ghinolfi Davide , Czigany Zoltan , Dondossola Daniele , Emamaullee Juliet , Yuksel Muhammed , Boteon Yuri L. , Al-Adra David , Ho Cheng-Maw , Abdelrahim Maen , Pang Li , Barbas Andrew , Meier Raphael , MacParland Sonya , Sayed Blayne Amir , Pavan-Guimaraes Juliana , Brüggenwirth Isabel M.A. , Zarrinpar Ali , Mas Valeria R. , Selzner Markus , Martins Paulo N. , Bhat Mamatha
Published: March 2024

The 2023 Joint Annual Congress of the International Liver Transplantation Society, European Liver and Intestine Transplant Association, and Liver Intensive Care Group of Europe were held in Rotterdam, the Netherlands, from May 3 to 6, 2023. This year, all speakers were invited to attend the Congress in person for the first time since the COVID-19 pandemic. The congress was attended by 1159 registered delegates from 54 countries representing 5 continents, with the 10 countries comprising the bulk of the delegates. Of the 647 abstracts initially submitted, 542 were eventually presented at the meeting, coming from 38 countries (mainly North America, Europe, and Asia) and 85% of them (462 abstracts) came from only 10 countries. Fifty-three (9.8%) abstracts, originated from 17 countries, were submitted under the Basic/Translational Scientific Research category, a similar percentage as in 2022. Abstracts presented at the meeting were classified as (1) ischemia and reperfusion injury, (2) machine perfusion, (3) bioengineering and liver regeneration, (4) transplant oncology, (5) novel biomarkers in liver transplantation, (6) liver immunology (rejection and tolerance), and (7) artificial intelligence and machine learning. Finally, we evaluated the number of abstracts commented in the Basic and Translational Research Committee-International Liver Transplantation Society annual reports over the past 5 y that resulted in publications in peer-reviewed journals to measure their scientific impact in the field of liver transplantation.
Novel technologies uncover novel ‘anti’-microbial peptides in
Hydra
shaping the species-specific microbiome
Authors: Klimovich Alexander , Bosch Thomas C. G.
Published: March 2024

The freshwater polyp
Hydra
uses an elaborate innate immune machinery to maintain its specific microbiome. Major components of this toolkit are conserved Toll-like receptor (TLR)-mediated immune pathways and species-specific antimicrobial peptides (AMPs). Our study harnesses advanced technologies, such as high-throughput sequencing and machine learning, to uncover a high complexity of the
Hydra
's AMPs repertoire. Functional analysis reveals that these AMPs are specific against diverse members of the
Hydra
microbiome and expressed in a spatially controlled pattern. Notably, in the outer epithelial layer, AMPs are produced mainly in the neurons. The neuron-derived AMPs are secreted directly into the glycocalyx, the habitat for symbiotic bacteria, and display high selectivity and spatial restriction of expression. In the endodermal layer, in contrast, endodermal epithelial cells produce an abundance of different AMPs including members of the arminin and hydramacin families, while gland cells secrete kazal-type protease inhibitors. Since the endodermal layer lines the gastric cavity devoid of symbiotic bacteria, we assume that endodermally secreted AMPs protect the gastric cavity from intruding pathogens. In conclusion,
Hydra
employs a complex set of AMPs expressed in distinct tissue layers and cell types to combat pathogens and to maintain a stable spatially organized microbiome.

This article is part of the theme issue ‘Sculpting the microbiome: how host factors determine and respond to microbial colonization’.
A new lexicon in the age of microbiome research
Authors: Bosch Thomas C. G. , Blaser Martin J. , Ruby Edward , McFall-Ngai Margaret
Published: March 2024

At a rapid pace, biologists are learning the many ways in which resident microbes influence, and sometimes even control, their hosts to shape both health and disease. Understanding the biochemistry behind these interactions promises to reveal completely novel and targeted ways of counteracting disease processes. However, in our protocols and publications, we continue to describe these new results using a language that originated in a completely different context. This language developed when microbial interactions with hosts were perceived to be primarily pathogenic, as threats that had to be vanquished. Biomedicine had one dominating thought: winning this war against microorganisms. Today, we know that beyond their defensive roles, host tissues, especially epithelia, are vital to ensuring association with the normal microbiota, the communities of microbes that persistently live with the host. Thus, we need to adopt a language that better encompasses the newly appreciated importance of host-microbiota associations. We also need a language that frames the onset and progression of pathogenic conditions within the context of the normal microbiota. Such a reimagined lexicon should make it clear, from the very nature of its words, that microorganisms are primarily vital to our health, and only more rarely the cause of disease.

This article is part of the theme issue ‘Sculpting the microbiome: how host factors determine and respond to microbial colonization’.
How infection-triggered pathobionts influence virulence evolution
Authors: Franz Mathias , Regoes Roland R. , Rolff Jens
Published: March 2024

Host–pathogen interactions can be influenced by the host microbiota, as the microbiota can facilitate or prevent pathogen infections. In addition, members of the microbiota can become virulent. Such pathobionts can cause co-infections when a pathogen infection alters the host immune system and triggers dysbiosis. Here we performed a theoretical investigation of how pathobiont co-infections affect the evolution of pathogen virulence. We explored the possibility that the likelihood of pathobiont co-infection depends on the evolving virulence of the pathogen. We found that, in contrast to the expectation from classical theory, increased virulence is not always selected for. For an increasing likelihood of co-infection with increasing pathogen virulence, we found scenario-specific selection for either increased or decreased virulence. Evolutionary changes, however, in pathogen virulence do not always translate into similar changes in combined virulence of the pathogen and the pathobiont. Only in one of the scenarios where pathobiont co-infection is triggered above a specific virulence level we found a reduction in combined virulence. This was not the case when the probability of pathobiont co-infection linearly increased with pathogen virulence. Taken together, our study draws attention to the possibility that host–microbiota interactions can be both the driver and the target of pathogen evolution.

This article is part of the theme issue ‘Sculpting the microbiome: how host factors determine and respond to microbial colonization’.
Evolutionary immunology to explore original antiviral strategies
Authors: Imler Jean-Luc , Cai Hua , Meignin Carine , Martins Nelson
Published: March 2024

Over the past 25 years, the field of evolutionary developmental biology (evo–devo) has used genomics and genetics to gain insight on the developmental mechanisms underlying the evolution of morphological diversity of animals. Evo–devo exploits the key insight that conserved toolkits of development (e.g.Hoxgenes) are used in animals to produce genetic novelties that provide adaptation to a new environment. Like development, immunity is forged by interactions with the environment, namely the microbial world. Yet, when it comes to the study of immune defence mechanisms in invertebrates, interest primarily focuses on evolutionarily conserved molecules also present in humans. Here, focusing on antiviral immunity, we argue that immune genes not conserved in humans represent an unexplored resource for the discovery of new antiviral strategies. We review recent findings on the cGAS-STING pathway and explain how cyclic dinucleotides produced by cGAS-like receptors may be used to investigate the portfolio of antiviral genes in a broad range of species. This will set the stage for evo–immuno approaches, exploiting the investment in antiviral defences made by metazoans over hundreds of millions of years of evolution.

This article is part of the theme issue ‘Sculpting the microbiome: how host factors determine and respond to microbial colonization’.
The roles of ABCB1/P-glycoprotein drug transporters in regulating gut microbes and inflammation: insights from animal models, old and new
Authors: Stoeltje Lauren , Luc Jenna K. , Haddad Timothaus , Schrankel Catherine S.
Published: March 2024

Commensal enteric bacteria have evolved systems that enable growth in the ecologic niche of the host gastrointestinal tract. Animals evolved parallel mechanisms to survive the constant exposure to bacteria and their metabolic by-products. We propose that drug transporters encompass a crucial system to managing the gut microbiome. Drug transporters are present in the apical surface of gut epithelia. They detoxify cells from small molecules and toxins (xenobiotics) in the lumen. Here, we review what is known about commensal structure in the absence of the transporter ABCB1/P-glycoprotein in mammalian models. Knockout or low-activity alleles of ABCB1 lead to dysbiosis, Crohn's disease and ulcerative colitis in mammals. However, the exact function of ABCB1 in these contexts remain unclear. We highlight emerging models—the zebrafish
Danio rerio
and sea urchin
Lytechinus pictus
—that are poised to help dissect the fundamental mechanisms of ATP-binding cassette (ABC) transporters in the tolerance of commensal and pathogenic communities in the gut. We and others hypothesize that ABCB1 plays a direct role in exporting inflammatory bacterial products from host epithelia. Interdisciplinary work in this research area will lend novel insight to the transporter-mediated pathways that impact microbiome community structure and accelerate the pathogenesis of inflammatory bowel disease when perturbed.

This article is part of the theme issue ‘Sculpting the microbiome: how host factors determine and respond to microbial colonization’.
Streptococcus pneumoniae serotype 3 population structure in the era of conjugate vaccines, 2001–2018
Authors: Cella Eleonora , Sutcliffe Catherine G. , Grant Lindsay R. , Tso Carol , Weatherholtz Robert C. , Littlepage Shea , Becenti Ladonna , Jubair Mohammad , Simons Brenna C. , Harker-Jones Marcella , Reid Raymond , Yazzie Del , Santosham Mathuram , O'Brien Katherine L. , Hammitt Laura L. , Azarian Taj
Published: March 2024

Background. Despite use of highly effective conjugate vaccines, invasive pneumococcal disease (IPD) remains a leading cause of morbidity and mortality and disproportionately affects Indigenous populations. Although included in the 13-valent pneumococcal conjugate vaccine (PCV13), which was introduced in 2010, serotype 3 continues to cause disease among Indigenous communities in the Southwest USA. In the Navajo Nation, serotype 3 IPD incidence increased among adults (3.8/100 000 in 2001–2009 and 6.2/100 000 in 2011–2019); in children the disease persisted although the rates dropped from 5.8/100 000 to 2.3/100 000.

Methods. We analysed the genomic epidemiology of serotype 3 isolates collected from 129 adults and 63 children with pneumococcal carriage (n=61) or IPD (n=131) from 2001 to 2018 of the Navajo Nation. Using whole-genome sequencing data, we determined clade membership and assessed changes in serotype 3 population structure over time.

Results. The serotype 3 population structure was characterized by three dominant subpopulations: clade II (n=90, 46.9 %) and clade Iα (n=59, 30.7 %), which fall into Clonal Complex (CC) 180, and a non-CC180 clade (n=43, 22.4 %). The proportion of clade II-associated IPD cases increased significantly from 2001 to 2010 to 2011–2018 among adults (23.1–71.8 %; P<0.001) but not in children (27.3–33.3 %; P=0.84). Over the same period, the proportion of clade II-associated carriage increased; this was statistically significant among children (23.3–52.6 %; P=0.04) but not adults (0–50.0 %, P=0.08).

Conclusions. In this setting with persistent serotype 3 IPD and carriage, clade II has increased since 2010. Genomic changes may be contributing to the observed trends in serotype 3 carriage and disease over time.
Racial and Ethnic Disparities in Clinical Outcomes among Patients with Takotsubo Syndrome; A Nation-Wide Analysis
Authors: Perry Jamal Christopher , Akinti Oluwasegun Matthew , Eneh Chukwuka , Aiwuyo Henry Osarumme , Poluyi Charles , Emmanuel Ukenenye , Doudu Esther , Becerra Henry Alberto , Ozbay Mustafa Bilal , Peterkin Kibwey Roderick , Thachil Rosy , Khan Abdullah
Published: March 2024

Background

Takotsubo syndrome (TTS), a stress-induced transient left ventricular dysfunction, remains poorly understood, with an estimated incidence of 1-2% among acute coronary syndrome cases. This study investigates racial and ethnic disparities in hospital outcomes and clinical characteristics of TTS.

Methods

We conducted a retrospective cohort study using the National Inpatient Sample data from 2016 to 2020, identifying TTS cases through validated ICD-10 codes. Statistical analysis was performed using Stata 18, with logistic regression models adjusting for confounders to identify disparities in outcomes.

Results

The study included 32,785 TTS hospitalizations; the majority were White (80.5%), followed by Black (6.7%) and Hispanic (5.8%) patients. Minority groups, mainly Black and Hispanic patients, were younger (average age 63) and predominantly from lower-income brackets, while paradoxical Asians had the highest income bracket. Notable findings include Black patients showed the highest rate of stroke (4.8%, OR 2.1, p = 0.003). The rate of cardiogenic shock was highest among Asians (11%, OR 2, p < 0.001). Mortality rates were elevated in Black (2%, OR 1.5, p < 0.001) and Asian populations (1.8%, OR 1.97, p < 0.001).

Conclusion

Significant racial and ethnic disparities exist in TTS outcomes, with minority groups having more in-hospital outcomes. These findings highlight the urgent need for targeted interventions and further research to reduce healthcare inequities in TTS management.
Forelimb movements contribute to hindlimb cutaneous reflexes during locomotion in cats
Authors: Harnie Jonathan , Al Arab Rasha , Mari Stephen , Yassine Sirine , Eddaoui Oussama , Jéhannin Pierre , Audet Johannie , Lecomte Charly , Iorio-Morin Christian , Prilutsky Boris I. , Rybak Ilya A. , Frigon Alain
Published: March 2024

During quadrupedal locomotion, central circuits interacting with somatosensory feedback coordinate forelimb and hindlimb movements. How this is achieved is not clear. To determine if forelimb movements modulate hindlimb cutaneous reflexes involved in responding to an external perturbation, we stimulated the superficial peroneal nerve in six intact cats during quadrupedal locomotion and during hindlimb-only locomotion (with forelimbs standing on stationary platform) and in two spinal-transected cats during hindlimb-only locomotion. We compared cutaneous reflexes evoked in six ipsilateral and four contralateral hindlimb muscles. Results showed similar occurrence and phase-dependent modulation of short-latency inhibitory and excitatory responses during quadrupedal and hindlimb-only locomotion in intact cats. However, the depth of modulation was reduced in the ipsilateral semitendinosus during hindlimb-only locomotion. Additionally, longer-latency responses occurred less frequently in extensor muscles bilaterally during hindlimb-only locomotion while short-latency inhibitory and longer-latency excitatory responses occurred more frequently in the ipsilateral and contralateral sartorius anterior, respectively. After spinal transection, short-latency inhibitory and excitatory responses were similar to both intact conditions, while mid- or longer-excitatory responses were reduced or abolished. Our results suggest that the absence of forelimb movements suppresses inputs from supraspinal structures and/or cervical cord that normally contribute to longer-latency reflex responses in hindlimb extensor muscles.

NEW & NOTEWORTHY

During quadrupedal locomotion, the coordination of forelimb and hindlimb movements involves central circuits and somatosensory feedback. To demonstrate how forelimb movement affects hindlimb cutaneous reflexes during locomotion, we stimulated the superficial peroneal nerve in intact cats during quadrupedal and hindlimb-only locomotion, as well as in spinal-transected cats during hindlimb-only locomotion. We show that forelimb movement influences the modulation of hindlimb cutaneous reflexes, particularly the occurrence of long-latency reflex responses.
DimericR25CPTH(1-34) Activates the Parathyroid Hormone-1 Receptorin vitroand Stimulates Bone Formation in Osteoporotic Female Mice
Authors: Noh Minsoo , Che Xiangguo , Jin Xian , Lee Dong-Kyo , Kim Hyun-Ju , Park Doo Ri , Lee Soo Young , Lee Hunsang , Gardella Thomas , Choi Je-Yong , Lee Sihoon
Published: March 2024

Osteoporosis, characterized by reduced bone density and strength, increases fracture risk, pain, and limits mobility. Established therapies of Parathyroid hormone (PTH) analogs effectively promote bone formation and reduce fractures in severe osteoporosis, but their use is limited by potential adverse effects. In the pursuit of safer osteoporosis treatments, we investigatedR25CPTH, a PTH variant wherein the native arginine at position 25 is substituted by cysteine. These studies were prompted by our finding of high bone mineral density in a hypoparathyroidism patient with the R25C homozygous mutation, and we explored its effects on PTH type-1 receptor (PTH1R) signaling in cells and bone metabolism in mice. Our findings indicate thatR25CPTH(1-84) forms dimers both intracellularly and extracellularly, and the synthetic dimeric peptide,R25CPTH(1-34), exhibits altered activity in PTH1R-mediated cAMP response. Upon a single injection in mice, dimericR25CPTH(1-34) induced acute calcemic and phosphaturic responses comparable to PTH(1-34). Furthermore, repeated daily injections increased calvarial bone thickness in intact mice and improved trabecular and cortical bone parameters in ovariectomized (OVX) mice, akin to PTH(1-34). The overall results reveal a capacity of a dimeric PTH peptide ligand to activate the PTH1Rin vitroandin vivoas PTH, suggesting a potential path of therapeutic PTH analog development.
Isolate-anchored comparisons reveal evolutionary and functional differentiation across SAR86 marine bacteria
Authors: Ramfelt Oscar , Freel Kelle C. , Tucker Sarah J. , Nigro Olivia D. , Rappé Michael S.
Published: March 2024

SAR86 is one of the most abundant groups of bacteria in the global surface ocean. However, since its discovery over 30 years ago, it has remained recalcitrant to isolation and many details regarding this group are still unknown. Here we report the cellular characteristics from the first SAR86 isolate brought into culture,CandidatusMagnimaribacter mokuoloeensis strain HIMB1674, and use its closed genome in concert with over 700 environmental genomes to assess the phylogenomic and functional characteristics of this order-level lineage of marine Gammaproteobacteria. The Magnimaribacterales invest significant genomic resources into the capacity for β-oxidation, which is present in most genomes in high gene copy numbers. This cyclical set of reactions is fed by components of cell membranes that includes lipids such as phosphatidylcholine, phosphatidylethanolamine, glycolipids, and sulfolipids. In addition to the widespread capacity to degrade the side chain of steroidal compounds via β-oxidation, several SAR86 sublineages also appear able to fully degrade the steroid polycyclic ring structure as well as other aromatic, polycyclic, and heterocyclic molecules. Read recruitment from publicly available metagenomes reveals that the Magnimaribacterales compose up to 6% of the global surface ocean microbial community. Only a subset of genera drive these high relative abundances, with some more globally dominant and others restricted to specific oceanic regions.CandidatusMagnimaribacter mokuoloeensis provides an unprecedented foundation through which to understand this highly abundant yet poorly understood lineage of marine bacteria, and charts a path to bring more representatives of this order into laboratory culture.
Causal evidence for increased theta and gamma phase consistency in a parieto-frontal network during the maintenance of visual attention
Authors: Bradley Claire , McCann Emily , Nydam Abbey S , Dux Paul , Mattingley Jason B
Published: March 2024

Endogenous visuo-spatial attention is under the control of a fronto-parietal network of brain regions. One key node in this network, the intra-parietal sulcus (IPS), plays a crucial role in maintaining endogenous attention, but little is known about its ongoing physiology and network dynamics during different attentional states. Here, we investigated the reactivity of the left IPS in response to brain stimulation under different states of selective attention. We recorded electroencephalography (EEG) in response to single pulses of transcranial magnetic stimulation (TMS) of the IPS, while participants (N=44) viewed bilateral random-dot motion displays. Individual MRI-guided TMS pulses targeted the left IPS, while the left primary somatosensory cortex (S1) served as an active control site. In separate blocks of trials, participants were cued to attend covertly to the motion display in one hemifield (left or right) and to report brief coherent motion targets. The perceptual load of the task was manipulated by varying the degree of motion coherence of the targets. Excitability, variability and information content of the neural responses to TMS were assessed by analysing TMS-evoked potential (TEP) amplitude and inter-trial phase clustering (ITPC), and by performing multivariate decoding of attentional state. Results revealed that a left posterior region displayed reduced variability in the phase of theta and gamma oscillations following TMS of the IPS, but not of S1, when attention was directed contralaterally, rather than ipsilaterally to the stimulation site. Under these same conditions, a right frontal cluster also displayed reduced theta variability and increased amplitude of TEPs after TMS of the IPS but not S1. Reliable decoding of attentional state was achieved after TMS pulses of both S1 and IPS. Taken together, our findings suggest that endogenous control of visuo-spatial attention leads to changes in the intrinsic oscillatory properties of the IPS and its associated fronto-parietal network.
Representing the dynamics of natural marmoset vocal behaviors in frontal cortex
Authors: Li Jingwen , Aoi Mikio C. , Miller Cory T.
Published: March 2024

Here we tested the respective contributions of primate premotor and prefrontal cortex to support vocal behavior. We applied a model-based GLM analysis that better accounts for the inherent variance in natural, continuous behaviors to characterize the activity of neurons throughout frontal cortex as freely-moving marmosets engaged in conversational exchanges. While analyses revealed functional clusters of neural activity related to the different processes involved in the vocal behavior, these clusters did not map to subfields of prefrontal or premotor cortex, as has been observed in more conventional task-based paradigms. Our results suggest a distributed functional organization for the myriad neural mechanisms underlying natural social interactions and has implications for our concepts of the role that frontal cortex plays in governing ethological behaviors in primates.
Glutamine deprivation alters TGF-β signaling in hepatocellular carcinoma
Authors: Gélabert Caroline , Campisano Sabrina , Golán Irene C. , Beyene Nateneal T. , Heldin Carl-Henrik , Chisari Andrea , Sancho Patricia , Moustakas Aristidis , Caja Laia
Published: March 2024

Metabolic reprogramming is one of the hallmarks of cancer. Glutamine is one of the most important nutrients that fuels the TCA cycle and therefore takes part in the production of energy. Glutamine is used as starting metabolite for the synthesis of nucleotides, fatty acids and non-essential amino acids. Since nutrients are uptaken from the blood stream, and considering the 3-dimensional state of solid tumors, access of nutrients is highly dependent on the location of individual cells within a tumor, which results in affecting their metabolic activity. This gives rise to two disctincts cell population: the ones that have access to nutrient and the ones that are nutrient-deprived. We studied the effect of the lack of glutamine by creating glutamine-resistent hepatocellular carcinoma cell lines chosen based on their epithelial (Hep3B) or mesenchymal phenotype (SNU-499 and HLF). We found that glutamine deprivation decreased the proliferation rate, clonogenicity and stemness frequency of the three cell lines but in a greater extent of the mesenchymal cells. Transcriptomic analysis performed in HLF cells showed that glutamine deprivation decreased the activation of signaling pathways involved in cell-cell junction, cell-extracellular matrix interactions and decreased the expression of the hallmarks of epithelial-to-mesenchymal transition. We therefore investigated the role of TGFβ, a master regulator of these three processes, by transcriptomic and functional analyses in epithelial (Hep3B) and mesenchymal cells (HLF). We found that the lack of glutamine strongly impared the activation of TGFβ signaling which correlated with an altered regulation of TGFβ target genes: the expression of mesenchymal genes was no longer induced by TGFβ while the epithelial genes were more strongly induced. Functional analyses showed that glutamine deprivation abolished the invasive capacities of HCCs and decreased cell adhesion. Altogehter, our results show that glutamine metabolism is necessary to maintain a mesenchymal phenotype and to maintain an efficient TGFβ signaling in hepatocellularcarcinoma.
High resolution mapping of novel non-transgressive hybrid susceptibility in barley exploited byP. teresf.maculatamaps to a single pentatricopeptide repeat-containing protein
Authors: Clare Shaun J. , Alhashel Abdullah F. , Li Mengyuan , Effertz Karl M. , Poudel Roshan Sharma , Zhang Jianwei , Brueggeman Robert S.
Published: March 2024

Hybrid genotypes can provide significant yield gains over conventional inbred varieties due to heterosis or hybrid vigor. However, hybrids can also display unintended negative attributes or phenotypes such as extreme pathogen susceptibility. The necrotrophic pathogenPyrenophora teresf.maculata(Ptm) causes spot form net blotch, which has caused significant losses to barley worldwide. Here, we report on a non-transgressive hybrid susceptibility locus in barley initially recognized because the three parental lines CI5791, Tifang and Golden Promise are resistant toPtmisolate 13IM.3, however F2progeny from CI5791 × Tifang and CI5791 × Golden Promise crosses exhibited extreme susceptibility. The susceptible phenotype segregated in a ratio of 1 resistant:1 susceptible representing a genetic segregation ratio of 1 parental (res):2 heterozygous (sus):1 parental (res) suggesting a single hybrid susceptibility locus. Genetic mapping using a total of 715 CI5791 × Tifang F2individuals (1430 recombinant gametes) and 149 targeted SNPs delimited the hybrid susceptibility locus designatedSusceptibility to Pyrenophora teres 2(Spt2) to an ∼198 kb region on chromosome 5H of the Morex V3 reference assembly. This single locus was independently mapped with 83 CI5791 × Golden Promise F2individuals (166 recombinant gametes) and 180 genome wide SNPs that colocalized to the sameSpt2locus. The CI5791 genome was sequenced using PacBio Continuous Long Read technology and comparative analysis between CI5791 and the publicly available Golden Promise genome assembly determined that the delimited region contained a single high confidenceSpt2candidate gene predicted to encode a pentatricopeptide repeat-containing protein.
Evaluating Paraspinal Muscle Response and Compensation via Musculoskeletal Modeling in Spinal Stenosis Surgeries
Authors: Jones Ryan , Kumaran Yogesh , Padgaonkar Adit , Hoffman Brett , Behrens Kyle , Elgafy Hossein , Tripathi Sudharshan , Goel Vijay K.
Published: March 2024

Introduction

Lumbar spinal stenosis is a common cause of lower back pain and weakness in elderly patients. The gold standard treatment for this is lumbar laminectomy which involves widespread muscle damage to the multifidus, a complete loss of the posterior tension band which contains the supraspinous and interspinous ligaments. However, in recent years minimally invasive techniques such as bilateral and unilateral laminotomy have become more popular and are showing efficacy in the decompression of spinal stenosis. Due to its minimally invasive approach, the muscle retraction required for laminotomy is less intensive than that required for laminectomy. The overall body of literature on the surgical treatment of spinal stenosis is sparse in its interrogation of the biomechanical outcomes of these techniques and to our knowledge, there are no current publications that incorporate muscle forces.

Methods

A previously validated thoracolumbar ribcage finite element (FE) model was used for this study. Three different surgeries, traditional laminectomy, unilateral and bilateral midline sparing approaches at L4-L5 segment were simulated by removing the spinous process, supraspinous, and interspinous ligaments. The segmental range of motion (ROM) for all models were acquired and input into a musculoskeletal modelling software to calculate muscle forces.

Results

Unilateral and bilateral laminotomy showed similar muscle forces for every muscle group in both flexion and extension motion. While comparing the muscle forces in laminotomy to the laminectomy in extension motion displayed an increase in Iliocostalis lumborum (IL) by 12 % and multifidus (MF) by 16% and decrease in transverse abdominus (TA) by 138% and erector spine (ES) by 12%. For flexion, there was an increase in IL by 35%, and MF by 12%.

Conclusion

Our results highlight that laminectomy, which involves the removal of paraspinal muscles and posterior ligamentous structures to relieve stenosis, can lead to increased instability and necessitate muscle compensation, particularly in adjacent and thoracic spine segments. Conversely, midline sparing approaches such as laminotomies, are associated with decreased muscle compensation across spinal segments and enhanced stability.
Selective enrichment ofMethylococcaceaeversusMethylocystaceaemethanotrophs via control of methane feeding schemes
Authors: Lee Ju Yong , Choi Munjeong , Song Min Joon , Kim Daehyun Daniel , Yun Taeho , Chang Jin , Ho Adrian , Myung Jaewook , Yoon Sukhwan
Published: March 2024

Methanotrophs are crucial in keeping environmental CH4emissions in check. However, how different groups of methanotrophs contribute to this important role in different environmental settings remain ambiguous. Here, in a simplified laboratory setting of well-mixed batch reactors fed continuous flow of CH4-containing gas, methanotrophic microbiomes were enriched from paddy soils under six different incubation conditions prepared as combinations of two different CH4mixing ratios (0.5% and 10% v/v) and three supplemented Cu2+concentrations (0, 2, and 10 μM). Monitoring of the temporal community shifts in the reactor microbiomes observed domination ofMethylocystisspp. in all three reactors fed 0.5% v/v, as further supported by the analyses ofpmoCABgenes in the shotgun metagenomes of the single-point samples from the same reactors. Copper deficiency did not select formmoXYZ-possessing methanotrophs. Instead, a cluster ofmbngenes with an abundance accounting for approximately 5% ofMethylocystispopulation was identified, suggesting a comparative ecological importance of methanobactin in Cu-deficient methanotrophy over soluble methane monooxygenases. These findings highlight the importance ofMethylocystisspp. in mitigating emissions from CH4hotspots, e.g., landfills and rice paddies, and suggest the feasibility of directed enrichment/isolation ofMethylocystisspp. for utilization in, for example, methanobactin and polyhydroxybutyrate production.

Synopsis

This study reports enrichment of a complex soil microbiota with 0.5% methane resulting in dominance of a specific group of methane-consuming bacteriaMethylocystis, highlighting their ecological significance as CH4sink.
Mitochondria drive microglial NRLP3 inflammasome activation via TSPO
Authors: Singh Aarti , Rigon Manuel , Caldeira Marta Gramaça , Faccenda Danilo , Xia Dong , Lopez-Tremoleda Jordi , Al-Khateeb Zahra Falah Hassan , Guo Tong , Abeti Rosella , Giunti Paola , Campanella Michelangelo
Published: March 2024

Uncontrolled microglial response is core to neuroinflammatory brain diseases. The correlation between the mitochondrial protein TSPO and inflammation has so far failed to explain whether TSPO positively or negatively regulates microglial function. The recent evidence on the species specificity of TSPO in microglia demands a deeper understanding of the protein biology in these brain-resident macrophages. To this end, we have here enrolled a murine model of microglial cells showing that TSPO is required for the priming of mitochondria to inflammation and a conduit for its escalation. Namely, in response to inflammatory cues TSPO is stabilised on the mitochondria where it binds and sequesters NOD-like receptor (NLR) protein (i), represses the PARK2-mediated mitophagy (ii) and engages the retrograde communication with the nucleus via the accumulation of the Nf-kB to promote the expression of pro-inflammatory genes (iii). Notably, the TSPO sustained inflammatory response drives cellular demise and ultimately leads to excitotoxicity (iv).

Our findings advance the current knowledge of TSPO widening the understanding of mitochondria in inflammation and indicating a target for their regulation.