bluuebunny/crossref_metadata_2025 huggingface dataset:
A field resource for the glioma cerebrospinal fluid proteome: impacts of resection and location on biomarker discovery
Authors: Riviere-Cazaux Cecile , Graser Christopher J , Warrington Arthur E , Hoplin Matthew D , Andersen Katherine M , Malik Noor , Palmer Elizabeth A , Carlstrom Lucas P , Dasari Surendra , Munoz-Casabella Amanda , Ikram Samar , Ghadimi Keyvan , Himes Benjamin T , Jusue-Torres Ignacio , Sarkaria Jann N , Meyer Fredric B , Van Gompel Jamie J , Kizilbash Sani H , Sener Ugur , Michor Franziska , Campian Jian L , Parney Ian F , Burns Terry C
Published: December 2024

Background

While serial sampling of glioma tissue is rarely performed prior to recurrence, cerebrospinal fluid (CSF) is an underutilized longitudinal source of candidate glioma biomarkers for understanding therapeutic impacts. However, the impact of key variables to consider in longitudinal CSF samples for monitoring biomarker discovery, including anatomical location and post-surgical changes, remains unknown.

Methods

Aptamer-based proteomics was performed on 147 CSF samples from 74 patients; 71 of whom had grade 2–4 astrocytomas or grade 2–3 oligodendrogliomas. This included pre- versus post-resection intracranial CSF samples obtained at early (1–16 days; n = 20 patients) or delayed (86–153 days; n = 11 patients) time points for patients with glioma. Paired lumbar versus intracranial glioma CSF samples were also obtained (n = 14 patients).

Results

Significant differences were identified in the CSF proteome between lumbar, subarachnoid, and ventricular CSF in patients with gliomas. Importantly, we found that resection had a significant, evolving longitudinal impact on the CSF proteome, with distinct sets of proteins present at different time points since resection. Our analysis of serial intracranial CSF samples suggests the early potential for disease monitoring and evaluation of pharmacodynamic impact of targeted therapies, such as bevacizumab and immunotherapies.

Conclusions

The intracranial glioma CSF proteome serves as a rich and dynamic reservoir of potential biomarkers that can be used to evaluate the effects of resection and other therapies over time. All data within this study, including detailed individual clinical annotations, are shared as a resource for the neuro-oncology community to collectively address these unanswered questions and further understand glioma biology through CSF proteomics.
Maternal-Infant Respiratory Syncytial Virus and Influenza A Virus Antibody Transfer in Preterm and Full-term Infants
Authors: Rumfelt Kalee E , Pike Mindy , Stolarczuk Jennifer E , Lekander Ava , Lauring Adam S , Eckert Linda O , Englund Janet A , Martin Emily T , Kachikis Alisa B
Published: December 2024

Background

Immunization against influenza and respiratory syncytial virus (RSV) protects pregnant individuals and their infants against infection via transplacental transport of immunoglobulin G (IgG). We sought to evaluate the quantity and efficiency of maternal influenza- and RSV-specific IgG transfer in pregnancies with preterm and full-term deliveries.

Methods

Delivery samples from 115 maternal-infant pairs (2018-2021) were analyzed for RSV prefusion F and IAV-H3 and IAV-H1 antibodies using electrochemiluminescence assays. We used Wilcoxon rank sum tests, t tests, Pearson correlation coefficients (PCCs), and linear regression to evaluate distributions of IgG results by maternal influenza vaccination status and preterm birth (<37 weeks).

Results

Approximately 70% of pregnant persons received influenza vaccine. Maternal and cord antibody concentrations were highest in the influenza-vaccinated group for IAV-H3 and IAV-H1 regardless of preterm birth status (maternal H3, P = .004; cord H3, P = .03; maternal H1, P = .0001; cord H1, P = .0002). Preterm infants had significantly lower cord to maternal IgG transfer ratios for IAV-H3 and RSV when compared with full-term infants (P ≤ .05). Correlations between maternal and cord IgG concentrations were significant (P ≤ .001) for all 3 viruses, with the strongest correlation for H3 (PCC: IAV-H3, 0.77; IAV-H1, 0.68; RSV, 0.62). Associations between maternal IgG transfer and preterm birth were significant for IAV-H3 and RSV (IAV-H3, β = −0.42; RSV, β = −0.63; P ≤ .05).

Conclusions

Maternal antibody following vaccination or infection is readily transferred across the placenta. Preterm infants have higher influenza IgG following maternal influenza vaccination and are at highest risk of lower IgG transfer ratios without vaccination.
Urogenital Schistosoma haematobium Cases at the Hospital for Tropical Diseases, London (1998-2018), and Suggested Pragmatic Follow-up Pathway for Non-endemic Settings
Authors: Warrell Clare E , Polley Spencer , Bodhani Rashmita , Coltart Cordelia E M , Rafferty Hannah , Nabarro Laura E , Godbole Gauri , Bustinduy Amaya L , Hsieh Michael H , Chiodini Peter L
Published: December 2024

Background

Characteristics of confirmed urogenital Schistosoma haematobium infections and outcomes in non-endemic regions are scarce in the literature and there is a minimal evidence base for appropriate management in this setting. Specific schistosomal urinary and urological complications include risk of hydronephrosis, renal impairment, and malignant transformation. Therefore, approach to follow-up should be robust and systematic.

Methods

This is a retrospective case-note review of all patients with confirmed S haematobium infection (defined as visible ova in terminal urine and/or histopathological diagnosis on biopsy) at the Hospital for Tropical Diseases (HTD), London, between 1998 and 2018. Outcomes of follow-up were reviewed and formulated into a pragmatic guideline for follow-up of these patients in this setting.

Results

A majority of the 186 patients with confirmed S haematobium infection presented before 2012. Young, male migrants were at highest risk of complications from chronic infection and were most prone to being lost to follow-up. One patient was referred with squamous cell carcinoma of the bladder found on biopsy with S haematobium infection.

Conclusions

We put forward a pragmatic pathway for S haematobium investigation and follow-up for patients presenting to nonendemic settings with the current resource capabilities of the United Kingdom.
The Prevalence of Multidrug Resistance in Enterobacterales Is Higher in Patients Undergoing Hematopoietic Stem Cell Transplantation
Authors: Andermann Tessa M , Brown Dylan , Holowka Thomas , Bartelt Luther A , Serody Jonathan S , Armistead Paul M , Jamieson Katarzyna J , Conlon Brian P , Rao Gauri G , Alby Kevin , van Duin David , Henderson Heather I
Published: December 2024

Background

Antimicrobial resistance is a global public health emergency. Patients undergoing hematopoietic stem cell transplantation (HCT) are at increased risk for severe infections with multidrug-resistant (MDR) organisms, although more data are needed on the relative burden of MDR Enterobacterales (MDR-E) in immunocompromised populations. In this study, we compare the prevalence of Enterobacterales resistance in cultures from patients undergoing HCT with that of non-HCT patients seeking care at a large healthcare system in North Carolina, USA.

Methods

We analyzed electronic health data from 52 067 patients aged ≥18 years with a culture positive for Enterobacterales species (2000–2023). Of these, 271 had undergone HCT prior to culture-recovered Enterobacterales. We compared resistance trends over time for specific antibacterial classes using a 5-year moving average and used generalized linear models to estimate prevalence ratios and differences of MDR-E in HCT versus non-HCT patients.

Results

HCT recipients overall had a higher prevalence of MDR-E (37.7% vs 19.4%) and resistance for all individual antibiotic classes analyzed. Comparing HCT vs non-HCT groups, the highest prevalence ratio was observed for resistance to aminoglycosides (2.10 [95% confidence interval {CI}, 1.65–2.68]); the largest adjusted absolute difference in nonsusceptibility was observed with quinolones (20.4 [95% CI, 14.9–25.8]). MDR-E infections were associated with double all-cause mortality at 1 year.

Conclusions

This large longitudinal study highlights how antimicrobial resistance has consistently been a substantial problem in HCT recipients over the prior 2 decades. Targeting antimicrobial resistance mitigation efforts will be key in reducing the risk of MDR infections in HCT.
Central sleep apnea and cardiovascular disease state-of-the-art
Authors: Javaheri Shahrokh , Giannoni Alberto , Somers Virend K , Malhotra Atul , Emdin Michele , Costanzo Maria R
Published: December 2024

Central sleep apnea, a rare polysomnographic finding in the general population, is prevalent in certain cardiovascular conditions including systolic and diastolic left ventricular dysfunction, atrial fibrillation, coronary artery disease, carotid artery stenosis, stroke, and use of certain cardiac-related medications. Polysomnographic findings of central sleep apnea with adverse cardiovascular impacts include nocturnal hypoxemia and arousals, which can lead to increased sympathetic activity both at night and in the daytime. Among cardiovascular diseases, central sleep apnea is most prevalent in patients with left ventricular systolic dysfunction; a large study of more than 900 treated patients has shown a dose-dependent relationship between nocturnal desaturation and mortality. Multiple small randomized controlled trials have shown mitigation of sympathetic activity when central sleep apnea is treated with nocturnal oxygen, continuous positive airway pressure, and adaptive servoventilation. However, two early randomized controlled trials with positive airway pressure devices have shown either a neutral effect on survival or excess premature mortality in the active treatment arm, compared to untreated central sleep apnea. In contrast, the results of the most recent trial using an advanced adaptive servoventilation device showed improved quality of life and no signal for mortality suggesting that treatment of central sleep apnea was at least safe. In addition to positive airway pressure devices, multiple medications have been shown to improve central sleep apnea, but no long-term trials of pharmacologic therapy have been published. Currently, phrenic nerve stimulation is approved for the treatment of central sleep apnea, and the results of a randomized controlled trial showed significant improvement in sleep metrics and quality of life.
Effect of dynamic interaction of estrous cycle and stress on synaptic transmission and neuronal excitability in the lateral habenula
Authors: Kim Woonhee , Chung ChiHye
Published: December 2024

The prevalence of depressive disorders in women has been reported in many countries. However, the cellular mechanisms mediating such sex differences in stress susceptibility remain largely unknown. Previously, we showed that lateral habenula (LHb) neurons are more activated in female mice than in male mice by restraint stress. Given the important role of LHb in depressive disorders, we aimed to investigate the synaptic differences between male and female LHb and to examine the possible impact of the estrous cycle on neurotransmission in LHb. We found that the passive and active properties of LHb neurons differed according to the estrous cycle. Spontaneous excitatory postsynaptic currents exhibited higher amplitudes during the diestrus stage and lower frequencies in females than in males, whereas inhibitory postsynaptic currents showed no significant differences. Acute stress‐induced hyperpolarization of resting membrane potentials (RMP) was observed in both sexes, with notable changes in female silent and tonic neurons. Stress exposure eliminated estrous cycle‐dependent RMP differences and introduced cycle‐specific excitability changes, especially in the metestrus and diestrus stages, suggesting that the hormonal cycle may set the synaptic tone of the LHb, thus modulating stress responses in females. Our study provides invaluable groundwork for understanding the detailed interaction between the estrous cycle and stress exposure in female LHb.
Not Only Caseload but Also Patient Selection Is Predictive of Mortality After Pancreatic Resection
Authors: Mantke Rene , Seliger Barbara , Ogino Shuji , Büchler Markus W , Hunger Richard
Published: December 2024

Background:

Centralization of pancreatic surgery in high-volume centers is regarded as a key strategy in improving the outcome quality. However, the specific factors, in addition to higher case volumes, that influence inhospital mortality remain unclear.

Methods:

In this retrospective observational study, the German nationwide diagnostic-related groups statistics were analyzed for 86,073 patients with pancreatic resections. Hospitals performing at least 50 resections per year were identified as high-volume pancreatic centers (HVPCs). Statistical analyses compared crude and adjusted estimates of inhospital mortality for patients treated in HVPCs and non-HVPCs. A generalized mixed model was used for risk adjustment, considering various factors such as age group, sex, diagnosis, and comorbidities (ClinicalTrail.gov, NCT06390891).

Results:

A total of 24.2% (n = 20,798) of all pancreatic resections were performed in 23 HVPCs. The crude inhospital mortality for all patients undergoing resection was 9.0%. Crude inhospital mortality in HVPCs was 5.5% compared with 10.1% in non-HVPCs (P < 0.001). HVPCs performed more complex resections including more concomitant procedures. On the other hand, HVPCs treated younger patients and patients with less complicated comorbidities. Statistical adjustment of comorbidities and patient characteristics resulted in a significant increase of inhospital mortality from 5.5% to 8.7% in HVPCs.

Conclusions:

HVPCs have significantly lower inhospital mortality than the other hospitals. Nevertheless, the superior quality of outcome can be attributed not only to the enhanced expertise of the centers but also, at least in part, to a healthier patient population on average. However, the extent to which this patient selection is due to active selection by the practitioners or other causes remains unclear.
The Risk of Intravenous Cement Leakage and Short-term Outcomes of Selective Cement-augmented Pedicle Screws
Authors: Takahashi Shinji , Sakai Daisuke , Ogasawara Shota , Sasaki Ryo , Uematsu Masato , Hyakumachi Takahiko , Hiyama Akihiko , Katoh Hiroyuki , Terai Hidetomi , Suzuki Akinobu , Tamai Koji , Nakamura Hiroaki , Yagi Mitsuru
Published: December 2024

Study Design:

Multicenter retrospective cohort study.

Objective:

To evaluate the efficacy and safety of using cement-augmented pedicle screw (CAPS) fixation only for the cephalad and caudal vertebral bodies.

Summary of Background Data:

Pedicle screw fixation is less effective in patients with low-quality bone. Although CAPS fixation has shown promise in improving stability and reducing screw loosening in such cases, cement leakage can have serious consequences.

Methods:

This study included 65 patients who underwent spinal surgery using CAPS and were followed up for >3 months. Four CAPSs were used in each patient, and 254 CAPSs were included in the analysis.

Results:

Of the 65 patients, 36.9% showed intravenous cement leakage, and a low bone mineral density (BMD) was associated with a higher risk of cement leakage. The use of a CAPS on the right side was also potentially associated with a higher risk of leakage. However, the shape and location of the leaked cement remained stable over time. Screw loosening occurred in 3.5% of the CAPSs and was associated with a lower cement volume.

Conclusion:

Cement leakage was related to lower BMD. Using CAPS exclusively at the lower or upper instrumentation levels might minimize the risk of cement leakage in osteoporotic patients.
Use of intrathecal fluorescein administered through an epidural catheter for repair of a skull base CSF leak during pregnancy: A case report
Authors: Murphy Zachary , Stucken Emily , McKean Erin , Pancaro Carlo , Meral Ryan , Khatibi Nabi , Schechtman Samuel
Published: December 2024

We present a 35-year-old gravida 9 para 5 female at 22 weeks gestation presenting for surgical repair of a skull base cerebrospinal fluid (CSF) leak given risk of recurrent infection. To optimize visualization of the leak, intrathecal fluorescein was administered. While this is commonly performed by placing a lumbar drain, given prior complications including postdural puncture headache (PDPH) from lumbar drains this patient wished to not have a lumbar drain postoperatively and the need for prolonged lumbar drainage was thought to be unnecessary given anticipated improved visualization for robust repair. An epidural catheter was placed intrathecally in the awake patient, which was immediately removed after slow, low-dose fluorescein injection. We hypothesized the smaller bore access for an epidural catheter positioned in the subarachnoid space at the L4-L5 level posed a lower risk of PDPH compared with the larger lumber drain. This approach also allowed for the monitoring of neurological changes during placement in the awake patient. This case demonstrated the feasibility of placing an epidural catheter into the intrathecal space for injection of fluorescein. Further research is warranted to understand whether this approach decreases risks, including PDPH as compared with the common approach with lumbar drains.
Evaluation of the effects of different mydriatic drops used on choroidal vascularity in healthy children
Authors: Soysal Gizem Gürbostan , Seyyar Sevim Ayca , Mercanlı Murat , Chiekhismailzadeh Yara , Balyemez Burçak , Çetinkaya Kübra , Kimyon Sabit
Published: December 2024

Purpose:

To evaluate the effects of mydriatics drops used primarily in routine eye examinations on the choroid tissue, which has a dense vascular network in the eye.

Methods:

This prospective observational study included 90 eyes of 90 healthy children. Optical coherence tomography (OCT) images were obtained for all children before dilation. They were randomly divided into two groups (46/44). The tropicamide group received 0.5% tropicamide and the phenylephrine group received 2.5% phenylephrine. After dilation, a second OCT image was obtained for all children.

Results:

Subfoveal choroidal thickness (SCFT) values ​​decreased significantly after dilation in the phenylephrine and tropicamide drop groups compared to pre-dilation measurements (p=0.001 for both). No significant difference was observed in the choroidal vascularity index (CVI) values ​​measured before and after dilation in either group (p=0.059, p=0.245).

Conclusion:

While 2.5% phenylephrine and 0.5% tropicamide caused a decrease in SCFT values ​​after dilatation, there was no significant difference in CVI values. These results emphasize that when examining choroidal thickness and vascularity in individuals with chorioretinal disease, the selection of mydriatic agent should be taken into consideration, especially in choroidal thickness.
Selection of the apposite vacuum extractor during operative delivery: A biomechanical study
Authors: Hsieh Ping-Lin , Wang Peng-Hui , Ke Jyun-Cheng , Chiang Kai-Jo , Lin Chi-Kang , Chang Fung-Wei , Su Kuo-Min , Su Kuo-Chih
Published: December 2024

Background:

Operative delivery is a technique used during vaginal or cesarean birth to facilitate the patient’s labor course through the assistance of a vacuum extractor. This method is increasingly used compared with forceps. This study aimed to investigate the forced effects of vacuum extractors comprising vacuum cups with different thicknesses on the fetal head and the vacuum extractor during vacuum-assisted delivery and to determine the optimal thickness for reducing the failure rate and minimizing neonatal and maternal morbidity.

Methods:

A biomechanical model was developed to examine the impact of vacuum cups with varying thicknesses. This simulation three-dimensional (3D) geometry model was used to evaluate hemispherical-shaped vacuum extractors made of silicone rubber having a similar cup diameter of 70 mm with varying thicknesses (1 mm to 5 mm), which were applied to the three models (flat surfaces, hemispherical balls, and fetal head). Under one boundary condition and two different loading conditions, finite element analysis was utilized to simulate the force of vacuum extractors on the fetal head during the process of operative delivery. The main observation indicators were the reaction forces of the constructed model, and von Mises stress on both the vacuum extractors and fetal head.

Results:

For the reaction forces on each axis, we found that the sum of the reaction force values on each axis was increased as the thickness of the vacuum extractor was increased, regardless of the surface type. Additionally, the reaction force of the fixed-support end was increased with the increased thickness of the vacuum extractor. The von Mises stress distributions of vacuum extractors comprising vacuum cups with different thicknesses, revealed that the thinner the cup, the greater the von Mises stress exerted on the extractor itself regardless of the surface type. The distribution of von Mises stress on the skull structure of the fetal head, showed that the thinner the cup, the greater the von Mises stress exerted on the skull structure regardless of the surface type.

Conclusion:

A thinner vacuum extractor cup may result in greater injury to the fetus; hence, a thicker vacuum extractor cup is preferably utilized during vacuum-assisted operative delivery. Using a thicker vacuum extractor should yield a higher successful delivery rate and reduce fetal injury.
Transcriptome of capsular contracture around breast implants mimics allograft rejection: a matched case-control study
Authors: Larsen Andreas , Fritz Blaine G , Weltz Tim K , Tran John V Q , Bak Erik E F , Hemmingsen Mathilde N , Ørholt Mathias , Vester-Glowinski Peter , Woetmann Anders , Litman Thomas , Bjarnsholt Thomas , Herly Mikkel
Published: December 2024

Background:

Capsular contracture is a frequent and severe complication following breast implant surgery. Although several theories on the pathophysiology exist, the exact molecular mechanisms remain unclear. This study aimed to identify the specific genes, signaling pathways, and immune cells associated with capsular contracture.

Methods:

Breast implant capsule biopsies were collected from women undergoing implant replacement after breast augmentation. Patients with capsular contracture (Baker III/IV) and healthy controls (Baker I) were included in equal numbers and matched based on implant brand, surface, plane, and rupture status. Whole transcriptome RNA-sequencing was used for gene expression profiling.

Results:

We analyzed biopsies from 51 breasts of 50 women, revealing 1,500 differentially expressed genes based on capsular contracture status. Our findings revealed that capsular contracture signaling pathways mimic allograft rejection with activation of both the innate immune system (e.g., IL1A/B, CXCl9, TREML4, CR1) and the adaptive immune system (e.g., CD80 and IFN-γ). Capsular contracture was associated with increased expression of macrophages, CD4+ T cells, B cells, and plasma cells with upregulation of several immunoglobulin genes (e.g., IGHD/IGHE). Moreover, several fibrosis-related genes were significantly upregulated (e.g., MMP1, MMP1, MMP12) and downregulated (TIMP4) in breasts with capsular contracture.

Conclusions:

The results indicate that B cells play a more crucial role in the development of capsular contracture than previously assumed. The disease mechanism resembles allograft rejection, indicating that capsular contracture is a form of immunological rejection of the breast implant.

Clinical Relevance Statement

This study identified key genes associated with capsular contracture, suggesting new drug candidates e.g., MMP1 inhibitors to improve breast implant surgery outcomes. Synergizing research on allograft rejection and capsular contracture could also lead to new treatment strategies.
Patient Perceptions of Pessaries for Treatment of Pelvic Organ Prolapse
Authors: Roberts Brittany L. , Marici Lauren , Villafuerte Ellen , Jacobs Bradley E. , Wolff Gillian F. , Rogers Rebecca G. , Dahl Jeanne Ann , Deverdis Erin C.
Published: December 2024

Importance

A vaginal pessary is a highly effective treatment for patients with pelvic organ prolapse (POP). Patient views of pessaries and how their beliefs affect whether they choose pessary treatment is unknown.

Objective

Our objective of this study was to describe the knowledge, understanding, and patient concerns regarding pessary use for POP management.

Study Design

We performed a qualitative study of women presenting with POP who were counseled about pessary use at their initial urogynecology visit. Participants completed interviews, which were recorded, de-identified, and transcribed. Transcriptions were coded for major themes by 2 independent researchers.

Results

Twenty patients with an average age of 63 ± 8.5 years participated. Most identified as sexually active (60%) and the majority had a high school education or less (80%). Thematic saturation was reached with themes of "Failure", "Convenience," "Self-Image," "Sexual Relations," "Cleanliness/Hygiene," "Physical Barriers," "Knowledge Deficits," and "Discomfort." Many patients not only viewed a pessary as a less invasive alternative to surgery but also considered it a temporary treatment. Many patients disliked the idea of having a “foreign body” in place and felt it may affect their hygiene. Although most patients believed it would alleviate their POP symptoms, many had concerns about sexual intercourse, discomfort, and fear that it may fall out. Most participants who were not sexually active thought a pessary would increase their sexual confidence.

Conclusions

Patient opinions about pessaries are often negative with preconceived notions surrounding utilization. Focused counseling addressing concerns and fears may improve a patient's comfort with a pessary as their choice of treatment modality.
Exploring Psychedelics Pharmacology: A Scoping Review Charting the Course of Psilocybin Pharmacokinetics
Authors: Manzano-Nunez Ramiro , Gomez Diego A. , Toledo-Mendoza Catalina , Perez-Otero Marta , Matilla Iris L. , Prats Claudia , Perez-Lopez Elena , Pardo Helmuth , Díaz-Pellicer Patricia , De La Torre-Fornell Rafael , Aldea Ana M.
Published: December 2024

Objectives

This scoping review aimed to synthesize the existing data about psilocybin pharmacokinetics to learn what has been described regarding body disposition and safety when psilocybin was used in controlled research settings.

Methods

We performed a scoping literature review following the framework proposed by the JBI manual for evidence synthesis. Controlled clinical trials reporting pharmacokinetic data of psilocybin were considered appropriate for inclusion. We extracted the data on psilocybin pharmacokinetics and summarized it from the available literature on this topic. We also performed an exploratory-descriptive analysis using study level data to examine the relationship between dose of psilocybin and maximum serum concentrations (Cmax).

Results

We initially identified 850 articles, of which 5 were included. These trials included 112 healthy volunteers who received psilocybin in a controlled clinical setting. The peak concentration of psilocin in plasma (Cmax) ranged from 8.2 ng/mL to 37.2 ng/mL (median = 17, IQR = 11.9 to 23.5). The maximal concentrations (Cmax) of psilocin were reached (Tmax) around 2 hours, ranging from 1.7 hours to 2.2 hours (median = 2, IQR = 1.9 to 2.1) after psilocybin oral administration. Elimination half-life was between 1.2 hours and 3.3 hours (median = 2.0, IQR = 1.6 to 2.8). A strong positive relationship between dose and Cmax (R
2 = 0.95) was found. No serious adverse events were observed. We did not find studies reporting pharmacokinetic data from patients with depression or cancer patients transitioning to palliative care.

Conclusions

In summary, this review unveils oral psilocybin pharmacokinetics in healthy adults, revealing gaps in its application to target populations like those with depression or in palliative care.
Comparison of EEG Signal Characteristics of Subdural and Depth Electrodes
Authors: Alkawadri Cigdem Isitan , Yan Qi , Kocuglu Kinal Ayse Gul , Spencer Dennis D. , Alkawadri Rafeed
Published: December 2024

Objectives:

Our study aimed to compare signal characteristics of subdural electrodes (SDE) and depth stereo EEG placed within a 5-mm vicinity in patients with drug-resistant epilepsy. We report how electrode design and placement collectively affect signal content from a shared source between these electrode types.

Methods:

In subjects undergoing invasive intracranial EEG evaluation at a surgical epilepsy center from 2012 to 2018, stereo EEG and SDE electrode contacts placed within a 5-mm vicinity were identified. Of these, 24 contacts (12 pairs) met our criteria for signal-to-noise ratio and data availability for final analysis. We used Welch method to analyze the correlation of power spectral densities of EEG segments, root mean square of 1-second windows, and fast-Fourier transform to calculate coherence across conventional frequency bands.

Results:

We observed a median distance of 3.7 mm between the electrode contact pairs. Time-aware analysis highlighted the coherence's strength primarily in the high-gamma band, where the median (r) was 0.889. In addition, the median power ratios between the SDE and stereo EEG signal was 1.99. This ratio decreased from high-gamma to infra-low frequencies, with medians of 2.07 and 0.97, respectively. The power spectral densities for the stereo EEG and SDE electrodes demonstrated a strong correlation, with a median correlation coefficient (r) of 0.99 and an interquartile range from 0.915 to 0.996.

Conclusions:

Signals captured by standard subdural and depth (intracranial EEG) electrodes within a 5-mm radius exhibit band-specific coherence and are not identical. The association was most pronounced in the high-gamma band, with coherence decreasing with lower frequencies. Our findings underscore the combined effects of electrode size, design, placement, preferred bandwidth, and the nature of the activity source on signal recording. Particularly, SDE employed herein may offer advantages for high-frequency signals, but the impact of electrode size on recordings necessitates careful consideration in context-specific situations.

Significance:

The findings relate to surgical epilepsy care and may inform the design of brain–computer interface.
Red blood cell distribution width-derived indces predicts long-term prognosis in acute heart failure
Authors: Zhang Miao , Zhu Jing , Mo Degang , Yuan Shanshan , Lin Fanhui , Dai Hongyan
Published: December 2024

Background

Red blood cell distribution width (RDW), a routine indicator of erythrocyte volume variability, has shown potential in recent years in the prognostic assessment of a variety of diseases, including acute heart failure (AHF). The predictive ability of RDW-derived indices, namely the hemoglobin-to-RDW ratio (HRR), the RDW-to-lymphocyte ratio (RLR), the RDW-to-platelet ratio (RPR), the RDW-to-albumin ratio (RAR), and the product of RDW and mean corpuscular volume (RDW×MCV), for the prognosis of AHF remains unclear.

Methods

The study included 4090 eligible patients in the MIMIC 3.0 database, screened variables using Lasso regression, assessed whether these derivatives independently predicted 1-year mortality from AHF by Cox proportional hazards model, and plotted survival curves and time-related ROC curves. Finally, the relationship between each indicator and outcome was analyzed by restricted cubic spline.

Results

Positive events occurred in 2085 (51%) patients with decreased HRR and increased RLR, RPR, RAR, and RDW×MCV (P<0.001).After Cox model adjustment, HRR, RPR, RAR, and RDW×MCV remained independent predictors of 1-year prognosis for AHF (RLR was not) and the relationship may be more linear. Of these, RPR had the greatest impact on survival time (HR = 1.89, 95%CI: 1.33-2.67) and RDW×MCV had the highest predictive efficacy (AUC=0.612).

Conclusion

RDW-derived indices HRR, RPR, RAR and RDW×MCV independently predicted 1-year mortality in AHF, and RLR had no independent predictive value.
Glycan analysis probes inspired by human lectins for investigating host-microbe crosstalk
Authors: Ghosh Soumi , Chorghade Rajeev , Diehl Roger C. , Dodge Greg J. , Bae Sunhee , Dugan Amanda E. , Halim Melanie , Wuo Michael G , Bartlett Helen , Herndon Liam , Kiessling Laura L. , Imperiali Barbara
Published: December 2024

Human lectins are critical carbohydrate-binding proteins that recognize diverse glycoconjugates from microorganisms and can play a key role in host-microbe interactions. Despite their importance in immune recognition and pathogen binding, the specific glycan ligands and functions of many human lectins remain poorly understood. Using previous proof-of-concept studies on selected lectins as the foundation for this work, we present ten additional glycan analysis probes (GAPs) from a diverse set of human soluble lectins, offering robust tools to investigate glycan-mediated interactions. We describe a protein engineering platform that enables scalable production of GAPs that maintain native-like conformations and oligomerization states, equipped with functional reporter tags for targeted glycan profiling. We demonstrate that the soluble GAP reagents can be used in various applications, including glycan array analysis, mucin- binding assays, tissue staining, and microbe binding in complex populations. These capabilities make GAPs valuable for dissecting interactions relevant to understanding host responses to microbes. The tools can be used to distinguish microbial from mammalian glycans, which is crucial for understanding the cross-target interactions of lectins in a physiological environment where both glycan types exist. GAPs have potential as diagnostic and prognostic tools for detecting glycan alterations in chronic diseases, microbial dysbiosis, and immune-related conditions.
MUTE drives asymmetric divisions to form stomatal subsidiary cells in Crassulaceae succulents
Authors: Cheng Xin , Lindner Heike , Hoffmann Lidia , Gomes Filho Antonio Aristides Pereira , Ruiz Duarte Paola , Boxall Susanna F , Gündogmus Yigit Berkay , Pritchard Jessica H , Haldenby Sam , Gemmell Matthew , Darby Alistair , Läderach Miro , Hartwell James , Raissig Michael T
Published: December 2024

Amongst the evolutionary innovations of many succulents is a photosynthetic lifestyle, where stomatal gas exchange is decoupled from light-dependent carbon fixation. Stomatal complexes in the emerging succulent modelKalanchoë laxifloraconsist of two guard cells surrounded by three anisocytic subsidiary cells (SCs). Here, we show that these SCs shuttle ions and thus likely support stomatal movements. Furthermore, gene editing, reporter lines and protein overexpression implicate the stomatal transcription factor MUTE in facilitating additional rounds of asymmetric divisions that form SCs in succulents. This is opposite to the role of MUTE inArabidopsis thaliana, where it stops rather than induces asymmetric divisions, but reminiscent of MUTE’s SC-related function in grasses. Together, our work deciphers an intricate genetic mechanism that generates innovative stomatal morphology in Crassulaceae succulents.
Impact of autologous serum on anin vitrogranuloma model to studyMycobacterium tuberculosisinfection dynamics
Authors: Bourg Chloé , Hodille Elisabeth , Ader Florence , Dumitrescu Oana , Genestet Charlotte
Published: December 2024

Tuberculosis (TB) remains a global health challenge, withMycobacterium tuberculosis(Mtb) persisting in granulomas, complex immune structures that balance containment and survival of the pathogen.In vitrogranuloma models have advanced TB research but often rely on commercial human serum, which may not fully replicate the native immune environment. Here, we investigated the role of autologous serum, either heat-inactivated or native, in granuloma-like structure (GLS) formation, bacterial dynamics, and immune responses. Using a human PBMC-based model to induce spontaneousin vitrogranuloma formation after infection with Mtb, we found that autologous serum significantly enhanced GLS formation and altered cytokine profiles compared to commercial serum. Native serum also reduced bacterial growth, likely due to active complement system-mediated immune responses. These findings highlight the importance of autologous serum in creating physiologically relevant models, crucial for preclinical evaluation of TB therapies. Incorporating patient-specific serum can improve model accuracy, enabling better exploration of host-pathogen interactions and targeted therapeutic strategies.
Sexually dimorphic ATF4 expression in the fat confers female stress tolerance inDrosophila melanogaster
Authors: Grmai Lydia , Mychalczuk Melissa , Arkalgud Aditya , Vasudevan Deepika
Published: December 2024

Metabolic differences between males and females have been well documented across many species. However, the molecular basis of these differences and how they impact tolerance to nutrient deprivation is still under investigation. In this work, we useDrosophila melanogasterto demonstrate that sex-specific differences in fat tissue metabolism are driven, in part, by dimorphic expression of the Integrated Stress Response (ISR) transcription factor, ATF4. We found that female fat tissues have higher ATF4 activity than their male counter parts under homeostatic conditions. This dimorphism was partly due to a female bias in transcript abundance of specificATF4splice isoforms. We found that the canonical sex determinantstransformer(tra) anddoublesex(dsx) drive such dimorphicATF4transcript abundance. These differences persist in a genetic model of nutrient deprivation, where female animals showed greater resistance to lethality than males in an ATF4-dependent manner. These results suggest that higher ATF4 activity confers higher tolerance to stress in females. Together, our data describe a previously unknown facet of ISR signaling wherein sexual identity of adipose tissue confers differential stress tolerance in males and females. Since energy storage mechanisms are known to be dimorphic and have been linked to ATF4 regulation, our studies provide a mechanistic starting point for understanding how sexual identity influences metabolic disease outcomes.
miR-126 modulates neural progenitor cell development
Authors: Bastiaans Jeroen , Glendinning Michael D. , de Marco Garcia Natalia , Stuhlmann Heidi
Published: December 2024

Noncoding microRNAs (miRNAs) play important roles in controlling signaling pathways by targeting multiple genes and altering their expression levels. MiR-126 is a known endothelial-specific miRNA that regulates vascular integrity and angiogenesis by enhancing proangiogenic actions of VEGF and FGF. MiR-126 is also expressed in several stem cell compartments, including embryonic stem cell (ESC) and hematopoietic stem/progenitor cells (HSPC) where it regulates cell differentiation and quiescence. Here we show that miR-126 is expressed as well in neural progenitor cells where it regulates cell differentiation by targeting genes of the IGF1R signaling pathway including IRS1, PI3K and AKT. Moreover, Hoxa9 and IGF-1 expression by neural progenitor cells is upregulated when miR-126 expression levels are reduced. Our data, implicating a role for miR-126 in manipulating cell development, could open a window of opportunities for clinical purposes and therapeutic strategies to achieve controlling neural progenitor cell behavior.

Highlights

Knockdown of miR-126 in neural progenitor cells increases cell proliferation

miR-126 modulates expression levels of HoxA9 and known target genes involved in the IGF1R signaling pathway in neural progenitor cells

Overexpression of miR-126 results in induced cell differentiation in neural progenitor cells

miR-126 affects motor neuron development in the thoracic region of the spinal cord

Knockdown of miR-126 expression results in increased IGF-1 expression
The association between routine immunisation and COVID-19 vaccination in small island developing states
Authors: Patel Cyra , Bilgin Gizem , Hayen Andrew , Kirk Martyn , Ali Akeem , Dey Aditi , Sargent Ginny , Sheel Meru
Published: December 2024

Objectives

Understanding the link between routine immunisation (RI) performance and vaccination during an epidemic can provide insights on health systems resilience and investments to strengthen health systems. We examined the relationship between RI performance and COVID-19 vaccination coverage in small island developing states (SIDS).

Methods

COVID-19 vaccination coverage at four timepoints (June 2021, December 2021, June 2022 and December 2022) in 55 SIDS was our primary outcome. We examined associations with coverage of six childhood immunisations (5-year mean annual coverage for 2015–2019), pandemic-related disruptions to RI, new vaccine introductions, health system performance measures, and economic and demographic characteristics. We calculated Spearman correlations for continuous variables and mean COVID-19 vaccination coverage by categorical variables.

Findings

We found COVID-19 vaccination coverage was higher in countries that sustained RI coverage during the pandemic, and where HPV, influenza and measles-containing (second dose) vaccines had been introduced. There were weak correlations (|r|<0.4) between coverage of COVID-19 vaccination and RI, with a few exceptions of moderate correlations with the birth dose of hepatitis B vaccine (June 2022: r=0.421, p=0.007; December 2022: r=0.438, p=0.005) and first dose of measles vaccine (December 2021: r=0.420, p=0.002). COVID-19 vaccination coverage was strongly correlated with the density of physicians (June 2021: 0.897, p<0.001; December 2021: 0.785, p<0.001) and moderately correlated with that of nurses and midwives (June 2021: 0.630, p=0.001; December 2021: 0.605, p=0.002). COVID-19 vaccination coverage was lower in SIDS with lower country income and development status.

Conclusions

Countries that achieved high COVID-19 vaccination coverage maintained RI coverage, demonstrating health system resilience. Our findings highlight the importance of having sufficient skilled health professionals and experience in introducing new vaccines targeting different age groups into national programs, particularly in small island settings.
Winter temperature effects in a cold-adapted northern population of a range-expanding spider: survival, energy stores, and differential gene expression
Authors: Ortiz-Movliav Carolina , Wolz Marina , Klockmann Michael , Kuß Andreas , Jensen Lars , Jensen Corinna , Wacker Alexander , Uhl Gabriele
Published: December 2024

Species expand their spatial distribution when environmental conditions are favorable or when mutations arise that allow them to live in previously unfavorable conditions. The European wasp spider,Argiope bruennichi, is known to have expanded its range poleward faster than climate change would predict. Northern edge populations show higher cold tolerance and are genetically differentiated from core populations, suggesting local adaptation to colder winter conditions. To investigate the degree and limits of plasticity in a cold-adapted population, we exposed overwintering juveniles (spiderlings) from Estonia - the northern edge of the distribution - to three winter regimes: two with a strong difference in day/night temperatures and an overall 10 degrees’ difference (warm and cold treatment) and one with moderate temperatures and less difference between day and night (moderate). We investigated if survival, lipid content, metabolites, and gene expression patterns differ depending on these temperature regimes. The survival probability of the spiderlings and their overall lipid content decreased over winter, with no difference between treatments, suggesting high resilience of the spiderlings towards very different temperature regimes at the edge of the distribution. At the end of winter, the content of saturated and monounsaturated fatty acids per spiderling also did not differ between treatments. However, omega-3 polyunsaturated fatty acids (PUFAs) levels were significantly lower in spiders exposed to the warm winter suggesting increased metabolic activity. We identified 4096 significant differentially expressed genes (DEGs) across the treatments, of which 1389 were specific for the moderate treatment, and 832 specific for the warm treatment, while 69 were unique for the cold treatment, showing a stronger temperature stress response to the moderate and warmer than to the cold treatment. Taken together, our results show thatA. bruennichihas physiological plasticity and the ability to cope with very different winter temperature regimes despite being cold adapted. However, warmer winters might come with metabolic costs that could impact on the spiderlingś survival and foraging success when they emerge from the egg sac in spring.
Towards community-driven visual proteomics with large-scale cryo-electron tomography ofChlamydomonas reinhardtii
Authors: Kelley Ron , Khavnekar Sagar , Righetto Ricardo D. , Heebner Jessica , Obr Martin , Zhang Xianjun , Chakraborty Saikat , Tagiltsev Grigory , Michael Alicia K. , van Dorst Sofie , Waltz Florent , McCafferty Caitlyn L. , Lamm Lorenz , Zufferey Simon , Van der Stappen Philippe , van den Hoek Hugo , Wietrzynski Wojciech , Harar Pavol , Wan William , Briggs John A.G. , Plitzko Jürgen M. , Engel Benjamin D. , Kotecha Abhay
Published: December 2024

In situcryo-electron tomography (cryo-ET) has emerged as the method of choice to investigate structures of biomolecules in their native context. However, challenges remain in the efficient production of large-scale cryo-ET datasets, as well as the community sharing of this information-rich data. Here, we applied a cryogenic plasma-based focused ion beam (cryo-PFIB) instrument for high-throughput milling of the green algaChlamydomonas reinhardtii, a useful model organism forin situvisualization of numerous fundamental cellular processes. Combining cryo-PFIB sample preparation with recent advances in cryo-ET data acquisition and processing, we generated a dataset of 1829 reconstructed and annotated tomograms, which we provide as a community resource to drive method development and inspire biological discovery. To assay the quality of this dataset, we performed subtomogram averaging (STA) of both soluble and membrane-bound complexes ranging in size from >3 MDa to ∼200 kDa, including 80S ribosomes, Rubisco, nucleosomes, microtubules, clathrin, photosystem II, and mitochondrial ATP synthase. The majority of these density maps reached sub-nanometer resolution, demonstrating the potential of thisC. reinhardtiidataset, as well as the promise of modern cryo-ET workflows and open data sharing towards visual proteomics.
Decoding primitive endoderm - epiblast interactions using mouse ICM embryoids
Authors: Tan Beatrice F. , Schäffers Olivier J.M. , Merzouk Sarra , Bindels Eric M. , Huylebroeck Danny , Gribnau Joost , Dupont Cathérine
Published: December 2024

Stem cell-based embryo models are promising alternatives for investigating early embryogenesis. We introduce two distinct models to replicate the dynamics between extra-embryonic endoderm and epiblast during mouse embryonic development. InducibleGata6(iGata6) embryoid bodies (EBs), exclusively derived from iGata6embryonic stem (ES) cells, are valuable for modeling the position-dependent development of the primitive endoderm. Inner cell mass (ICM) embryoids, conversely, efficiently formed by aggregating ‘wild-type’ and iGata6ES cells, accurately and at a comparable pace simulatein vivodevelopment from E3.5 to E7.5. Notably, ICM embryoids model cell sorting and through a rosette-like stage, the transition of the epiblast from naïve to primed pluripotency. Furthermore, the absence of extra-embryonic ectoderm-like cells in this model, directs both the epiblast and visceral endoderm towards an anterior developmental fate. As such, iGata6EBs and ICM embryoids are powerful tools for advancing our understanding of cell fate decisions during early embryonic development in mice.