bluuebunny/crossref_metadata_2025 huggingface dataset:
TNF alpha Inhibitors in Cardiac Sarcoidosis: A Systematic Review and Meta-Analysis
Authors: Mahmood Asma , Raja Mahnoor Farooq , Imran Habiba , Zahoor Bushra , Khan Khakwani Mohammad Sadiq , Duseja Nikhil , Rahman Ihtisham , Murtaza Aiman , Abid Hafiz Muhammad Faizan , Sattar Muhammad Sohail , Bajaj Neha , Bajaj Saneha , Tariq Laiqa , Shafiq Aimen
Published: November 2024

Background:

Recent studies have focused on treating cardiac sarcoidosis (CS) with corticosteroids primarily mitigating symptoms and reducing the risk of mortality and other cardiovascular complications. A promising new treatment approach involves tumor necrosis factor (TNF) alpha inhibitors.

Methodology:

A systematic search was conducted on PubMed, the Cochrane Library, and Elsevier’s Science Direct databases to identify studies comparing TNF alpha inhibitors with other drugs in CS patients who had heart failure. The analyses were conducted using the random-effects model.

Results:

The study’s primary outcome is an increase in ejection fraction (EF), secondary outcomes include a reduction in the dose of prednisone at 6 and 12 months, maximum standardized uptake value by cardiac tissue, and fluorodeoxyglucose uptake by cardiac myocytes on positron emission tomography scan. The total number of pooled participants was 154 out of which 140 met the Heart Rhythm Society criteria for CS. The pooled analysis showed that treatment with the TNF alpha inhibitors was associated with a significant increase in EF [weighted mean difference (WMD), 46.272; 95% confidence interval (CI), 40.60–51.94, P < 0.001; I
2, 75.74%], reduction in the dose of prednisone at 6 months (WMD, 9.20; 95% CI, 7.65–10.75; P < 0.001; I
2, 13.33%) and at 12 months (WMD, 6.40; 95% CI, 4.74–8.07; P < 0.001; I
2, 9.37%); decrease in myocardial maximum standardized uptake value (WMD, 1.99; 95% CI, 0.91–3.06; P < 0.001; I
2: 97%) and reduction in fluorodeoxyglucose uptake by cardiac myocytes (WMD, 1.55; 95% CI, 1.09–2.00; P < 0.001; I
2, 32.29) on positron emission tomography scans.

Conclusions:

The research findings suggest that TNF alpha inhibitors improve EF, reduce required steroid dosage, and improve clinical outcomes. Nonetheless, further high-quality randomized controlled trials with large sample sizes are needed to assess other impacts of this therapy on patients with CS.
Patient-triggered Events Poorly Predict the Presence of Atrial Tachyarrhythmia on Ambulatory Electrocardiogram Monitors in Patients With Heart Failure
Authors: Herner Maranda , Abedin Zameer , Torre Michael , Zhang Yue , Orton Cody , Lyons Ann , Steinberg Benjamin A.
Published: November 2024

Background:

Ambulatory electrocardiogram (AECG) monitoring is an attractive method for objectively identifying atrial fibrillation (AF) symptoms by documenting simultaneous arrhythmia with symptomatic episodes. However, no study yet has evaluated this simultaneous symptom-rhythm correlation in patients with heart failure (HF). We aimed to measure the correlation between symptoms and atrial arrhythmia (ATAF) episodes among patients with HF and known AF using prolonged AECG monitoring.

Methods:

We analyzed ATAF events and patient-triggered symptomatic events (PTSEs) on AECG monitors in adults with a history of AF and HF.

Results:

Among 959 monitors, we identified a total of 26,634 events, including 15,787 ATAF events and 4950 PTSE. The mean age was 70 years, 48% were female, and 91% were Caucasian. Among 4950 PTSEs, only 1116 demonstrated ATAF (23%). PTSE showed a low correlation with ATAF, with a moderate inverse tetrachoric correlation of −0.62 (bootstrapped 95% confidence interval: −0.61 to −0.63). The mean heart rate (HR) of symptomatic ATAF events was 115 bpm (SD: 33), compared with asymptomatic ATAF (107 bpm, SD: 33, P < 0.001). The mean HR of all symptomatic events was 92 bpm (SD: 28) and of asymptomatic events was 99 bpm (SD: 30), P < 0.001.

Conclusions:

Our study found that symptomatic events on AECG monitors poorly predict ATAF episodes, ATAF episodes are rarely noted as symptomatic, and poor HR control fails to fully explain AF symptoms in patients with known AF and HF. Our study encourages further research into other symptom assessments, such as patient-reported outcomes and a more comprehensive approach to AF treatment in HF rather than primarily symptom based.
Even a Low Comorbidity Burden Predicts Poor Outcomes in Chronic Heart Failure
Authors: Elias Catarina , Neves Ana , Gouveia Rita , Madureira Sérgio , Ribeirinho-Soares Pedro , Soares-Carreira Marta , Pereira Joana , Almeida Jorge , Lourenço Patrícia
Published: November 2024

Background:

Patients with heart failure often have multiple cardiovascular risk factors (CVRFs) and comorbidities (CMBs). We evaluated the impact of additive CMB and CVRF on heart failure prognosis.

Methods:

We retrospectively analyzed ambulatory patients with systolic dysfunction between January 2012 and May 2018. Follow-up was until January 2021. The endpoint was all-cause death. CVRF analyzed arterial hypertension, diabetes mellitus, and smoking. CMB evaluated coronary artery disease, noncoronary atherosclerotic disease, respiratory disease, dementia, anemia, chronic kidney disease, inflammatory/autoimmune disease, active cancer, and atrial fibrillation. Classification according to the number of CVRFs and/or CMBs is <2 and ≥2. The independent prognostic impact of CVRF/CMB burden was assessed with multivariate Cox regression.

Results:

Most patients had ≥2 CMBs (67.9%). Regarding CVRF, 14.9% presented none, 40.2% had 1, and 32.1% had 2. During a median 49-month follow-up, 419 (49.1%) patients died. Mortality was higher among patients with ≥2 CVRFs (56.1 versus 43.4% in those with <2) and in those with ≥2 CMBs (57.7 versus 31.0%). While patients with 1 CMB had similar mortality than those with none. Patients with ≥2 CMBs had higher long-term mortality risk: hazard ratio (HR), 2.47 (95% CI, 1.95–3.14). In patients with ≥2CVRFs, the HR of dying is 1.39 (95% CI, 1.14–1.70). When taken together, there was a clear survival disadvantage for patients with ≥2 CVRFs/CMBs—adjusted HR, 2.20 (95% CI, 1.45–3.34).

Conclusions:

The presence of only 2 CVRFs/CMBs more than doubles the patients´ risk of dying. CVRF and CMB should be assessed as part of routine patient management.
Characteristics and Outcomes of Descemet Membrane Endothelial Keratoplasty for Treatment of Failed Endothelial Keratoplasty
Authors: Price Marianne O. , Navarro Luis Valdes , Feng Matthew T. , Gang Anjulie , Price David A. , Price Francis W.
Published: November 2024

Purpose:

To evaluate Descemet membrane endothelial keratoplasty (DMEK) for failed endothelial keratoplasty (EK).

Methods:

We reviewed 362 consecutive DMEK cases for failed EK (Descemet stripping endothelial keratoplasty (DSEK) or DMEK), 118 for early EK failure, and 244 for late failure in 333 eyes of 323 patients without penetrating keratoplasty. Rejection and graft survival rates were assessed with Kaplan–Meier analysis.

Results:

Overall, 85% of cases had 1 prior EK and 15% had 2 to 5. The rate of medically or surgically managed glaucoma was 21% in eyes with 1 failed EK, 51% in eyes with 2, and 80% in eyes with ≥3, P <0.0001. The mean postoperative corrected visual acuity was 20/25 ± 1 line at 1 and 5 years in eyes without vision-limiting comorbidity. The 5-year rejection episode rate was 4%. One- and 5-year survival rates of DMEK regrafts for early failure of an initial EK were 98% and 94%, respectively. One- and 5-year survival rates among all cases of DMEK for EK failure were 96% and 91% in eyes not treated for glaucoma preoperatively, 88% and 81% in eyes with medically managed glaucoma, and 88% and 30% in eyes with a trabeculectomy or tube shunt.

Conclusions:

DMEK for failed EK provided rapid visual rehabilitation with low risk of rejection. Graft survival was associated with glaucoma status and original indication for keratoplasty, with Fuchs dystrophy having the most favorable prognosis. Survival rates were highest in eyes treated for early failure of an initial EK.
Definitive Treatment of Lisch Epithelial Corneal Dystrophy via Staged Keratectomy and Targeted Minor Limbal Excision With Cautery
Authors: Tuteja Sahib Y. , Lockington David
Published: November 2024

Purpose:

We demonstrate a novel approach for the definitive treatment of Lisch epithelial corneal dystrophy via an unintentionally staged alcohol keratectomy and intentionally targeted minor limbal excision with cautery.

Methods:

A 46-year-old woman presented with visually significant corneal changes, suspected to be Lisch epithelial corneal dystrophy after clinical examination, anterior segment optical coherence tomography, and confocal microscopy. Alcohol keratectomy was performed with complete resolution, but there was visually significant recurrence at 2 years. As the abnormal epithelial recurrence originated in a linear tapered pattern from a focal superior limbal region, minor limbal excision with cautery and alcohol keratectomy was performed.

Results:

Histopathological analysis demonstrated cytoplasmic vacuolation and glycogen granules. The limbal tissue demonstrated normal histological features. The patient's vision returned to baseline on reepithelialization with a clear cornea, with no recurrence in over 5-year follow-up.

Conclusions:

Our targeted two-staged approach provides definitive treatment for Lisch epithelial corneal dystrophy and highlights the focal limbal origin of abnormal cells.
Fasciotomy for Chronic Exertional Compartment Syndrome of the Deep Posterior Lower Leg Compartment: A Prospective Study
Authors: van den Heuvel-Weiss Chris , Goossens Sari , Janssen Loes , van Eerten Percy , de Bie Rob , Scheltinga Marc
Published: November 2024

Objective:

Patients with lower leg deep posterior chronic exertional compartment syndrome (dp-CECS) experience exercise-induced calf pain and tightness. Retrospective studies suggest that outcome after a fasciotomy is suboptimal. This prospective case series determined success rates of a fasciotomy and identified factors predicting outcome.

Design:

Severity and intensity of pain and tightness were scored at baseline (BL) and 3 and 12 months postoperatively (follow-up [FU]3, FU12). Outcome measures were symptoms, return to sports, and patient-reported success.

Patients:

Data of patients with dp-CECS (n = 74, 51% males, age 28 ± 12 years) operated between 2013 and 2022 in a single center were analyzed.

Results:

Pain scores during rest and during exercise were greatly attenuated (rest BL: 8 ± 1, FU3: 4 ± 1, FU12: 3 ± 0; exercise BL: 20 ± 1, FU3: 8 ± 1, FU12: 8 ± 1; both P < 0.001). At FU3, rates of success and return to sports were 56% and 63%, respectively. At FU12, success was maintained in 48% and 80% had returned to sports. Length of symptom duration and not opening the flexor hallucis compartment were related to a lower chance of return to sports (P < 0.05).

Conclusions:

Outcome after a fasciotomy for lower leg dp-CECS is successful in approximately half of patients. Long duration of symptoms and not opening the flexor hallucis compartment are risk factors for failure.
Platelet-Poor Plasma for the Treatment of Acute Hamstring Muscle Injuries in Collegiate Football Athletes: A Cohort Study
Authors: Kruse Ryan C. , Volfson Elena
Published: November 2024

Objective:

To evaluate the efficacy of platelet-poor plasma injections for the treatment of acute hamstring muscle strains.

Design:

Cohort study.

Setting:

Outpatient Sports Medicine Clinic.

Participants:

Twenty consecutive patients with an acute hamstring muscle injury from 2021 to 2022 were included.

Interventions:

Platelet-poor plasma injection into the hamstring muscle strain.

Main Outcome Measures:

Time (days) until return to full unrestricted participation in sport.

Results:

All patients were male collegiate football athletes, with an average age of 20 (±1.6) years old. The most commonly injured muscle was the semitendinosus (65%). After treatment with platelet-poor plasma, patients on average returned to full, unrestricted participation in sport at 29.4 (±7.2) days postinjury, with a statistically significant improvement in pain as early as 2 weeks postinjection. No recurrent injuries to the affected hamstring muscles were seen within 12 months.

Conclusions:

PPP may be a safe and effective treatment for acute hamstring muscle strains and may potentially expedite time to return to play.
Using Career Accelerators to Broaden Your Influence
Authors: Kingston Mary Beth
Published: November 2024

In 2024, Mary Beth Kingston, PhD, RN, FAAN, received the American Organization for Nursing Leadership (AONL) prestigious Lifetime Achievement Award. This award honors an AONL member recognized by the nursing community as a significant leader in the nursing profession and who has served AONL in an important leadership capacity. Kingston retires in December 2024 from her position as executive vice president and chief nursing officer at Advocate Health, Charlotte, North Carolina, the nation's 3rd largest nonprofit integrated health system. As AONL Board President in 2019, she played an instrumental role in the rebranding of the organization. Kingston spoke at a thought leader session at the AONL annual conference in April 2024. The following column is based on her remarks.
The Impact of Professional Governance on Hope, Resilience, and Empowerment
Authors: Partridge Alison , Jorgenson Marcey , Johnson Emily , Lott Tanya
Published: November 2024

OBJECTIVE

The purpose of this cross-sectional descriptive study was to examine the relationship of professional governance, resilience, and empowerment among RNs in clinical practice in 1 healthcare system.

BACKGROUND

Given the emotional and physical demands of nursing, especially in recent years, exploring ways that hope-inducing and resilience-building models can support professional practice is vital to the current and future nursing workforce.

METHODS

An anonymous survey consisting of demographic questions, the Adult Hope Scale, Connor-Davidson Resilience Scale, and the Conditions for Work Effectiveness Questionnaire II was offered to 1450 RNs in a nonprofit community-based healthcare system for volunteer participation.

RESULTS

Nurses who formally participated in professional governance nursing councils reported higher hope, resilience, and work effectiveness scores compared with nurses who did not participate in professional governance.

CONCLUSIONS

Based on these initial results, encouraging and creating avenues for the participation of RNs in professional governance are paramount to build a resilient, hopeful, and empowered workforce.
Clinical Nurse Specialist Coaching Improves Transition Preparedness in Older Adults
Authors: Lindell Deb L. , Larsen Laura
Published: November 2024

Person-centered coaching provided by clinical nurse specialists (CNSs) is an effective, acceptable, and feasible evidence-based intervention. Psychosocial distress experienced by older adults and their families during transitions of care can contribute to adverse events. CNS coaching demonstrated increased self-reported preparedness for healthcare transitions and knowledge-of-care options. CNS coaching promoted engagement and self-efficacy. Nurse administrators can incorporate this intervention in a variety of care settings to improve outcomes related to transitions of care.
Nurse Leader Perspectives on Precepting in a Graduate Nursing Administration Practicum
Authors: Hickman Linda J , Petri Laura , Connors James
Published: November 2024

OBJECTIVE

To describe practicum experiences as perceived by nurse leader preceptors of graduate students in a nursing administration practicum.

BACKGROUND

Practicum experiences in graduate nursing administration programs provide students with exposure to the real-life experiences of nurse leaders, bridging the gap between academic knowledge gained and the application of that information to the workplace. The literature lacks best practices for graduate nursing administration practicum experiences.

METHODS

Eight nurse leaders were interviewed using a semistructured format. Data were transcribed and subjected to selective thematic analysis.

RESULTS

Five themes were identified: professional and personal growth, transition of education into practice, academic partner engagement and support, time, and contributions to the organization.

CONCLUSION

Leadership practicum experiences provide a real-world perspective and are an essential part of growing future nurse leaders. This study yielded invaluable insight from nurse leader preceptors, recommendations for structuring graduate nursing administration practicums, and implications for sustaining resilient academic-practice partnerships.
Key Factors Supporting Nursing Students’ Academic Success and Recommendations to Enhance Learning Outcomes
Authors: Bahari Ghareeb
Published: November 2024

Background:

Understanding the factors that contribute to nursing students’ low self-efficacy and high stress levels is necessary to improve educational practices.

Purpose:

To determine the impact of self-efficacy and demographic factors on nursing students’ stress levels and academic success and to provide strategic recommendations for nurse educators.

Methods:

This cross-sectional study included data of 145 nursing students collected using a structured questionnaire that assesses self-efficacy, stress, and covariates. Bivariate and multivariate tests were conducted to explore potential relationships among variables.

Results:

The results indicated significant relationships among self-efficacy, stress, and demographic factors. While self-efficacy levels were influenced by gender and marital status, stress levels appeared to be affected by gender, age, and the academic semester. Self-efficacy and stress among nursing students were also significantly associated.

Conclusion:

Nurse educators should develop a supportive learning environment, better mentorship programs, and effective mental health awareness to improve students’ confidence and academic success.
Widespread 18F-FDG Uptake in Osseous Tuberculosis Without Pulmonary Tuberculosis
Authors: Feng Yuan , Lan Xiaoli , Zhang Xiao
Published: November 2024

A 30-year-old man with a 5-month history of lumbar pain was hospitalized due to worsening pain and restricted mobility. CT and MRI scans indicated multiple vertebral destructions, prompting further assessment with 18F-FDG PET/CT. PET/CT imaging showed widespread and avid 18F-FDG uptake in the bones, mainly in the vertebrae. No other suspicious lesions were detected. Pathology subsequently confirmed the presence of Mycobacterium tuberculosis. This case illustrates 18F-FDG PET/CT imaging of osseous tuberculosis, characterized by widespread 18F-FDG accumulation without pulmonary tuberculosis.
Lymphoscintigraphy for the Evaluation of Primary Lymphedema
Authors: Delgado Bolton Roberto C. , Calapaquí Terán Adriana K. , Almeida Ludmila Santiago , Treglia Giorgio , Giammarile Francesco
Published: November 2024

The diagnostic workup of primary lymphedema includes lymphoscintigraphy, a diagnostic test that provides objective data derived from the characteristics of the lymphatic flow and the lymphatic nodes. Several empirical scoring systems have been proposed with the aim of harmonizing the procedure. Here we comment the latest one, reflecting on the relevance of these tools to make possible multicenter research, based on intraobserver and interobserver reliability with the aim to, in the long run, improve patient outcomes.
Cancer Integrin Imaging With 68Ga-Trivehexin PET-CT in Head and Neck Squamous Cell Carcinoma Improves Diagnostic Accuracy
Authors: Emerson Ralph , Agrawal Kanhaiyalal , Singh Parneet , Patro P Sai Sradha , Kumar Navneet
Published: November 2024

Oral squamous cell carcinoma (OSCC) is one of the most common malignancies worldwide. Locoregional nodal involvement by OSCC is commonly encountered. Current conventional and functional imaging modalities have limited diagnostic accuracy in nodal assessment, particularly in head and neck cancer. Thus, definitive management of head and neck malignancies customarily addresses the locoregional nodes along with the primary malignancy. However, OSCC, particularly tongue cancer, shows erratic lymphatic drainage and thus commonly requires extensive bilateral neck dissection, leading to significant morbidity. Cancer integrin imaging with 68Ga-trivehexin PET-CT can offer highly specific result and thus has the potential for effective tailored management.
Superiority of 68Ga-Trivehexin PET/CT Over 18F-FDG PET/CT in the Evaluation of Lymph Nodes in Patients With Breast Cancer
Authors: Kömek Halil , Güzel Yunus , Kaplan İhsan , Yilmaz Ece Eşsiz , Can Canan
Published: November 2024

A patient with left upper quadrant breast cancer who had 18F-FDG PET/CT imaging underwent 68Ga-Trivehexin PET/CT. 68Ga-Trivehexin PET/CT showed higher radiotracer accumulation in the primary tumor, left internal mammary lymph nodes, and axillary lymph nodes compared with 18F-FDG PET/CT. However, Trivehexin uptake was not observed in FDG-positive lymph nodes in the mediastinum and left hilar region. Benign cytological findings were noted in the biopsy of the subcarinal lymph node. This case demonstrates that the use of 68Ga-Trivehexin PET/CT in suspicious lymph nodes in areas difficult to biopsy in breast cancer cases can contribute to accurate staging.
Treatment of Post-Septal Orbital Cellulitis due to Odontogenic Infection
Authors: Sacchetin Isadora Bortolo , Brito Gabriel Conceição , Martins Ligia Pozzobon
Published: November 2024

Orbital cellulitis happens when the region behind the orbital septum is affected. It consists an urgency because of its potential risks of complications, such as vision loss, cavernous sinus thrombosis, or Lemierre Syndrome. This article reports a case of a subperiosteal and orbital cellulitis, which had a periapical lesion in the left first molar as it´s focus. Because of the urgency of those cases, the surgeon needs to make an early diagnosis and prompt approach.
How I Do It: Simplified Transcystic Antegrade-only Robotic Common Bile Duct Exploration (RCBDE)
Authors: Porter Eleah D. , Carge Michael , O’Field Heather , Kelli Mohamed , Johnson Sarah E. , Vosburg Ralph Wesley , Santos Byron Fernando
Published: November 2024

Background:

Data consistently supports a surgery-first approach to common bile duct (CBD) stones in patients with a gallbladder via laparoscopic CBD exploration (LCBDE). LCBDE has equivalent efficacy and decreased cost as compared with cholecystectomy plus endoscopic retrograde cholangiopancreatography (ERCP). However, adoption has been low due to the technical limitations of laparoscopy. We describe a straightforward and highly reproducible robotic CBDE (RBCDE) technique.

Methods:

A cystic ductotomy is made after obtaining a critical view of safety. Through a 5 mm port, a wire-ready cholangiogram catheter is secured in the cystic duct and intraoperative cholangiogram performed. Based on stone burden, small versus large, either an antegrade balloon snowplow (push stones forward) or sphincteroplasty is performed over a wire under fluoroscopy. If concern persists for retained stones, choledochoscopy is performed.

Conclusions:

Our simplified antegrade-only RCBDE technique allows surgeons to consistently offer a surgery-first, single-stage approach to CBD stones in patients with a gallbladder.
Dysregulated Proteins in Plasma Distinguishing Syndromic from Non-syndromic Heritable Thoracic Aortic Disease
Authors: Seim Bjørn Edvard , Khan Yusuf , Holt Margrethe Flesvig , Ratajska Aleksandra , Michelsen Annika , Ringseth Monica Myklebust , Lundblad Runar , Halvorsen Bente , Krohg-Sørensen Kirsten , Osnes Liv T. N. , Aukrust Pål , Paus Benedicte , Kvitting John-Peder Escobar , Ueland Thor
Published: November 2024

BACKGROUND

Thoracic aortic aneurysms (TAA) are often found in younger individuals and approximately 20% may be associated with heritable thoracic aortic disease (HTAD). There are some data on genomic biomarkers reflecting inflammation and extracellular matrix remodeling in HTAD. However, data that accurately reflect the corresponding protein changes are scarce. Our aim was to quantify proteins by using targeted proteomics in HTAD patients versus healthy controls (HC).

METHODS

Patients with Loeys-Dietz syndrome (LDS,n= 8), Marfan syndrome (MFS,n= 11), and Aortic aneurysm, familial thoracic 6 syndrome (AAT6,n= 7) were recruited. For comparison, blood samples were drawn from 16 healthy controls (HC). Plasma samples were analyzed by targeted proteome analysis of 276 proteins using immunoaffinity proteomics.

RESULTS

Seven proteins were elevated when comparing HTAD to HC, displaying two patterns: i) Oncostatin M (OSM) and Pentraxin-3 (PTX3) were significantly higher in both LDS and MFS, with comparable levels in AAT6, reflecting a generalized increase in HTAD. ii) increased levels of TNF Receptor Superfamily Member 9 (TNFRSF9), Granulysin (GNLY), Glycoprotein 1b-alpha (GP1BA), Vasorin (VASN) and CD5 were restricted to the LDS subgroup and correlated positively with Th17 and platelet counts.

CONCLUSIONS

The general increase in OSM and PTX3 in HTAD may reflect early but common mechanisms related to vascular inflammation while the distinct increase in TNFRSF9, GNLY, VASN, GP1BA and CD5 in LDS patients, may reflect involvement of Th17 inflammatory response mechanisms in the progression of TAA.
Understanding the Dynamics of Biomass Deconstruction bythe Cellulolytic AnaerobeClostridium thermocellum
Authors: Yarbrough John M. , Stich Dominik G. , Hengge Neal N. , Xu Qi , Chung Daehwan , Ziegler Samantha J. , Huang Shu , Moraïs Sarah , Mizrahi Itzhak , Bayer Edward A. , Bomble Yannick J.
Published: November 2024

Clostridium thermocellumis one of the most efficient microorganisms for the deconstruction of cellulosic biomass. To achieve this high level of cellulolytic activity,C. thermocellumuses large multienzyme complexes known as cellulosomes to break down complex polysaccharides, notably cellulose, found in plant cell walls. The attachment of bacterial cells to the nearby substrateviathe cellulosome has been hypothesized to be the reason for this high efficiency. The region lying between the cell and the substrate has shown great variation and dynamics that are affected by the growth stage of cells and the biomass used for growth. Here, we utilized both photoactivation localization microscopy (PALM) and stochastic optical reconstruction microscopy (STORM) in combination with Density-Based Spatial Clustering of Applications with Noise (DBSCAN) to study the distribution ofC. thermocellumcellulosomes at different stages of growth when actively growing on soluble and insoluble substrates, providing a clearer picture of the dynamics of cellulosome populations at the enzyme microbe substrate interface. This research demonstrates the promising application of novel optical methodologies in tandem with targeted mutations withinC. thermocellumto test the prevailing theories regarding the mechanisms of cellulosomes and their potential to shuttle onto the biomass for the attachment ofC. thermocellumto improve biomass deconstruction.
Beta burst characteristics and coupling within the sensorimotor cortical-subthalamic nucleus circuit in Parkinson’s disease
Authors: Yao Pan , Abdi-Sargezeh Bahman , Sharma Abhinav , Liu Tao , Tan Huiling , Hahn Amelia , Starr Philip , Little Simon , Oswal Ashwini
Published: November 2024

Background

Bursts of exaggerated subthalamic nucleus (STN) beta activity contribute to clinical impairments in Parkinson’s disease (PD). Few studies have explored the characteristics and coupling of bursts across the sensorimotor cortical-STN circuit.

Objective

We sought to (1) establish the characteristics of sensorimotor cortical and STN bursts during naturalistic behaviours, and (2) determine the predictability of STN bursts from motor cortical recordings.

Methods

We analysed 1,478 hours of wirelessly streamed bilateral sensorimotor cortical and STN recordings from 5 PD patients.

Results

STN bursts were longer than cortical bursts and had shorter inter-burst intervals. Long bursts (>200ms) in both structures displayed temporal overlap (>30%), with an estimated cortico-STN conduction delay of 8ms. Furthermore, approximately 27% of all STN bursts were preceded by a cortical burst.

Conclusion

Cortical beta bursts tend to precede STN beta bursts, with short delays. However, subcortical mechanisms are also likely to contribute to STN burst initiation and propagation.
Influence of acute myocardial ischemia on arrhythmogenesis: a computational study
Authors: Corda Alessandra , Pagani Stefano , Vergara Christian
Published: November 2024

The early phase of acute myocardial ischemia is associated with an elevated risk of ventricular reentrant arrhythmias. Indeed, after partial or total occlusion of a coronary artery, some regions of the heart experience a reduction in myocardial blood flow. This causes metabolic and cellular processes, such as hypoxia, hyperkalemia and acidosis, which lead to changes in the transmembrane ionic dynamics. The effect of such alterations may result in the formation of electrical loops and reentries. Computational models could simulate the generation of arrhythmias, possibly persistent, in condition of ectopic beats and in presence of acute myocardial regions. Since quantitative information (extent, localization, ...) about acute ischemic regions are hardly available from clinics, to date, computational models only integrate imaging data from chronic infarcted ventricles. This may not accurately reflect the acute condition. This work presents a novel patient-specific electrophysiological model, based on images of myocardial blood flow maps acquired during a pharmacologically induced acute ischemic event. The model personalization is obtained with the partitioning of the left ventricle geometries on the basis of the myocardial blood flow maps. First, we aim to numerically investigate the induction and sustainment of reentrant drivers in patient-specific scenarios, in order to assess their arrhythmic propensity. Secondly, we perform an intra-patient sensitivity analysis, where different levels of acute ischemia are virtually depicted for the most arrhythmogenic patient. Our results suggest that the amount of ischemic regions seems to have less influence on arrhythmogenesis than their pattern.
Heterogeneous endocrine cell composition defines human islet functional phenotypes
Authors: Evans-Molina Carmella , Pettway Yasminye D. , Saunders Diane C. , Sharp Seth A. , Bate Thomas SR. , Sun Han , Durai Heather , Mei Shaojun , Coldren Anastasia , Davis Corey , Reihsmann Conrad V. , Hopkirk Alexander L. , Taylor Jay , Bradley Amber , Aramandla Radhika , Poffenberger Greg , Eskaros Adel , Jenkins Regina , Shi Danni , Kang Hakmook , Rajesh Varsha , Thaman Swaraj , Feng Fan , Cartailler Jean-Philippe , Powers Alvin C. , Abraham Kristin , Gloyn Anna L. , Niland Joyce C. , Brissova Marcela
Published: November 2024

Phenotyping and genotyping initiatives within the Integrated Islet Distribution Program (IIDP), the largest source of human islets for research in the U.S., provide standardized assessment of islet preparations distributed to researchers, enabling the integration of multiple data types. Data from islets of the first 299 organ donors without diabetes, analyzed using this pipeline, highlights substantial heterogeneity in islet cell composition associated with hormone secretory traits, sex, reported race and ethnicity, genetically predicted ancestry, and genetic risk for type 2 diabetes (T2D). While α and β cell composition influenced insulin and glucagon secretory traits, the abundance of δ cells showed the strongest association with insulin secretion and was also associated with the genetic risk score (GRS) for T2D. These findings have important implications for understanding mechanisms underlying diabetes heterogeneity and islet dysfunction and may provide insight into strategies for personalized medicine and β cell replacement therapy.
Targeted protein degradation via CAR endocytosis of antigen in T cells
Authors: Wang Youguang , Yin Na , Peng Min
Published: November 2024

Targeted protein degradation (TPD) relies on molecules engaging host protein degradation machinery. Here, we developed a novel TPD platform based on antigen endocytosis and degradation by chimeric antigen receptor (CAR) T cells. T cells expressing a CAR with TNFR1 as the antigen-binding domain (TNFR1T) were able to bind, endocytose, and degrade TNF in vitro. To enhance in vivo expansion and persistence of TNFR1T cells, BCOR and ZC3H12A were depleted, generating TNFR1TIFcells. In a human TNF transgenic mouse model of rheumatoid arthritis, a single infusion of TNFR1TIFcells sustainably reduced serum hTNF to near wild-type levels, leading to long-term disease remission. This approach extends CAR T cell targets from cells to extracellular proteins, enabling long-term degradation of inflammatory cytokines and durable remission in chronic inflammatory diseases.
The genome of a sea spider corroborates a shared Hox cluster motif in arthropods with reduced posterior tagma
Authors: Papadopoulos Nikolaos , Kulkarni Siddharth S. , Baranyi Christian , Fromm Bastian , Setton Emily V.W. , Sharma Prashant P. , Wanninger Andreas , Brenneis Georg
Published: November 2024

Background

Chelicerate evolution is contentiously debated, with recent studies challenging traditional phylogenetic hypotheses and scenarios of major evolutionary events, like terrestrialization. Sea spiders (Pycnogonida) represent the uncontested marine sister group of all other chelicerates, featuring a – likely plesiomorphic – indirect development mode. Accordingly, pycnogonids hold the potential to provide crucial insight into early chelicerate genome evolution and ancestral principles of chelicerate body patterning. Leveraging this potential, however, has hitherto been hampered by the lack of high-quality genomic resources for pycnogonids.

Results

We employed long-read sequencing and proximity ligation data to assemble the first near chromosome-level sea spider genome forPycnogonum litorale, complemented by developmental transcriptomes and a high-fidelity Iso-Seq dataset. The assembly has a size of 471Mb in 57 pseudochromosomes, a repeat content of 61.05%, 15,497 predicted protein-coding genes, and is highly complete (95.8% BUSCO Arthropoda score, 95.7% of conserved microRNA families present). We identified a single, intact Hox gene cluster that lacksabdominal-A/Hox9, suggesting the loss of this Hox gene.

Conclusions

Our high-quality genomic and transcriptomic resources establishP. litoraleas a key research organism for modern studies on chelicerate genome evolution, development, and phylogeny. The presence of a single Hox cluster in theP. litoralegenome further strengthens the inference that no whole-genome duplication occurred at the base of the chelicerate tree. The lack ofabdAsuggests that the combination ofabdAloss and posterior tagmata reduction is a common theme in arthropod evolution, as it is shared with other, distantly related arthropod taxa with a vestigial opisthosoma/abdomen.
Neural signatures of temporal anticipation in human cortex represent event probability density
Authors: Grabenhorst Matthias , Poeppel David , Michalareas Georgios
Published: November 2024

Temporal prediction is a fundamental function of neural systems. Recent advances suggest that humans anticipate future events by calculating probability density functions, rather than hazard rates. However, direct neural evidence for this mechanism is lacking. We recorded neural activity using magnetoencephalography as participants anticipated auditory and visual events distributed in time. We show that temporal anticipation, measured as reaction times, approximates the event probability density function, but not hazard rate. Temporal anticipation manifests as spatiotemporally patterned activity in three anatomically and functionally distinct parieto-temporal and sensorimotor cortical areas. In both audition and vision, each of these areas revealed a marked neural signature of anticipation: Prior to sensory cues, activity in a specific frequency band of neural oscillations, spanning alpha and beta ranges, encodes the event probability density function. Strikingly, these neural signals predicted reaction times to imminent sensory cues. These results show that supra-modal representations of probability density across cortex underlie the anticipation of future events.
Polytope: High-resolution epitope barcoding forin vivospatial fate-mapping
Authors: Postrach Daniel , Pritchard Colin E. J. , Frank Larissa , van Leeuwen Tom , Messal Hendrik A. , Krimpenfort Paul , van Rheenen Jacco , Rodewald Hans-Reimer
Published: November 2024

Tracing the fate of individual cells and their progeny remains a challenging task. While imaging-based fate-mapping provides spatial information, it generally lacks complexity due to limited label diversity, resulting in diminished capture of comprehensive lineages and fate maps. Here, we introduce ‘Polytope’, an epitope barcoding system capable of generating up to 512 unique color codes. Comprising nine epitope tag cassettes flanked by loxP sites, Polytope allows random excision via Cre recombinase, creating unique color codes detectable through multiplexed imaging. Using an engineered Polytope mouse, we traced the fate of hundreds of clones across tissuesin vivo, from embryonic development until adulthood. Together, Polytope enables high-resolution imaging-based fate-mapping through endogenous epitope barcoding, comprehensively capturing the spatial organization of complex clonal dynamicsin situ.

One-Sentence Summary

Polytope is an imaging-based barcoding system to trace lineages at clonal and spatial resolution in living organisms using a diverse set of color-coded markers.
Semantic integration demands modulate large-scale network interactions in the brain
Authors: Nieberlein Laura , Martin Sandra , Williams Kathleen A. , Gussew Alexander , Cyriaks Sophia D. , Scheer Maximilian , Rampp Stefan , Prell Julian , Hartwigsen Gesa
Published: November 2024

The ability to integrate semantic information into the context of a sentence is essential for human communication. Several studies have shown that the predictability of a final keyword based on the sentence context influences semantic integration on the behavioral, neurophysiological, and neural level. However, the architecture of the underlying network interactions for semantic integration across the lifespan remains unclear.

In this study, 32 healthy participants (30-75 years) performed an auditory cloze probability task during functional magnetic resonance imaging (fMRI), requiring lexical decisions on the sentence’s final words. Semantic integration demands were implicitly modulated by presenting sentences with expected, unexpected, anomalous, or pseudoword endings. To elucidate network interactions supporting semantic integration, we combined univariate task-based fMRI analyses with seed-based connectivity and between-network connectivity analyses.

Behavioral data revealed typical semantic integration effects, with increased integration demands being associated with longer response latencies and reduced accuracy. Univariate results demonstrated increased left frontal and temporal brain activity for sentences with higher integration demands. Between-network interactions highlighted the role of task-positive and default mode networks for sentence processing with increased semantic integration demands. Furthermore, increasing integration demands led to a higher number of behaviorally relevant network interactions, suggesting that the increased between-network coupling becomes more relevant for successful task performance as integration demands increase.

Our findings elucidate the complex network interactions underlying semantic integration across the aging continuum. Stronger interactions between various task-positive and default mode networks correlated with more efficient processing of sentences with increased semantic integration demands. These results may inform future studies with healthy old and clinical populations.
TcCARP3 modulates compartmentalized cAMP signals involved in osmoregulation, infection of mammalian cells, and colonization of the triatomine vector in the human pathogenTrypanosoma cruzi
Authors: Carlson Joshua , Ahmed Milad , Hunter Riley , Hoque Syeda Farjana , Benoit Joshua B. , Chiurillo Miguel A. , Lander Noelia
Published: November 2024

Trypanosoma cruziis the causative agent of Chagas disease, a zoonotic infectious disease considered a leading cause of cardiomyopathy, disability, and premature death in the Americas. This parasite spends its life between a mammalian host and an arthropod vector, undergoing essential transitions among different developmental forms. HowT. cruzisenses microenvironmental changes that trigger cellular responses necessary for parasite survival has remained largely unknown. Cyclic AMP (cAMP) is a universal second messenger that has been shown to regulate key cellular processes in trypanosomes, in which cyclic AMP response proteins (CARPs) have been proposed to be modulators or effectors of a PKA-independent signaling pathway. In this study we aimed to investigate the role of TcCARP3 in cAMP signaling throughoutT. cruzilife cycle. Our results show that TcCARP3 shares a dual localization (flagellar tip and contractile vacuole complex) with adenylate cyclase 1 (TcAC1) in the main developmental stages of the parasite. We also found that TcCARP3 directly interacts with several TcACs, modulating the intracellular content of cAMP. Through generation ofTcCARP3knockout, addback, and overexpression cell lines we showed that modulation of gene expression affects the parasite’s ability to differentiate, respond to osmotic stress, invade mammalian cells and replicate within them, and colonize the hindgut of the triatomine vector. In addition, we identified several signaling proteins interacting with TcCARP3 in what we propose are cAMP signaling microdomains. Our results unveil a key role for TcCARP3 as modulator of cAMP signals necessary for parasite differentiation and survival throughoutT. cruzilife cycle.

IMPORTANCE

Cyclic AMP signaling pathways are poorly understood in the stercorarian parasiteTrypanosoma cruzi. Specifically, the mechanisms driving the activation of TcACs in response to microenvironmental stress are completely unknown. This study unveils the role of TcCARP3 in modulating the content of cAMP through the interaction with several TcACs and putative cAMP effectors inT. cruzi. Particularly, TcCARP3 interacts with TcAC1 in the main developmental stages of this parasite’s life cycle, where both proteins display a dual localization pattern. These results provide new evidence supporting the compartmentalization of cAMP signals in trypanosomes. Moreover, our data unequivocally demonstrates that TcCARP3 is required for key cellular processes for parasite survival, such as response to osmotic stress, host cell invasion, intracellular replication, and the ability to colonize the hindgut of the triatomine vector. In summary, we found that TcCARP3 is an adenylate cyclase regulator, necessary for the life cycle progression ofT. cruzi.
Regional heterogeneities of oligodendrocytes determine biased distribution pattern of Ranvier nodes along single axons in sound localization circuit
Authors: Egawa Ryo , Hiraga Kota , Matsui Ryosuke , Watanabe Dai , Kuba Hiroshi
Published: November 2024

Distribution of Ranvier nodes along myelinated axons is a critical determinant of conduction velocity, significantly influencing spike arrival timing and hence neural circuit function. The patterns of nodal distribution are not necessarily uniform but vary across brain regions and even along individual axons. Although various factors could contribute to these patterns, the complexity arising from multicellular interactions between oligodendrocytes and axons has left the underlying regulatory mechanisms unclear. In this study, we identified the factors contributing to the emergence of a biased nodal distribution pattern along single axons using the chick brainstem auditory circuit as a model, in which the distance between adjacent nodes (internodal length) varies along the axons of avian cochlear nucleus neurons in a region-dependent manner, thereby enabling precise binaural integration for sound localization. 3D morphometry revealed that these axons were almost fully myelinated by oligodendrocytes exhibiting distinct morphologies and cell densities across regions after hearing onset. The structure of axons did not affect internodal length. Inhibiting vesicular release from the axons did not affect internodal length and oligodendrocyte morphology, either, but caused unmyelinated segments on the axons by suppressing oligodendrogenesis near the presynaptic terminals. These results suggest that the regional heterogeneity in the intrinsic properties of oligodendrocytes determines the biased nodal distribution pattern in the sound localization circuit, while activity-dependent signaling supports the pattern by ensuring adequate oligodendrocyte density. Our findings highlight the importance of oligodendrocyte heterogeneity in fine-tuning neural circuit function.
Amyloplasts are necessary for full gravitropism in thallus ofMarchantia polymorpha
Authors: Hashimoto-Sugimoto Mimi , Norizuki Takuya , Segami Shoji , Ohta Yusaku , Suetsugu Noriyuki , Ueda Takashi , Morita Miyo Terao
Published: November 2024

Gravitropism is a response in which plants sense gravity and determine the direction of organ growth and development. This trait is important for adaptation in land plants. The molecular mechanisms of gravitropism have been studied mainly in flowering plants, but there is limited research on other organisms. In this study, we examined the gravitropic response of the liverwortMarchantia polymorpha, a model for investigating the evolution of land plants. We found the tips of the thallus extend upward and form several straight narrow structures in the dark. These growth directions were always in the opposite direction of gravity, and clinostat treatment disrupted them. The parenchymatous cells in the narrow structures contained amyloplasts, and the sedimentation of the amyloplasts preceded the gravitropic curvature, suggesting their role as statoliths. The starchless mutants, Mppgm1 andMpaps1were generated, and an abnormal direction of growth was observed in the narrow structures, but they tended to elongate upward. These observations indicate that although amyloplasts are required for complete gravitropism, plants can sense gravity without well-developed amyloplasts. These results suggest that land plants use amyloplasts as statoliths but also have amyloplast-independent mechanisms of gravitropism. These results suggest that land plants use amyloplasts as statoliths but also have amyloplast-independent mechanisms of gravitropism.

Highlight

InM. polymorpha,amyloplasts act as statoliths in parenchyma cells and are important in gravitropism but it was not completely lost without starch granules.