bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanosensitive Ca2+ channel TRPV1 activated by low‐intensity pulsed ultrasound ameliorates acute kidney injury through Notch1‐Akt‐eNOS signaling
Authors: Huangfu Qi , Zhang Jun , Xu Jiaju , Xu Jinming , Yang Zhangcheng , Wei Jingchao , Yang Liuqing , Shu Yichang , Sun Chengfang , Wang Bohan , Chen Yi , Wen Jiaming , Cai Ming
Published: January 2025

Acute Kidney Injury (AKI) is a significant medical condition characterized by the abrupt decline in kidney function.Low‐intensity pulsed ultrasound (LIPUS), a non‐invasive therapeutic technique employing low‐intensity acoustic wave pulses, has shown promise in promoting tissue repair and regeneration. A novel LIPUS system was developed and evaluated in rat AKI models, focusing on its effects on glomerular filtration rate (GFR), blood urea nitrogen (BUN), serum creatinine (SCr), and the Notch1‐Akt‐eNOS signaling pathway. The results demonstrated that LIPUS treatment improved GFR, BUN, SCr levels, and renal pathology in AKI rats. In vitro experiments using HUVEC cells revealed that LIPUS stimulation promoted angiogenesis, cell migration mechanically‐dependent calcium ion influx, which was partially attenuated by TRPV1 knockdown. RNA sequencing analysis indicated LIPUS‐induced activation of the Notch pathway, phosphorylation of Akt and eNOS. Furthermore, inhibition or genetic silencing of Notch1 abolished the beneficial effects of LIPUS on angiogenesis, renal function, and Akt‐eNOS phosphorylation in both cells and AKI rats. These findings suggest that LIPUS‐induced calcium influx promotes Akt‐eNOS phosphorylation, nitric oxide (NO) production, angiogenesis, and improved renal function in AKI via Notch1‐Akt‐eNOS signaling, positioning LIPUS as a promising therapeutic strategy for AKI by targeting vascular regeneration.
Circadian rhythm disruptions exacerbate inner ear damage in a murine endolymphatic hydrops model
Authors: Pang Bo , Bai Yijiang , Chen Yongjia , Zhang Shuai , Xu Zhenhang , Li Chenglong , Nie Zequn , Liu Heng , Guo Zihang , Ling Jie , Mei Lingyun
Published: January 2025

Meniere's disease (MD) is an inner ear disease characterized by endolymphatic hydrops (EH). Maintaining a regular daily routine is crucial for MD patients. However, the relationship between circadian rhythms and MD remains unclear. Therefore, we investigated the effect of circadian rhythm on endolymphatic hydrops and its underlying mechanisms. Mice with endolymphatic hydrops were subjected to chronic jet lag (CJL) conditions to simulate the MD patients under circadian rhythm disruptions. We assessed whether this disruption would exacerbate inner ear damage with endolymphatic hydrops. RNA‐seq of the inner ear and bioinformatic analysis were performed. Then, the expression of PER2, AQP2, AQP4, AQP5, and BDNF were assessed, and the morphological changes were evaluated in the inner ear. Our findings showed circadian rhythm disruption affected the cochlear internal clock genes in the inner ear, particularly in mice with EH. EH mice under CJL conditions exhibited exacerbated hearing impairment and an increased severity of EH. GO enrichment analysis revealed that the regulation of fluid homeostasis and neurotransmitter release at synapses were significantly enriched. Disruption of circadian rhythms disturbed the expression pattern of PER2, reduced BDNF levels, and affected the expression of aquaporins in the cochlea. Moreover, the disruption of circadian rhythm compromised inner hair cell synapses and auditory nerve fibers. This study indicated that disruption of circadian rhythms may exacerbate inner ear damage in endolymphatic hydrops mice by affecting the aquaporins and compromising synapses and auditory nerves in the inner ear. BDNF and PER2 may play a central role in these pathophysiological processes.
Factors Associated With Postoperative Pain Trajectory, Nausea, and Vomiting After Total Knee Arthroplasty
Authors: Chen Ti-Hsuan , Wu Chih-Cheng , Chen Jun-Peng
Published: January 2025

Objectives:

Postoperative pain, nausea, and vomiting (PONV)﻿ adversely affect postoperative rehabilitation after total knee arthroplasty (TKA). We aimed to identify factors associated with postoperative pain trajectory and PONV and evaluated the effects of different analgesic modalities.

Methods:

We retrospectively reviewed patients undergoing unilateral primary TKA from 2017 to 2022. Patients received either general or spinal anesthesia. Patient-controlled analgesia (PCA) included patient-controlled epidural analgesia (PCEA) and intravenous analgesia (PCIA). Outcome variables included maximal pain intensity at certain times (before surgery, and 24 h and 48 h after surgery); and incidence of PONV. A generalized estimating equation was used to determine the correlation between PCA usage and longitudinal pain score at 48 hours follow-up after surgery. Multivariable logistic regression analyses were used to evaluate PONV after adjusting for potential confounders.

Results:

In total, 2510 patients were included in the analyses﻿. Patients without PCA intervention and with higher BMI reported greater acute postoperative pain. Furthermore, women and lower BMI were associated with higher rates of PONV. After adjusting for confounding factors, the PCEA group had a lower pain score than both the no PCA group (β estimate =−0.443, 95% CI= [−0.561 to −0.324], P<0.001) and the PCIA group (mean difference=−0.227, 95% CI = [−0.328 to −0.126], P <0.001).

Conclusion:

General anesthesia and PCA had no effect on the PONV incidence after TKA. Greater BMI﻿ correlated with higher pain scores but a lower likelihood of PONV. Epidural PCA provided superior acute postoperative analgesia without increasing the incidence of PONV.
The Moderating Role of Ethnicity on Depressive and Anxiety Symptoms and Pain Catastrophizing in Hispanic/Latinx and Non-Hispanic/Latinx White Youth With Chronic Pain
Authors: Moreno Joaquin E. , Nestor Bridget A. , Mitcheson Morgan , Nelson Sarah
Published: January 2025

Objectives:

Chronic pain (CP) significantly impacts emotional and physical well-being and overall quality of life across diverse populations in the United States (US). Notably, under-represented minoritized (URM) groups, such as Hispanic/Latinx (H/L) youth, may experience disproportionate effects due to health disparities and lack of access to quality health care. However, this remains understudied. This study aimed to examine the association between CP and its related psychosocial factors—depressive and anxiety symptoms, and pain catastrophizing—in H/L youth, as compared with Non-Hispanic White (NHW) youth.

Methods:

The current study sample included 58 self-identifying H/L and 58 NHW youth seeking CP treatment at a large Northeastern tertiary pain clinic, ages 12 to 18 years old, (M=15.49, SD=1.71), of which 88% identified as biologically female. Participant samples for each group were age and-sex-matched.

Results:

Significant associations were found between anxiety and depressive symptoms and pain catastrophizing for youth in both groups. Ethnicity significantly moderated the associations between pain catastrophizing and depressive symptoms and between anxiety and depressive symptoms, with NHW youth with pain exhibiting stronger relations between these constructs when compared with H/L youth with pain.

Discussion:

Our results suggested that for NHW youth with CP, greater tendencies toward catastrophizing and experiences of anxiety may more strongly contribute to depressive symptoms, when compared with their Hispanic/Latinx youth counterparts. Further investigation of pain-coping mechanisms among H/L youth and other youth from historically marginalized populations (e.g., racial/ethnic minoritized groups) will help advance clinical understanding of sociocultural variability in links between pain-related psychosocial outcomes in the CP experience.
Impaired macroscopic CSF flow by sevoflurane in humans – both during and after anesthesia
Authors: Zimmermann Juliana , Sorg Christian , Müller Leander , Zistler Franziska , Neumaier Viktor , Bonhoeffer Moritz , Ranft Andreas , Golkowski Daniel , Priller Josef , Zimmer Claus , Ilg Rüdiger , Preibisch Christine , Schneider Gerhard , Nuttall Rachel , Zott Benedikt
Published: January 2025

Background:

According to the model of the glymphatic system, the directed flow of cerebrospinal fluid (CSF) is a driver of waste clearance from the brain. In sleep, glymphatic transport is enhanced, but it is unclear how it is affected by anesthesia. Animal research indicates partially opposing effects of distinct anesthetics but corresponding results in humans are lacking. Thus, this study aims to investigate the effect of sevoflurane anesthesia on CSF flow in humans, both during and after anesthesia.

Methods:

Using data from a functional magnetic resonance imaging (fMRI) experiment in 16 healthy human subjects before, during, and 45 minutes after sevoflurane mono-anesthesia of 2vol%, we related grey matter blood-oxygenation-level dependent (BOLD) signals to CSF flow, indexed by fMRI signal fluctuations, across the basal cisternae. Specifically, CSF flow was measured by CSF fMRI signal amplitudes, global grey matter (gGM) functional connectivity by the median of inter-regional GM fMRI Spearman rank correlations, and gGM-CSF basal cisternae coupling by Spearman rank correlations of fMRI signals.

Results:

Anesthesia decreased cisternal CSF peak-to-trough amplitude (median difference Mdn-diff = 1.00, 95% CI [0.17 1.83], p = .013), disrupted the global, cortical BOLD-fMRI-based connectivity (Mdn-diff = 1.5, 95% CI [0.67, 2.33], p < 0.001) and, global grey matter (gGM)-CSF coupling (Mdn-diff = 1.19, 95% CI [0.36, 2.02], p = 0.002). Remarkably, the impairments of global connectivity (Mdn-diff = 0.94, 95% CI [0.11, 1.77], p = 0.022) and gGM-CSF coupling (Mdn-diff = 1.06, 95% CI [0.23, 1.89], p = 0.008) persisted after re-emergence from anesthesia.

Conclusions:

Collectively, our data show that sevoflurane impairs macroscopic CSF flow via a disruption of coherent gGM activity. This effect persists, at least for a short time, after regaining consciousness. Future studies need to elucidate whether this contributes to the emergence of postoperative neurocognitive symptoms, especially in older patients or those with dementia.
The Role of Processed Electroencephalography in the Detection and Management of Acute Cerebral Ischemia: A Scoping Review
Authors: Hewson David W. , Mankoo Alex , Bath Philip M. , Barley Mark , Dhillon Permesh , Malik Luqman , Krishnan Kailash
Published: January 2025

Processed electroencephalography (pEEG) is increasingly used to titrate the depth of anesthesia. Whether such intra-procedural pEEG monitoring can offer additional information on cerebral perfusion or acute focal or global cerebral ischemia is unknown. This scoping review aimed to provide a narrative analysis of the current literature reporting the potential role of pEEG in adults with acute cerebral ischemia. In keeping with the scoping review methodology, a broad search strategy was defined, including descriptions of encephalography in acute ischemic stroke, carotid endarterectomy, cardiac surgery, and cardiac arrest. Additional screening of citations was conducted by 2 independent assessors. From 310 records, 28 full-text articles met inclusion criteria. Most identified studies were observational in design, and described the diagnostic ability of pEEG to identify cerebral hypoperfusion or its prognostic sensitivity after stroke or carotid surgery. No studies were identified that evaluated pEEG in the specific setting of endovascular therapy for acute ischemic stroke. Low sensitivity associations between pEEG indices and cerebral blood flow were highlighted, which may be influenced by cerebral autoregulatory thresholds. Despite the associations reported in observational studies, this review identified significant uncertainty in the role of pEEG during cerebral ischemia. There is a paucity of high-level observational (cohort or case-control) or randomized trial research examining the possible role of pEEG for the detection and management of cerebral ischemia during acute stroke, including during endovascular therapy, or in other common scenarios of acute cerebral ischemia.
Is percutaneous heel cord tenotomy a necessary component in the Ponseti treatment of idiopathic clubfoot deformity?
Authors: Cao Lisa , Parenti Sarah , Jo Chan-Hee , Riccio Anthony I.
Published: January 2025

This study aimed to compare outcomes of idiopathic clubfeet (IC) treated with a percutaneous heel cord tenotomy (PHCT) at the conclusion of Ponseti casting with those that were not. A retrospective review of patients enrolled in a single institution prospective clubfoot registry over 19 years was performed. Patients under the age of 3 months with untreated IC managed via the Ponseti method that had a minimum of 2 years follow-up were included. Dimeglio score, number of casts to achieve correction, bracing compliance, need for subsequent procedures, and outcomes using the Richards classification were compared between patients who underwent a PHCT as part of their initial treatment and those that did not. A total of 1184 clubfeet in 791 patients met inclusion criteria; and 863 feet (73%) underwent a PHCT in clinic as part of initial Ponseti treatment. A total of 23% (75/321) of feet that did not undergo initial PHCT ultimately required a later PHCT or tendo-Achilles lengthening for recurrent equinus. Multivariate analysis demonstrated that an initial PHCT decreased the likelihood of requiring any additional surgical procedure by 30% (odds ratio: 0.70, P = 0.02). While an initial tenotomy was not predictive of clinical outcomes (P = 0.09), the rate of fair and poor outcomes is more than double from 13.6 to 30% when an initial tenotomy was not performed in feet with Dimeglio scores of 13 or greater (P = 0.02). Incorporation of a PHCT at the conclusion of Ponseti casting may reduce the need for subsequent and more invasive surgical interventions in IC patients, especially those with Dimeglio scores of 13 or greater. Level of evidence: therapeutic level III.
Stereotactic body radiotherapy and poly (ADP-ribose) polymerase inhibitors in ovarian cancer: a knowledge and attitudes survey in collaboration with the Italian Association of Radiation Oncology (AIRO) and Multicenter Italian Trials in Ovarian Cancer (MITO) groups
Authors: Macchia Gabriella , Pezzulla Donato , Russo Donatella , Campitelli Maura , Lucci Simona , Fanelli Mara , Deodato Francesco , Fagotti Anna , Gambacorta Maria Antonietta , Savarese Antonella , Pignata Sandro , Aristei Cynthia , Ferrandina Gabriella
Published: January 2025

The aim of this study was to present a nationwide survey on the specialist’s attitudes towards stereotactic body radiotherapy (SBRT) combined with poly (ADP-ribose) polymerase inhibitors (PARPi) with oligometastatic/oligoprogressive/oligorecurrent ovarian cancer (oMPR-OC) patients. The 19-item questionnaire was developed by specialists and distributed online. Replies were stratified by categories and analyzed using descriptive statistics. Respondents (N = 100) were radiation oncologists (57%), medical oncologists (32%), and gynecologic oncologists (11%). Fifty-four percent of respondents considered medical oncologists as the primary oncologists for oMPR-OC, while 23% preferred radiation oncologists and 15% favored gynecologic oncologists. Seventy-three percent discuss these cases in the Multidisciplinary Tumor Board, while 15, 6, and 2% send the patients straight to SBRT, surgery, or chemotherapy, respectively. Seventy-four percent of the experts interviewed were treated with SBRT less than 10 oMPR-OC patients. Concomitant treatment was highly heterogeneous, but it had little to no reported side effects. A significant variation in how PARPi is managed during SBRT was found: 34% do not interrupt the administration, while 52% pause and restart it later. Forty-three percent of respondents believe that the PARPi dosage should not be reduced when administered concurrently with SBRT. Sixty-nine percent of respondents believe that the SBRT dose should not be decreased while receiving PARPi if the constraints are met. The majority of respondents (40%) favored expert consensus for enhancing the clinical management of oMPR-OC, while 34% preferred clinical guidelines. A lack of or low toxicity with the combination of PARPi and SBRT was perceived, and a significant degree of heterogeneity concerning clinical protocols for their combination. Moreover, it emphasizes the low number of patients who have received this treatment approach nationwide.
An Unusual Case of Polypoidal Choroidal Vasculopathy Associated With Mirabegron Use: A Case Report and Review of the Literature
Authors: Raffi Hasan , Boyle Robert , Krachmalnick Sara , Ajlan Radwan
Published: January 2025

A case report of a 24-year-old female on mirabegron who presented with vision loss and found to have choroidopathy. After cessation of mirabegron, visual acuity improved and choroidopathy stabilized suggesting a relation between mirabegron and choroidopathy. This case highlights the important implication that early detection of mirabegron-associated choroidopathy- and cessation- may play an important role in optimization of visual outcomes.
Venoarterial Extracorporeal Membrane Oxygenation for Support of Vasodilatory Shock in Children Due to Toxicological Ingestions
Authors: Pepin Lesley , Nguyen HoanVu , Kilgore Stephanie , Wang George Sam , Kim John S.
Published: January 2025

Venoarterial extracorporeal membrane oxygenation (VA ECMO) may provide temporary hemodynamic support for patients with severe vasodilatory shock due to toxicologic ingestion. In a series of 10 cases of children less than 18 years of age who received VA ECMO support for toxicologic-induced vasodilatory shock, there were eight survivors and two nonsurvivors who died of significant neurologic injury. Upon initiation of ECMO support, survivors had decline in Vasoactive-Inotrope Scores (VIS). With the exception of one survivor who had a VIS range of 5–10, the seven remaining survivors had reduction in VIS by half at a median of 5.3 (interquartile range [IQR]: 3.7–12) hours. Nonsurvivors demonstrated no VIS reduction on ECMO before death. Six of 10 patients received continuous renal replacement therapy (CRRT) while on ECMO and potentially had augmentation of toxin clearance or treatment of severe acidosis as a result. Of the eight survivors, four patients had ECMO-related bleeding or thrombotic complications (three patients with stroke and one patient with extremity compartment syndrome). Venoarterial extracorporeal membrane oxygenation, with and without CRRT, may have potential utility and benefit in supporting poisoned patients with vasodilatory shock.
FibroScan Discordance With Liver Biopsy Significantly Overestimates Advanced Fibrosis and Cirrhosis in MASLD Subjects With Class 3 Obesity
Authors: Velji-Ibrahim Jena , Woodard Jordan , Alden Jay , Abrams Gary A.
Published: January 2025

Goals:

To investigate the effect of obesity on the stages of fibrosis discordance between FibroScan and liver biopsy.

Background:

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of liver disease worldwide. Accurate fibrosis assessment is essential in MASLD patients for prognosis and treatment. Vibration-controlled transient elastography using FibroScan can overestimate liver fibrosis in obese patients.

Study:

This retrospective study included 245 MASLD patients who underwent FibroScan and liver biopsy. Participants were included with FibroScan controlled attenuation parameter (CAP) 250+, 10 liver stiffness measurements (LSM) with IQR/med ≤30%, and 10+ portal tracts on biopsy. Discordance was defined as a ≥2 stage difference between FibroScan and liver biopsy. Participants were stratified by BMI and obesity class to assess their association with discordance. We conducted a post hoc analysis to determine the implication of discordance on resmetirom eligibility. Data was entered into SPSS v28.

Results:

Among 245 patients, 29.4% exhibited a ≥2 stage discordance between FibroScan and biopsy. Class 3 obesity was significantly associated with discordance (38.6%) compared with class 2 obesity (24.6%) and class 0 to 1 obesity (18.4%). FibroScan suggested cirrhosis in 66 (57.9%) participants with class 3 obesity, however, liver biopsy confirmed cirrhosis in only 16 (24.2%) subjects and identified 28 (42.4%) subjects with stages 2 to 3 fibrosis, making them potentially eligible for resmetirom.

Conclusions:

FibroScan significantly overestimates advanced fibrosis and cirrhosis in class 3 obesity. A second noninvasive test is warranted for accurate liver-directed therapeutic allocation and to minimize unnecessary biopsies in MASLD management.
FAP-Targeted SPECT/CT and PET/CT Imaging for Breast Cancer Patients
Authors: McGale Jeremy , Khurana Sakshi , Howell Harrison , Nakhla Abanoub , Roa Tina , Doshi Parth , Shirini Dorsa , Huang Alice , Duong Phuong , Backhaus Philipp , Liao Matthew , Kaur Harleen , Fontani Amelia McNiven , Hung Isabella , Pandit-Taskar Neeta , Haberkorn Uwe , Gulati Amit , Naim Asmâa , Sinigaglia Mathieu , Bebawy Maria , Girard Antoine , Seban Romain-David , Dercle Laurent
Published: January 2025

Breast cancer presents a significant global health challenge, necessitating continued innovation in diagnostic and therapeutic approaches. Recent advances have led to the identification of cancer-associated fibroblasts, which are highly prevalent in breast cancers and express fibroblast activation proteins (FAPs), as critical targets. FAP-specific radiotracers, when used with PET/CT and SPECT/CT, have significant potential for improving early breast cancer detection, staging, treatment response monitoring, and therapeutic intervention. This review provides insight into FAP-targeted molecular imaging, exploring advanced techniques for protein status assessment, development of early-phase targeted therapies, and other emerging applications. The advent of FAP-targeted imaging stands to significantly enhance personalized oncologic care, leading to improved breast cancer management and overall patient outcomes.
What’s the Gut Doing in the Chest? Interpositio Hepatodiaphragmatica (Chilaiditi Sign) Revisited on 18F-FDG PET/CT
Authors: Gondhane Abhay , Malhotra Gaurav
Published: January 2025

A 47-year-old woman, a diagnosed case of syndrome of inappropriate secretion of antidiuretic hormone, underwent 18F-FDG PET/CT to detect occult malignancy for suspected paraneoplastic etiology. Abnormal FDG uptake was noted in the right lower chest region, which was correlated on corresponding CT images to be colonic activity interposed between the liver and elevated diaphragm, also known as Chilaiditi sign. Even though rare, Chilaiditi sign should be considered as a differential diagnosis of hypermetabolic activity in the right lower chest region on 18F-FDG PET/CT scan that is done to look for occult tumor as shown in this case.
Study on Time Distribution and Pathogenic Bacteria of Infection After Auricular Reconstruction With Tissue Expansion for Microtia
Authors: Jia Xuanye , Su Ruonan , Zhi Jiajun , Jiang Fengli , Jiang Haiyue , Pan Bo
Published: January 2025

Background:

Postoperative infection is one of the main complications that affect the surgical effect of auricular reconstruction with tissue expansion. Understanding the susceptible time and distribution of pathogens is especially important for the treatment.

Method:

The data of patients with infection after auricular reconstruction with tissue expansion from September 1, 2018 to August 30, 2024 were collected retrospectively. The microbe species identification results, diagnosis time of infection, surgical methods, and kinds of pathogenic bacteria were analyzed. Statistical methods were used to analyze and calculate the difference in infection time and the distribution of pathogenic bacteria.

Result:

From September 1, 2018 to August 30, 2024, 237 cases of infection after auricle reconstruction with tissue expansion were diagnosed, and 252 strains of 18 kinds of pathogenic bacteria were detected. Among them, S. aureus (85 strains, 33.73%) and S. epidermidis (40 strains, 15.87%) were the 2 main pathogens. Postoperative infection mainly occurred in the first stage (72 cases, 30.38%) and the second stage (98 cases, 41.35%). The MRSA infection rate in the second stage (24.46%) was significantly higher than that in the other stages. The infection rate was significantly higher in winter (from November to January) (P<0.05). There was no significant difference among other seasons (P>0.05).

Conclusion:

The main pathogen of infection after ear reconstruction with tissue expansion is Staphylococcus aureus, and winter is the peak period of infection. There are some differences in infection rate and distribution of pathogenic bacteria in different stages of surgery.
Enhanced Recovery After Surgery Protocol Compliance and Early Outcomes for Elective Colorectal Procedures by Race/Ethnicity and Socioeconomic Status
Authors: Antoniv Marta , Maldonado Luisa Jane , Nikiforchin Andrei , Gershanik Esteban Fabian , Bleday Ronald
Published: January 2025

Objective:

To explore the association of socioeconomic status (SES) and race/ethnicity with perioperative metrics within the Enhanced Recovery After Surgery (ERAS) framework to identify gaps for equity-informed improvements.

Summary Background Data:

Although ERAS pathways improve perioperative outcomes through standardized care, disparities in protocol adherence and postoperative outcomes persist, particularly for vulnerable populations.

Methods:

We conducted a retrospective cohort study using a single-institution database of elective colorectal surgeries (2018-2021). Patients were categorized and assessed by SES and race/ethnicity.

Results:

Overall, 1,519 patients were analyzed: 180 had low SES (11.8%) and 1,339 – high SES (88.2%). Low SES patients had lower rates of bowel preparation completion, use of the electronic patient portal, and carbohydrate loading pre-surgery. Low SES was associated with a longer median length of stay (LOS) (4 vs. 3 days, P<0.001). Multivariate logistic regression analysis showed low SES was linked to higher odds of infectious (OR 2.46, 95%CI: 1.31-4.63) and all in-hospital complications (OR 1.50, 95%CI: 1.06-2.12). Among racial/ethnic cohorts, Black patients had lower rates of documented preoperative patient education, longer median LOS (5 vs. 3-4 days, P=0.002), and increased odds of respiratory complications (OR 4.11, 95%CI: 1.56-10.85).

Conclusions:

Low SES was linked to lower compliance with important process measures, higher infectious and all in-hospital complication rates, and longer LOS. Despite high rates of protocol compliance, Black race/ethnicity showed an association with increased odds of respiratory complications and extended LOS. Adjustments to perioperative protocols could address such disparities, helping to improve postoperative outcomes of colorectal surgeries.
Research Agenda for Entrustable Professional Activities Among US Surgical Specialties
Authors: Sandhu Gurjit , Jones Andrew , Barry Carol L. , Buyske Jo , Mellinger John D. , Lindeman Brenessa
Published: January 2025

The magnitude of advances in surgical care inspires awe consistent with the impact of these developments on patients’ lives. With this comes greater knowledge, new practices, and novel technologies for integration into residency training, making the skillset required of today’s residents quite different from those in the past. Competency-based medical education and learner-centered approaches offer innovative and studied methodologies for teaching, learning, and assessment to meet the demands of today’s educational environment. The authors provide an overview of competency-based medical education, its association with Accreditation Council for Graduate Medical Education Milestones as a competency framework, a description and outline of the emerging execution of Entrustable Professional Activities in the surgical disciplines, and a research agenda focused on Entrustable Professional Activities for American Board of Surgery certified surgical specialties in the United States. The research agenda includes five domains of inquiry: entrustment and practice readiness; bias and environment; distinguishing features and certification; qualitative feedback; and patient outcomes, and builds upon prior work by ten Cate et al. by expanding upon their organizing framework to also include the element of time. Additionally, the authors provide questions and suggest data integration strategies that might foster a breadth of studies investigating the utility of Entrustable Professional Activities in surgical training. Collectively engaging in such a process of evaluation early in the process of competency-based reform will serve to optimize education, assessment, and ultimately patient care.
Defining an NK Cell–enriched Rejection-like Phenotype in Liver Transplant Biopsies From the INTERLIVER Study
Authors: Madill-Thomsen Katelynn S. , Gauthier Patrick T. , Abouljoud Marwan , Bhati Chandra , Bruno David , Ciszek Michał , Durlik Magdalena , Feng Sandy , Foroncewicz Bartosz , Grąt Michał , Jurczyk Krzysztof , Levitsky Josh , McCaughan Geoff , Maluf Daniel , Montano-Loza Aldo , Moonka Dilip , Mucha Krzysztof , Myślak Marek , Perkowska-Ptasińska Agnieszka , Piecha Grzegorz , Reichman Trevor , Tronina Olga , Wawrzynowicz-Syczewska Marta , Zeair Samir , Halloran Philip F.
Published: January 2025

Background.

Initial analysis of liver transplant biopsies in the INTERLIVER study (ClinicalTrials.gov; unique identifier NCT03193151) using rejection-associated transcripts failed to find an antibody-mediated rejection state (ie, rich in natural killer [NK] cells and with interferon-gamma effects). We recently developed an optimization strategy in lung transplants that isolated an NK cell–enriched rejection-like (NKRL) state that was molecularly distinct from T cell–mediated rejection (TCMR). Here we apply the same strategy to a liver transplant biopsy population.

Methods.

We used this strategy to search for a molecular NKRL state in 765 consented liver transplant biopsies collected at participating international centers for gold-standard histology and molecular assessment by genome-wide microarrays. Validation through a training set-test set approach of an optimized selection of variables as inputs into unsupervised rejection classification identified an NKRL state in livers.

Results.

The full model classified 765 biopsies into the following molecular phenotypes, characterized by their gene expression: no-rejection 54%, TCMR 16%, NKRL 13%, and injury 16%. Top TCMR transcripts were expressed in effector T cells; top NKRL transcripts were almost exclusively expressed in NK cells; and both had increased interferon-γ-inducible transcripts, which were more pronounced in TCMR. Most TCMR biopsies had significant parenchymal injury, molecular fibrosis, and abnormal biochemistry. NKRL biopsies had no excess of injury, fibrosis, or biochemistry abnormalities.

Conclusions.

Optimized rejection algorithms indicate that some liver transplants manifest an NKRL state that is well tolerated in the short term postbiopsy and with minimal injury and relatively normal biochemistry, while also underscoring the potential of TCMR to produce extensive parenchymal injury.
Understanding Liver Transplantation Outcomes Through the Lens of Its Tissue-resident Immunobiome
Authors: Prosser Amy C. , Klenerman Paul , Lucas Michaela
Published: January 2025

Tissue-resident lymphocytes (TRLs) provide a front-line immunological defense mechanism uniquely placed to detect perturbations in tissue homeostasis. The heterogeneous TRL population spans the innate to adaptive immune continuum, with roles during normal physiology in homeostatic maintenance, tissue repair, pathogen detection, and rapid mounting of immune responses. TRLs are especially enriched in the liver, with every TRL subset represented, including liver-resident natural killer cells; tissue-resident memory B cells; conventional tissue-resident memory CD8, CD4, and regulatory T cells; and unconventional gamma-delta, natural killer, and mucosal-associated invariant T cells. The importance of donor- and recipient-derived TRLs after transplantation is becoming increasingly recognized, although it has not been examined in detail after liver transplantation. This review summarizes the evidence for the roles of TRLs in liver transplant immunology, focusing on their features, functions, and potential for their harnessing to improve transplant outcomes.
Using the natural capital framework to integrate biodiversity into sustainable, efficient and equitable environmental-economic decision-making
Authors: Binner Amy R. , Addicott Ethan T. , Balmford Ben , Day Brett H. , Mancini Mattia C. , Williamson Danny , Bateman Ian J.
Published: January 2025

One of Georgina Mace’s many transformational research contributions was to provide a universally applicable framework for incorporating any or all elements and connections of the natural environment within conventional economic decision-making. We apply this natural capital framework to consider the overall effects of a suite of land-use policy options intended to promote the conservation and renewal of biodiversity. Options considered include sharing, sparing, three-compartment sparing, rewilding and organic farming regimes. Each is assessed in terms of its impact on both domestic and global biodiversity. Reinforced by an empirical application considering land use in Great Britain, we show that while policy has prioritized sharing options, evidence supports land sparing and three-compartment approaches as more efficient, sustainable and equitable alternatives.

This article is part of the discussion meeting issue ‘Bending the curve towards nature recovery: building on Georgina Mace's legacy for a biodiverse future’
An African perspective to biodiversity conservation in the twenty-first century
Authors: Bezeng Bezeng S. , Ameka Gabriel , Angui Chia Michelle Valérie , Atuah Laura , Azihou Fortuné , Bouchenak-Khelladi Yanis , Carlisle Frank , Doubi Bi Tra Serges , Gaoue Orou G. , Gatarabirwa Wenceslas , Gitau Consolata , Hilton-Taylor Craig , Hipkiss Alex , Idohou Rodrigue , Kaplin Beth A. , Kemp Lucy , Mbawine Jacqueline S. , Logah Vincent , Matiku Paul , Ndang’ang’a Paul Kariuki , Nana Eric D. , Mundi Onella N. N. , Owusu Erasmus H. , Rodríguez Jon Paul , Smit-Robinson Hanneline , Yessoufou Kowiyou , Savolainen Vincent
Published: January 2025

Africa boasts high biodiversity while also being home to some of the largest and fastest-growing human populations. Although the current environmental footprint of Africa is low compared to other continents, the population of Africa is estimated at around 1.5 billion inhabitants, representing nearly 18% of the world’s total population. Consequently, Africa’s rich biodiversity is under threat, yet only 19% of the landscape and 17% of the seascape are under any form of protection. To effectively address this issue and align with the Convention on Biological Diversity’s ambitious ‘30 by 30’ goal, which seeks to protect 30% of the world’s land and oceans by 2030, substantial funding and conservation measures are urgently required. In response to this critical challenge, as scientists and conservationists working in Africa, we propose five recommendations for future directions aimed at enhancing biodiversity conservation for the betterment of African society: (i) accelerate data collection, data sharing and analytics for informed policy and decision-making; (ii) innovate education and capacity building for future generations; (iii) enhance and expand protected areas, ecological networks and foundational legal frameworks; (iv) unlock creative funding channels for cutting-edge conservation initiatives; and (v) integrate indigenous and local knowledge into forward-thinking conservation strategies. By implementing these recommendations, we believe Africa can make significant strides towards preserving its unique biodiversity, while fostering a healthier society, and contributing to global conservation efforts.

This article is part of the discussion meeting issue ‘Bending the curve towards nature recovery: building on Georgina Mace's legacy for a biodiverse future’.
Identification of Starmerella aleppica f.a., sp. nov. and large indels in the rRNA cistron that split the Starmerella genus
Authors: Sipiczki Matthias , Baghela Abhishek
Published: January 2025

Yeast strains representing a novel asexual ascomycetous species were isolated from seven Malva sylvestris flowers. Sequencing of the chromosomal regions coding for the D1/D2 domains of the large subunit ribosomal RNA, the ITS1-5.8S-ITS2 segments and parts of the gene coding for the small subunit ribosomal RNA showed that the isolates were conspecific. Comparative analysis of these sequences and the corresponding sequences of the type strains of ascomycetous yeasts revealed that the strains represent a hitherto undescribed species belonging to the sensu stricto subclade of the genus Starmerella. The new species is osmotolerant and can develop invasive pseudohyphae, but does not form spores. For the new species, the name Starmerella aleppica f.a. (forma asexualis) is proposed. The holotype, preserved in a metabolically inactive state, is CBS 12960T (extype cultures: 2-1361 and CCY 90-2-1, NCAIM Y.02123). The GenBank accession numbers of barcode sequences are JX515983 (D1/D2 domain), JX515985 (ITS1-5.8S-ITS2 and partial 18S rRNA gene), PQ613837 (TEF1 partial sequence) and PQ613838 (RPB2 partial sequence). MycoBank: MB855459. The analysis of the D1/D2 and internal transcribed spacer (ITS) sequences of the type strains of species of the genus identified multiple multinucleotide indels that can be used as taxonomic markers (InDel markers). The indel patterns of the subclades are very different and homogeneous within the subclades. This result reinforces the idea raised, but also refuted, in previous studies that the Starmerella subclades may represent different genera.
Over-expressed KRT8 in the cytotrophoblast shell promotes the development of preeclampsia
Authors: Chen Miaomiao , Yang Xiaohong , Chen Xiangyi , Yin Hen , Wu Junbo , Peng Jing , Sha Menghan , Liu Chunyan , Dai Qianwen , Zhao Kai , Zhao Yun
Published: January 2025

Preeclampsia is a “placenta-derived disorder” characterized disease, which remains a major unaddressed public health problem. The differentiation and development of cytotrophoblasts and extravillous trophoblasts are two crucial processes, which are tightly regulated. And any abnormal regulation can lead to the occurrence of pregnancy-related diseases such as preeclampsia. In this article, we performed Spatial transcriptomics on tissues of PE and Normal, and found a large amount of extravillous trophoblasts (EVTs) were accumulated in the cluster 8 (cytotrophoblast shell) of PE_decidua, and Trajectory analysis revealed KRT8 was over-expressed in the cytotrophoblast shell of PE_decidua. The accumulation of EVTs caused by the increase of KRT8 promotes the development of preeclampsia.
Pre-stimulation of Precision-Cut bovine udder slices with zymosan before LPS exposure indicates indicators for trained immunity
Authors: Filor Viviane , Myslinska Joanna , Saliani Amitis , Dalli Jesmond , Steinbach Sabine , Olinga Peter , Bäumer Wolfgang , Werling Dirk
Published: January 2025

Mastitis in cattle poses a significant health challenge and results in substantial economic losses for the dairy industry. This study aimed to establish precision-cut bovine udder slices (PCBUS) as an in vitro model to explore the potential of stimulating trained immunity in the udder. The goal was to investigate whether this approach could influence the early pathophysiological processes of mastitis and pave the way for developing new therapeutic strategies for udder inflammation in future research. PCBUS remained viable in culture for up to two weeks. When stimulated with E. coli-derived lipopolysaccharide (LPS), zymosan (an inducer of trained immunity), or pre-incubated with zymosan followed by LPS stimulation, the slices exhibited distinct responses in terms of pro-inflammatory cytokine production and lipid mediator profiles. Additionally, cytokine production was influenced by the presence or absence of fetal calf serum (FCS), highlighting the potential limitations of FCS in in vitro studies. While the current experimental setup did not definitively confirm the induction of trained immunity in the bovine udder, it validated the utility of PCBUS as a robust in vitro model for studying bovine udder inflammation. This model offers a promising platform for developing innovative mastitis treatments, particularly given the growing concern over antimicrobial resistance. It also provides a valuable tool for advancing our understanding of immune responses in the bovine udder. By adapting the precision-cut tissue slice technique to bovine udders, this model enables extensive research into new therapeutic approaches and supports basic research efforts to characterize complex pathophysiological processes associated with mastitis.
Endovascular structures of the basilar artery: forms of the basilar nonfusion spectrum
Authors: Sługocki Mikołaj , Rzepliński Radosław , Tarka Sylwia , Stępień Tomasz , Tomaszewski Michał , Kucewicz Michał , Kępczyńska Gabriela , Małachowski Jerzy , Ciszek Bogdan
Published: January 2025

Introduction

Cerebrovascular diseases are a growing social and clinical problem, and their pathogenesis is currently being thoroughly investigated. The intravascular anatomy of the cerebral circulation remains poorly understood, although an increasing number of endovascular interventions are being conducted during the course of diagnosis and treatment. The purpose of this study was to describe intravascular structures in the vertebrobasilar system and to investigate the hemodynamic consequences of their presence.

Methods

Thirty anatomical specimens of the human brain were analyzed via angioscopy of the vertebrobasilar system, and the presence of intravascular structures was documented. Additional histological studies were performed. The effect on blood flow was simulated using computational fluid dynamics by studying 5 different cases.

Results

In 8 cases (26.7%), the following endovascular structures were visualized: 6 strings, one septum, and one chord. The histological structure showed a layered pattern, resembling that of the arterial wall: the outermost tunica intima, the innermost adventitia and the tunica media in between. Blood flow simulations revealed several areas of disturbed flow, including areas of low wall shear stress and recirculations, as well as areas of elevated wall shear stress.

Conclusions

Intravascular structures are common in the basilar artery. The reason for their formation is the incomplete fusion of the longitudinal neural arteries, and together with fenestrations, they belong to the basilar nonfusion spectrum. The presence of structures can cause technical difficulties and ischemic complications related to endovascular interventions. Hemodynamic changes caused by endovascular structures can promote atherosclerosis, thromboembolism, narrowing of the pontine arteries and the development of aneurysms.
Bleeding Risk with Combination Antithrombotic Therapy: A Propensity-Score Matched Analysis
Authors: Farrokh Salia , Nalleballe Krishna , Onteddu Sanjeeva , Suarez Jose I. , Bösel Julian , Shah Vishank A.
Published: January 2025

Background

Limited data exist on the safety of combining antiplatelets and anticoagulants (AC) for secondary stroke prevention in acute ischemic stroke (AIS). We sought to examine the hemorrhage risk with combining single (SAPT) or dual antiplatelet therapy (DAPT) with AC in AIS patients with concomitant atrial fibrillation (AF) and acute myocardial infarction (MI).

Methods

This retrospective cross-sectional cohort study used TriNetX, a federated health analytics database that collects real-time electronic health records data from 76 participating healthcare organizations in the United States. Through queries performed on March 31, 2023, adult patients with simultaneous diagnoses of AIS, AF and acute MI were identified using ICD-10 codes over the past 20 years. Propensity score-matched analysis, matching for demographics and vascular co-morbidities, compared the odds for acute spontaneous ICH and GI bleeding at 3-months, 12-months and throughout follow-up within TriNetX, between three matched sub-cohorts: AC alone, AC+SAPT, and AC+DAPT.

Results

Among 144,434 AIS patients with AF and MI (mean age, 71.9 years; 43.3% female), 8772 (6.1%) patients received AC alone, 88,430 (61.2%) received AC+SAPT, and 47,232 (32.7%) received AC+DAPT. After propensity-score matching, 8,706 patients were included in each sub-cohort. Compared to AC alone, AC+SAPT and AC+DAPT showed no significant increase in ICH risk at 3 and 12 months but increased long-term risk throughout follow-up (odds ratio [95% confidence intervals] for AC+SAPT, 1.26 [1.11-1.44], p<0.001; for AC+DAPT, 1.34 [1.18-1.53],p<0.001). Gastrointestinal (GI) bleeding risk was elevated at all time-points with combination therapies.

Conclusion

Within the limitations of a retrospective cross-sectional study using administrative data, this large propensity-score matched analysis demonstrates that combining antiplatelets with anticoagulants after AIS may be associated an increased risk of ICH only in the long-term, beyond 12-months, but with an increased risk of acute GI bleeding in the short and long-term. Larger prospective studies are warranted to confirm our findings.
Paediatric Palliative Care following Hospital discharge: Prevalence and factors associated with non-continuity of palliative care for children with cancer in Busoga sub-region-eastern Uganda; A mixed methods study
Authors: Ajambo Miriam , Rujumba Joseph , Mwaka Savio , Nyanzi Joseph Gavin , Nalwanga Damalie , Balagadde Joyce
Published: January 2025

Background

Palliative care (PC) is crucial for children with cancer to alleviate suffering and enhance quality of life. However, continuity of pediatric palliative care (PPC) can be disrupted by factors such as lack of knowledge, stigma, bureaucratic hurdles, inadequate referral systems, and staffing shortages. There is limited data on the prevalence and factors associated with non-continuity of PPC in Uganda. This study explores the prevalence and factors contributing to non-continuity of PC among children with cancer in Uganda with Busoga Region in Eastern Uganda as a case study.

Methodology

This cross-sectional mixed-methods study was conducted at two specialized tertiary facilities in Uganda managing pediatric cancer. Data were extracted from online databases for 307 children treated from 2019 to 2023, of whom 80 were alive during the study. Caregivers of 77 children participated in interviews, and nine key informants from the two facilities and the only regional facility providing PC upon downward referral were also interviewed. Descriptive statistics summarized data as proportions or percentages, and bivariate analysis used crude odds ratios to identify significant associations. Key informant interviews were transcribed and analyzed thematically using the socio-ecological model.

Results

The prevalence of non-continuity of PC was 96.1% (95% CI: 88.4-98.0). Barriers identified included: individual-level gaps in caregiver knowledge; relationship-level issues such as inappropriate cultural beliefs; health system-level challenges like limited human resources, inadequate training and funding, poor coordination and referral pathways, and service access issues; and policy-level concerns, including the lack of a national palliative care policy.

Conclusion

The high prevalence of non-continuity of PC for children with cancer in Busoga highlights significant deficiencies in integrating palliative care into pediatric oncology services in Uganda. Addressing these challenges requires urgent government action to enhance palliative care funding and resources.