bluuebunny/crossref_metadata_2025 huggingface dataset:
Frustrations in Providing Orthopaedic Trauma Care: An OTA Member Survey Study
Authors: Kleinsmith Rebekah M. , Doxey Stephen A. , Puckett Haley D. , Duckworth Elizabeth A. , Milshteyn Michael , Hill Austin D. , Cunningham Brian P.
Published: December 2024

OBJECTIVES:

To determine sources of frustration for surgeons and how they might affect job satisfaction within the orthopaedic trauma community.

METHODS:

Design:

Cross-Sectional Survey Study.

Setting:

International Online Survey.

Participant Selection Criteria:

After approval by the OTA research committee, the survey was available to all active and associate OTA Members.

Outcome Measures and Comparisons:

A 25-question survey regarding potential common causes of frustration, operating room (OR) utilization, and career satisfaction was electronically distributed to the Orthopaedic Trauma Association (OTA) membership.

RESULTS:

Four hundred seventy-one surgeons participated in the survey (response rate 27.5%). The highest ranked source of frustration was OR turnover time, followed by staff turnover, and OR scheduling. Most reported they were very satisfied with their career (n = 240, 51.0%). The top 3 strategies to increase career satisfaction from most to least effective were increased compensation, case delay reduction, and decreased work hours. Most surgeons reported that if their number 1 frustration was solved, they would feel a higher level of career satisfaction (very satisfied: n = 344, 73.1%). Most felt their cases did not start on time (n = 273, 58.0%), with most respondents reporting that their cases were delayed on average between 15 and 60 minutes (n = 222, 81.9%). The number 1 ranked reason for case start delays was OR turnover and case setup, followed by the anesthesia team.

CONCLUSIONS:

Many surgeons within the orthopaedic trauma community reported concern with OR turnover time and staff turnover. Addressing these sources of frustration is crucial to maintaining surgeon well-being and can aid in optimizing delivery of patient care. Future studies should seek out institutions that have successfully addressed these common frustrations and identify potential strategies to improve the delivery of orthopaedic trauma care across North America.
The menopausal transition and multiple physiologic measures of early brain health in the Coronary Artery Risk Development in Young Adults study
Authors: Tahir Muna J. , Xie Yang , Nasrallah Ilya M. , Elbejjani Martine , Wellons Melissa F. , Bryan R. Nick , Dolui Sudipto , Erus Guray , Launer Lenore J. , Schreiner Pamela J.
Published: December 2024

Objective

This study proposed to investigate the cross-sectional and longitudinal associations of menopausal status with physiologic brain magnetic resonance imaging measures.

Methods

The sample included women from the Coronary Artery Risk Development in Young Adults study who self-reported their reproductive histories and participated in the brain magnetic resonance imaging substudies at the year 25 (n = 292) and year 30 (n = 258) follow-up examinations. Menopausal status was classified based on natural menstrual cycle regularity/cessation at both time points. Gray matter cerebrovascular reactivity (CVR) was calculated as mean percent change in blood oxygen level–dependent signals in activated voxels following a breath-hold challenge. Gray matter cerebral blood flow (CBF) was assessed using pseudo-continuous arterial spin labeling. Linear regression models were used to examine cross-sectional and longitudinal associations of menopausal status with gray matter CVR and CBF after adjustment for potential age-related covariates.

Results

Women were mean age 50 years at year 25; 37% were Black; and 46% were postmenopausal. Relative to premenopause or perimenopause, postmenopause was associated with lower gray matter CVR at year 30 cross-sectionally (1.86% vs 1.69%, P = 0.03, respectively) and longitudinally for women who were postmenopausal at both time points (−0.32% [95% CI, −0.63% to −0.02%]) after covariate adjustment. Mean CVR values were also lower for these women when compared with women who remained premenopausal or perimenopausal (1.71% compared with 2.04%, respectively). Menopausal status was unrelated to either concurrent or longitudinal gray matter CBF.

Conclusions

These findings suggest that the ability of vessels to adapt in response to hypercapnia may be impaired during menopause, even within a relatively short time window.
N-Acetylcysteine enhances low-dose estrogen efficacy against ischemia-reperfusion injury in estrogen-deprived obese insulin-resistant rats
Authors: Sivasinprasasn Sivaporn , Chattipakorn Kenneth , Pratchayasakul Wasana , Chattipakorn Siriporn C. , Chattipakorn Nipon
Published: December 2024

Objectives

Postmenopausal women are at higher risk of metabolic syndrome and cardiovascular disease, which are aggravated by obesity. Although estrogen provides cardiometabolic protection, chronic high-dose treatment could be harmful. This study investigated the efficacy of combined N-acetylcysteine (NAC) and low-dose estrogen treatment against cardiometabolic dysfunction in female estrogen-deprived obese rats with cardiac ischemia-reperfusion (I/R) injury.

Methods

Bilateral ovariectomized (O) female Wistar rats were fed a high-fat diet (H) for 12 weeks. Then, rats were treated for 4 weeks with one of the following: vehicle (OH; sesame oil), regular-dose estrogen (E; 50 μg/kg/d), low-dose estrogen (e; 25 μg/kg/d), NAC (N; 100 mg/kg/d), or combined low-dose estradiol with NAC (eN). All rats then underwent cardiac I/R injury, and the left ventricle (LV) function and mitochondrial function were investigated (n = 6/group). Statistical analysis was performed by one-way ANOVA followed by Fisher's least significant difference post hoc test.

Results

Body weight, visceral fat, plasma glucose, and plasma cholesterol were significantly increased with impaired LV function and heart rate variability in OH rats. OH-E rats had decreased plasma insulin and Homeostatic Model Assessment for Insulin Resistance index. Both OH-E and OH-eN rats had similarly improved heart rate variability and LV function. During cardiac I/R, OH-E and OH-eN rats had preserved left ventricular ejection fraction, stroke volume, and attenuated arrhythmias. Impaired cardiac mitochondrial function and infarct size were similarly reduced in OH-E and OH-eN rats.

Conclusions

Combined NAC and low-dose estrogen treatment shares similar efficacy as regular-dose estrogen in attenuating cardiac dysfunction, cardiac mitochondrial dysfunction, and protecting the heart against I/R injury in estrogen-deprived obese insulin-resistant rats.
Validation of the Laryngeal Cognitive-affective Tool in a Taiwanese Population
Authors: Krause Amanda J. , Yadlapati Rena , Wong Ming-Wun , Taft Tiffany , Pandolfino John E. , Gyawali C. Prakash , Chen Chien-Lin
Published: December 2024

Background and Aim:

The laryngeal cognitive-affective tool (LCAT) was recently validated in the US to assess laryngeal-specific hypervigilance and anxiety. The aim of this study was to examine LCAT validity in the Taiwanese population.

Methods:

This prospective single-center study enrolled adults from Hualien Tzu Chi Hospital with laryngeal symptoms for >6 months.

Results:

One hundred four patients included: mean age 49.5 years (SD 13.3), 69% female, mean BMI 25.3 kg/m2 (5.8), and mean LCAT 25.9 (15.2). The LCAT had excellent internal consistency (α=0.969) and split-half reliability (Guttman=0.925).

Conclusions:

The LCAT is newly validated in the Taiwanese population and assesses laryngeal-specific cognitive-affective processes in patients with chronic laryngeal symptoms.
Evaluating Continuous Glucose Monitoring After Total Pancreatectomy With or Without Islet Autotransplantation
Authors: Bashir Ayat , Joseph Nejo , Hammond John S. , White Steve , Abu-El-Haija Maisam , Drewes Asbjørn Mohr , Shaw James A. M. , Pandanaboyana Sanjay
Published: December 2024

Objectives

This scoping review aims to provide evidence synthesis of continuous glucose monitoring (CGM) and insulin pump use after undergone total pancreatectomy (TP) with or without islet autotransplantation (TPIAT).

Methods

The review was conducted adhering to PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) checklist.

Results

Fifteen studies including 147 patients (adult n = 71/pediatric n = 76) reported on CGM use post-TP (n = 42) and TPIAT (n = 105). Four were randomized controlled trials and 10 observational studies. Six studies evaluated CGM use in the perioperative and 6 in the immediate postoperative period (n = 8) with variable follow-up (14 hours to 20 months). CGM was used as a stand-alone device (8 studies), which allowed assessment of glycemic variability (n=5) and detection of hypoglycemia (n = 1), resulting in lower glucose levels (n = 1). Six studies evaluated insulin pump with CGM with reduction in postoperative mean glucose (n = 4) and hypoglycemic episodes (n = 2). No patient-reported outcome measures (PROMs) or quality of life (QoL) measures were reported.

Conclusions

CGM can be used following TP for glucose monitoring and/or linked with insulin pump device in the perioperative period with improved glycemic control. However, the data are limited by short follow-up and lack of PROMs and QoL measures.
High Diagnostic Yield of Fine Needle Biopsy for Pancreatic Serous Cystadenomas – a Multi-Center Study
Authors: Kim Grace E. , Mercado Michael , Barrett Margarita Riojas , Breese Miles , Umar Shifa , Ayoub Fares , Chen Dennis , Othman Mohamed O. , Siddiqui Uzma D.
Published: December 2024

Background

Distinguishing serous cystadenoma, a benign pancreatic cyst, from potentially malignant mucinous pancreatic cystic lesions carries significant clinical and prognostic implications; and while endoscopic ultrasound-guided fine needle aspiration is the standard diagnostic tool, its low diagnostic yield often results in additional workup.

Objective

This study evaluates diagnostic yield of fine needle biopsy (FNB) on lesions suggestive of serous cystadenoma on endoscopic ultrasound.

Methods

Patients with microcystic EUS appearance were identified through retrospective chart review in two institutions. Prior cross sectional imaging diagnosis was also obtained. All microcystic lesions with classic “honeycomb” appearance for serous cystadenoma on EUS were targeted for FNB and their pathology evaluated. Patients were identified through database search from 2015 to 2022 and procedure information was obtained through a retrospective chart review from two large academic centers.

Results

Thirty-one patients with suspected serous cystadenoma who underwent EUS-FNB were included. EUS FNB was successful in obtaining diagnosis in 96.8% of patients. Serous cystadenoma was diagnosed via EUS FNB in 27 of 31 patients (87.1%). Of the remaining four patients, there was one invasive pancreatic ductal adenocarcinoma, one pancreatic neuroendocrine tumor, one intraductal papillary mucinous neoplasm, and one nondiagnostic sample.

Conclusion

EUS-FNB sampling for histopathology is a safe and accurate diagnostic tool for pancreatic serous cystadenoma. When microcytic lesions are found on endoscopic ultrasound, our study results suggest that fine needle biopsy for histopathology should be considered as the initial diagnostic evaluation tool given the demonstrated improved diagnostic yield for serous cystadenoma.
Serum trypsin is a reliable biomarker of pancreas function
Authors: Gummadi Vybhav Venkatesh , Gonska Tanja
Published: December 2024

Pancreatic diseases pose significant diagnostic and therapeutic challenges necessitating robust biomarkers for accurate diagnosis, management and monitoring of pancreas function. Pancreas function can be measured with direct (invasive) and indirect tests. However, both approaches do not allow continuous disease monitoring to identify disease progression or therapeutic response. We demonstrate literature evidence suggesting that trypsin, an important pancreatic digestive enzyme, holds promise as such a continuous biomarker. On one hand, assessment of trypsin concentration in the serum sensitively and specifically detects pancreas inflammation; whereas on the other hand, declining trypsin levels in serum showed good correlation with direct pancreatic function tests to identify exocrine pancreatic insufficiency. With this comprehensive review, we aimed to evaluate the existing evidence on the utility of trypsin as a continuous biomarker, spanning from acute to chronic pancreatitis and pancreas function, highlighting its potential in monitoring disease evolution on an individual patient level.
Psychological Symptom Cluster Severity Profiles Are Associated With Higher Levels of Stress and Worse Quality of Life in Postmenopausal Women With Breast Cancer
Authors: Harris Carolyn S. , Conley Yvette P. , Rosenzweig Margaret Q. , Erickson Kirk I. , Cooper Bruce A. , Bender Catherine M.
Published: December 2024

Background

Although common, the severity of the psychological symptom cluster (PSC) (ie, co-occurrence of anxiety, depression, fatigue, sleep disturbance) varies among women with breast cancer. In addition, the impact of various types of stress and other risk factors on its severity are understudied, and the influence of the PSC on quality of life (QOL) outcomes remains poorly characterized.

Objective

To identify subgroups of postmenopausal women with breast cancer with distinct PSC severity profiles following surgery and evaluate whether these subgroups differed in terms of demographic and clinical characteristics, symptoms, social and posttraumatic stress, and QOL.

Methods

Following surgery, 159 postmenopausal women with early-stage, hormone receptor–positive breast cancer completed assessments of anxiety, depression, fatigue, sleep disturbance, cognitive function, physical symptoms, stress, and QOL. Latent profile analysis was used to identify subgroups of women based on the severity of the prespecified PSC. Parametric and nonparametric tests were used to evaluate for subgroup differences.

Results

Three distinct PSC severity subgroups were identified (ie, Lower [71.7%], Moderate [23.9%], Higher [4.4%]). Compared with the Lower subgroup, the Moderate subgroup was less likely to have received prior radiation, and the Moderate and Higher subgroups had worse perceived cognitive function, higher symptom burden, higher posttraumatic stress, and lower QOL. Clinically relevant sleep disturbance was common across PSC subgroups.

Conclusions

PSC severity is associated with higher posttraumatic stress and poorer QOL following breast surgery. Sleep disturbance is a common problem and may be undertreated.

Implications for Practice

Assessments of posttraumatic stress and sleep disturbance are needed for timely intervention.
Development and Preliminary Testing of the Withdrawal Assessment Tool-Alpha 2 Agonist: An Assessment Instrument for Monitoring Iatrogenic Withdrawal Symptoms in Children Receiving an Alpha-2 Agonist
Authors: Solodiuk Jean C. , Donado Carolina , Wickerham Lia , Goodyear Lindsay , Hayes John , Mortell Rachel E. , Greco Christine D. , Curley Martha A. Q.
Published: December 2024

OBJECTIVES:

To develop and conduct preliminary testing of the Withdrawal Assessment Tool-Alpha 2 Agonist (WAT-A2A) to monitor dexmedetomidine and clonidine withdrawal symptoms in acutely ill children.

DESIGN:

Three-phase instrument development study. Phase 1: retrospective chart review of symptoms exhibited by children with documented dexmedetomidine withdrawal; phase 2: WAT-A2A instrument construction based on phase 1 data; and phase 3: prospective testing of the WAT-A2A in children weaning from alpha 2 agonists (A2As).

SETTING:

Academic free-standing children’s hospital.

PATIENTS:

Acutely ill children weaning from at least 5 days of dexmedetomidine. Excluded were children concurrently weaning other sedatives.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Phase 1: In 83 of 303 children weaning from at least 5 days of dexmedetomidine who had clinician documentation and were managed for A2A withdrawal, 88% (n = 72) exhibited at least a 20% increase in heart rate (HR), 83% (n = 69) exhibited agitation or change in usual state behavior, 46% (n = 38) exhibited at least a 20% increase in diastolic blood pressure (DBP), and when documented, 56% (27/48) exhibited tremors during their A2A withdrawal episode. Phase 2: The WAT-A2A was constructed, based on phase 1 data, and includes four items: HR, state behavior, DBP, and tremors. Phase 3: The WAT-A2A was tested and performed well in 82 children weaning from A2A. The total WAT-A2A score correlated with clinician subjective assessment of A2A withdrawal (Spearman correlation = 0.5; p < 0.001). Inter-rater agreement, comparing paired ratings of prospectively collected WAT-A2A data, indicated moderate inter-rater reliability.

CONCLUSIONS:

Acutely ill children receiving sedation with an A2A for more than 5 days may develop physiologic dependence, requiring gradual dosing reductions. While further psychometric testing is advised, the WAT-A2A provides an objective instrument to help clinicians quantify dexmedetomidine withdrawal symptoms in acutely ill children may facilitate A2A weaning and limit unnecessary variation in practice.
Foreign Body Perforating the Descending Colon Incidentally Detected on 18F-FDG PET/CT
Authors: Duarte Paulo Schiavom , Coura-Filho George Barberio , Sapienza Marcelo Tatit , Zhuang Hongming , Buchpiguel Carlos Alberto
Published: December 2024

A 78-year-old woman was diagnosed having unresectable tongue cancer 6 months ago, for which she received radiation therapy. She was on enteral nutrition for more than 2 months due to dysphagia and underwent an 18F-FDG PET/CT for restaging. The images showed uptake in a left cervical node. In addition, there was a focal uptake in the descending colon corresponding to a foreign body in its anterior wall, which was removed by colonoscopy.
18F-FDG PET/CT Imaging of Myoepithelial Carcinoma in the Left Femur
Authors: Huang Shuhui , Xie Hangyu , Huang Rui
Published: December 2024

Myoepithelial carcinoma of bone is uncommon. We presented the imaging features of myoepithelial carcinoma of the left femur in a 61-year-old man on 18F-FDG PET/CT. Lytic bone destruction and the formation of a slightly low-density soft tissue mass extending to adjacent muscles with intense and circular FDG uptake were found on 18F-FDG PET/CT. Postoperative pathology confirmed the diagnosis of myoepithelial carcinoma.
FDG PET/CT in Papillary Intralymphatic Angioendothelioma of the Spleen
Authors: Jiao Benzheng , Liu Hongxia , Ma Xiaobo , Dong Aisheng , Zhao Hongguang
Published: December 2024

Splenic papillary intralymphatic angioendothelioma is extremely rare. We describe FDG PET/CT and MRI findings of splenic papillary intralymphatic angioendothelioma in a young adult. The splenic tumor showed hypodensity and increased FDG uptake with SUVmax of 4 on PET/CT, heterogeneous signal intensity with internal hypointense stellate scars on T2-weighted image, and progressive centripetal enhancement on dynamic contrast-enhanced T1-weighted images. This case indicates that papillary intralymphatic angioendothelioma should be included in the differential diagnosis of FDG-avid splenic lesions.
Classification of unsequenced Mycobacterium tuberculosis strains in a high-burden setting using a pairwise logistic regression approach
Authors: Rancu Isabel , Sobkowiak Benjamin , Warren Joshua L. , Ciobanu Nelly , Codreanu Alexandru , Crudu Valeriu , Colijn Caroline , Cohen Ted , Chitwood Melanie H.
Published: December 2024

Over the past three decades, molecular epidemiological studies have provided new opportunities to investigate the transmission dynamics of M. tuberculosis. In most studies, a sizable fraction of individuals with notified tuberculosis cannot be included, either because they do not have culture-positive disease (and thus do not have specimens available for molecular typing) or because resources for conducting sequencing are limited. A recent study introduced a regression-based approach for inferring the membership of unsequenced tuberculosis cases into transmission clusters based on host demographic and epidemiological data. This method was able to identify the most likely cluster to which an unsequenced strain belonged with an accuracy of 35%, though in a low burden setting where a large fraction of cases occurred among foreign-born migrants. Here, we apply a similar model to M. tuberculosis WGS data from the Republic of Moldova, a setting of relatively high local transmission. Using a maximum cluster span of ~40 SNPs and a cluster size cutoff of n ≥ 10, we could best predict the specific cluster to which each clustered case was most likely to be a member with an accuracy of 17.2%. In sensitivity analyses, we found that a more restrictive (~20 SNPs threshold) or permissive (~80 SNPs) threshold did not improve performance. We found that increasing the minimum cluster size improved prediction accuracy. These findings highlight the challenges of transmission interference in high burden settings like Moldova.
Advanced Peptide Nanoparticles Enable Robust and Efficient delivery of gene editors across cell types
Authors: Gustafsson Oskar , Krishna Supriya , Borate Sophia , Ghaeidamini Marziyeh , Liang Xiuming , Saher Osama , Cuellar Raul , Birdsong Björn K. , Roudi Samantha , Estupiñán H. Yesid , Alici Evren , Smith CI Edvard , Esbjörner Elin K. , Spuler Simone , de Jong Olivier Gerrit , Escobar Helena , Nordin Joel Z. , Andaloussi Samir EL
Published: December 2024

Efficient delivery of the CRISPR/Cas9 system and its larger derivatives, base editors, and prime editors remain a significant challenge, particularly in tissue-specific stem cells and induced pluripotent stem cells (iPSCs). This study optimized a novel family of cell-penetrating peptides, hPep, to deliver gene-editing ribonucleoproteins. The hPep-based nanoparticles enable highly efficient and biocompatible delivery of Cre recombinase, Cas9, base-, and prime editors. Using base editors, robust and nearly complete genome editing was achieved in the human cells: HEK293T (96%), iPSCs (74%), and muscle stem cells (80%). This strategy opens promising avenues for ex vivo and, potentially, in vivo applications. Incorporating silica particles enhanced the system’s versatility, facilitating cargo-agnostic delivery. Notably, the nanoparticles can be synthesized quickly on a benchtop and stored as lyophilized powder without compromising functionality. This represents a significant advancement in the feasibility and scalability of gene-editing delivery technologies.
Distinct metabolic profiles of circulating plasmacytoid dendritic cells in systemic sclerosis patients stratified by clinical phenotypes
Authors: Ferreira Beatriz H. , Mazeda Carolina , Dourado Eduardo , Simões João L. , Prata Ana Rita , Argüello Rafael J. , Duarte Iola F. , Pierre Philippe , Almeida Catarina R.
Published: December 2024

Background

Plasmacytoid dendritic cells (pDCs) play a key role in systemic sclerosis (SSc) pathophysiology. However, despite the recognised importance of metabolic reprogramming for pDC function, their metabolic profile in SSc remains to be elucidated. Thus, our study aimed to investigate the role of pDC metabolism in SSc.

Methods

Peripheral blood mononuclear cells (PBMCs) were isolated from the blood of healthy donors and SSc patients. SCENITH™, a single-cell flow cytometry-based method, was applied to infer the metabolic profile of circulating pDCs from patients with SSc. pDCs (CD304+Lin-) at steady-state or stimulated with CpG A were analysed. Toll-like receptor (TLR)9 activation was confirmed by ribosomal protein S6 phosphorylation.

Results

Circulating pDCs from 10 healthy donors and 14 SSc patients were analysed. pDCs from anti-centromere antibody-positive (ACA+) patients displayed higher mitochondrial dependence and lower glycolytic capacity than those from anti-topoisomerase I antibody- positive (ATA+) patients. Furthermore, cells from both ACA+patients and limited cutaneous SSc (lcSSc) patients showed a stronger response towards TLR9 activation than cells from ATA+, anti-RNA polymerase III antibody-positive (ARA+) or diffuse cutaneous SSc (dcSSc) patients.

Conclusions

Our results show that pDCs from ACA+patients rely more on oxidative phosphorylation (OXPHOS) and are more responsive to external stimuli, suggesting that pDCs from ATA+patients may be more activated or exhausted. These findings point for the possible contribution of pDC metabolism to SSc clinical course, unveiling new potential targets for therapeutic approaches in SSc.
Broadscale reconnaissance of coral reefs from citizen science and deep learning
Authors: Lawson Christopher L. , Chartrand Kathryn M. , Roelfsema Chris M. , Kolluru Aruna , Mumby Peter J.
Published: December 2024

Coral reef managers require various forms of data. While monitoring is typically the preserve of scientists, larger scale reconnaissance data that can be used to inform spatial decisions does not usually require such precise measurement. There is an increasing need to collect such broadscale, up-to-date environmental data at massive scale to prioritise limited conservation resources in the face of global disturbances. Citizen science combined with novel technology presents an opportunity to achieve data collection at the required scale, but the accuracy and feasibility of new tools must be assessed. Here we show that a citizen science program that collects seascape images and analyses them using a combination of deep learning and online citizen scientists can produce accurate benthic cover estimates of key coral groups. The deep learning and citizen scientist analysis methods had different but complementary strengths depending on coral category. When the best performing analysis method was used for each category in all images, mean estimates from 8086 images of percent benthic cover of branchingAcropora, platingAcropora, and massive-form coral were ∼99% accurate compared to expert assessment of the same images, and >95% accurate at all coral cover ranges tested. The effort to achieve 95% accuracy at a site – our ecologically relevant target based on the accuracy of other tools – was attainable based on citizen scientist involvement in pilot years of the program, with 18-80 images needed depending on coral type and reef state. Power analyses showed that sampling up to 114 images per site was needed to detect a 10% absolute difference in coral cover per category (power = 0.8), accounting for natural heterogeneity. However, the benthic cover of ‘all other coral groups’ as a single category could only be estimated with 95% accuracy at 60% of survey sites and for images with 10-30% coral cover. Disaggregating this ‘other coral’ group into more distinct coral categories may improve accuracy. Overall, citizen science can provide an accuracy that is acceptable for many end-users for select coral morphologies. Such a combination of emerging technology and citizen science presents an attainable tool for collecting inexpensive, widespread reconnaissance data of coral reefs that can complement higher resolution survey programs or be an accessible tool for resource-poor locations.
Long-term high temperatures affect seed maturation and seed coat integrity inBrassica napus
Authors: Prabhullachandran Unnikannan , Urbánková Ivana , Medaglia-Mata Alejandro , Creff Audrey , Voxeur Aline , Petřík Ivan , Pěnčík Aleš , Novák Ondřej , Landrein Benoit , Hejátko Jan , Robert Hélène S.
Published: December 2024

Temperatures above the optimum growth temperature affect seed development, producing seeds with ruptured seed coats. This phenotype is associated with accelerated embryo development. However, the molecular mechanism underlying this effect remains unclear.

To investigate the occurrence of temperature-induced seed coat rupture, we combined detailed phenotyping approaches of oilseed rape seeds with transcriptomics, histology, immunolabelling, hormone and cell wall profiling.

Our data suggest that high temperatures accelerate embryo growth, resulting in the formation of larger embryos but not larger seeds. The formation of large embryos increased the mechanical pressure exerted by the embryo on the seed coat cells, reducing their thickness. The seed coat began to mature prematurely with the accumulation of demethylesterified pectin, possibly making the cell wall stiffer. Application of abscisic acid, a hormone involved in seed dormancy, did not rescue the seed coat rupture phenotype. Hormonal and transcriptional profiling indicated that the embryo did not enter dormancy.

Prolonged high temperatures during seed development accelerated embryo growth by stimulating cell division, while the seed coat, which depends on cell elongation, could not withstand the tension exerted by the embryo, started seed maturation and eventually ruptured.
HIFα isoform specific activities drive cell-type specificity ofVHL-associated oncogenesis
Authors: Lima Joanna D.C.C. , Hooker Madeleine , Li Ran , Barros Ayslan B. , Masson Norma , Pugh Christopher W. , Mole David R. , Adam Julie , Ratcliffe Peter J. , Kurlekar Samvid
Published: December 2024

Cancers arising from dysregulation of generally operative signaling pathways are often tissue specific, but the mechanisms underlying this paradox are poorly understood. Based on striking cell-type specificity, we postulated that these mechanisms must operate early in cancer development and set out to study them in a model of von Hippel Lindau (VHL) disease. Biallelic mutation of the VHL ubiquitin ligase leads to constitutive activation of hypoxia inducible factors HIF1A and HIF2A and is generally a truncal event in clear cell renal carcinoma. We used an oncogenic tagging strategy in whichVHL-mutant cells are marked by tdTomato, enabling their observation, retrieval, and analysis early afterVHL-inactivation. Our findings reveal markedly different consequences of HIF1A and HIF2A activation, but that both contribute to renal cell-type specific consequences ofVHL-inactivation in the kidney. Early involvement of HIF2A in promoting proliferation within proximal tubular epithelium supports therapeutic targeting of HIF2A early in VHL disease.
BECLIN-1 is Essential for the Maintenance of Gastrointestinal Epithelial Integrity by Regulating Endocytic Trafficking, F-actin Organization and Lysosomal Function
Authors: Juliani Juliani , Tran Sharon , Harris Tiffany J. , De Cruz Peter , Ellis Sarah L. , Gleeson Paul A. , Mariadason John M. , Duszyc Kinga , Yap Alpha S. , Lee Erinna F. , Fairlie Walter D.
Published: December 2024

Disrupted intestinal homeostasis and barrier function are key contributors to the development of various diseases, including inflammatory bowel disease (IBD). BECLIN-1, a core component of two class III phosphatidylinositol 3-kinase (PtdIns3K) complexes, has a dual role in autophagy and endocytic trafficking. Emerging evidence suggests it is involved in maintaining intestinal integrity which involves its endocytic trafficking function. To gain insights into the fatal gastrointestinal (GI) phenotype observed in BECLIN-1 knockout adult mice, organoids derived from these animals were used to investigate the role of BECLIN-1 in GI epithelial function. BECLIN-1 deletion led to disrupted localization of CADHERIN-1/E-CADHERIN to adherens junctions (AJs) and OCCLUDIN to tight junctions (TJs), resulting in the mislocalization of these critical barrier proteins. Lysosomal dysfunction was also observed, characterized by impaired cargo degradation. In addition, the filamentous actin (F-actin) cytoskeleton became disorganized though this was not associated with changes in the interaction between F-actin and CATENIN BETA-1/BETA-CATENIN nor in alterations in BETA-CATENIN localization, though BETA-CATENIN levels were reduced. These effects were all less pronounced or absent in organoids lacking the autophagy-only regulator ATG7 (autophagy related 7), further emphasizing the involvement of BECLIN-1’s protein trafficking role in the maintenance of gut homeostasis and barrier function. These findings provide new insights into processes involved in epithelial dysfunction, deepening our understanding of mechanisms underlying intestinal disease.
IKZF2-ERBB4 gene fusion leads toERBB4overexpression in Anal Squamous Cell Carcinoma but with no benefit for ERBB4 inhibition
Authors: Sophie Richon , Anne Schnitzler , Julien Lazartigues , Adrien Briaux , Sophie Vacher , Botty Rania El , Elsy El Alam , Pascale Mariani , Cindy Neuzillet , Astrid Lièvre , Wulfran Cacheux , Ivan Bièche , Virginie Dangles-Marie
Published: December 2024

Anal squamous cell carcinoma (ASCC) is a rare tumour, but with increasing incidence for local and metastatic tumours. Current therapy is based on chemoradiotherapy, associated with immunotherapy in advanced stages, with frequent side effects, poor results in advanced stages and recurrence. New therapeutics, including targeted therapies, are then needed. In this context, we identified here aIKZF2-ERBB4gene fusion in a patient ASCC tumour, leading to overexpressed mRNA encoding a functional ERBB4 protein. This gene fusion has been already reported in other tumour types but not yet investigated as therapeutical target. The matched patient tumour-derived xenograft displays the same gene fusion and mRNA overexpression. It provided biological material for anti-ERBB4 testing in different cell models (in vivoxenograft,in vitrocell cultures). We used afatinib and lapatinib, 2 chemical pan-ERBB inhibitors approved in clinics, with anti-ERBB4 properties. ERBB4 inhibition did not lead to tumour growth inhibition although afatinib and lapatinib dramatically decreased ERBB4 phosphorylation with impact on downstream signalling MAPK/ERK but not PI3K/AKT pathways. Likewise, specificERBB4knock-outing did not affect tumour cell proliferation. These ‘negative’ results must be put in line with reported potential crosstalk between PI3K/AKT and MAPK/ERK pathways in therapeutic resistance.
Proximity to Explosive Synchronization Determines Network Collapse and Recovery Trajectories in Neural and Economic Crises
Authors: Lee UnCheol , Kim Hyoungkyu , Kim Minkyung , Oh Gabjin , Park Ayoung , Joo Pangyu , Pal Dinesh , Tracey Irene , Warnaby Catherine E. , Sleigh Jamie , Mashour George A.
Published: December 2024

When complex systems move away from criticality—a balance between order and chaos—they are no longer optimized. Furthermore, when criticality is lost too quickly, or recovery is delayed, system damage can result. However, the mechanism for these abnormally fast or slow critical transitions remains unknown. Here, we show that the proximity of a complex network to explosive synchronization (ES), a first-order phase transition, determines the trajectories of criticality loss and recovery after perturbations. Our computational models revealed characteristic dynamics based on network proximity to ES, enabling us to infer network phase transition types from empirical data and predict criticality transition patterns. We validated our predictions using empirical data from the human brain under anesthesia and the stock market during an economic crisis, demonstrating that early and prolonged recoveries can be systematically predicted. This study has implications for designing resilient networks that withstand perturbations and recover quickly.
The DNA Mismatch repair protein, MSH6 is a novel regulator of PD-L1 expression
Authors: Brooksbank Kirsten , Smith Charlotte , Maniati Eleni , Gibson Amy , Tse Wai Yiu , Hall Amy Kate , Wang Jun , Sharp Tyson V , Martin Sarah A
Published: December 2024

Immune checkpoint inhibitors (ICIs) are extremely effective in a subgroup of mismatch repair-deficient (MMRd) cancers, but ∼50% remain resistant to treatment. We have shown for the first time that this may be due to the differential regulation of factors linked to response to ICIs upon loss of the different MMR genes. Here, we show that increased PD-L1 expression is observed upon loss of the MMR genes MLH1, MSH2 and PMS2. However, this is not true upon loss of MSH6. Here, we show that this is due to a novel role for MSH6 as a direct regulator of PD-L1 transcription, dependent on recruitment by the histone trimethyltransferase SETD2. Next-generation sequencing of MLH1 and MSH6 knockout (KO) cells revealed that MSH6 KO cells have significantly lower microsatellite instability in comparison to MLH1 KO cells, despite MSH6 KO cells having a higher mutational burden. These findings emphasise the need for gene-specific stratification in the MMRd cohort.
Sex-dependent latent chilling injury changes estimates of thermal tolerance in a model insect
Authors: El-Saadi Mahmoud I. , Allen Mitchell C. , MacMillan Heath A.
Published: December 2024

Thermal tolerance limits are closely associated with insect distribution. Thermal injury sets limits to mobility or survival after removal from the stress, and these limits are frequently integrated into models describing or predicting climate suitability for species of interest. Cold stress severity, sex, and prior thermal acclimation status can all influence lower thermal limits. There is a growing understanding of chilling injuries initially manifest, but we poorly understand repair or further injury that may happen after rewarming. We exposed male and femaleDrosophila melanogasterto an acute or chronic cold stress before assessing their mobility over a 24 h period. Females progressively worsened under both conditions, but male mobility neither worsened nor improved. Female mobility declined slower in flies recovering at cooler temperatures, and cold acclimation significantly mitigated latent injury in females following the same degree of initial injury, regardless of recovery temperature. We conclude that latent chilling injury can be sex-specific, occurs independently from mechanisms driving tissue damage in the cold, is temperature-dependent, and is mitigated by prior thermal acclimation. We argue that latent chilling injury and the factors that influence it should be more carefully considered in estimating tolerance limits.
Constructing a holistic map of cell fate decision by hyper solution landscape
Authors: Zhang Xiaoyi , Li Zhiyuan , Zhang Lei
Published: December 2024

The Waddington landscape metaphor has inspired extensive quantitative studies of cell fate decisions using dynamical systems. While these approaches provide valuable insights, the intrinsic nonlinear complexity and the parameter dependence limits systematic analysis of fate transitions. Here, we introduce the Hyper Solution Landscape (HSL), a parameter-independent methodology showing a comprehensive structure of all possible landscape configurations for gene regulatory networks. Building on the concept of solution landscape that primarily captures the complete stationary points in static landscape, HSL connects different solution landscapes to reflect dynamic changes of the landscapes associated with bifurcations. Applied to the Cross-Inhibition with Self-activation motif, HSL analysis identifies key hyperparameters driving distinct directional changes in cell fate propensity. Importantly, different routes through the HSL between the same initial and final states can produce markedly different fate distributions. This enables rational design of transition strategies. We validate HSL’s utility in the seesaw model of cellular reprogramming, establishing a powerful framework for understanding and engineering cell fate decisions.
The impact of taxonomic change on the Amazonian palm flora
Authors: Stropp Juliana , Pereira Andreza S. S. , Emilio Thaise , Meyer Leila , Trad Rafaela , Alves-Martins Fernanda , Ladle Richard J. , Hortal Joaquín
Published: December 2024

Although species taxonomy is an ever-evolving discipline, taxonomic change is rarely accounted for in macroecological studies. By tracking the history of species description and synonymizations of more than 900 described names of Amazonian palms, we reveal shifts in species counts across space and time, the factors associated with taxonomic lumping, and the time needed to detect synonyms. The Amazonian palm flora results from a gradual accumulation of new descriptions, followed by decline due to the recognition of approximately 800 heterotypic synonyms. Most of these synonyms were detected in the mid-1990s, leading to a 4.5-fold decrease in species counts in ten years. The time to detect synonyms ranged from 3 to 227 years. Species with large populations, widespread distributions, early descriptions, also those that occur in Western Amazonia were more frequently lumped. The impact of taxonomic change on species counts is dependent on taxa, region, and time period considered. Biases in these counts are pronounced in the absence of taxonomic revisions, as undetected synonyms can inflate estimates of species richness. By quantifying the magnitude of such bias, this study offers conceptual and methodological insights on how incorporating taxonomic progress into macroecological analyses can provide a more accurate understanding of biodiversity patterns.
NKG2A-mediated immune modulation of natural killer cells byStaphylococcus aureus
Authors: Davies Kate , Rizek Al-Motaz , Kollnberger Simon , Wang Eddie C. Y. , Eberl Matthias , Underwood Jonathan , McLaren James E.
Published: December 2024

Natural killer (NK) cells are specialized lymphocytes that help protect against viruses and cancer. However, in the context of bacterial infections, NK cells can be harmful, rather than protective. Such immune pathogenesis by NK cells has been linked to the over-production of pro-inflammatory cytokines like interferon-γ (IFN-γ). In this context, IFN-γ-deficient mice display increased survival rates in response toStaphylococcus aureus(S. aureus), which causes life-threatening, invasive systemic infections with high mortality rates in humans. However, little is known about how NK cells respond toS. aureusin humans. In this study, we found that the peripheral blood of patients with bloodstreamS. aureusinfection was enriched for NKG2A+NK cells with greater cytokine producing capacity, compared to those hospitalized withEscherichia colibloodstream infections. As a possible mechanistic cause, superantigens fromS. aureuspromoted the expansion of CD57−NKG2A+NK cells which produced IFN-γ through an IL-12-independent mechanism and exhibited reduced levels of CD16 compared to unstimulated NK cells. These data suggest thatS. aureusbloodstream infection in humans promotes a phenotypic shift towards NKG2A+NK cells with greater IFN-γ producing capacity, providing a plausible way to promote inflammation-driven disease pathogenesis.

AUTHOR SUMMARY

Natural Killer (NK) cells are specialized immune cells that provide crucial defence against viruses but can also respond to bacterial infections, especially in humans. During bloodstream infection byStaphylococcus aureus, a Gram-positive bacterial pathogen that causes life-threatening infections in humans, NK cells may actually be harmful, rather than protective, to the host. However, very little is known about the NK cell response to invasiveStaphylococcus aureusinfections in humans. Here, we show that human patients with bloodstreamStaphylococcus aureus, but notEscherichia coli, infections have an increased frequency of NK cells with increased pro-inflammatory capacity. Furthermore, we show that toxins produced byStaphylococcus aureus, which help the bacteria evade the protective effects of T cells the immune system (“superantigens”), promoted the expansion of these pro-inflammatory NK cells, providing a possible mechanistic cause for their increased presence in patients with bloodstreamStaphylococcus aureusinfections. Collectively, these results suggest thatStaphylococcus aureusinfection triggers phenotypic and functional changes in NK cells that provide a plausible way to promote inflammation-driven disease pathogenesis
Tracking antigen-specific T cell response to cancer immunotherapy
Authors: Shagina I.A. , Nakonechanaya T.O. , Izosimova A.V. , Yuzhakova D.V. , Skatova V.D. , Lupyr K.R. , Izraelson M. , Davydov A.N. , Shugay M. , Britanova O.V. , Chudakov D.M. , Sharonov G.V.
Published: December 2024

In each human or model animal, T cell receptor (TCR) of each effector/memory T cell clone recognizes from one to several cognate peptide-MHC complexes (pMHC). Limited knowledge on TCR repertoire specificities restricts our capacity to rationally interpret this information, both diagnostically and in preclinical research. Here we 1) develop cost-efficient wet lab and computational pipeline to identify mouse TCRs specific to particular peptides, 2) produce dataset of helper T cells (Th) TCR beta CDR3s specific to B16 melanoma neoantigens in the I-Ab pMHCII context, available in VDJdb, and 3) apply this dataset to track tumor-specific T cell response to the CTLA4 blocking immunotherapy on orthotopic B16 melanoma model. We show that tumor promotes clonally independent Tregs carrying tumor-specific TCRs characteristic for Th cells. We further show that CTLA4 blockade promotes Th clonal expansion and induces general, non-tumor-specific Th-to-Treg plasticity. Altogether, we provide a universal pipeline for the investigation of mouse T cell responses at the antigen-specific level, facilitating development and validation of immunotherapeutic and vaccination approaches.
Generative AI divide: How College Students’ Backgrounds Affect Their Gen AI Literacy
Authors: Jiang Jingbo , Shao Aiqun
Published: December 2024

In the field of education, generative artificial intelligence has a profound impact, mainly reflected in areas such as personalized learning, automated assignment evaluation, content generation, and open educational resources. However, some scholars have begun to discuss whether this technology may lead to new inequalities. Therefore, this study aims to explore how user background affects the performance of generative artificial intelligence technology through empirical research while focusing on the potential educational inequalities that may arise in the era of generative AI. The research found that generative artificial intelligence literacy is correlated with grade level, institutional tier, and academic discipline, with higher-grade students, those from prestigious universities, and those studying Applied Sciences and Natural Sciences demonstrating better performance.
The Immunoregulatory Architecture of the Adult Oral Cavity
Authors: Fernandes Matuck Bruno , Huynh Khoa , Pereira Diana , Zhang XiuYu , Kunz Meik , Kumar Nikhil , Easter Quinn T. , Fernandes Alexandre , Ghodke Ameer , Predeus Alex , Szabo Lilli , Harnischfeger Nadja , Khavandgar Zohreh , Beach Margaret , Perez Paola , Nilges Benedikt , Moreno Maria , Ko Kang , Teichmann Sarah , Kimple Adam , Pringle Sarah , kretzschmar Kai , Warner Blake M , Sequeira Ines , Liu Jinze , Byrd Kevin M
Published: December 2024

The oral cavity is a critical barrier with immunosurveillance capabilities. A detailed understanding of its cellular, molecular, and spatial architecture is essential for advancing precision medicine across aerodigestive tissues. Here, we present the first integrated atlas of human adult oral and craniofacial tissues, derived from single-cell RNA sequencing of ~250,000 cells from 70 samples across 13 niches, including salivary glands and oral mucosae. Complementary spatial atlases using a 40-plex protein and 300-plex transcriptomics panels were developed, covering >2 million cells. Using our new AstroSuite package, we identified 8 tissue cellular neighborhoods (TCNs) and 17 multicellular interaction modules (MCIMs) across gland and mucosae in health. Diverse fibrovascular TCNs emerged as centralized hubs, coordinating immune cell migration and activation. Mucosal hubs within stroma displayed higher immune cell density, diversity, and activation than glands, underscoring differences in functional architecture. In keratinized and nonkeratinized mucosae, common fibrovascular hubs, and MCIMs revealed a specialized biogeography of immunoregulation. Under chronic inflammation, mucosal TCNs were fragmented, and MCIMs involving fibroblasts and immune cells were reorganized and expanded. Focused analysis of tertiary lymphoid structures (TLS) and fibroblasts identified TLS-associated MCIMs and drug candidates targeting these spatial interactions, offering a foundational framework for broadly dissecting mucosal immunity to guide precision medicine approaches.