bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Corneal Biomechanics and Intraocular Pressure With Scleral Lenses of Different Diameters
Authors: Queiruga-Piñeiro Juan , Martínez-Alberquilla Irene , Rodríguez-Uña Ignacio , Barros Alberto , Lozano-Sanroma Javier , Cueto Luis Fernández-Vega , Merayo-Lloves Jesús
Published: February 2025

Purpose:

To evaluate the short-term influence of scleral lenses (SL) with different diameters on intraocular pressure (IOP) and corneal biomechanics. A secondary objective was to investigate the relationship between fluid reservoir (FR) thickness and IOP and biomechanical parameters.

Methods:

Thirty healthy subjects were randomly fitted with L1 (diameter of 15.80 mm) and L2 (diameter of 16.80 mm) on the right eye and worn for 2 hr. On IOP and corneal biomechanical parameters were measured with the CORVIS ST before and after SL removal. Fluid reservoir thickness at 0 and 2 hr of wear was measured using anterior segment optical coherence tomography.

Results:

Biomechanical parameters decreased after removal of L1 (−1.04±1.47 mm Hg) (P<0.01) and L2 (−0.80±1.74 mm Hg) (P=0.02). The biomechanical parameters A1T (−0.11±0.18 ms) (P=0.01) and SP-A1 (−4.29±9.97 mm Hg/mm) (P=0.02) decreased after L1 removal, whereas a decrease in highest concavity time (−0.21±0.50 m/s) (P=0.03) and an increase in highest concavity radius (+0.17±0.43 mm) (P=0.04) were observed after L2 removal. A significant, negative, and moderate correlation was found between highest concavity deformation amplitude and FR thickness with L1 (r=−0.42, P=0.02).

Conclusions:

The small changes in corneal biomechanical parameters and IOP values induced by short-term SL wear have no significant clinical impact and were not influenced by the diameter of the SL.
Primary CD4+ T-Cell Lymphoproliferative Disorder of Conjunctiva
Authors: Margo Curtis E. , DeAngelis Kendra D.
Published: February 2025

Purpose:

The purpose of this study was to describe a patient with a primary CD4+ T-cell lymphoproliferative disorder of conjunctiva.

Methods:

Case report and review of the literature.

Results:

An 81-year-old man was referred for asymptomatic bilateral conjunctival masses that on biopsy revealed a proliferation of mature CD4+ lymphocytes associated with T-cell receptor γ gene rearrangement. The histopathology and immunophenotypic profile in the absence of disease elsewhere bore resemblance to primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder.

Conclusions:

In 2016, the World Health Organization reclassified primary cutaneous CD4+ small/medium T-cell lymphoma to a lymphoproliferative disorder because neither dissemination nor death had been documented. This case displays similarities with the latter but has nonconforming features. Multicentric clonal expansion of T cells do not inevitably indicate lymphoma. Lymphoproliferative disorders that display features of reactive hyperplasia and lymphoma and are not easily classified need to be carefully monitored.
Accuracy of the Heijl–Krakau Method During Blind-spot Stimulation with the Head Mounted Imo Perimeter in Patients with Glaucoma and Glaucoma Suspects
Authors: Eura Mariko , Nomoto Hiroki , Matsumoto Chota , Ishibashi Takuya , Tanabe Fumi , Yoshikawa Keiji , Nanno Mami , Kusaka Shunji
Published: February 2025

Précis:

13.9% of fixation loss responses by the Heijl-Krakau method were observed even in stable fixation eyes. The Heijl-Krakau method would overestimate the fixation loss responses.

Purpose:

This study aimed to evaluate the accuracy of the Heijl–Krakau method by measuring eye positions during blind-spot stimulation.

Methods:

Two thousand one hundred fifty-three eyes of 1155 glaucoma and glaucoma-suspect patients. All patients underwent a head-mounted perimeter imo test. The imo has an eye tracking system that records eye position during tests and assists the device with stimulating corrected points corresponding to eye movement. All stimulus presentations were classified into three groups: 1. fixation loss (FL) stimulus: responded to Heijl–Krakau stimuli; 2. non-FL stimulus: did not respond to Heijl–Krakau stimuli; 3. total stimuli: all other stimuli except for Heijl–Krakau stimuli. We compared the amount of fixation displacement between the FL, non-FL, and total stimuli by the Mann–Whitney U test. Relationships between the FL and mean deviation (MD), the FL and age were analyzed.

Results:

The median fixation displacements with the FL, non-FL, and total stimuli were 3.2°, 1.4° and 1.5°, respectively. The fixation displacement in the FL stimulus group was greater than that in the non-FL and total stimuli groups (P<0.001). When we defined fixation displacement in the range of less than 1° as “stable eye fixation”, 13.9% of the stimulus points corresponded to “stable eye fixation” with the FL stimulus. No significant relationships were found in the FL and MD, as well as in the FL and age.

Conclusion:

In glaucoma and glaucoma suspected patients, after allowance for eye movement by imo patients still responded to the Heijl-Krakau blind spot monitor on 13.9% of occasions.. Our results suggest that the Heijl–Krakau method overestimates the FL response in glaucoma and glaucoma suspected patients.
Comparison of percutaneous versus cutdown access in patients after endovascular abdominal aortic repair: a randomized controlled trial (SWEET-EVAR trial)
Authors: Zhou Yuhang , Wang Jiarong , Zhao Jichun , Yuan Ding , Weng Chengxin , Huang Bin , Wang Tiehao
Published: February 2025

Introduction:

The optimal choice of either percutaneous or cutdown access for endovascular abdominal aortic repair (EVAR) remains uncertain due to insufficient evidence, particularly regarding patient-centered outcomes (PCOs). This study aimed at comparing both clinician-reported outcomes (ClinROs) and PCOs of percutaneous versus cutdown access in patients after EVAR.

Methods:

The study was a single-blind, single-center, non-inferiority, randomized controlled trial. After eligibility screening, patients diagnosed with abdominal aortic diseases were randomly assigned to either the intervention group receiving percutaneous EVAR or the control group receiving cutdown EVAR. Primary ClinRO was access-related complications, and primary PCO was time return to normal life/work.

Results:

Overall, 120 patients (containing 240 accesses) were allocated to either intervention group (n = 62) or control group (n = 58). Percutaneous EVAR (10/124, 8.1%) was non-inferior and not superior to cutdown EVAR (17/116, 14.7%) regarding access-related complications (P = 0.110; OR: 0.521, 95% CI: 0.225–1.157). As for PCOs, the recovery time back to normal life or work was superior in percutaneous EVAR compared to cutdown EVAR (16 vs. 28 days, P = 0.025; median difference: 7 days, 95% CI: 0–13 days). Moreover, percutaneous access did better in other PCOs, including a reduction in the duration of access-related pain (4 vs. 8 days, P = 0.001), decreased use of analgesics for access-related pain (0/61, 0% vs. 6/55, 10.9%; P = 0.026), and improved quality of life scores at 2 weeks following EVAR (0.876 vs. 0.782; P = 0.022). Prespecified subgroup analyses demonstrated percutaneous access significantly reduced the incidence of access-related complications compared to cutdown access in patients with thick subcutaneous tissue (1/42, 2.4% vs. 7/32, 21.9%; P = 0.026).

Conclusion:

In patients without massive common femoral artery calcification, percutaneous access may accelerate postoperative recovery and enhance patient experience and quality of life following EVAR, but did not provide obvious advantages regarding access-related complications.
Evaluating the learning curve for flexible ureteroscopic thulium fiber laser lithotripsy using CUSUM analysis
Authors: Li Zhilong , Wu Shaojie , Tang Xiaoyu , Luo Yongwen , Wang Du , Liu Tongzu , Li Sheng , Wang Xinghuan
Published: February 2025

Objectives:

Effective training methods and learning curve (LC) assessment are crucial for more difficult endoscopic procedures. The present study sought to assess the LC of ureteral flexible scopes for thulium fiber laser (TFL) lithotripsy and determine the effectiveness of using a porcine kidney model in training modality, to inform future training.

Methods:

Postgraduate medical students without experience in ureteroscopy were recruited, and surgical data were collected from 10 consecutive flexible ureteroscopic (fURS) lithotripsy procedures performed on our homemade porcine kidney training model. Cumulative sum (CUSUM) analysis and pooled mean CUSUM curves were applied to determine the LC turning points (TPs), and pre-LC and post-LC data were compared with that of an experienced attending physician.

Results:

Data from 110 surgeries were included in the analysis. The mean number of surgical units to overcome the LC for the duration of fURS TFL lithotripsy was 4. The operation time, number of tissue damage, and number of central visual shifts were significantly lower in students after the TP than before. No statistically significant difference in operation time was found between the students after the LC (817.50 [703.75-964.75]) and the surgeon group (732.50 [51.00-822.25]).

Conclusion:

Overcoming the LC of fURS TFL lithotripsy requires four surgeries, and the developed ex vivo porcine kidney is a conveniently accessible and effective clinical training model.
Comparison of submucosal and subserosal approach in ICG-guided laparoscopic lymphadenectomy in gastric cancer patients: long-term outcomes of a phase 3 randomized clinical trial
Authors: Zhong Qing , Shang-Guan Zhi-Xin , Liu Zhi-Yu , Wu Dong , Huang Ze-Ning , Wang Hua-Gen , Chen Jun-Yun , Wu Jin-Xun , Li Ping , Xie Jian-Wei , Zheng Chao-Hui , Chen Qi-Yue , Huang Chang-Ming
Published: February 2025

Background

Previous studies have demonstrated similar short-term efficacy between subserosal (SSA) and submucosal (SMA) approaches for ICG injection in gastric cancer (GC). This study aims to compare the long-term oncological outcomes of these two injection methods for lymph node (LN) tracing in ICG-guided laparoscopic gastrectomy.

Materials and methods

This study was a phase 3, open-label, randomized clinical trial (FUGES-019). A total of 266 patients with resectable gastric adenocarcinoma (cT1-4a, N0/ +, M0) were enrolled. We report predefined long-term secondary outcomes, including three-year actual overall survival (OS), three-year actual disease-free survival (DFS), and recurrence patterns.

Results

Of the 266 participants, 259 patients were included in the per-protocol analysis; 129 in the SSA group and 130 in the SMA group. The actual OS in the SSA group (87.6%) was comparable to that in the SMA group (90.8%, P = 0.41), as were the 3-year actual DFS rates (SSA: 82.9% vs. SMA: 88.5%, Log-rank P = 0.19). Per-protocol analysis confirmed the equivalence of the SSA compared with the SMA. The most common type of recurrence was multiple site metastasis (11 of 259[4.24%]), with no differences in recurrence types across cancer stages. Further stratified analysis based on pT, pN staging, tumor size, and BMI showed no significant differences between the two groups.

Conclusion

The 3-year outcomes of the FUGES-019 trial confirm the equivalence of SSA and SMA in ICG-guided laparoscopic lymphadenectomy for GC, supporting the previous short-term findings. The subserosal approach can be recommended for ICG administration based on clinical considerations.
Iatrogenic nerve injury following pelvic ring injury: a network meta-analysis
Authors: Su Yu-Cheng , Hsu Yung-Heng , Chou Ying-Chao , Chen I-Jung , Lai Chih-Yang , Yu Yi-Hsun
Published: February 2025

Background:

Pelvic ring injuries are common in multi-trauma patients and can be life-threatening, necessitating prompt surgical intervention to improve outcomes. However, surgery can lead to complications such as iatrogenic nerve injury. This network meta-analysis aimed to improve outcomes in multi-trauma patients with pelvic ring injuries by evaluating the incidence of iatrogenic nerve injuries, identifying vulnerable nerves, and comparing different fixation methods.

Materials and Methods:

A systematic search of MEDLINE, EMBASE, and Scopus from inception to 5 December 2023, revealed 29 comparative studies on the incidence of iatrogenic nerve injury in 1561 adult patients with pelvic ring injuries. Data were extracted on study and patient characteristics, iatrogenic nerve injury incidences, and specific nerve injuries. A random-effects model assessed treatment effects, with subgroup analysis and meta-regression. The main outcomes included odds ratios (ORs) and confidence intervals (CIs) for iatrogenic nerve injuries.

Results:

Compared with closed reduction internal fixation, robotic-assisted techniques had the highest, and open reduction internal fixation had the lowest ORs for iatrogenic nerve injuries. The robotic-assisted approach ranked best with an OR of 0.22 (95%CI: 0.02–2.16), while closed reduction internal fixation with the anterior approach (OR: 0.71; 95%CI: 0.21–2.48) and open reduction internal fixation with the anterior approach performed the worst. The lateral femoral cutaneous nerve was injured in all open reduction internal fixation with anterior approach procedures and in 66.7% of open reduction internal fixation with posterior approach procedures. Meta-regression showed a significantly lower OR for iatrogenic nerve injuries in patients aged >41.4 years in the open reduction internal fixation with anterior approach group (OR: 0.02; 95%CI: 0.001–0.63; p = 0.026) compared with younger patients.

Conclusion:

The robotic-assisted technique may result in the fewest iatrogenic nerve injuries during the treatment of pelvic ring injuries. The posterior approach may also reduce the risk of iatrogenic nerve injuries.
Glioma-induced neural functional remodeling in the hand motor cortex: precise mapping with ECoG grids during awake craniotomy—experimental research
Authors: Chang Tao , Wu Yihan , Quan Yuxin , Chen Siliang , Liao Jiawei , Zhao Wenyu , Li Yu , Fang Yuan , Zong Yixuan , Liu Yanhui , Jiang Ning , Mao Qing , He Jiayuan , Yang Yuan
Published: February 2025

Background:

The dilemma of achieving ‘onco-functional balance’ in gliomas affecting the motor cortex highlights the importance of functionally-guided resection strategies. While accurate mapping of eloquent areas often requires frequent electrical stimulation, this practice can lead to side effects like seizures and postoperative deficits. To enhance safety in functional mapping, we studied how gliomas impact hand movement areas and assessed the effectiveness of cortical electrical activity for functional mapping in this setting.

Materials and Methods:

We recruited patients with gliomas affecting the motor cortex and individuals with an unaffected motor cortex for awake craniotomy. During the procedures, electrocorticography (ECoG) grids were employed to record signals under three conditions: resting state, finger movements, and wrist movements. We then quantified the distances from the positively stimulated sites to the specific anatomical landmarks. Additionally, we analyzed the relationship between the ECoG power features and the stimulation responses.

Results:

The cortical layout for finger activity in the MCG group was more dispersed and overlapped, typically clustering near the central sulcus and Sylvian fissure. The predictive performance of ECoG mapping exhibited significant variability across different frequency bands and clinical scenarios. Specifically, the area under the curve (AUC) for the Non-MCG group during the resting state reached its peak, with a value of 0.802 for Gamma3 (95% CI = 0.729-0.875) and 0.865 for broadband (95% CI = 0.804-0.926). In contrast, the MCG group achieved the highest AUC during wrist movements, with Gamma3 at 0.785 (95% CI = 0.719-0.849) and broadband at 0.824 (95% CI = 0.753-0.890).

Conclusion:

Gliomas in the motor cortex disrupt the distribution of hand activity, complicating intraoperative functional mapping. As a novel and reliable approach, ECoG technique can complement and guide direct cortical stimulation for precise mapping, potentially reducing its frequency, minimizing the risk of functional deficits, and achieving a balance between maximal tumor resection and neurological preservation.
Multiparametric MRI and transfer learning for predicting positive margins in breast-conserving surgery: a multi-center study
Authors: Zhao Xue , Bai Jing-Wen , Jiang Sen , Li Zhen-Hui , He Jie-Zhou , Du Zhi-Cheng , Fan Xue-Qi , Li Shao-Zi , Zhang Guo-Jun
Published: February 2025

This study aimed to predict positive surgical margins in breast-conserving surgery (BCS) using multiparametric MRI (mpMRI) and radiomics. A retrospective analysis was conducted on data from 444 BCS patients from three Chinese hospitals between 2019 and 2024, divided into four cohorts and five datasets. Radiomics features from preoperative mpMRI, along with clinicopathological data, were extracted and selected using statistical methods and LASSO logistic regression. Eight machine learning classifiers, integrated with a transfer learning (TL) method, were applied to enhance model generalization. The model achieved an AUC of 0.889 in the internal test set and 0.771 in the validation set. Notably, TL significantly improved performance in two external validation sets, increasing the AUC from 0.533 to 0.902 in XAH and from 0.359 to 0.855 in YNCH. These findings highlight the potential of combining mpMRI and TL to provide accurate predictions for positive surgical margins in BCS, with promising implications for broader clinical application across multiple hospitals.
Black angels and the call for advocacy
Authors: Ferguson Laurie Anne
Published: February 2025

The Black Angels: The untold story of the Nurses who helped cure Tuberculosis is the story of the nurses who helped cure tuberculosis. It is really a tale of two stories, the first recounting the battle of Black nurses escaping the Jim Crow south only to experience systemic and institutional racism in the north, and secondly of tuberculosis an infectious and often deadly disease, which has plagued humanity for centuries. “The Black Angels,” is a must read for all in health care, not simply for the history lesson but for the urgent message for today.
Practical considerations for choosing transoral laser microsurgery versus transoral robotic surgery for supraglottic laryngeal cancers
Authors: Lechien Jerome R. , Chiesa-Estomba Carlos M. , Hans Stéphane
Published: February 2025

Purpose of review

To review the pros and cons of treating supraglottic laryngeal cancer with transoral laser microsurgery (TOLM) or transoral robotic surgery (TORS).

Recent findings

The use of TORS is limited by the cost and the availability of the robots despite a faster learning curve than TOLM. The laryngeal exposure difficulty, the use of long instruments, and the restricted view of the surgical field consist of the primary limitations of TOLM, which are addressed in TORS technology through a 30° view of surgical fields, and the 180° amplitude of the instruments. The indications of TOLM and TORS are similar and include cT1-T2 and some selected cT3 with moderate invasion of the preepiglottic space. The rates of positive margins in TORS-SGL are lower than those of TOLM-supraglottic laryngectomy (SGL), while both approaches report similar duration of hospital stays. Patients treated with TORS report higher rates of percutaneous gastrostomy and temporary tracheotomy compared to TOLM. The feeding tube and oral diet re-start appear comparable between both groups. The overall survival, disease-free survival, local, regional, and relapse-free survival rates of TORS are reported to be higher than those found for TOLM SGL.

TORS and TOLM SGL are well tolerated and effective approaches for cT1, cT2, and some selected cT3 LSCC. The functional and surgical outcomes appear comparable. TORS could have superior survival and loco-regional outcomes than TOLM, which could be attributed to the fastest TORS learning curve, and its superiority in terms of tumor/operating field visualization, and instrument movements.
Point-of-Care Ultrasound Diagnosis of Restrictive Cardiomyopathy in a 3-Year-Old Patient
Authors: Nguyen Thuy , Rathakrishnan Arjith , Bompard Madison , She Trent , Chicaiza Henry
Published: February 2025

Restrictive cardiomyopathy is a rare form of cardiomyopathy in children, representing only 2.5%–3% of all pediatric cardiomyopathies, and is typically diagnosed between the ages of 6 and 10. The underlying etiology varies depending on age and region; however, idiopathic, genetic, and endomyocardial fibrosis are among the most common. Cohort studies have demonstrated mortality as high as 50% within 2 years of diagnosis, as well as high rates of adverse events including thromboembolism, pulmonary hypertension, and sudden cardiac death. There is a paucity of literature on point-of-care ultrasound (POCUS) for the diagnosis of pediatric restrictive cardiomyopathy. We present a case of a 3-year-old female whose diagnosis of heart failure was rapidly identified via POCUS which subsequently expedited life-saving treatment.
Comparison of Transoral and Transcutaneous Approaches for Gender-Affirming Thyroid Cartilage Reduction: A Case Series of 246 Patients
Authors: Deng Iris Y. , Nguyen Nghiem H. , Argame Alexander A. , Lee James C. , Chu Michael W.
Published: February 2025

Background:

Thyroid cartilage reduction (TCR) for gender-affirming neck surgery can reduce prominent thyroid notches and improve dysphoria. TCR can be performed with a transoral or transcutaneous approach. This study aims to review TCR approaches and outcomes.

Methods:

A retrospective chart review of all TCRs at a multi-institutional, integrated healthcare system from May 2016 to July 2024 was performed. Patient demographics, operative details, and post-operative complications were reviewed. Major complications included invasive interventions (corticosteroid injections for scars, fluid drainage, etc) or intraoperative complications. Minor complications included infections, hypertrophic scarring, and temporary voice changes. Chi square tests and Mann-Whitney U tests were performed to evaluate differences in postoperative outcomes by surgical approach.

Results:

A total of 246 patients underwent TCR with 207 patients (84.1%) in the transcutaneous group and 39 patients (15.9%) in the transoral group. The median patient age was 30.7 years (interquartile range, IQR 24.9-39.0). Median BMI was 22.7 kg/m2 (IQR 20.6-25.5). There were no significant differences between transcutaneous and transoral groups, for median age (30.1 years vs 33.4 years, p=0.08) or median BMI (22.6 kg/m2 vs 23.7 kg/m2, p=0.28). Total major complication was 9.3% and minor complication was 10.6%. There were no significant differences between transcutaneous and transoral groups in rates of major (9.2% vs 10.3%, p=0.83) or minor (12.1% vs 2.6%, p=0.08) complications.

Conclusion:

TCR can be an effective treatment for neck dysphoria. Transoral approach avoids visible neck scars and is not associated with increased peri-operative complications. Further research is needed to determine the long-term outcomes of TCR.
Interpretable learning of effective dynamics for multiscale systems
Authors: Menier Emmanuel , Kaltenbach Sebastian , Yagoubi Mouadh , Schoenauer Marc , Koumoutsakos Petros
Published: February 2025

The modelling and simulation of high-dimensional multiscale systems is a critical challenge across all areas of science and engineering. It is broadly believed that even with today’s computer advances resolving all spatio-temporal scales described by the governing equations remains a remote target. This realization has prompted intense efforts to develop model-order reduction techniques. In recent years, techniques based on deep recurrent neural networks (RNNs) have produced promising results for the modelling and simulation of complex spatiotemporal systems and offer large flexibility in model development as they can incorporate experimental and computational data. However, neural networks lack interpretability, which limits their utility and generalizability across complex systems. Here, we propose a novel framework of interpretable learning effective dynamics (iLED) that offers comparable accuracy to state-of-the-art RNN-based approaches while providing the added benefit of interpretability. The iLED framework is motivated by Mori–Zwanzig and Koopman operator (KO) theory, which justifies the choice of the specific architecture. We demonstrate the effectiveness of the proposed framework in simulations of three benchmark multiscale systems. Our results show that the iLED framework can generate accurate predictions and obtain interpretable dynamics, making it a promising approach for solving high-dimensional multiscale systems.
Unbiased multi-omics network-based data integration allows clinically relevant outcome-predicting clustering of individuals with heart failure
Authors: Esenkova Ekaterina E. , Koeck Thomas , Lerner Raissa , Baker Dhanwin , Bauer Katrin I. , Nuber Maximilian , Valentini Giorgio , Bindila Laura , Wild Philipp S. , Casiraghi Elena , Araldi Elisa
Published: February 2025

Heart failure is a multifaceted clinical syndrome, in which the heart fails to supply adequate blood to meet the body’s oxygen and nutrients needs. Evidence indicates multi-level molecular shifts in heart failure subjects, necessitating unbiased molecular stratification of patients with heart failure. This study utilized AI-based multimodal integration method to analyse 359 lipids and 538 proteins measured in participants of the MyoVasc heart failure cohort. Patient similarity networks were constructed, and spectral clustering, an unsupervised machine learning technique, identified clinically relevant subgroups predictive of patient outcomes. Comparative analyses of cluster-defining proteins and lipids revealed molecular-level insights into heart failure clinical subtypes. In addition to metabolic dysfunctions such as diabetes mellitus, the clinical profiles and outcomes of the identified eight subgroups also showed kidney and liver function indicators. The unbiased molecular characterization was particularly notable in clusters lacking clear, established clinical distinctions, suggesting novel insights into previously uncharacterized patient subgroups. The results show that network-based integration enables to unbiasedly characterize novel molecular subgroups, providing a foundation for improved understanding and management of heart failure.
White and Clearing: New Optical Tissue Clearing Method
Authors: Llorente Vicente , Fernández-Cortés Elena , Sanderson Daniel , Salazar Julia , Ripoll Jorge , Desco Manuel , Gómez-Gaviro María Victoria
Published: February 2025

Abstract

Optical tissue clearing techniques can render large-scale tissue samples and whole organs transparent to apply cell-resolution 3D imaging techniques, revolutionizing the fields of biological research and pathological diagnosis, and providing never-before seen structural information. There are several widely used protocols, but they have shortcomings, both in complexity of use and in suboptimal results in certain tissues and organs.

Here, we describe a new method dubbed “White and Clear” (WaC) using 2,2’-thiodiethanol (TDE) as a dynamic Refractive Index (RI)-matching reagent alongside a lipid-extraction and a pigment-bleaching step using dilute hydrogen peroxide (H2O2), to provide ease of use and enhanced clearing effect on all kinds of samples and allow for the clearing parameters to be finely adjusted in order to obtain the best results in each situation.
Melanization regulates wound healing by limiting polyploid cell growth in theDrosophilaepithelium post injury
Authors: Gonzalez-Baez Loiselle , Mortati Elizabeth , Mitchell Lillie , Losick Vicki P.
Published: February 2025

Wound healing requires a localized response that restricts growth, remodeling, and inflammation to the site of injury. In the fruit fly,Drosophila melanogaster,the epithelium heals puncture wounds through cell growth instead of cell division. Epithelial cells on wound margin both fuse and duplicate their genome to generate a multinucleated, polyploid cell essential for tissue repair. Despite the essential role of polyploidy in wound healing, the signals that initiate and regulate the extent of cell growth at the wound site remain poorly understood. One of the first steps in wound healing requires the deposit of melanin at the site of injury, which persists as a melanin scar. The melanin scar forms within hours after a puncture wound and is dependent on the activation of three prophenoloxidase genes (PPO1, PPO2, and PPO3). Using a triple loss of function mutant (PPOnull), we have uncovered a novel role for melanization in regulating wound healing by limiting polyploid cell growth post injury. Thus, melanization is required for efficient wound closure and its loss leads to an unexpected exacerbation of polyploid cell growth in the surrounding epithelial cells. This occurs, in part, through the early entry of epithelial cells into the endocycle, which may be due to altered gene expression as a result of delayed JNK signaling and other pathways. In conclusion, we have found that polyploid cell growth requires melanization at the injury site to control the extent of cell growth and regulate wound repair.

Puncture wounds in insects are known to lead to production of a pigmented (melanin) deposit that can persist as a scar, remodeling the site of damage. It has long been speculated that the melanin scar is necessary for tissue repair, thus we used the fruit fly as a model to determine how loss of scar formation affects wound healing. In doing so, we discovered that the melanin scar is necessary to restrict cell growth and facilitate efficient wound closure. Thus, revealing a pivotal role for scar formation in coordinating cell growth, which may be conserved in other organisms.
An invariant schema emerges within a neural network during hierarchical learning of visual boundaries
Authors: Elder James R. , Zheng Jie , Shimelis Lydia B. , Rutishauser Ueli , Lin Milo M.
Published: February 2025

Neural circuits must balance plasticity and stability to enable continual learning without catastrophic forgetting, a pervasive feature of artificial neural networks trained using end-to-end learning (e.g. backpropagation). Here, we apply an alternative, hierarchical learning algorithm to the cognitive task of boundary detection in video clips. In contrast to backpropagation, hierarchical training converges to a network executing a fixed schema and generates firing statistics consistent with single-neuron recordings from human subjects performing the same task. The hierarchically trained network’s schema circuit remains invariant following training on sparse data, with additional data serving to refine the upstream representation.
Genome-wide association studies of binge-eating behaviour and anorexia nervosa yield insights into the unique and shared biology of eating disorder phenotypes
Authors: Termorshuizen Jet D , Davies Helena L , Lee Sang-Hyuck , Huckins Laura M , Bulik Cynthia M , Breen Gerome , Coleman Jonathan RI ,   the Eating Disorder Working Group of the Psychiatric Genomics Consortium
Published: February 2025

Eating disorders (EDs)—including anorexia nervosa (AN), bulimia nervosa, and binge-eating disorder—are clinically distinct, but exhibit high symptom overlap and comorbidity. Genomic analyses to date have only examined AN. We conducted the first genome-wide association meta-analysis of binge-eating behaviour (BE; 39,279 cases, 1,227,436 controls, all from European genetic ancestries), alongside new analyses of AN (24,223 cases, 1,243,971 controls, all from European genetic ancestries) and its subtypes. We implicated six genomic loci associated with BE, including known associations with higher body mass index (BMI) and impulse-control behaviours. BE and AN exhibit genetic similarity, including positive genetic correlation with psychiatric disorders, and genetic dissimilarity, including opposing genetic correlations with anthropometric traits. Genomic structural equation modelling analyses indicate that most genetic signal in EDs is independent of BMI. We have extended ED genomics beyond AN; work is underway to diversify further, incorporating multiple diagnoses and global genetic ancestries.
Reply to: “Model mimicry limits conclusions about neural tuning and can mistakenly imply unlikely priors”
Authors: Rideaux Reuben , Bays Paul M , Harrison William J
Published: February 2025

In Harrison, Bays, and Rideaux (2023), we presented evidence from electroencephalographical recordings of humans that there is an over representation of horizontal orientations in the visual cortex. Wolf and Rademaker (2024) raise concerns about an analysis used in our study and provide an alternative explanation for our results. Here we address their concerns and provide additional magnetencephalography data supporting the conclusions of our original study.
Deep visual multi-omics profiling reveals mechanisms that underly cancer cell differentiation and aggressiveness in clear cell renal cell carcinoma
Authors: Bolck Hella A. , Migh Ede , Kriston Andras , Zajac Natalia H. , Kreutzer Susanne , Totu Tiberiu , Leary Peter , Kovacs Ferenc , Rutishauser Dorothea , Pfammatter Sybille , Grossmann Jonas , Litchfield Cassandra , Buljan Marija , Rupp Niels J. , Horvath Peter , Moch Holger
Published: February 2025

Clear cell renal cell carcinoma (ccRCC) exhibits significant intra-tumoral heterogeneity (ITH) at both morphological and genetic levels, complicating treatment and contributing to disease progression1,2. Among these, rhabdoid ccRCCs stand out as highly aggressive tumors distinguished by cells with unique morphological features and poor clinical outcomes3. However, the correlation between distinct morphological phenotypes, specific molecular alterations, and their influence on tumor behavior remains poorly understood. Understanding the link between clinically relevant morphological features and their molecular underpinnings will be critical for developing more effective treatments targeting key cellular subsets responsible for tumor progression. In this study, we integrated advanced AI-based image analysis with single-cell isolation and multi-omics profiling to dissect the link between clinically relevant morphological and molecular features of ccRCC cells. Using a novel digital pathology workflow, we quantified low-grade, high-grade, and rhabdoid morphologies in ccRCC diagnostic images with unprecedented precision. Subsequently, isolation of two sets of 1,000 morphologically distinct cells for detailed mRNA and protein expression analyses, revealed significant increasing dysregulation associating with higher histopathological grades. Rhabdoid ccRCC cells (grade 4) demonstrated distinct molecular profiles, including upregulated FOXM1-driven proliferation, disrupted cell-matrix interactions, and enhanced immune evasion pathways. Despite high T-cell infiltration in rhabdoid areas, we identified a rhabdoid-specific immunosuppressive network driven by cytokines, IFN-beta, and integrin signaling, likely contributing to T-cell exhaustion. These findings provide a basis for novel therapeutic strategies targeting these pathways in combination with immunotherapy to improve outcomes for patients with aggressive rhabdoid ccRCC.

Key Points

ccRCC is characterized by well-established morphological heterogeneity but the correlation with the underlying molecular aberrations remained elusive.

By integrating AI-based image analysis with single cell isolation and deep multi-omics profiling, we dissect the molecular intricacies of ccRCC, from targeted collection of 1,000 morphologically distinct cells.

Our results demonstrate significant dysregulation of gene and protein expression correlating with higher histopathological grades in ccRCC.

Aggressive ccRCC cells with rhabdoid differentiation (grade 4) display distinct molecular profiles, as they upregulate FOXM1-mediated proliferation, ECM remodeling and the immune evasion responses, suggesting new therapeutic avenues enhancing ICI efficacy in these patients.
Challenges in replicating layer-specificity of working memory processes in human dlPFC
Authors: Chaimow Denis , Degutis Jonas Karolis , Haenelt Daniel , Trampel Robert , Weiskopf Nikolaus , Lorenz Romy
Published: February 2025

Although working memory reliably activates the dorsolateral prefrontal cortex (dlPFC), the functional significance of its distinct cytoarchitectonic layers is not well understood in humans. A recent functional magnetic resonance (fMRI) study at 7T demonstrated for the first time layer-specific responses in the human dlPFC during working memory. Superficial layers were more active during the delay period when working memory items needed to be manipulated compared to mere maintenance. In contrast, deeper layers were more active during the motor response to a probe compared to non-action. Like many current layer fMRI studies, this study relied on several manual and semi-manual processing steps, including the selection of regions of interest. To test the replicability of these findings, we conducted a pre-registered replication of this study in 21 subjects using a fully automated and reproducible analysis pipeline. Our results do not show the same layer-specific effects. Although we observed higher activity in the superficial layers in response to working memory manipulation during the delay period, we did not find any evidence for stronger deep layer involvement during motor response in the probe period. We argue that our results are biologically plausible in light of previous research as well as methodological considerations inherent in layer fMRI acquisition and analysis. Consequently, we conclude that the evidence regarding the functional role of different layers within the human dlPFC during working memory remains inconclusive. A focus on replicability, reproducibility, and a better understanding of the influence of methodological choices will help layer fMRI become a more routine tool in cognitive neuroscience.
Usefulness of autofluorescence detection of the parathyroid glands with PTeye™ system. Scope review
Authors: Pardal-Refoyo José Luis , Pardal-Peláez Beatriz
Published: February 2025

Introduction and Objective

Near-infrared (NIR) fluorescence is used to visualize anatomical structures and physiological activities in real time. The objective is to synthesize the advantages and disadvantages of the PTeye™ system in the identification of parathyroid glands during thyroid and parathyroid surgery.

Method

A literature review of the scope of primary research articles in databases such as PubMed, WoS and Cochrane was carried out, using the search strategy “(autofluorescence AND (parathyroid glands)) AND PTeye™” until January 27, 2025. We included studies with any methodology that evaluated the identification of parathyroid glands with autofluorescence in thyroid or parathyroid surgery with PTeye™ technology. Review articles, editorials, and individual clinical cases were excluded.

Results

We included 8 studies that met the inclusion criteria. The results showed that PTeye™ has high accuracy in identifying parathyroid glands, with identification rates above 90%. The use of PTeye™ reduced the need for additional tests such as freeze biopsies and increased the surgeon’s confidence in identifying parathyroid tissue. However, some false positives were identified, including thyroid nodules and lymph nodes. The device proved to be easy to use and provided real-time feedback.

Conclusions

PTeye™ is a useful tool to improve the identification of parathyroid glands during surgery, increasing surgeon confidence and reducing the rate of postoperative hypocalcemia. Although it has some disadvantages, such as the possibility of false positives and the need for a learning curve, its benefits outweigh these limitations. More studies are needed to confirm these findings and assess their long-term impact.
A spatially resolved single cell proteomic atlas of Small Bowel Adenocarcinoma
Authors: Dereli Zeynep , Bozorgui Behnaz , Sanchez Maga , Hornstein Nicholas , Thibault Guillaume , Wang Huamin , Mills Gordon B. , Weinstein John N. , Overman Michael J. , Korkut Anil
Published: February 2025

Small bowel adenocarcinoma (SBA) is a rare malignancy marked with a poor prognosis. The cellular and proteomic heterogeneity within the tumor immune microenvironment (TIME) of SBA is a likely driver of prognosis, disease progression and response to therapy. We have addressed a major gap in knowledge of the TIME in SBA using highly multiplexed, protein imaging of the SBA tumor-immune ecosystem generating a comprehensive, single-cell level, spatial, proteomic atlas of TIME in > 600,000 cells from 136 tumor and matched normal samples from clinically and genomically annotated SBA patients (N=37). The SBA TIME Atlas informs on spatial distribution and interactions of tumor-intrinsic processes, diverse immune cell types, immune checkpoints, and vascularization. Enrichment of proliferating epithelial tissue, stem cells, and likely pro-tumor immune signatures in the tumor niche is contrasted by the representation of naïve and early-effector T-cells in the epithelial compartments of adjacent normal tissues. Epithelial-stem-immune cell spatial architectures within tumor and matched-normal niches were strongly associated with patient survival, suggesting malignancy is driven by spatial architecture beyond the tumor microenvironment. The blueprints of therapeutically actionable immune checkpoints at the interface between epithelial and microenvironmental T-cells as well as macrophages have established a guideline for precision immunotherapies tailored to the TIME composition in SBA. We expect that this SBA atlas will contribute to a deeper understanding of the immune contexture in this rare disease as well as other gastrointestinal cancers and help guide future precision immune-oncology strategies.
Hookworm genes encoding intestinal excreted-secreted proteins are transcriptionally upregulated in response to the host’s immune system
Authors: Schwarz Erich M. , Noon Jason B. , Chicca Jeffrey D. , Garceau Carli , Li Hanchen , Antoshechkin Igor , Ilík Vladislav , Pafčo Barbora , Weeks Amy M. , Homan E. Jane , Ostroff Gary R. , Aroian Raffi V.
Published: February 2025

Hookworms are intestinal parasitic nematodes that chronically infect ∼500 million people, with reinfection common even after clearance by drugs. How infecting hookworms successfully overcome host protective mechanisms is unclear, but it may involve hookworm proteins that digest host tissues, or counteract the host’s immune system, or both. To find such proteins in the zoonotic hookwormAncylostoma ceylanicum, we identified hookworm genes encoding excreted-secreted (ES) proteins, hookworm genes preferentially expressed in the hookworm intestine, and hookworm genes whose transcription is stimulated by the host immune system. We collected ES proteins from adult hookworms harvested from hamsters; mass spectrometry identified 565A. ceylanicumgenes encoding ES proteins. We also used RNA-seq to identifyA. ceylanicumgenes expressed both in young adults (12 days post-infection) and in intestinal and non-intestinal tissues dissected from mature adults (19 days post-infection), with hamster hosts that either had normal immune systems or were immunosuppressed by dexamethasone. In adultA. ceylanicum, we observed 1,670 and 1,196 genes with intestine- and non-intestine-biased expression, respectively. Comparing hookworm gene activity in normal versus immunosuppressed hosts, we observed almost no changes of gene activity in 12-day young adults or non-intestinal 19-day adult tissues. However, in intestinal 19-day adult tissues, we observed 1,951 positively immunoregulated genes (upregulated at least two-fold in normal hosts versus immunosuppressed hosts), and 137 genes that were negatively immunoregulated. Thus, immunoregulation was observed primarily in mature adult hookworm intestine directly exposed to host blood; it may include hookworm genes activated in response to the host immune system in order to neutralize the host immune system. We observed 153 ES genes showing positive immunoregulation in 19-day adult intestine; of these genes, 69 had ES gene homologs in the closely related hookwormAncylostoma caninum, 24 in the human hookwormNecator americanus, and 24 in the more distantly related strongylid parasiteHaemonchus contortus. Such a mixture of rapidly evolving and conserved genes could comprise virulence factors enabling infection, provide new targets for drugs or vaccines against hookworm, and aid in developing therapies for autoimmune diseases.
Host serine proteases and antiviral innate immunity as potential therapeutic targets in influenza A virus infection-induced COPD exacerbations
Authors: Bai Haiqing , Rodas Melissa , Si Longlong , Man Yuncheng , Ji Jie , Plebani Roberto , Mercer Johnathan D. , Powers Rani K. , Belgur Chaitra , Jiang Amanda , Hall Sean R. R. , Prantil-Baun Rachelle , Ingber Donald E.
Published: February 2025

Lung manifestations of chronic obstructive pulmonary disease (COPD) are often exacerbated by influenza A virus infections; however, the underlying mechanisms remain largely unknown and hence, therapeutic options are limited. Using a physiologically relevant human lung airway-on-a-chip (Airway Chip) microfluidic culture model lined with human airway epithelium from COPD or healthy donors interfaced with pulmonary microvascular endothelium, we observed that Airway Chips lined with COPD epithelium exhibit an increased sensitivity to influenza virus infection, as is observed clinically in COPD patients. Differentiated COPD airway epithelial cells display increased inflammatory cytokine production, barrier function loss, and mucus accumulation upon virus infection. Transcriptomic analysis revealed gene expression profiles characterized by upregulation of serine proteases that may facilitate viral entry and downregulation of interferon-related genes associated with antiviral immune responses. Importantly, treatment of influenza virus-infected COPD epithelium with a protease inhibitor, nafamostat, ameliorated the disease phenotype as evidenced by dampened viral replication, reduced mucus accumulation, and improved tissue barrier integrity. These findings suggest that targeting host serine proteases may represent a promising therapeutic avenue against influenza-afflicted COPD exacerbations.