bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-Term Outcomes of a 360-Degree Intracorneal Ring Implantation for Keratoconus: A 10-Year Follow-Up
Authors: Khorrami-Nejad Masoud , Jadidi Khosrow , Hasan Zeinab Fadhil , Aghamolaei Hossein , Sattar Abed Qaysser , Majdi Ali
Published: February 2025

Purpose:

To evaluate the long-term visual, refractive, and tomographic outcomes of a 360-degree intracorneal ring implant for treating keratoconus (KC).

Methods:

This historical cohort study included 29 eyes of 29 patients with KC who underwent MyoRing implantation. Uncorrected and best-corrected distance visual acuity, refraction, keratometry, and corneal thickness were evaluated preoperatively and at 5 and 10 years postoperatively.

Results:

Significant improvements were observed in all outcome measures at 5 and 10 years postoperatively compared with the preoperative values (P < 0.001). Uncorrected distance visual acuity improved from 1.25 ± 0.34 logarithm of the minimum angle of resolution (logMAR) preoperatively to 0.36 ± 0.24 logMAR at 5 years but showed regression to 0.48 ± 0.35 logMAR at 10 years. Corrected distance visual acuity similarly showed improvement from 0.50 ± 0.24 logMAR preoperatively to 0.18 ± 0.12 logMAR at 5 years, with some regression to 0.25 ± 0.22 logMAR at 10 years. Spherical equivalent improved from −9.38 ± 4.09 diopters (D) preoperatively to −2.70 ± 1.54 D at 5 years but regressed to −3.29 ± 2.22 D at 10 years. Although corneal flattening was observed at 5 years, a slight steepening trend was noted at 10 years. Corneal thickness exhibited an increase after 5 years (P < 0.001), but this trend reversed by the 10-year mark.

Conclusions:

MyoRing implantation demonstrated significant initial improvements in visual, refractive, and tomographic outcomes in patients with KC; however, some regression toward preoperative values was observed by the 10-year follow-up. This highlights the importance of continued monitoring to assess the long-term impact of the implant and to manage any potential late effects.
Somatosensory and clinical profiles of patients with spine-related and clinical framework-based neck–arm pain
Authors: Kapitza Camilla , Ballenberger Nikolaus , Luedtke Kerstin , Schmid Annina B. , Tampin Brigitte
Published: February 2025

Spine-related neck–arm pain is heterogeneous and may present on a spectrum between nociceptive and neuropathic pain. A recently developed mechanism-based clinical framework for spine-related pain distinguishes between spinally referred pain without neurological deficits (somatic referred pain, heightened nerve mechanosensitivity, radicular pain), with neurological deficits (radiculopathy), and mixed-pain presentations. This study investigated differences in somatosensory and clinical profiles of patients with unilateral spine-related neck–arm pain grouped according to the clinical framework. Patients (n = 113) underwent a clinical examination, after which they were classified into a subgroup(s). They completed questionnaires to assess function (Neck Disability Index), psychosocial factors (Tampa Scale of Kinesiophobia, pain catastrophizing scale, Depression, anxiety, and stress scale), neuropathic pain (Douleur neuropathique 4), and central sensitization features (Central Sensitization Inventory). Standardized quantitative sensory testing (QST) was performed over the maximal pain area and contralateral side. The radiculopathy group showed a significant loss of function on the symptomatic vs asymptomatic side in cold (P = 0.024) and warm detection (P = 0.004), thermal sensory limen (P = 0.001), mechanical detection (P = 0.001), increased windup ratio (P = 0.014), and cold hyperalgesia (P = 0.049). No other subgroup showed significant side differences in QST parameters. Symptom descriptors, such as burning (P < 0.031), tingling (P < 0.018), pins and needles (P < 0.031), numbness (P < 0.016), spontaneous pain (P < 0.001), and electric pain/shock (P < 0.026) were more common in the radicular/radiculopathy groups compared with the somatic/mechanosensitivity groups. There were no differences in psychosocial parameters between the groups. The phenotypic profiles support the construct of the clinical examination and patient classification and its application in clinical practice according to a clinical framework for spine-related pain.
International consensus recommendations for the RAPID procedure in liver transplantation
Authors: Malagó Massimo , Line Pål-Dag , Balci Deniz
Published: February 2025

Introduction:

Since its beginning in 1963, Liver Transplantation (LT) has significantly advanced, now including transplant oncology. As indications broaden, donor supply reduces. The two-stage RAPID procedure (initially abbreviated as “Resection And Partial Liver Segment 2/3 Transplantation With Delayed Total Hepatectomy”) has emerged to address the use of small-for-size (SFS) grafts. However, a comprehensive evaluation of RAPID is essential given its novelty, scarcity, and diverse outcomes reported.

Methods:

The RAPID Consensus International Society of Liver Surgeons (ISLS) 2023 Zurich initiative established evidence around the RAPID procedure using the Danish Model of Consensus. Engaging an international community of specialists, the initiative ensured multidisciplinary involvement and used the GRADE framework to evaluate the quality of evidence and grade the recommendations.

Results:

Comprehensive discussions and debates led to internationally recognized recommendations addressing perioperative measures for RAPID. Key recommendations highlighted the significance of standardized nomenclature, specific indications, graft criteria, surgical techniques, optimal interstage timings, and measures to manage potential complications.

Conclusion:

The consensus provides recommendations for the RAPID procedure, emphasizing transparency and outcome reporting. Establishing dedicated registries can improve care standards which may ensure the benefits of RAPID by maximizing patient safety and improving outcomes.
Exploring genes associated with metabolic dysfunction as therapeutic targets for head and neck cancers: a novel strategy
Authors: Yin Si-Yue , Liu Yu-Chen , Yang Yi-Pin , Liang Bing-Yu , Fu Zi-Yue , Fan Min , Zhang Yu-Chen , Xie Zi-Hui , Han Ke , Wang Jian-Peng , Zhang Lei , Zhang Liang , Tong Bu-Sheng , Han Yan-Xun , Zhang Cong-Jun
Published: February 2025

Evidence suggests a potential link between metabolic dysfunction and head and neck cancer (HNC). This study investigates the potential causal relationships between metabolic dysfunction and HNC using genetic data. While no significant causal associations were identified between metabolic indicators and HNC risk, the research revealed that inhibition of certain genes could reduce cancer risk. Specifically, inhibiting SLC5A2 was associated with a decreased risk of HNC and oropharyngeal cancer (OPC), while KCNJ11 inhibition was linked to a reduced risk of oral cavity cancer (OCC). Additionally, inhibiting SLC5A1 and CACNB2 showed a connection to lower OPC risk. These findings suggest that targeting these genes could offer promising therapeutic strategies for preventing and treating HNC, as well as improving both preoperative and postoperative management in affected patients.
Comparison of Different Membranes for Continuous Renal Replacement Therapies: An In Vitro Study
Authors: Malard Benjamin , Hulko Michael , Koch Julia , Speidel Rose , Pouchoulin Dominique , Echeverri Jorge , Yessayan Lenar
Published: February 2025

Inflammatory mediators play a major role in the development and progression of acute kidney injury (AKI). Continuous renal replacement therapy (CRRT) removes these mediators from the blood using AN69-M, AN69-ST, and HF1400 filters to target low and middle-molecular weight molecules. We characterized the in vitro removal performance of each filter in a 72 hour simulated CRRT procedure. Urea clearance with AN69-M and AN69-ST remained stable (52.4 and 51.2 ml/minute, respectively) but decreased with HF1400 (47.0 ml/minute; p < 0.001). Vancomycin clearance remained stable for AN69 filters but decreased for HF1400. Interleukin (IL)-8 was removed primarily via adsorption with the AN69 filters (92.2 and 91.2 ml/minute for AN69-M and AN69-ST, respectively), but clearance was significantly lower with HF1400 (8.4 ml/minute). Tumor necrosis factor (TNF)-α clearance was higher with AN69-ST compared with AN69-M or HF1400 (10.3, 1.8, and 2.3 ml/minute, respectively). β2-microglobulin clearance was higher with both AN69-based filters. The hydrogel water repartition of AN69 filters was different, with a higher percentage of bound water in AN69-ST versus AN69-M (30.5% ± 0.2% and 19.3% ± 1.5%, respectively; p < 0.05). These results suggest that clearance profiles of CRRT filters differ according to their properties; further investigation is needed to translate this into clinical improvements.
What Stage of Intraoperative Margin Reflex Distance Should be Used as a Guide in Blepharoptosis Repair?
Authors: Kokubo Kenichi , Katori Nobutada , Hayashi Kengo , Fujiwara Bunrei , Oi Kousuke , Ikeda Hiroaki , Hayashi Ayato
Published: February 2025

Levator aponeurosis advancement is one of the most well-known surgical procedures performed for blepharoptosis globally. Nevertheless, a patient’s condition at 6 months after surgery is difficult to accurately predict before or during levator aponeurosis advancement. This study aimed to determine which margin reflex distance (MRD) during levator aponeurosis advancement strongly correlates with MRD at 6 months after surgery. This study included 126 eyelids of 63 patients who underwent bilateral levator aponeurotic advancement for acquired ptosis and were followed up for >6 months. Frontal-view photographs were taken in the sitting position for all patients before surgery, during surgery (at the time of levator aponeurosis fixation to the tarsal plate, at the time of double eyelid formation, and at the time immediately after surgery), and at 1, 3, and 6 months after surgery. Subsequently, the MRD was measured using a photograph displayed on the personal computer screen. The time of double eyelid formation showed a higher correlation with all time points (1, 3, and 6 mo after surgery) than the time of levator aponeurosis fixation and the time immediately after surgery. In particular, the correlation coefficients at 6 months after surgery were 0.243 (P=0.006) when the levator aponeurosis was fixed, 0.348 (P=0.000063) when the double eyelid was created, and 0.278 (P=0.002) immediately after surgery. The MRD at the time of double eyelid formation during surgery is important for determining postoperative eyelid opening.
Effects of Peripheral Nerve Block on Perioperative Recovery Following Major Thoracic and Abdominal Surgery
Authors: Zhang Zhen , Li Chen , Xu Zhen-Zhen , Ma Jia-Hui , Wang Dong-Xin
Published: February 2025

Objective:

To test the hypothesis that peripheral nerve block (PNB) use might be associated with improved perioperative outcomes following major surgery.

Summary Background Data:

PNB has been used to improve postoperative analgesia.

Methods:

This was a retrospective cohort study with propensity score matching. We included patients aged ≥65 years who underwent major (≥2 h) non-cardiac thoracic and abdominal surgery under general anesthesia. Data were analyzed according to whether patients received PNB or not during anesthesia. Our primary outcome was the length of hospital stay; secondary outcomes included occurrence of major complications in hospital after surgery.

Results:

A total of 1,915 patients were included in the full cohort, of whom 1,316 received PNB and 599 did not; 1,174 patients remained in the cohort after matching, with 587 in each group. Length of hospital stay after surgery was shorter in patients who received PNB than in those who did not (7 days [5 to 9] with PNB vs. 7 days [5 to 11] without PNB: HR 1.15, 95% CI 1.02 to 1.29, P=0.012). When compared with patients who did not receive PNB, those who received PNB developed fewer major complications during hospital stay (RR 0.41, 95% CI 0.30 to 0.58, P<0.001). Patients with PNB required less supplemental analgesia within 72 h (RR 0.70, 95% CI 0.59 to 0.84, P<0.001).

Conclusions:

Use of PNB was associated with shortened length of hospital stay and reduced major complications in older patients after major non-cardiac thoracic and abdominal surgery, possibly due to improved analgesia.
Multimodality Therapy Including Pleurectomy/Decortication in Pleural Mesothelioma: Long-Term Outcomes in 152 Consecutive Patients A Retrospective Cohort Study
Authors: Lang-Lazdunski Loïc , Zhi Zhang Yu , Nicholson Andrew G
Published: February 2025

Objective:

Evaluate the long-term outcomes of pleurectomy decortication, systemic chemotherapy and prophylactic radiotherapy in pleural mesothelioma (PM).

Summary background data:

There is no known cure for PM and cytoreductive surgery remains controversial.

Methods:

Retrospective analysis of a cohort of patients treated consecutively between October 2004 and October 2019. Patients with PM were referred to our clinic and those with favorable prognostic factors and with completely resectable disease were selected for trimodality therapy. Our treatment protocol involved total pleurectomy decortication (P/D) and hyperthermic intrapleural povidone-iodine, prophylactic chest wall radiotherapy and systemic chemotherapy. 18FDG-PET-CT was used routinely to diagnose disease recurrence. Further systemic therapies were administered when appropriate. Survival and prognostic factors were analyzed using the Kaplan-Meier method and univariate and multivariate Cox regressions.

Results:

152 consecutive patients had P/D performed with curative intent. Median age was 64 years and the male/female ratio was 123/29. Thirty-one patients (20.4%) had received chemotherapy preoperatively. Thirty-five patients (23%) underwent extended resections. Sixty-four patients (42%) suffered a postoperative complication, but 90-day mortality was nil. Histological types were epithelioid in 107 patients (70.4%) and non-epithelioid in 45 (29.6%). Pathological stages were: I:88, II: 0, III: 63, and IV:1 (8th TNM classification). Six patients (4%) did not receive systemic chemotherapy and three (2%) no radiotherapy, postoperatively. Seventy-four patients (48.7%) received further systemic therapies for relapse. Median overall survival was 31.7 months, 35.0 months for epithelioid and 18.3 months for non-epithelioid histology. Histological type was the only predictor of overall survival, independent of resection status, pathological stage, or lymph node status, on multivariate analysis.

Conclusions:

P/D is a safe and well-tolerated procedure resulting in no mortality and acceptable morbidity. Most patients can receive radiotherapy and systemic chemotherapy in due time and receive further therapies on relapse, resulting in prolonged survival mainly in those with early-stage epithelioid mesothelioma.
The Diabetes Remission Index (DRI)
Authors: Ghusn Wissam , Ma Pearl , Vierkant Robert A. , Mundi Manpreet , Fehervari Matyas , Ikemiya Kayla , Hage Karl , Acosta Andres , Camilleri Michael , Abu Dayyeh Barham , Higa Kelvin , Ghanem Omar M.
Published: February 2025

Objective:

To develop and validate two predictive models, the Diabetes Remission Index (DRI) and the Weight Loss-Adjusted Diabetes Remission Index (W-DRI), for assessing type 2 diabetes (T2D) remission following metabolic and bariatric surgery (MBS).

Summary Background Data:

Metabolic and bariatric surgery, including Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), is highly effective in achieving T2D remission, but outcomes vary across populations. Predicting remission remains critical for individualized patient care and optimizing surgical outcomes. Existing tools focus on general outcomes, and a specific model incorporating weight loss data has been lacking.

Methods:

This multicenter, retrospective cohort study included patients with T2D and overweight/obesity (BMI ≥27 kg/m²) who underwent RYGB or SG between 2008 and 2018. Institution 1 (I-1) data (n=503) was used to develop and internally validate the models, while Institution 2 (I-2) data (n=409) was used for external validation. The DRI model incorporated preoperative variables, and the W-DRI model additionally included post-surgical weight loss. Predictive accuracy was assessed using AUC, calibration plots, and stratified analyses.

Results:

In I-1, 44.7% of patients achieved T2D remission, with a DRI model AUC of 0.80. In I-2, 52.6% achieved remission, with a model AUC of 0.78. Incorporating weight loss improved W-DRI predictive accuracy (AUC: 0.82 in I-1, 0.79 in I-2). Calibration plots demonstrated strong agreement between predicted and observed remission rates. An online DRI and W-DRI calculator is available via the Mayo Clinic webpage: https://newsnetwork.mayoclinic.org/dri-calculator/.

Conclusions:

The DRI and W-DRI models accurately predict T2D remission post-MBS, enabling personalized patient care and informed decision-making. Further validation across diverse populations is warranted.
Brexpiprazole augmentation in treatment-resistant obsessive-compulsive disorder: a preliminary retrospective observational study
Authors: Giacovelli Luca , Piccoli Eleonora , Landi Paola , Vismara Matteo , Benatti Beatrice , Dell'Osso Bernardo
Published: February 2025

Obsessive-compulsive disorder (OCD) is a chronic illness associated with significant functional impairment. Monotherapy with serotonin reuptake inhibitors (SRIs) often leads to only partial improvement of symptoms. In such cases, a common, well established, treatment approach for most patients is the augmentation of SRI therapy with antipsychotic medications. Brexpiprazole is an atypical antipsychotic agent that acts as a partial agonist of 5-HT1A, D2, and D3 receptors. Purpose of this retrospective observational study was to evaluate the effectiveness and tolerability of brexpiprazole as augmentation to SRIs in patients with treatment-resistant OCD. This preliminary study included a sample of 10 patients diagnosed with treatment-resistant OCD who underwent a 12-week trial of augmentative brexpiprazole, starting at a dose of 1 mg/day, with dosage adjustments based on clinical judgment. Treatment response was assessed through changes in the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) total score from baseline to the end of the 12-week observation period. Adverse events were systematically recorded. Significant improvement was observed after the 12-week period: at the endpoint, seven patients (70%) achieved a ≥25% reduction in Y-BOCS total score compared to baseline, with five of them (50% of the overall sample) showing a more robust clinical response (≥35% reduction). Mild adverse effects, such as sedation and weight gain, were reported by two participants (20% of the overall sample). These findings suggest that brexpiprazole may offer a promising effectiveness and tolerability profile in the management of treatment-resistant OCD.
Efficient and Secureµ-Training andµ-Fine-Tuning for Edge-Based TinyML Personalization with Future-Guided Self-Distillation
Authors: Huang Zhaojing , Yu Leping , Herbozo Contreras Luis Fernando , Kavehei Omid
Published: February 2025

This study presents a novel approach for training and fine-tuning machine learning models for bio-signal analysis on edge medical devices. The proposed technique applies to various physiological signals, with electrocar-diogram (ECG) data used as a case study. Our methodology integrates full training with a novel technique termedµ-Training, in which a compact model’s encoder and decoder layers are frozen while the middle layer remains trainable. We evaluate the effectiveness of this approach across different stages, including full training,µ-Training, andµ-Fine-Tuning. The model’s performance is assessed using in-sample data from the Telehealth Network of Minas Gerais (TNMG) dataset and out-of-sample testing on the China Physiological Signal Challenge 2018 (CPSC) dataset. Results indicate that the combined training approach matches or outperforms traditional full training and fine-tuning while significantly enhancing computational efficiency. Additionally, the model is deployed on an edge device forµ-Fine-Tuning, demonstrating its capability even in resource-constrained environments. We utilize Radxa Zero hardware for demonstration and deployment, though the method is compatible with a range of edge devices. We further investigated model size optimization to identify the optimal cost-efficiency trade-off and integrated a novel self-distillation technique, which improves performance across almost all metrics. Our findings show that this approach boosts computational efficiency and resource utilization—making it promising for real-time bio-signal processing on edge devices. Self-distilledµ-Training also has potential beyond medical and TinyML applications. To demonstrate its effectiveness, we integrated self-distilledµ-Training into the standard procedure and found it outperforms conventional training.
Effects of Unexpected Underfoot Perturbations During Turning on Measures of Mediolateral Stability and Corresponding Recovery Strategies
Authors: Ho Tyler K. , Kreter Nicholas , Jensen Cameron , Son JunSeop , Kramer Paula , Fino Peter C.
Published: February 2025

Humans regularly walk across uneven terrain, which demands the use of reactive control strategies to maintain forward progress and stability. While reactive control during walking has been well described during straight gait, it is unclear how reactive control differs during turning gait. Because turning is asymmetrical, perturbations to the inside and outside limbs may elicit different reactive adjustments. This study investigates how unexpected underfoot perturbations alter stability measures during turning and how individuals alter their foot placement to maintain stability after such perturbations. Seven healthy adults completed walking trials around a circular track while wearing mechanized shoes that pseudo-randomly delivered underfoot perturbations to either the inside or outside limb. We calculated mediolateral margin of stability corrected for centripetal acceleration (ML MoSC), step width, and step length from kinematic data. Linear mixed effects models compared the effects of perturbation type (inversion vs eversion), perturbation limb (inside vs outside), and their interaction for each outcome measure. ML MoSCwas affected by both perturbation type and perturbation limb, with larger changes observed during eversion, and outside, perturbations. Changes to step width and step time during two recovery steps after each perturbation were primarily influenced by the perturbation limb – outside perturbations elicited consistent changes during two recovery steps compared to one altered step after inside perturbations. Perturbations to the outside limb during turning disrupt gait longer than perturbations to the inside limb. This difference across perturbation limb may indicate that outside steps are more important to maintaining and recovering stability than inside ones during turning.
Development of itaconate polymer microparticles for intracellular regulation of pro-inflammatory macrophage activation
Authors: Woodworth Kaitlyn E. , Froom Zachary S.C.S. , Osborne Natasha D. , Rempe Christian N. , Wheeler Brenden , Medd Kyle , Callaghan Neal I. , Qian Huikang , Acharya Abhinav P. , Charron Carlie , Huyer Locke Davenport
Published: February 2025

Itaconate (IA) is an endogenous metabolite and a potent regulator of the innate immune system. Its use in immunomodulatory therapies has faced limitations due to inherent challenges in achieving controlled delivery and requirements for high extracellular concentrations to achieve internalization of the highly polar small molecule to achieve its intracellular therapeutic activity. Microparticle (MP)-based delivery strategies are a promising approach for intracellular delivery of small molecule metabolites through macrophage phagocytosis and subsequent intracellular polymer degradation-based delivery. Toward the goal of intracellular delivery of IA, degradable polyester polymer-(poly(itaconate-co-dodecanediol)) based IA polymer microparticles (IA-MPs) were generated using an emulsion method, forming micron-scale (∼ 1.5 µm) degradable microspheres. IA-MPs were characterized with respect to their material properties and IA release kinetics to inform particle fabrication. Treatment of murine bone marrow-derived macrophages with an optimized particle concentration of 0.1 mg/million cells enabled phagocytosis-mediated internalization and low levels of cytotoxicity. Flow cytometry demonstrated IA-MP-specific regulation of IA-sensitive inflammatory targets. Metabolic analyses demonstrated that IA-MP internalization inhibited oxidative metabolism and induced glycolytic reliance, consistent with the established mechanism of IA-associated inhibition of succinate dehydrogenase. This development of IA-based polymer microparticles provides a basis for additional innovative metabolite-based microparticle drug delivery systems for the treatment of inflammatory disease.
Fabrication of radiopaque, drug-loaded resorbable polymer for medical device development
Authors: Melancon Sophie T. , San Valentin Erin Marie , Bolinas Dominic Karl M. , Bernardino Marvin , Mishra Archana , Canlas Gino , Chintalapani Gouthami , Jacobsen Megan C. , Barcena Allan John R. , Huang Steven Y.
Published: February 2025

Resorbable medical devices provide temporary functionality before degrading into safe byproducts. One application is absorbable inferior vena cava filters (IVCFs), which prevent pulmonary embolism (PE) in high-risk patients with contraindications to anticoagulants.

However, current absorbable IVCFs are limited by radiolucency and local clot formation risks. This study aimed to develop radiopaque, drug-loaded resorbable IVCFs with enhanced imaging and therapeutic capabilities.

Poly-p-dioxanone (PPDO) sutures were infused with gadolinium nanoparticles (GdNPs) and dipyridamole (DPA), an anti-thrombotic agent. GdNPs were synthesized with an average diameter of 35.76 ± 3.71 nm. Gd content was 371 ± 1.6 mg/g (PPDO-Gd) and 280 ± 0.3 mg/g (PPDO-Gd+DPA), while DPA content was 18.20 ± 5.38 mg/g (PPDO-DPA) and 12.91 ± 0.83 mg/g (PPDO-Gd+DPA). Suture thickness (0.39-0.49 cm, P = 0.0143) and melting temperature (103.61-105.90, P = 0.0002) statistically differed among the different groups, while load-at-break did not (4.39-5.38, P = 0.2367). Although suture thickness and melting temperatures differed significantly, load-at-break was preserved and did not alter the mechanical and degradation properties of the various IVCFs. Micro-CT imaging revealed enhanced radiopacity for Gd-containing IVCFs (2,713 ± 105 HU for PPDO-Gd, 1,516 ± 281 HU for PPDO-Gd+DPA). Radiopacity decreased gradually over 10–12 weeks. Clot-trapping efficacy was maintained, and no hemolysis or cellular toxicity was observed.

In conclusion, the GdNP- and DPA-infused PPDO IVCFs demonstrated improved radiopacity, anti-thrombotic potential, and compatibility with routine imaging, without compromising mechanical strength or safety.
Strong circulation ofAngiostrongylus cantonensisin a protected Mediterranean wetland. Implications for resident and migratory wildlife
Authors: de Macedo Marcia Raquel Pegoraro , Jaume-Ramis Sebastià , Paredes-Esquivel Claudia
Published: February 2025

Angiostrongylus cantonensis, the rat lungworm, is a metastrongyloid nematode responsible for eosinophilic meningitis and an emerging pathogen of global concern. While its presence has been reported in various regions, including the Canary Islands and mainland Spain, data from the Balearic Islands remain limited. This study investigates the prevalence ofA. cantonensisin rodents from the Natural Park of s’Albufera, Mallorca, a protected wetland ecosystem. A total of 43 rodents were captured and necropsied, includingRattus norvegicus, R. rattusandApodemus sylvaticus. The overall prevalence ofA. cantonensisin rats was 46.15% (95% CI: 30.43–62.62%), with no significant differences between species, seasons, or sexes. However, adult rats exhibited significantly higher infection rates than juveniles (p = 0.05). Notably, infection intensity and parasite abundance were positively correlated with host weight (ρ = 0.60, p < 0.001). Given the co-occurrence of infected rodents and gastropods, our findings suggest the establishment ofA. cantonensisin Mallorca, raising concerns about zoonotic transmission risks. The study highlights the need for continued surveillance and public health awareness to mitigate potential human and wildlife exposure in this ecologically significant area.
General model with biclustering for target selection in severe preeclampsia
Authors: Majumdar Abhishek , Wang Biao , Li Lang , Chang Qing , Cheng Lijun
Published: February 2025

Preeclampsia is a complex and multifactorial disease and a leading cause of death in pregnancy with no current effective treatment strategies, especially severe preeclampsia. A new general regression model with biclustering scalability is developed to quantify causal relationship from genes to gene products to clinical phenotypes among multiple datasets. It can identify those key genes and relationships between gene expression and clinical phenotype, which will be interpreted further, for molecular mechanism disclosure and effective drug development by pathway enrichment analysis. We observed pattern variation of gene expression relating to clinical phenotype among three preeclampsia datasets in parallel. Eighty-one genes are recommended as potential druggable targets for severe preeclampsia by their highly correlation between gene expression variation with preeclampsia clinical phenotypes in hypertension, HELLP (Hemolysis, Elevated Liver enzymes and Low Platelets) syndrome, proteinuria, and gestation week. Genes ENG, Flt and NEU1 and NEU2 show overexpression in severe preeclampsia in attenuating hypertension and proteinuria in multiple datasets of preeclampsia. Those genes are involved in the angiogenic factors and vascular molecular function. Treatment with either Flt or NEU1 have exciting clinical implications, and likely will transform the detection and treatment for patients with severe preeclampsia. The novel network mathematical models can quantify a causal relationship from genes to gene products to clinical phenotypes, and they can model causal influences of genes that are either monomorphic or polymorphic among heterology datasets, which is suggesting that key gene expression variation may be more likely to influence complex clinical phenotype variation in preeclampsia among multiple datasets.
The influence of anatomical shape variations of wrist bones on kinematic parameter extraction in CT scans
Authors: Haenen Maranda , Hummelink Stefan , Karstanje Eline , Sechopoulos Ioannis , van der Heijden Brigitte
Published: February 2025

Introduction

Four-Dimensional Computed Tomography (4DCT) shows promise in diagnosing wrist pathologies such as scapholunate ligament lesions (SLL). Two parameters indicative of SLL lesions in these scans, the scapholunate angle (SLA) and the capitolunate angle (CLA), might be affected by anatomical shape variations. Therefore, this study characterizes the impact of anatomical shape variations on SLA and CLA estimates from 4DCT scans.

Methods

3D CT images retrieved from 4DCT scans of healthy wrists were used. Scans were automatically segmented using an Artificial Intelligence-based algorithm. A statistical shape model (SSM) was created for each bone separately. The quality of each SSM was assessed using a leave-one-out approach by calculating the root mean squared error (RMSE). Next, local coordinate systems (LCSs) were assigned to the SSMs while shape variations were introduced. The rotational deviation of the LCSs was calculated by a combined rotation around the three axes. Finally, the SLAs and CLAs were calculated for all possible bone shape combinations.

Results

SSMs of the carpal bones and radius were created using 106 and 99 scans, respectively, with a maximum RMSE across all SSMs of 0.65 mm. The 95thpercentile of the rotational deviations of the LCSs of the carpal bones and radius were below 3°. The resulting uncertainty due to anatomical variations in the calculation of the SLA and CLA was 2-3°.

Conclusion

Anatomical shape variations hardly influence the SLA, CLA, and LCSs of the carpal bones and radius so the methods to estimate the LCSs can be used to estimate relevant kinematic parameters in 4DCT scans.
CONVEX VERSUS LINEAR TRANSDUCER IN COVID-19 LUNG ULTRASOUND: A PROSPECTIVE COMPARATIVE COHORT
Authors: Gil-Rodríguez Jaime , Peregrina-Rivas José-Antonio , Aranda-Laserna Pablo , Martos-Ruíz Michel , Montero-Alonso Miguel Ángel , Benavente-Fernández Alberto , Melchor Juan , Guirao-Arrabal Emilio , Quero José Hernández
Published: February 2025

Background and purpose

It is currently unknown whether ultrasound transducer differences influence COVID-19 pneumonia images. Our aim was to describe and compare the results obtained using convex and linear transducers for image acquisition in COVID-19 lung ultrasound.

Methods

This is a single centre prospective cohort study, comparing convex and linear probes in 16 adult patients with SARS-CoV-2 pneumonia. We analysed 12 lung-fields and described the presence of pleural thickening, pleural irregularity, B-lines, >3 B-lines, coalescing B-lines, subpleural consolidation, pulmonary consolidation and pleural effusion in each of these fields and with both transducers. In addition, the Lung Ultrasound Score (LUS) was calculated for every patient using the two transducers.

Result

The mean LUS difference between both transducers was statistically significant in the right lower lateral, upper and lower posterior quadrants; as well as in the left lower anterior and upper posterior quadrants. Furthermore, mean total LUS difference was also statistically significant (15.81 convex vs. 10.81 linear; p = 0.001). The most frequently described findings with the convex transducer compared to the linear transducer were pleural irregularity, pleural thickening, >3 B-lines, coalescing B-lines and subpleural consolidation. On the opposite side, pleural effusion was more frequently described with the linear probe.

Conclusions

Lung ultrasound in COVID-19 pneumonia is a transducer-dependent technique. This difference is more pronounced in posterior quadrants and in the cardiac area. Although both linear and convex transducers are suitable for the evaluation of COVID-19 pneumonia, the convex probe provides more information than the linear probe if only one of the two is accessible.
Evaluation andIn SituLibrary Expansion of Small Molecule MHC-I Inducers
Authors: Kelly Joey J. , Newkirk Sarah E. , Chordia Mahendra D. , Pires Marcos M.
Published: February 2025

Immunotherapy has emerged as a powerful strategy for combating cancer by harnessing the patient immune system to recognize and eliminate malignant cells. The major histocompatibility complex class I (MHC-I) has a pivotal role in the recognition step. These surface proteins present cancer-specific neoantigens to CD8+ T cells, which triggers activation and T cell-mediated killing. However, cancer cells can often evade immune detection by downregulating MHC-I surface expression, which renders the immune response less effective. In turn, this resistance mechanism offers an opportunity to bolster MHC-I surface expressionviatherapeutic interventions. Here, we conducted an initial comprehensive evaluation of previously purported small molecule MHC-I inducers and identified heat shock protein 90 (Hsp90) inhibitors as privileged inducers of MHC-I surface expression. With a core scaffold in hand, we employed anin situclick chemistry-based derivatization strategy to generate 380 novel compounds in the same family. New agents from this library showed high levels of induction, with one of the triazole-based analogs,CliMB-325, also enhancing T cell activation and exhibiting lower toxicity, which could potentiate some immunotherapeutic modalities. Moreover, we demonstrated the potential of a click chemistry-based diversification strategy for the discovery of small molecules to counter immune evasion.
NGSTroubleFinder: A tool for detection and quantification of contamination and kinship across human NGS data
Authors: Valentini Samuel , Venturelli Tecla , Gallego Xavier , Perez-Cano Laura , Guney Emre
Published: February 2025

Quality control is a fundamental but often neglected step in any NGS pipeline. Detecting issues like cross-sample contamination and sample swaps is essential to control the data integrity. Here, we present NGSTroubleFinder, a novel python tool to detect cross-sample contamination in human Whole-Genome and Whole-Transcriptome Sequencing data, sample swaps and mismatches between the reported and the inferred genetic and transcriptomic sexes. NGSTroubleFinder is implemented in Python and incorporates a custom-built parallelized pileup engine written in C. The tool reports extensive information on the samples both in textual and HTML format including key plots for easy interpretation of the results.

Availability and Implementation

NGSTroubleFinder is written in Python and C, and it can be easily installed with pip. The tool source code and the models are freely available on github (https://github.com/STALICLA-RnD/NGSTroubleFinder) and a containerized version is available on dockerhub (https://hub.docker.com/r/staliclarnd/ngstroublefinder).
Automated assessment of the mouse body-language reveals pervasive behavioral disruption in a two-hit model of psychiatric vulnerability
Authors: Canicatti Viviana , Cibin Vanes , Berardi Nicoletta , Bozzi Yuri , Sale Alessandro , Chelini Gabriele
Published: February 2025

The influence of early-life experiences is widely acknowledged as a crafting tool that sculpts complex behavioral patterns and well-being of living organisms. The use of preclinical models can provide invaluable insight into how a negative environmental push interplays with genetic make-up in shaping psychiatric vulnerability. However, the assessment of psychiatric traits in cross-species studies often relies on the use of surrogate metrics as a proxy for the internal state, limiting the interpretation to context-dependent outcomes. In this work, we exploited a validated computational tool for digitalized ethological screening to identify spontaneous hallmarks of altered behavioral functioning in a dual-hit mouse model of psychiatric vulnerability. To do so, mice carrying heterozygous deletion of the gene coding for Contactin-associated protein-like 2 (Cntnap2+/-) and their wild-type (WT) littermates were raised with limited bedding and nesting (LBN). These animals were compared to both WT andCntnap2+/-mice raised in standard conditions, mapping their spontaneous behavior during freely-moving exploration. Our data show that descriptors of motility state or surrogate anxiety indicators largely failed in detecting subtle diversion from control conditions. By contrast, automated segmentation of the body-language revealed a significant impact of both genotype and early-life experience in shaping the spontaneous behavioral programming. Thus, using unsupervised clustering, we unveiled two alternative neurobehavioral profiles within our dataset. We found that one of the identified profiles largely overlapped withCntnap2+/-mice raised with LBN, while the other was equally shared among controls. We conclude that the coincidence of early-life adversity andCntnap2haploinsufficiency drastically reshapes behavioral structure in rodents.

SIGNIFICANCE STATEMENT

Enhancing the predictive and face validity of preclinical models in psychiatric research remains a significant challenge due to the inherent heterogeneity and complexity of these conditions. While animal models are crucial for understanding the risk factors involved, replicating the full complexity of these conditions continues to pose difficulties. In this study, we use a tool for digitalized behavioral screening to investigate emotional hallmarks in a double-hit (environmental and genetic) mouse model of vulnerability for psychiatric disorder, glimpsing subliminal behavioral disturbances not captured with traditional assessments. Our findings highlight the effectiveness of novel computational tools in identifying subtle behavioral deviations and support the hypothesis that gene-environment interaction contributes to shape alternative behavioral structure in mice.
Leopard Cats Occupied Human Settlements in China for 3,500 years before the Arrival of Domestic cats in 600-900 CE around the Tang Dynasty
Authors: Han Yu , Hu Songmei , Liu Ke , Xu Xiao , Doherty Sean , Jamieson Alexandra Elizabeth , Manin Aurelie , Martins Sofia Granja , Yang Miaomiao , Yu Chong , Wang Juan , Wu Zhuang , Chen Canping , Han Sicheng , Lu Daowei , Peng Lanhui , Wu Xianzhu , Li Ziyi , Fan Wenquan , Cai Quanfa , Cui Zongliang , Yuan Jing , Li Zihan , Liu Yang , Li Zhipeng , Liu Zhendong , Ma Qian , Shao Jing , Sun Zhouyong , Xing Fulai , Yang Wuzhan , Yang Shugang , Yue Lianjian , Zhang Pengcheng , Wang Weilin , Zhang Huanyuan , Zhuang Yan , Sun Xin , Pan Yan , Wu Xiaohong , Frantz Laurent A. F. , Yu He , Alves Joel M. , Larson Greger , Luo Shu-Jin
Published: February 2025

The earliest cats in human settlements in China were not domestic cats (Felis catus), but native leopard cats (Prionailurus bengalensis). To trace when and how domestic cats arrived in East Asia, we analyzed 22 feline bones from 14 sites across China spanning 5,000 years. Nuclear and mitochondrial genomes revealed that leopard cats began occupying anthropogenic scenes around 5,400 years ago and last appeared in 150 CE. Following several centuries’ gap of archeological feline remains, the first known domestic cat (706–883 CE) in China was identified in Shaanxi during the Tang Dynasty. Genomic analysis suggested a white or partially white coat and a link to a contemporaneous domestic cat from Kazakhstan, indicating a likely dispersal route via the Silk Road. The two felids once independently occupied ancient anthropogenic environments in China but followed divergent paths and reached different destinations in human-animal interactions.
Role of genetic frustrations in cell reprogramming
Authors: Yao Yuxiang , Zhu Jieying , Li Wenfei , Pei Duanqing
Published: February 2025

The cell fate transition is a fundamental characteristic of living organisms. By introducing external perturbations, it is possible to artificially intervene in cell fate and trigger cell reprogramming. Revealing the general principle underlying the induced phenotypic reshaping of cell populations remains a central focus in the field of cell biology. In this study, we investigate the energetic and dynamic features of induced cell phenotypic transition from differentiated somatic state to pluripotent state by constructing a Boolean genetic network model. The simulation and experimental results highlight the critical role of genetic frustration in initiating cell fate transitions, although the two ending phenotypic states are typically featured by minimal frustration. In addition, the altered gene expression profiles exhibit a scale-free distribution, suggesting that there exist a small number of critical genes responsible for the cell fate transition. This study provides important insights into the dynamic principles governing effective cell reprogramming caused by artificial or exogenous interventions.
From ashes to adaptation: the impact of wildfires on the diet ofPodarcis lusitanicusrevealed by DNA metabarcoding
Authors: Simões Catarina , Vasconcelos Diana S. , Xavier Raquel , Santos Xavier , Rato Catarina , Harris D. James
Published: February 2025

Fire has long been recognized as an important ecological and evolutionary force in plant communities, but its influence on animals, particularly regarding predator-prey interactions, remains understudied. This study focuses on the impact of wildfires on the diet ofPodarcis lusitanicus, a lizard species inhabiting a fire-prone region in the Iberian Peninsula. Faecal samples were collected from 12 distinct locations in Northern Portugal, at sites that burned in two distinct years (2016 and 2022), and in sites unburned since at least 2016.Podarcis lusitanicusis a generalist arthropod predator with dietary flexibility. Given the turnover of arthropod species after fire, it is expected to find variations in diet caused by different fire histories, especially between unburnt and recently burnt sites. Using DNA metabarcoding approach, employing high-throughput sequencing, the study revealed that while prey richness remained unaffected by wildfire regime, significant shifts occurred in diet composition between more recently burned and unburned areas, demonstrating a likely influence on prey availability after a more recent fire. Specifically, we found that differences in diet composition between these two fire regimes were due to the presence ofTapinomaants and jumping spiders (Salticus scenicus) in unburned areas, while these were absent in areas burned in 2022. Interestingly, diets in unburned areas and areas burned in 2016 showed no significant differences, highlighting the lizards’ adaptability and the habitat’s resilience over time.Talitroides topitotumwas found in dominance in both burnt areas, suggesting that this species may be fire tolerant. In addition, families such as Cicadellidae and Noctuidae were found to be more associated with more recently burned areas. The use of DNA metabarcoding in this study was essential to provide a more detailed and accurate view of predator-prey interactions in ecosystems susceptible to fire, providing a better understanding of changes in prey consumption in these environments.
PatientProfiler:A network-based approach to personalized medicine
Authors: Lombardi Veronica , Di Rocco Lorenzo , Meo Eleonora , Venafra Veronica , Di Nisio Elena , Perticaroli Valerio , Nicolaeasa Mihail Lorentz , Cencioni Chiara , Spallotta Francesco , Negri Rodolfo , Sacco Francesca , Perfetto Livia
Published: February 2025

Deciphering the intricate mechanisms underlying reprogramming in cancer cells is a crucial challenge in oncology as it holds the key to advance our ability to diagnose and treat cancer patients. For this reason, comprehensive and patient-specific multi-omic characterization of tumor specimens has become increasingly common in clinical practice. While these efforts have advanced our understanding of the molecular mechanisms underlying breast cancer progression, the identification of personalized therapeutic approaches remains a distant goal. The main shortcoming is the absence of a robust computational framework to integrate and interpret the available multi-dimensional data and to drive translational solutions.

To fill this gap, we developedPatientProfiler, a computational pipeline that leverages causal interaction data, annotated in our in-house manually-curated resource, SIGNOR, to address how the genetic and molecular background of single patients contributes to the establishment of a malignant phenotype.PatientProfileris an open-source, R-based package composed of several functions that allows multi-omic data analysis and standardization, generation of patient-specific mechanistic models of signal transduction, and extraction of network-based prognostic biomarkers.

To benchmark the tool, we retrieved genomic, transcriptomic, (phospho)proteomic, and clinical data derived from 122 treatment-naïve breast cancer biopsies, available at the CPTAC portal. Thanks to this approach, we identified patient-specific mechanistic models (one patient, one network) that recapitulate dysregulated signaling pathways in breast cancer. This collection of models provides valuable insights into the underlying mechanisms of tumorigenesis and disease progression. Moreover, in-depth topological exploration of these networks has allowed us to define seven communities (subnetworks), each associated with a unique transcriptomic signature and a distinct prognostic value.

In summary, our work demonstrates thatPatientProfileris a tool for patient-specific network analysis, advancing personalized medicine towards the identification of actionable biomarkers and tailored therapeutic strategies.