bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-invasive prenatal testing for dominant single-gene disorders using targeted next-generation sequencing
Authors: Zhang Hongyun , He Jun , Teng Yanling , Shi Qingxin , Liu Fang , Peng Can , Linpeng Siyuan , Liu Yingdi , Zhu Huimin , Wen Juan , Liang Desheng , Li Zhuo , Wu Lingqian
Published: February 2025

Background

Current non-invasive prenatal testing (NIPT) based on cell-free DNA (cfDNA) mainly targets the detection of chromosome aberrations but not dominant single-gene disorders (dSGDs).

Aim

This prospective pilot study aims to evaluate the clinical utility of a plasma cfDNA and targeted next-generation sequencing-based NIPT approach for dSGDs (NIPT-dSGD), with a particular focus on neurodevelopmental disorders (NDDs).

Design

Prospective pilot study.

Methods

The NIPT-dSGD method targeted 34 genes, including 25 correlated to NDDs and nine correlated to Noonan spectrum, skeletal, craniosynostosis and other syndromic disorders. Retrospective samples first validated NIPT-dSGD and then performed for a prospective cohort of 567 pregnant women seeking NIPT-dSGD. The testing results were compared to invasive prenatal or postnatal genetic diagnosis by whole-exome sequencing and Sanger sequencing.

Results

Of the 535 samples with qualified NIPT-dSGD analysis, 11 (2.1%) had one pathogenic or likely pathogenic variant in one of the 34 genes. Three of the 11 variants were paternally inherited, and eight were de novo. Five positive cases had normal ultrasound parameters and three of them had disease-causing variants in NDD genes. Particularly, one family had two pregnancies with de novo variants of two different genes (GRIN2B: c.1606G>A and ARID1B: c.6100A>G). NIPT-dSGD did not generate any false-positive or negative results, achieving 100% of sensitivity (95% CI, 71.7–100%) and 100% of specificity (95% CI, 99.0–100%).

Conclusion

NIPT-dSGD provides accurate genetic testing for de novo and paternally inherited variants of dominant genes, including those that do not cause any ultrasound abnormalities, which could assist clinicians and families in better pregnancy management.
Results of the joint IAEA/EEAE Intercomparison exercise on radioanalytical characterization of NORM samples in the European region
Authors: Karfopoulos Konstantinos , Domingos Filipa , de With Govert , Michalik Bogusław , Okyar H Burçin , Maramathas Christos , Salpadimos Nikos , Potiriadis Constantinos , Neculae Valentina , Ďurecová Alžbeta , Drábová Veronika , Pinak Miroslav
Published: February 2025

Naturally Occurring Radioactive Material (NORM) may pose radiological risks across various industrial processes. Characterizing NORM is challenging due to radionuclide diversity, complex material matrices, and the multiple analytical techniques required. This study documents an Intercomparison Exercise (ICE) on the radioanalytical characterization of NORM, organized by International Atomic Energy Agency and EEAE to evaluate participants’ abilities to implement appropriate radioanalytical techniques and promote harmonization, thus contributing to ongoing optimization efforts into radiation protection of workers and the public. Thirty-one laboratories from 21 countries participated and determined the activity concentrations of long-lived radionuclides such as 40K, 238U, 226Ra, and 232Th in two ICE items, most through gamma spectrometry. Improper handling and insufficient testing of equilibria status within uranium and thorium series were key sources of unsatisfactory results. Notably, laboratories’ accreditation status did not correlate with analytical accuracy. Overall, study findings highlight improvements are needed in sample preparation, assumptions’ validation and measurement uncertainty budget estimation procedures.
Feed efficiency and fecal microbiome of nursery pigs from parents with divergent breeding value for feed conversion ratio
Authors: Wu Yujia , Azevedo Paula , Jin Shunshun , Xu Haoxiang , Lei Huaigang , Verschuren Lisanne , Rodas-Gonzalez Argenis , Nyachoti Martin , Yang Chengbo
Published: February 2025

Improving feed efficiency (FE) is essential for the swine industry’s economic and environmental sustainability. Genetic selection, particularly through estimating breeding values for feed conversion ratio (EBV_FCR), is a common strategy to enhance FE. However, the biological mechanisms underlying phenotypic variations in FE between pigs with different EBV_FCR values are not fully understood. This study investigates these mechanisms by examining growth performance, nutrient and energy digestibility, and fecal microbiota composition and functionality of pigs at the nursery stage. The study involved 128 pigs, weaned at 21 days (±2 days) and with an initial body weight of 6.87 kg (±0.34 kg). These pigs, selected from dam and sire lines with divergent EBV_FCR values, were randomly assigned to 32 pens with four pigs each. Pigs were fed a corn and soybean meal-based diet, divided into two feeding phases of 2 weeks each, under similar rearing conditions. Results indicated no significant differences in average daily feed intake (ADFI), average daily body weight gain (ADG), or feed efficiency (FE, gain:feed) between pigs from different EBV_FCR lines (P > 0.05). Similarly, nutrient digestibility showed no significant variation (P > 0.05). While the overall fecal microbiota taxonomic composition was similar between the groups, there was a trend toward higher beta diversity in the microbiota of pigs from parents with lower EBV_FCR (high efficiency pigs, H pigs) (P < 0.083). Carbohydrate and amino acid metabolism were predominant in all pigs, regardless of genetic background, with similar predicted microbiota functionality across groups. The study concluded that genetic differences based on parents divergent EBV_FCR did not affect growth performance, nutrient utilization, or microbiota characteristics at the nursery stage. This suggests that while EBV_FCR based genetic selection does not impact early-stage performance or microbiome responses, its effects may differ in older pigs, warranting further research.
Leaving Against Medical Advice: What's a Nurse to Do?
Authors: Walker Joan Marie , de Melo-Martín Inmaculada
Published: February 2025

Each year approximately 1% to 2% of patient acute care discharges in United States hospitals are described as against medical advice (AMA). AMA discharges are associated with higher patient morbidity, increased risk of readmission, and higher mortality. Most discussions dealing with AMA discharge tend to focus on physicians. However, nurses have a pivotal role in the care process and in ensuring the safety of patients. The aim of this paper is to increase awareness regarding nurses' ethical responsibilities when confronting AMA discharges. We highlight nurses' leadership role in discharge planning and argue that they have moral obligations to promote as safe a discharge as possible. Such obligations are consistent with nursing codes of ethics, according to which nurses have a primary moral duty to promote patients' well-being. Moreover, nurses' training, expertise, and scope of practice place them in an ideal situation to address problems related to AMA discharges. We also offer suggestions that can contribute to helping nurses to fulfill their ethical responsibilities in this context.
Toward an Appreciation of the Physical Work Environment for Nurses
Authors: Kirton Carl A.
Published: February 2025

Where nurses work makes a difference.
Assessing the Utility and Challenges of Machine Learning in Spinal Deformity Management
Authors: Khan Jibran A. , Houdane Abdelrafour , Hajja Amro , Nassar Joseph E. , Alsoof Daniel , Diebo Bassel G. , Sardar Zeeshan M. , Abd-El-Barr Muhammad M. , Bourghli Anouar , Konbaz Faisal
Published: February 2025

Study design.

Systematic review

Objective.

To review the application of machine learning (ML) in scoliosis management, while addressing the limitations and challenges in implementing ML in scoliosis practice.

Summary of Background Data.

ML has revolutionized medical research, particularly in scoliosis management, enabling automated assessment of diagnosis, disease progression, and treatment response.

Methods.

A systematic review of the literature was conducted following the PRISMA guidelines and was registered in the PROSPERO database. The literature search included the PubMed, Embase, and Google Scholar databases. Studies since 2019 were included if they used ML models in scoliosis management. Studies that did not meet the inclusion criteria were excluded. Data extraction focused on the scoliosis type, sample size, model utility, ML model architecture, model development, training data, cross-validation, single- or multi-center study design, and study/model limitations.

Results.

The study included 63 articles that underwent full-text review. The most commonly studied disorders were adolescent idiopathic scoliosis (n=48) and adult spinal deformity (n=15), with five studies including other disorders and one not specifying. The uses of ML were diagnosis/classification (n=38), operative outcomes (n=11), prognosis (n=7), and risk assessment (n=7). The most used models included convolutional neural networks (n=38), random forest (n=11), and support vector machines (n=9). Only 16 studies reported external validation, while none implemented their model in practice. Common limitations reported were small sample size, artifacts obscuring images, potential selection bias, limited variety in disease severity, exclusion of parameters, lack of patient diversity, varying accuracy with curve site and severity, retrospective study, and lack of external validation.

Conclusion.

The current state of machine learning in scoliosis management is promising, showing potential for improving diagnosis and optimizing treatments. However, significant challenges remain. To fully understand the benefits of ML, larger, multi-center studies with more validation and effective implementation strategies are needed.
Characterization of Spine Implant Device Recalls
Authors: Goheer Haseeb E. , Botros Mina , Ghattas Yasmine S. , Yang Phillip T. , Irwin Rebecca M. , Puvanesarajah Varun
Published: February 2025

Study Design.

Observational epidemiological study.

Objective.

To identify and comprehensively assess reasons for recalls of spinal implant devices used in patients over the past 21 years.

Summary of Background Data.

The number of spine implant devices on the market continues to rise. Although the Food and Drug Administration (FDA) regulates the safety of these devices, there is a paucity of literature on the reasons spine implant devices are recalled.

Methods.

The FDA device recall database was queried using the search term “spine” for recalls between 2003 and 2024. Data were collected regarding recall class, recall reason, FDA 510(k)/premarket approval decision date, product manufacturer, and device indication. The data was then reviewed to identify recalls for spine implant devices.

Results.

A total of 386 spine implant devices were identified between January 2003 and December 2024. Among all recalls classified, 3.4% (n=13) were class I, 88.1% (n=340) were class II, and 8.5% (n=33) were class III. The most common reasons for recall were “Device/Component design” (52.8%) and “Packing/Processing Control” (24.1%). The median number of devices recalled by manufacturers included in the study was two with the highest being 41 devices.

Conclusions.

Overall, 76.9% of spine implant recalls reviewed were primarily due to issues with device design and processing control. 88.1% of recalls were classified with a class II FDA designation. This is the first study to present a retrospective regulatory analysis of FDA spine implant recalls and highlights the importance of premarket analysis and postmarketing surveillance to improve device safety.

Level of Evidence.

4.
Dual Sustained-Release BMP7-Nanoparticle Hydrogel Scaffolds for Enhanced BMSC Neuronal Differentiation and Spinal Cord Injury Repair
Authors: Sun Xudong , Zhang Heng , Huang Shiyuan , Li Kuanxin , Wang Xuyi
Published: February 2025

Study Design:

Preclinical experimental study

Objective:

To explore the use of hydrogels as bioactive scaffolds for encapsulating bone marrow mesenchymal stem cells (BMSCs) to enhance their therapeutic potential in spinal cord injury (SCI). This study further aims to evaluate the added value of a BMP7 nanoparticle delivery system in overcoming the limitations of BMSCs alone for SCI repair.

Summary of Background Data:

SCI leads to significant neuron loss and functional impairment. While BMSC-based stem cell therapies show promise, their efficacy is limited by challenges such as the instability of bone morphogenetic protein (BMP)-7 in inducing neuronal differentiation. High concentrations of BMP7, though effective in promoting neuronal differentiation, may cause inflammation, necessitating the development of a delivery system for sustained and localized release.

Methods:

BMSCs were isolated from Sprague-Dawley rats, and BMP-7’s effects on neuronal differentiation were assessed via western blotting. BMP7-loaded nanoparticles (NPs) and BMSCs were co-loaded into a gelatin methacrylate (Gel-MA) hydrogel scaffold, with a cell loading density of 1 × 10⁵ cells/μl. BMP7 was encapsulated at a 0.04% (w/V) concentration, corresponding to approximately 0.4 ng BMP7 per μl of hydrogel. Optimization was performed using mechanical, cytotoxicity, and neuronal marker analyses. Scaffold properties, including water absorption, BMP7 release, and BMSC morphology, were characterized. Therapeutic efficacy was evaluated in a rat SCI model using motor function recovery, histological analysis, and molecular assessments.

Results:

BMP-7 effectively promoted BMSC differentiation into neurons while suppressing glial cell development. The BMP7-NPs/Gel-MA scaffold ensured sustained BMP7 release, achieving optimal differentiation at a 0.04% (w/V) BMP7 concentration. In vivo, the scaffold combined with BMSCs enhanced neuronal proliferation and differentiation, stimulated myelin regeneration, reduced lesion volume, and significantly improved motor function recovery.

Conclusion:

The BMP7-NPs/Gel-MA scaffold provides sustained delivery of BMP-7, effectively directing BMSC differentiation into neuron-like cells while avoiding glial commitment. Combined with BMSCs, it offers a promising therapeutic strategy for SCI repair.
Nondrainage Scleral Buckling in the Modern Vitrectomy Era
Authors: Barile Gaetano R , Gupta Rohun , Engelbert Michael , Kaden Talia R , Schiff William M
Published: February 2025

Purpose:

To evaluate outcomes of rhegmatogenous retinal detachment (RRD) treated with a scleral buckle (SB) without external drainage of subretinal fluid during the modern vitrectomy era.

Methods:

The records of 107 eyes of 107 patients that underwent treatment with nondrainage SB surgery for primary RRD with at least 3 months of follow-up were reviewed.

Results:

SB surgery included segmental elements (radial, 44.9%; circumferential, 23.4%) and encircling procedures (31.8%). Most (68.2%) patients were under age 60 years, and most eyes (89.7%) were phakic. Single breaks were present in 53.3% of the eyes. The macula was attached preoperatively in 66 (61.7%) eyes. Myopia > 5.5 diopters (35.5%) and lattice degeneration (48.6%) were notable risk factors. Posterior vitreous detachment (PVD) was present in 37.4% of the eyes. Single surgery retinal reattachment was achieved in 104 eyes; three of these eyes also received pneumatic gas injections postoperatively. Four eyes underwent anatomically successful repeat surgery, including one eye that developed a recurrent RRD after release of an encircling element. One eye underwent removal of an exposed SB without sequalae, and one eye developed persistent diplopia treated with prism.

Conclusions:

With proper case selection, nondrainage SB remains an excellent surgical procedure for repair of RRD in the modern vitrectomy era.
Intraoperative Three-Dimensional Fluorescein Angiography-Guided Pars Plana Vitrectomy for the Treatment of Multiple Retinal Diseases
Authors: Wang Xi , Ling Ruolan , Cheng Hongzhuang , Shen Yadan , Chen Li , Ning Xinru , Guo Chuyun , Li Jie , Jie Zhong , Wang You
Published: February 2025

Purpose:

To explore the effectiveness and practicality of intraoperative fluorescein angiography (IOFA) in both common and rare retinal diseases.

Methods:

We conducted a case series study involving three patients with vascular abnormality from various causes. A custom-designed, single-photon ultra-wideband spectral light source and integrated filters were utilized to perform IOFA. The cases included one patient with diabetic retinopathy, one with Coat’s disease, and one with familial exudative vitreoretinopathy (FEVR). IOFA was performed, and individualized treatment was conducted based on the angiographic findings.

Results:

All three patients had successful IOFA, and two of them also underwent pars plana vitrectomy (PPV) guided by the IOFA results. Postoperative outcomes were favorable, with controlled disease progression and improved or stable vision. The diabetic retinopathy patient’s vision improved significantly post-surgery, the Coats disease patient’s retinal detachment resolved without recurrence, and the FEVR patient showed no further bleeding on follow-up.

Conclusion:

The integration of an enhanced light source and filters reduced the transition time from standard surgical mode to angiography mode to just 10 seconds. Moreover, this study demonstrates that IOFA can effectively guide PPV surgeries and treatment for both common and rare retinal vascular diseases, offering a promising direction for personalized retinal disease management. In addition, further research and clinical trials are warranted to confirm the efficacy of IOFA-guided targeted retinal photocoagulation, particularly in diabetic retinopathy-induced vitreous hemorrhage.
Isolated vitritis as the presenting feature of disseminated Mycobacterium chelonae subspecies gwanakae, a novel subspecies
Authors: Massenzio Samantha S , Kuriyan Ajay E. , Milman Tatyana , Pecora Nicole D. , Pettengill Matthew A. , Zurlo John J , Deaner Jordan D
Published: February 2025

Purpose:

To report a case of isolated vitritis as the presenting feature of a disseminated infection with Mycobacterium chelonae subspecies gwanakae, a novel subspecies.

Methods:

Case report.

Results:

A 66-year-old male who presented with progressive floaters and blurred vision was found to have isolated vitritis of the left eye. Diagnostic vitrectomy revealed acid-fast bacilli in the vitreous. Whole genome sequencing identified the organism as Mycobacterium chelonae subspecies gwanakae, a recently identified novel subspecies. The patient was admitted for further evaluation and treatment. Punch biopsies of the numerous ulcerative skin lesions revealed acid-fast bacilli. Magnetic resonance imaging revealed osteomyelitis underlying the soft tissue infections, requiring incision and drainage. Biopsy of the bone also revealed acid-fast bacilli. He was treated with weekly intravitreal amikacin and empiric intravenous azithromycin, imipenem, and tobramycin. His ocular infection responded well to treatment with resolution of the vitritis and improvement in visual acuity. Unfortunately, his systemic condition deteriorated, and he declined further intervention, ultimately succumbing to his systemic infection 12 weeks after presentation.

Conclusion:

Isolated vitritis can be the presenting feature of a severe disseminated Mycobacterium chelonae subspecies gwanakae infection.
Active Osseointegrated Steady-State Implant System: Surgical and Clinical Performance
Authors: Ordoñez-Ordoñez Leornardo , Caraballo José Agustin , Ortiz Jorge Guillermo Cabrera , Eslait Francisco Gonzalez , Saffon Rafael Jaramillo , Lora José Gabriel , Hernandez Santiago , Guzman Jose , Rincon Luz Adriana , Buzo Byanka Cagnacci
Published: February 2025

Purpose

We aimed to investigate the surgical outcomes and clinical performance of an active osseointegration implant system that uses piezoelectric technology.

Methods

This national, multicenter, prospective, repeated measures study was approved by the Ethics Committee (opinion no. CEISH 0559-2019). The sample included patients with conductive hearing loss (CHL), mixed hearing loss (MHL), or single-sided deafness (SSD) who were eligible for osseointegrated implant surgery. Surgical parameters were assessed, along with functional and effective gain (FG and EG) and self-perception of benefits, which were evaluated between 3 and 6 months after activation. Participants also completed the Client Oriented Scale of Improvement (COSI) questionnaire to subjectively report expected and perceived benefits.

Results

A total of 580 participants aged 5 to 73 years were included in the study between June 2020 and April 2023. Most participants were diagnosed with CHL (58.8%), followed by MHL (28.8%) and SSD. 11.4% of the surgeries involved conversion of other devices to the piezoelectric system. The mean surgery duration was 54 min, and the mean skin thickness was 5.6 mm. Soft tissue reduction was required for 4% of the participants, while 21.2% required bone polishing. The mean PTA (pure tone average) FG was 38.6 dB for participants with CHL, 44.4 dB for those with MHL, and 66.1 dB for those with SSD.

Conclusion

These results confirmed the clinical safety, performance, and benefits of an innovative active transcutaneous bone conduction implant with a piezoelectric transducer design for patients with CHL, MHL, or SSD.
Surgical Transcanal Procedure for Injection of Cells and Substances into the Human Cochlear Modiolus
Authors: Cayé-Thomasen Per , Erfurt Peter , Baumhoff Peter , Kral Andrej , Navntoft Charlotte Amalie
Published: February 2025

Introduction

Cochlear implants (CIs) enhance hearing by stimulating spiral ganglion neurons (SGNs) but are less effective in individuals with compromised SGN functionality. Advances in regenerative medicine suggest that local delivery of medical drugs or cell therapy could regenerate the auditory nerve. This study evaluates a minimally invasive technique for precise delivery of cell-sized beads, simulating cell therapy, into the cochlear modiolus of human temporal bones.

Methods

Ten fresh-frozen human temporal bone specimens were used. Five bones served to establish the injection trajectory using a tungsten rod probe, and the remaining five for injecting microbeads into the modiolus. The surgical procedure involved accessing the middle ear via the external ear canal, performing a cochleostomy at the first cochlear turn, and drilling into the modiolus. Beads were injected into the modiolus using a Hamilton syringe connected to an injection pump, followed by micro-computed tomography imaging and histological assessment.

Results

Accurate placement of the tungsten rod probe within the modiolus was achieved in four out of five bones. Microbead injections indicated 89 to 97% retention within the modiolus, with minimal leakage. The technique showed consistent trajectory with low variability.

Conclusion

The study demonstrates the feasibility of a minimally invasive, precise injection method for delivering and retaining cell-sized beads into the cochlear modiolus. This technique enables future local delivery of medical drugs or cell therapy drugs aimed at hearing restoration, benefiting both current CI users and CI candidates. Further research is necessary to evaluate precision, reproducibility, and long-term outcomes of the procedure.
Machine Learning–Based First-Day Mortality Prediction for Venoarterial Extracorporeal Membrane Oxygenation: The Novel RESCUE-24 Score
Authors: Hsu Jung‑Chi , Pai Chen-Hsu , Lin Lian‑Yu , Wang Chih-Hsien , Wei Ling-Yi , Chen Jeng-Wei , Chi Nai-Hsin , Huang Shu-Chien , Yu Hsi-Yu , Chou Nai-Kuan , Hsu Ron-Bin , Chen Yih-Sharng
Published: February 2025

Extracorporeal membrane oxygenation (ECMO) provides critical cardiac support, but predicting outcomes remains a challenge. We enrolled 1,748 adult venoarterial (VA)-ECMO patients at the National Taiwan University Hospital between 2010 and 2021. The overall mortality rate was 68.2%. Machine learning with the random survival forest (RSF) model demonstrated superior prediction for in-hospital mortality (area under the curve [AUC]: 0.953, 95% confidence interval (CI): 0.925–0.981), outperforming the Sequential Organ Failure Assessment (SOFA; 0.753 [0.689–0.817]), Acute Physiology and Chronic Health Evaluation (APACHE) II (0.737 [0.672–0.802]), Survival after Venoarterial ECMO (SAVE; 0.624 [0.551–0.697]), ENCOURAGE (0.675 [0.606–0.743]), and Simplified Acute Physiology Score (SAPS) III (0.604 [0.533–0.675]) scores. Failure to achieve 25% clearance at 8 hours and 50% at 16 hours significantly increased mortality risk (HR: 1.65, 95% CI: 1.27–2.14, p < 0.001; HR: 1.25, 95% CI: 1.02–1.54, p = 0.035). Based on the RSF-derived variable importance, the RESCUE-24 Score was developed, assigning points for lactic acid clearance (10 for <50% at 16 hours, 6 for <25% at 8 hours), SvO2 <75% (3 points), oliguria <500 ml (2 points), and age ≥60 years (2 points). Patients were classified into low risk (0–2), medium risk (3–20), and high risk (≥21). The medium- and high-risk groups exhibited significantly higher in-hospital mortality compared with the low-risk group (HR: 1.93 [1.46–2.55] and 5.47 [4.07–7.35], p < 0.002, respectively). Kaplan–Meier analysis confirmed that improved lactic acid clearance at 8 and 16 hours was associated with better survival (log-rank p < 0.001). The three groups of the RESCUE-24 Score also showed significant survival differences (log-rank p < 0.001). In conclusion, machine learning can help identify high-risk populations for tailored management. Achieving optimal lactic acid clearance within 24 hours is crucial for improving survival outcomes.
Evaluating Concordance Between Complete Blood Count and Point-of-Care Tests in Pediatric Extracorporeal Membrane Oxygenation
Authors: Lull Jordan R. , Sethi Louisa M. , Alexander Robin , Nicol Kathleen K. , Muszynski Jennifer A.
Published: February 2025

The accuracy of point-of-care (POC) hemoglobin (Hgb) and hematocrit (Hct) testing in pediatric patients on extracorporeal membrane oxygenation (ECMO) is unknown. Point-of-care testing uses less blood volume and could decrease iatrogenic anemia. However, inaccurate results could lead to repeat testing or increased risk of red blood cell (RBC) transfusions. We performed a single-center, retrospective study to quantify agreement between laboratory and POC tests for Hgb and Hct in pediatric ECMO. Patients were included if laboratory and POC values were recorded within 5 minutes of each other. Discordance was defined as discrepancy of >0.5 g/dl (Hgb) or >1.5% (Hct). Exclusion criteria included >18 years of age, cannulated at outside hospital, or ECMO support <24 hours. One hundred thirty-six patients with an average age of 2 months were included. Fifty-one percent were female. Sixty-six percent were supported with VA ECMO. Two hundred seventy-nine values compared laboratory with inline and 59 compared laboratory with blood gas analyzer. Forty-one percent of values were discordant, with the majority of discordant POC value less than the lab value. Our findings suggest that using POC values could increase RBC transfusions, though further study is needed to determine the effects of POC tests on transfusion burden and to evaluate factors predictive of discordance.
Coincidental occurrence of severe factor XII deficiency in a case of mild hemophilia A: a unique coagulation laboratory diagnostic conundrum
Authors: Kulkarni Bipin P. , Shanmukhaiah Chandrakala , Ghargi Kirti , Pandey Puloma , Kharat Shruti , Pawar Prachi , Shinde Sayali , Kawankar Nikesh , Shanbhag Sharda
Published: February 2025

We present a unique case of severe factor XII (FXII) deficiency in a mild hemophilia A patient. The co-occurrence of these two inherited coagulation disorders poses laboratory diagnostic challenges. We discuss the clinical presentation, laboratory findings, and molecular characterization of this unique case.
Update in paediatric asthma
Authors: Bush Andrew
Published: February 2025

Purpose of review

The field of paediatric asthma is rapidly moving, with the advent of new biologicals for severe asthma and increased understanding of preschool wheeze amongst other developments and insights.

Recent findings

There is increasing evidence of efficacy in children for biologics directed against Type 2 inflammation (especially mepolizumab and dupilumab) as well encouraging evidence that Tezepelumab may be effective against Type 2 low phenotypes. The importance of airway remodelling and infection in the pathophysiology of preschool wheeze is increasingly appreciated. The treatment of preschool wheeze is moving from symptom-based to biomarker driven therapies. Other important areas are prediction of risk of asthma attacks, the SMART regime, the importance of climate change and reducing greenhouse gas emissions from inhalers while ensuring adequate therapy for young children, the association of early adverse environmental factors including childhood poverty and deprivation and the switch to race-neutral lung function equations.

We are increasingly moving towards personalized medicine and the use of biomarkers to guide treatment of wheeze at all ages, but we need to move from counting cells to determining their functional status. Airway wall structural changes rather than inflammation may drive the progression of preschool wheeze to school age asthma
Sodium benzoate for the treatment of hepatic encephalopathy in humans and animals: a systematic review and meta-analysis
Authors: van Zoest Danny , Gal Bram , Agha Ayaz H. , den Hoed Caroline M. , Langendonk Janneke G. , Wagenmakers Margreet A.E.M. , Peltenburg Chantal
Published: February 2025

Background and aim

Hepatic encephalopathy (HE) is a life-threatening condition where brain function is impaired mainly due to high systemic ammonia levels. HE is associated with a high 1-year mortality. No universally accepted guidelines for the treatment of HE exist. Nitrogen scavengers, such as sodium benzoate (SB), have been proven very effective to treat hyperammonemia in patients with urea cycle defects, in acute and chronic settings. We hypothesized that SB can also be an effective treatment of HE caused by end-stage liver disease or portosystemic shunting, as long as liver function is partially intact. The aim of this meta-analysis is to study the effect of SB in humans and animals with HE due to end-stage liver disease or portosystemic shunting.

Methods

Embase, Medline (Ovid and PubMed), Web-of-Science, Cochrane, and Google Scholar were searched on 19 July 2021, both human and animal studies were eligible.

Results

Sixteen studies were included, consisting of four clinical trials, five animal studies, and seven case reports, including 314 subjects. Meta-analysis included 284 subjects. The standardized mean difference (SMD) of SB’s ammonia-lowering effect was 0.89 SMD [95% confidence interval (CI): 0.27–1.51] in clinical trials and 1.63 SMD (95% CI: −0.12 to 3.39) in animal studies. Considerable heterogeneity was present in the included studies.

Conclusion

SB seems to be an effective treatment for HE or hyperammonemia caused by end-stage liver disease or portosystemic shunting. However, additional high-quality studies are necessary for more robust conclusions.
Efficacy and safety of tofacitinib for the treatment of moderate-to-severe ulcerative colitis in biologic-naive patients
Authors: Liatsos Christos , Tzouvala Maria , Michalopoulos Georgios , Giouleme Olga , Karmiris Konstantinos , Kozompoli Dimitra , Mousourakis Konstantinos , Kyriakos Nikolaos , Giakoumis Marios , Striki Athanasia , Karoubalis Ioannis , Bellou Georgia , Zacharopoulou Eirini , Katsoula Anastasia , Kalogirou Maria , Viazis Nikos
Published: February 2025

Background and aims

Tofacitinib has been approved for the treatment of patients with moderate-to-severe ulcerative colitis independently of prior therapies. We aimed to assess the efficacy and safety of tofacitinib in biologic-naive patients.

Methods

This was a retrospective analysis of prospectively collected data extracted from the notes of patients with moderate-to-severe ulcerative colitis naive to advanced therapies, who were treated with tofacitinib [10 mg twice daily (b.i.d.) for 8 or 16 weeks followed by a 5 mg b.i.d. maintenance dose] in six Greek Hospitals, who had a follow-up of at least 26 weeks after treatment initiation.

Results

Overall, 48 patients were included. Clinical response was seen in 30 (62.5%) and 32 (66.6%) patients at week 8 and 16, respectively. Clinical remission, corticosteroid-free clinical remission, biochemical response, and endoscopic remission at week 26 was observed in 26 (54.2%), 26 (54.2%), 28 (60.8%), and 29 (60.4%) patients, respectively. No major adverse events or infections were recorded.

Conclusion

In this retrospective ongoing cohort study, tofacitinib demonstrated clinical response at weeks 8 and 16 in more than 60% and steroid-free clinical remission at week 26 in more than 50% of biologic-naive patients with moderate-to-severe ulcerative colitis with a good safety profile, indicating that tofacitinib is an effective first-line treatment for this group of patients.
Leveraging drug-target Mendelian randomization for tailored lipoprotein-lipid lowering
Authors: Gagnon Eloi , Arsenault Benoit J.
Published: February 2025

Purpose of review

The study of naturally occurring genetic variation in human populations has laid the foundation for proprotein converts subtilisin/kexin type 9 inhibitors, and more recently new classes of lipid-lowering drugs such as lipoprotein(a) inhibitors and lipoprotein lipase pathway activators. These emerging therapies lower plasma lipoprotein-lipid levels that are not adequately managed by traditional low-density lipoprotein (LDL) cholesterol-lowering medications. By targeting different risk factors, these therapies could help manage the important residual cardiovascular risk of LDL cholesterol medications.

Recent findings

We review the latest insights into the pharmacological and genetic modulation of these new therapeutic targets. We highlight that the drugs remarkably recapitulate the lipid effects observed in genetic studies. In addition to lowering lipoprotein-lipid levels, robust genetic evidence support that these drugs may prevent cardiometabolic outcomes.

Emerging lipid-lowering therapies could launch a new era for preventive medicine in which treatments are optimally tailored to patient's lipoprotein-lipid profiles.
Tree balance in phylogenetic models
Authors: Kersting Sophie J. , Wicke Kristina , Fischer Mareike
Published: February 2025

Tree shape statistics, particularly measures of tree (im)balance, play an important role in the analysis of the shape of phylogenetic trees. With applications ranging from testing evolutionary models to studying the impact of fertility inheritance and selection, or tumour development and language evolution, the assessment of measures of tree balance is important. Currently, a multitude of at least 30 (im)balance indices can be found in the literature, alongside numerous other tree shape statistics. This diversity prompts essential questions: how can we assist researchers in choosing only a small number of indices to mitigate the challenges of multiple testing? Is there a preeminent balance index tailored to specific tasks? This research expands previous studies on the examination of index power, encompassing almost all established indices and a broader array of alternative models, such as a variety of trait-based models. Our investigation reveals distinct groups of balance indices better suited for different tree models, suggesting that decisions on balance index selection can be enhanced with prior knowledge. Furthermore, we present the R software package
poweRbal
which allows the inclusion of new indices and models, thus facilitating future research on the power of tree shape statistics.

This article is part of the theme issue ‘"A mathematical theory of evolution": phylogenetic models dating back 100 years’.
Multiple merger coalescent inference of effective population size
Authors: Zhang Julie , Palacios Julia A.
Published: February 2025

Variation in a sample of molecular sequence data informs about the past evolutionary history of the sample’s population. Traditionally, Bayesian modelling coupled with the standard coalescent is used to infer the sample’s bifurcating genealogy and demographic and evolutionary parameters such as effective population size and mutation rates. However, there are many situations where binary coalescent models do not accurately reflect the true underlying ancestral processes. Here, we propose a Bayesian non-parametric method for inferring effective population size trajectories from a multifurcating genealogy under the

Λ

-coalescent. In particular, we jointly estimate the effective population size and the model parameter for the Beta-coalescent model, a special type of

Λ

-coalescent. Finally, we test our methods on simulations and apply them to study various viral dynamics as well as Japanese sardine population size changes over time. The code and vignettes can be found in the phylodyn package.

This article is part of the theme issue ‘“A mathematical theory of evolution”: phylogenetic models dating back 100 years’.
Characterisation of the virome of Culicoides brevitarsis Kieffer (Diptera: Ceratopogonidae), a vector of bluetongue virus in Australia
Authors: Sharpe Stephen R. , Madhav Mukund , Klein Melissa J. , Blasdell Kim R. , Paradkar Prasad N. , Lynch Stacey E. , Eagles Debbie , López-Denman Adam J. , Ahmed Khandaker Asif
Published: February 2025

Graphical abstract

A metatranscriptomics study of a dominant bluetongue virus vector, Culicoides brevitarsis from Australia, identified 10 complete/near-complete viral genomes including 7 novel species.
Disentangling Rhythmic and Aperiodic Neural Activity: Investigating the Role of GABA Modulation in Sensorimotor Beta Oscillations
Authors: Barone Jacopo , Rossiter Holly E. , Muthukumaraswamy Suresh , Singh Krish D.
Published: February 2025

Beta oscillations (13–30 Hz) in the sensorimotor cortex are fundamental to motor control and are disrupted in motor disorders such as Parkinson’s disease and stroke. Animal studies and pharmacological research in humans have implicated GABAergic mechanisms in modulating these oscillations. Here, we explored the impact of GABAergic modulation on sensorimotor beta oscillations using magnetoencephalography (MEG) during a finger abduction task, with participants administered gaboxadol and zolpidem, two GABA-A positive allosteric modulators. We combined traditional oscillatory analyses with spectral parametrisation methods to separate periodic and aperiodic neural components. Time-frequency representations (TFRs) showed that gaboxadol induced a stronger modulation of beta dynamics than zolpidem, leading to deeper beta desynchronisation during movement and a more pronounced post-movement beta rebound. When accounting for aperiodic activity, gaboxadol showed modest effects limited to movement initiation, with increased beta power during movement onset but no significant impact during post-movement rebound. In contrast, zolpidem significantly enhanced beta power and altered aperiodic components, suggesting differential influences on GABAergic modulation and excitation-inhibition balance. These results underscore the necessity of distinguishing between periodic and aperiodic signals in spectral measures to improve the interpretation of neural oscillatory data.
Amoebicidal Action of Licorice-Derived Compounds: Mechanisms and Effects AgainstAcanthamoeba castellanii
Authors: Chen Lijun , Dong Dai , Jing Wenwen , Zhou Qingtong , Feng Meng , Cheng Xunjia
Published: February 2025

Background

Acanthamoebais a widely distributed unicellular eukaryotic organism, causingAcanthamoebakeratitis, granulomatous amoebic encephalitis and chronic infectious ulcers. At present, there are no effective drugs available for treatingAcanthamoebainfections, highlighting the urgent need for the development of novel anti-Acanthamoebatherapies.

Purpose

This study aims to investigate the inhibitory effect of licorice onA. castellaniitrophozoites growth and elucidate its molecular mechanisms.

Methods

The effect of licorice on trophozoite viability was assessed employing the CellTiter-Glo assay, while the viability of cells was evaluated via CCK-8 assay. Apoptotic cells were identified through Hoechst 33,342/PI double staining and caspase-3 detection. ROS level was measured via flow cytometry utilising DCFH-DA. Mitochondrial dysfunction was analysed with JC-1 and mtSOX Deep Red staining. RNA sequencing and RT-qPCR analysis were conducted to investigate the potential anti-Acanthamoebamechanism.

Results

Our results showed that isoliquiritigenin (ISL) and glabridin (GLA) effectively inhibitedA. castellaniitrophozoite growthin vitrodose-and time-dependently. ISL and GLA induced several apoptosis features, including Hoechst/PI-positive staining and increased caspase-3 expression. ISL and GLA increased intracellular ROS production, decreased SOD expression and mitochondrial membrane potential and enhanced mitochondrial ROS generation. ISL and GLA effectively prevent host cells fromA. castellaniitrophozoites invasion. RNA sequencing indicated that ISL may modulate the NAD+metabolic process, while GLA may influence the sterol metabolic process. ISL reduced the NAD+/NADH ratio, while GLA lowered the levels of 7-dehydrocholesterol inA. castellaniitrophozoites.

Conclusion

These findings suggest that ISL and GLA may serve as the active components of licorice for treatingA. castellaniitrophozoites. Our findings suggest that ISL suppresses trophozoites by regulating NAD+metabolism, while GLA inhibits trophozoites through the regulation of sterol metabolism.

Abstract Figure
Large inverse Faraday effect for Rydberg states of free atoms and isolated donors in semiconductors
Authors: Wong Patrick J. , Khaymovich Ivan M. , Aeppli Gabriel , Balatsky Alexander V.
Published: February 2025

We report on the induction of magnetization in Rydberg systems by means of the inverse Faraday effect and propose the appearance of the effect in two such systems: Rydberg atoms proper and shallow dopants in semiconductors. Rydberg atoms are characterized by a large orbital radius. This large radius gives such excited states a large angular moment, which when driven with circularly polarized light translates to a large effective magnetic field Beff. We calculate this effect to generate effective magnetic fields of O(1µT)×(ω1THz)−1(I10Wcm−2)n4 in the Rydberg states of atoms such as Rb and Cs for off-resonant photon beams with frequency ω and intensity I expressed in units of the denominators and n the principal quantum number. Additionally, terahertz spectroscopy of phosphorus-doped silicon reveals a large cross section for excitation of shallow dopants to Rydberg-like states, which even for small n have the potential to be driven similarly with circularly polarized light to produce an even larger magnetization. Our theoretical calculations estimate Beff as

O

(

10

2

T

)

for Si:P with a beam intensity of 108Wcm−2.

Published by the American Physical Society
2025
Anomalous Quasielastic Scattering Contribution in the Centrosymmetric Multi-
q
Helimagnet
SrFeO3
Authors: Andriushin Nikita D. , Grumbach Justus , Kulbakov Anton A. , Tymoshenko Yuliia V. , Onykiienko Yevhen A. , Firouzmandi Reza , Cheng Erjian , Granovsky Sergey , Skourski Yurii , Ollivier Jacques , Walker Helen C. , Kocsis Vilmos , Büchner Bernd , Keimer Bernhard , Doerr Mathias , Inosov Dmytro S. , Peets Darren C.
Published: February 2025

Centrosymmetric compounds which host three-dimensional topological spin structures comprise a distinct subclass of materials in which multiple-q magnetic order is stabilized by anisotropy and bond frustration in contrast to the more common path of antisymmetric exchange interactions. Here we investigate static and dynamic magnetic properties of the cubic perovskite SrFeO3—a rare example of a centrosymmetric material hosting two types of topological spin textures: skyrmionlike and hedgehog-lattice phases. Our detailed magnetization and dilatometry measurements describe the domain selection processes and phase transitions in SrFeO3. Spin excitations are investigated using inelastic neutron scattering for all three zero-field phases. In the higher-temperature ordered phases, high-energy magnons increasingly lose coherence, so that spin fluctuations are dominated by a distinct quasielastic component at low energies. We anticipate that this could be generic to symmetric helimagnets in which the chiral symmetry is spontaneously broken by the magnetic order.

Published by the American Physical Society
2025
Cryo-EM structures of apo and atorvastatin-bound human 3-hydroxy-3-methylglutaryl-coenzyme A reductase
Authors: Karuppasamy Manikandan , van Rooyen Jason
Published: February 2025

The enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) regulates the level of cholesterol by catalysing the formation/production of mevalonate and has therefore become an important pharmaceutical target for coronary heart disease. Here, we report the cryo-EM structure of the catalytic part of the enzyme in the apo form and bound with its inhibitor atorvastatin, a commonly used drug in cardiovascular disease, at resolutions of 2.1 and 2.3 Å, respectively. In the cryo-EM maps, part of the N-domain corresponding to amino acids 439–487 is well ordered and could be modelled completely. Atorvastatin molecules were found to occupy all four active sites of the tetrameric complex, and the binding does not alter the conformation of the protein or the active site. The method described here exploits graphene oxide as an additional support and could be used as an alternative to elucidate the structures of pharmaceutical target compounds that are difficult to co-crystallize with human HMGR and for sparsely available samples in drug discovery.