bluuebunny/crossref_metadata_2025_split huggingface dataset:
565 – Safety and pharmacokinetic profiles of a humanized monoclonal antibody TQH2722 targeting interleukin 4 receptor alpha (IL-4Rα) in health adult subjects
Authors: Lin Pingping , Sun Feifei , Xu Yi , Ban Rongxin , Jiang Xin , Fu Yao , Gao Xiaomeng , Cao Yu 
Published: February 2024

Abstract

Introduction/Background
TQH2722 is a humanized monoclonal antibody targeting interleukin 4 receptor alpha (IL4Rα) which leads to the dual-blockade of interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling, inhibiting the T-helper cell type 2 immune pathway. Th2 inflammation is implicated in the pathobiology of diseases such as asthma and atopic dermatitis. We describe the safety and pharmacokinetic results from a first-in-human study in healthy subjects.

Objectives
To evaluate the safety, tolerability, pharmacokinetic characteristics, and immunogenicity of TQH2722 injection in healthy adult subjects.

Methods
This randomized, double-blind, placebo-controlled, ascending-dose phase I study (NCT05409326) was conducted in China. Each adult subject received a single subcutaneous (sc.) TQH2722 dose or placebo in single ascending-dose (SAD) cohorts, and 4 doses of TQH2722 or placebo administrated Q2W in multiple ascending-dose (MAD) cohorts. Pharmacokinetic samples were collected prior to first dose administration through 56 days after initial dosing in SAD cohorts. In the MAD cohorts, samples were collected before every administration until 56 days after last dosing.

Results
As of 28 September 2023, all subjects had completed the study, with the database locked while remaining unblinded. Sixty-six (66) healthy subjects were enrolled in this study. The SAD cohorts consisted of single doses of TQH2722 of 50 mg (n-4), 150 mg (n=10 active, 2 placebo), 300, 600, and 1200 mg cohorts, each receiving TQH2722 (n=8) or placebo (n=2). Ten subjects were enrolled in each of the 150 and 600 mg MAD cohorts receiving TQH2722 (n=8) or placebo (n=2). No dose-limiting toxicities or SAEs were observed and only 3 subjects experienced a grade 3 AE including 1 subject of increased triglycerides, 1 subject with increased creatine kinase and 1 subject with decreased blood potassium). All other AEs were of grade 1 or 2. The incidence and severity of AEs were not dose dependent. No SAEs or AEs led to treatment discontinuation. The pharmacokinetics of TQH2722 were indicative of an anti-receptor mAb in that TQH2722 exhibited nonlinear target-mediated clearance. Maximum serum concentration was reached after 2.78-6.75 days with the half-life of a single sc. administration of TQH2722 increasing by dose level, ranging between 4 and 18 days.

Conclusions
TQH2722 was safe and well tolerated in healthy volunteers. Injection site reactions and laboratory abnormalities were the most reported AEs, with grade 1-2 as the major severity. Most AEs resolved on their own. Single dosing showed non-linear increases of the drug exposure as the dosage increased. These data support further clinical development of TQH2722 as a therapeutic treatment for patients with Atopic Dermatitis and other related diseases mediated by Th2 inflammation.
566 - Efficacy of dupilumab treatment in atopic hand and foot dermatitis across morphological subtypes: results from a phase 3, randomized, double-blind, placebo-controlled trial
Authors: Worm Margitta , Simpson Eric L , Honari Golara , Soong Weily , Pinter Andreas , Masuda Koji , Shao Liyang , Dubost-Brama Ariane , Bansal Ashish , Korotzer Andrew , Rossi Ana B 
Published: February 2024

Abstract

Introduction/Background
Dupilumab has previously shown to significantly improve signs, symptoms, and quality of life in patients with moderate-to-severe atopic hand and foot dermatitis.

Objective
To investigate the efficacy of dupilumab across morphological subtypes in patients with moderate-to-severe atopic hand and foot dermatitis.

Methods
The phase 3, randomized, double-blind LIBERTY-AD-HAFT (NCT04417894) trial enrolled patients aged ≥12 years with moderate-to-severe (Investigator’s Global Assessment [IGA] score of 3/4) atopic hand and foot dermatitis. Patients were randomized to dupilumab monotherapy 300 mg every 2 weeks (q2w) in adults; 200/300 mg q2w in adolescents, or placebo for 16 weeks. This analysis reports the percent change from baseline in modified total lesion sign score (mTLSS) by hand and foot morphological subtypes: chronic dry fissured, hyperkeratotic (palmar/plantar), and other.

Results
133 patients enrolled into this study and were randomized to dupilumab (n = 67) or placebo (n = 66). Atopic hand and foot morphologies were reported in 3 categories: chronic dry fissured (n = 63), hyperkeratotic (palmar/plantar; n = 37), and other (n = 33) In the “other” category, dyshidrotic was the most frequent morphology (n = 13). mTLSS values were similar at baseline for all morphological subtypes. At Week 16, greater improvements were seen in the percent change from baseline (SE) in mTLSS for patients receiving dupilumab vs placebo in all categories: chronic dry fissured (−65.6% [5.1] vs −31.5% [6.2]), hyperkeratotic (palmar/plantar; −58.2% [7.6] vs −11.8% [7.7]), and other (−64.5% [11.6] vs −29.9% [9.0]). Safety was consistent with the known dupilumab safety profile in patients with atopic dermatitis.

Conclusions
The efficacy of dupilumab remains consistent across different hand and foot dermatitis morphologies and shows higher treatment benefit across subtypes compared with placebo.
537 - The distribution of thyroid disease by age in pediatric vitiligo
Authors: Silverberg Nanette B 
Published: February 2024

Abstract

Background
Thyroid disease is a comorbid autoimmune disorder linked to vitiligo.

Objective
To identify the age distribution of pediatric vitiligo cases in order to understand when screening should begin.

Methods
An IRB-exempt survey of pediatric vitiligo patients.

Results
Thyroid disease was reported in 14 children out of 205 children who specifically responded regarding presence of thyroid disease, Of the 14 children reporting sex with thyroid disease, 12 were female (85.7%) and 2 were unknown. Race/ ethnicity included 8 Caucasian (57.1%), Indian 2 (14.2%), Unknown 3 (21.4%), and Black 1 (7.1 %). Average age of diagnosis of thyroid disease in vitiligo patients (self-reported) was 9.7 years (Range 6 years-18 years).

Limitations
The survey design has limitations, and the number of reported cases is low overall.

Conclusion and Relevance
Thyroid disease appears uncommon as a comorbidity in pre-school children. All races may be at risk. The role of family history is unknown. Presentation is almost exclusively in girls. This data suggests that screening can be reserved for females and guided by age and symptoms.
High frequency oscillation network dynamics predict outcome in non-palliative epilepsy surgery
Authors: Lin Jack , Smith Garnett C , Gliske Stephen V , Zochowski Michal , Shedden Kerby , Stacey William C 
Published: February 2024

Abstract
High frequency oscillations are a promising biomarker of outcome in intractable epilepsy. Prior high frequency oscillation work focused on counting high frequency oscillations on individual channels, and it is still unclear how to translate those results into clinical care. We show that high frequency oscillations arise as network discharges that have valuable properties as predictive biomarkers. Here, we develop a tool to predict patient outcome before surgical resection is performed, based on only prospective information. In addition to determining high frequency oscillation rate on every channel, we performed a correlational analysis to evaluate the functional connectivity of high frequency oscillations in 28 patients with intracranial electrodes. We found that high frequency oscillations were often not solitary events on a single channel, but part of a local network discharge. Eigenvector and outcloseness centrality were used to rank channel importance within the connectivity network, then used to compare patient outcome by comparison with the seizure onset zone or a proportion within the proposed resected channels (critical resection percentage). Combining the knowledge of each patient’s seizure onset zone resection plan along with our computed high frequency oscillation network centralities and high frequency oscillation rate, we develop a Naïve Bayes model that predicts outcome (positive predictive value: 100%) better than predicting based upon fully resecting the seizure onset zone (positive predictive value: 71%). Surgical margins had a large effect on outcomes: non-palliative patients in whom most of the seizure onset zone was resected (‘definitive surgery’, ≥ 80% resected) had predictable outcomes, whereas palliative surgeries (&lt;80% resected) were not predictable. These results suggest that the addition of network properties of high frequency oscillations is more accurate in predicting patient outcome than seizure onset zone alone in patients with most of the seizure onset zone removed and offer great promise for informing clinical decisions in surgery for refractory epilepsy.
A case report of isolated arrhythmogenic left ventricular cardiomyopathy: phenotypes, diagnosis, and treatment
Authors: Lan Yang , Wei Lai , Pan Cuizhen , Lin Tzuchun , Yan Yan 
Published: February 2024

Abstract

Background
Isolated arrhythmogenic left ventricular cardiomyopathy (IALVC) is a hereditary cardiomyopathy that is characterized by the replacement of left ventricular (LV) cardiomyocytes with fibrous and adipose tissue.

Case summary
A 55-year-old male patient presented with recurrent chest pain and palpitations characterized by episodes of monomorphic ventricular tachycardia and T-wave inversion. Coronary angiography was conducted to rule out myocardial ischaemia as the cause of chest pain. Echocardiography results revealed ventricular aneurysm formation at the apex of the left ventricle. Structural alterations of the cardiac magnetic resonance were consistent with the diagnosis of arrhythmogenic left ventricular cardiomyopathy with LV alterations without right ventricular involvement. Pathological staining of the lesion area further confirmed the diagnosis of IALVC. The TTN1 c.17617 C&gt;A mutation in arrhythmogenic cardiomyopathy was identified using whole exome sequencing. His symptoms improved by the treatments including implantable cardioverter defibrillator (ICD) implantation, radiofrequency ablation, and ventricular aneurysm resection.

Discussion
The patient presented with IALVC with apical fibrofatty displacement and underwent surgical management, highlighting the importance of multimodal imaging, gene analysis, and histopathological findings for timely diagnosis, and emphasizing the benefits of life-saving therapy, including ICD implantation, radiofrequency ablation, and ventricular aneurysm resection. These findings contribute to a deeper understanding of the clinical presentation and outcome of IALVC.
Intraoperative indocyanine green imaging as an adjunctive technique to reduce any circumflex artery damage during mitral valve surgery: a feasibility study
Authors: Savini Carlo , Costantino Antonino , Fiorentino Mariafrancesca , Zucchetta Fabio , Cavallucci Andrea , Mikus Elisa 
Published: February 2024

Abstract
Iatrogenic injuries to the circumflex coronary artery during mitral valve surgery are probably underestimated (reported rates of 0.3–1.8%). This complication arises from the artery's close proximity to the mitral annulus, particularly at the anterolateral commissure. The study aimed to assess this risk in a patient group prone to such injury. The surgical procedure utilized a minimally invasive approach and indocyanine green-based fluorescence imaging. This technique allows a real-time visualization of the circumflex artery, aiding precise placement of annular sutures and minimizing the risk of injury. The method, applied in 6 patients, integrates preoperative assessments with intraoperative fluorescence imaging, ensuring accurate arterial depiction and preventing iatrogenic damage. The study highlights the safety and efficacy of fluorescence imaging, especially in identifying vessel anomalies, indicating potential applications in various cardiac procedures.
Small dense low-density lipoprotein cholesterol and coronary artery calcification in the Multi-Ethnic Study of Atherosclerosis
Authors: Rikhi Rishi , Schaich Christopher L , Hafzalla George W , Patel Nisha A , Tannenbaum Jordan E , German Charles A , Polonsky Tamar , Tsai Michael Y , Ahmad Muhammad Imtiaz , Islam Tareq , Chevli Parag A , Shapiro Michael D 
Published: February 2024

Abstract

Aims
Elevated small dense LDL cholesterol (sd-LDL-C) increases atherosclerotic cardiovascular disease (CVD) risk. Although coronary artery calcification (CAC) is widely used for predicting CVD events, few studies have examined the relationship between sd-LDL-C and CAC.

Methods and results
This study included 4672 individuals with directly measured baseline sd-LDL-C and CAC from the Multi-Ethnic Study of Atherosclerosis [mean (standard deviation) age: 61.9 (10.4) years; 52.5% women; 47.3% with baseline CAC (mean score &gt;0)]. We used multi-variable general linear models and restricted cubic splines with the goodness of fit testing to evaluate the association of sd-LDL-C with the presence of CAC. Odds ratios [OR (95% confidence interval)] were adjusted for demographics and cardiovascular risk factors, including estimated total LDL-C. Higher quartiles of sd-LDL-C were associated with the presence of CAC, even after accounting for total LDL-C. Compared with the lowest quartile of sd-LDL-C, participants in Quartiles 2, 3, and 4 had higher odds for the presence of baseline CAC [Quartile 2 OR: 1.24 (1.00, 1.53); Quartile 3 OR: 1.51 (1.19, 1.93); and Quartile 4 OR 1.59 (1.17, 2.16)]. Splines suggested a quadratic curvilinear relationship of continuous sd-LDL-C with CAC after adjustment for demographics and CVD risk factors (quadratic vs. first-order sd-LDL-C terms likelihood ratio test: P = 0.015), but not after accounting for total LDL-C (quadratic vs. first-order terms: P = 0.156).

Conclusion
In a large, multi-ethnic sample without known CVD, higher sd-LDL-C was associated with the presence of CAC, above and beyond total LDL-C. Whether selective direct measurement of sd-LDL-C is indicated to refine cardiovascular risk assessment in primary prevention warrants further investigation.
Successful outpatient parenteral antibiotic therapy with cefiderocol for osteomyelitis caused by multi-drug resistant Gram-negative bacteria: a case report
Authors: Schellong Paul , Wennek-Klose Janett , Spiegel Christian , Rödel Jürgen , Hagel Stefan 
Published: February 2024

Abstract

Objectives
Post-traumatic osteomyelitis attributed to metallo-β-lactamase (MBL)-producing Gram-negative bacteria presents a challenging clinical scenario. Cefiderocol emerges as a viable treatment option within the limited therapeutic options available.

Patient/case description
In this brief report, we present a case of a Ukrainian patient with osteomyelitis caused by multi-drug resistant Pseudomonas aeruginosa, which was successfully treated with cefiderocol, facilitated in part by outpatient parenteral antibiotic therapy (OPAT).

Results and discussion
Administration of Cefiderocol via OPAT can present a safe and effective option for treatment of post-traumatic osteomyelitis with multi-drug resistant Pseudomonas aeruginosa. A possible effect on iron homeostasis of extended treatment duration with cefiderocol may be taken into consideration.
Round-up of fashion-related IP decisions 2023
Authors:   The Bird & Bird IP Team, Mestroni Shariqa , Wijesena Shehana , Lewis Lynne , Švecová Denisa , Lexman-nová Karin , Gustafsson Amalie , Baun Emilie , Arbant Géraldine , Vrhovac Pava , Grundmann Mascha , Präger Julia , Andreotta Cristiana , Massalongo Sara , Rombolá Francesca , Dorenbosch Nina , Kostrzewa Julia , Żuk Mateusz , Cueto Antonio , Danos Christine , Hughes Ciara , Naia Alessandra 
Published: February 2024

Abstract
In 2023, courts and competent authorities in Australia, Czech Republic, Denmark, France, Germany, Italy, the Netherlands, Poland, Spain and the United Kingdom delivered a series of important rulings of interest to and affecting the fashion sector. This contribution provides a round-up of the most significant fashion-related IP judgments issued in the period 1 January to 31 December 2023. The analysis is organized by substantive IP right and enforcement aspects, and is organized by country.
SumoPred-PLM: human SUMOylation and SUMO2/3 sites Prediction using Pre-trained Protein Language Model
Authors: Palacios Andrew Vargas , Acharya Pujan , Peidl Anthony Stephen , Beck Moriah Rene , Blanco Eduardo , Mishra Avdesh , Bawa-Khalfe Tasneem , Pakhrin Subash Chandra 
Published: February 2024

Abstract
SUMOylation is an essential post-translational modification system with the ability to regulate nearly all aspects of cellular physiology. Three major paralogues SUMO1, SUMO2 and SUMO3 form a covalent bond between the small ubiquitin-like modifier with lysine residues at consensus sites in protein substrates. Biochemical studies continue to identify unique biological functions for protein targets conjugated to SUMO1 versus the highly homologous SUMO2 and SUMO3 paralogues. Yet, the field has failed to harness contemporary AI approaches including pre-trained protein language models to fully expand and/or recognize the SUMOylated proteome. Herein, we present a novel, deep learning-based approach called SumoPred-PLM for human SUMOylation prediction with sensitivity, specificity, Matthew's correlation coefficient, and accuracy of 74.64%, 73.36%, 0.48% and 74.00%, respectively, on the CPLM 4.0 independent test dataset. In addition, this novel platform uses contextualized embeddings obtained from a pre-trained protein language model, ProtT5-XL-UniRef50 to identify SUMO2/3-specific conjugation sites. The results demonstrate that SumoPred-PLM is a powerful and unique computational tool to predict SUMOylation sites in proteins and accelerate discovery.
Displacement-pressure biparametrically regulated softness sensory system for intraocular pressure monitoring
Authors: Cheng Yu , Zhan Yifei , Guan Fangyi , Shi Junli , Wang Jingxiao , Sun Yi , Zubair Muhammad , Yu Cunjiang , Guo Chuan Fei 
Published: February 2024

ABSTRACT
High intraocular pressure (IOP) is one of the high-risk pathogenic factors of glaucoma. Existing methods of IOP measurement are based on the direct interaction with the cornea. Commercial ophthalmic tonometers based on snapshot measurements are expensive, bulky, and their operation requires trained personnel. Theranostic contact lenses are easy to use, but they may block vision and cause infection. Here, we report a sensory system for IOP assessment that uses a soft indentor with two asymmetrically deployed iontronic flexible pressure sensors to interact with the eyelid-eyeball in an eye-closed situation. Inspired by human fingertip assessment of softness, the sensory system extracts displacement-pressure information for soft evaluation, achieving high accuracy IOP monitoring (&gt;96%). We further design and custom-make a portable and wearable ophthalmic tonometer based on the sensory system and demonstrate its high efficacy in IOP screening. This sensory system paves a way towards cost-effective, robust, and reliable IOP monitoring.
Toward Nuclear Physics from Lattice QCD on Quantum Computers
Authors: Yamamoto Arata , Doi Takumi 
Published: February 2024

Abstract
One of the ultimate missions of lattice quantum chromodynamics (QCD) is to simulate atomic nuclei from the first principles of the strong interaction. This is an extremely hard task for current computational technology, but might be reachable in the coming quantum computing era. In this paper, we discuss the computational complexities of classical and quantum simulations of lattice QCD. It is shown that the quantum simulation scales better as a function of nucleon number and thus will outperform classical simulation for large nuclei.
Oxidative stress in metabolic dysfunction‐associated steatotic liver disease (MASLD): How does the animal model resemble human disease?
Authors: Jakubek Patrycja , Kalinowski Piotr , Karkucinska‐Wieckowska Agnieszka , Kaikini Aakruti , Simões Inês C. M. , Potes Yaiza , Kruk Beata , Grajkowska Wieslawa , Pinton Paolo , Milkiewicz Piotr , Grąt Michał , Pronicki Maciej , Lebiedzinska‐Arciszewska Magdalena , Krawczyk Marcin , Wieckowski Mariusz R. 
Published: February 2024

AbstractDespite decades of research, the pathogenesis of metabolic dysfunction‐associated steatotic liver disease (MASLD) is still not completely understood. Based on the evidence from preclinical models, one of the factors proposed as a main driver of disease development is oxidative stress. This study aimed to search for the resemblance between the profiles of oxidative stress and antioxidant defense in the animal model of MASLD and the group of MASLD patients. C57BL/6J mice were fed with the Western diet for up to 24 weeks and served as the animal model of MASLD. The antioxidant profile of mice hepatic tissue was determined by liquid chromatography‐MS3 spectrometry (LC–MS/MS). The human cohort consisted of 20 patients, who underwent bariatric surgery, and 6 controls. Based on histological analysis, 4 bariatric patients did not have liver steatosis and as such were also classified as controls. Total antioxidant activity was measured in sera and liver biopsy samples. The hepatic levels of antioxidant enzymes and oxidative damage were determined by Western Blot. The levels of antioxidant enzymes were significantly altered in the hepatic tissue of mice with MASLD. In contrast, there were no significant changes in the antioxidant profile of hepatic tissue of MASLD patients, except for the decreased level of carbonylated proteins. Decreased protein carbonylation together with significant correlations between the thioredoxin system and parameters describing metabolic health suggest alterations in the thiol‐redox signaling. Altogether, these data show that even though the phenotype of mice closely resembles human MASLD, the animal‐to‐human translation of cellular and molecular processes such as oxidative stress may be more challenging.