bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unlocking the potential of protein-derived peptides to target G-quadruplex DNA: from recognition to anticancer activity
Authors: Merlino Francesco , Marzano Simona , Zizza Pasquale , D’Aria Federica , Grasso Nicola , Carachino Alice , Iachettini Sara , Biroccio Annamaria , Fonzo Silvia Di , Grieco Paolo , Randazzo Antonio , Amato Jussara , Pagano Bruno 
Published: June 2024

Abstract
Noncanonical nucleic acid structures, particularly G-quadruplexes, have garnered significant attention as potential therapeutic targets in cancer treatment. Here, the recognition of G-quadruplex DNA by peptides derived from the Rap1 protein is explored, with the aim of developing novel peptide-based G-quadruplex ligands with enhanced selectivity and anticancer activity. Biophysical techniques were employed to assess the interaction of a peptide derived from the G-quadruplex-binding domain of the protein with various biologically relevant G-quadruplex structures. Through alanine scanning mutagenesis, key amino acids crucial for G-quadruplex recognition were identified, leading to the discovery of two peptides with improved G-quadruplex-binding properties. However, despite their in vitro efficacy, these peptides showed limited cell penetration and anticancer activity. To overcome this challenge, cell-penetrating peptide (CPP)-conjugated derivatives were designed, some of which exhibited significant cytotoxic effects on cancer cells. Interestingly, selected CPP-conjugated peptides exerted potent anticancer activity across various tumour types via a G-quadruplex-dependent mechanism. These findings underscore the potential of peptide-based G-quadruplex ligands in cancer therapy and pave the way for the development of novel therapeutic strategies targeting these DNA structures.
Future Deployment and Comparison to the Restructuring Plan
Authors: Clarke Ian , Mackenzie Patrick , Zeng Kai 
Published: May 2024

Abstract
This chapter explicates CVA's future development and its comparison to the restructuring plans under Part 26A of the Companies Act 2006. Across Europe, debtors use numerous variety of structures such as bank loans and debt securities. The chapter primarily focuses on common financing, liability structures, CVA features, a case study, and the future deployment of processes in a restructuring context. The key differences between CVAs and restructuring plans are the eligibility of companies, people bound by the agreements, voting, class composition, fairness, and process. However, CVAs are expected to continue to play an instrumental role as either standalone restructuring tools or restructuring non-financial liabilities of debtors.
Design, fabrication and clinical characterization of additively manufactured tantalum hip joint prosthesis
Authors: Zhao Dewei , Cheng Liangliang , Lu Faqiang , Zhang Xiuzhi , Ying Jiawei , Wei Xiaowei , Cao Fang , Ran Chunxiao , Zheng Guoshuang , Liu Ge , Yi Pinqiao , Wang Haiyao , Song Liqun , Wu Bin , Liu Lingpeng , Li Lu , Wang Xiaohu , Li Junlei 
Published: June 2024

Abstract
The joint prosthesis plays a vital role in the outcome of total hip arthroplasty. The key factors that determine the performance of joint prostheses are the materials used and the structural design of the prosthesis. This study aimed to fabricate a porous tantalum (Ta) hip prosthesis using selective laser melting (SLM) technology. The feasibility of SLM Ta use in hip prosthesis was verified by studying its chemical composition, metallographic structure and mechanical properties. In vitro experiments proved that SLM Ta exhibited better biological activities in promoting osteogenesis and inhibiting inflammation than SLM Ti6Al4V. Then, the topological optimization design of the femoral stem of the SLM Ta hip prosthesis was carried out by finite element simulation, and the fatigue performance of the optimized prosthesis was tested to verify the biomechanical safety of the prosthesis. A porous Ta acetabulum cup was also designed and fabricated using SLM. Its mechanical properties were then studied. Finally, clinical trials were conducted to verify the clinical efficacy of the SLM Ta hip prosthesis. The porous structure could reduce the weight of the prosthesis and stress shielding and avoid bone resorption around the prosthesis. In addition, anti-infection drugs can also be loaded into the pores for infection treatment. The acetabular cup can be custom-designed based on the severity of bone loss on the acetabular side, and the integrated acetabular cup can repair the acetabular bone defect while achieving the function of the acetabular cup.
Market Power and the Transmission of Loan Subsidies
Authors: Ornelas Jose Renato Haas , Pedraza Alvaro , Ruiz-Ortega Claudia , Silva Thiago Christiano 
Published: June 2024

Abstract
We study a large-scale Brazilian loan subsidy program to expand long-term credit. The government subsidizes banks’ funding costs for lenders, who then allocate credit to firms at regulated interest rates below a maximum ceiling. We propose and test a mechanism allowing banks to circumvent the rate caps and capture part of the subsidy. We show that when issuing a subsidized loan, lenders with market power use a cross-product pricing strategy, whereby they increase the price of other products to the same client. Our results have important policy implications for the design and effectiveness of government interventions in credit markets. (JEL G21, H81, E43)
Serum interleukin-34 levels in dermatomyositis: a potential biomarker for anti-MDA5-antibody-associated interstitial lung disease
Authors: Kuzumi Ai , Fukasawa Takemichi , Yamashita Takashi , Matsuda Kazuki M , Kotani Hirohito , Yoshizaki-Ogawa Asako , Sato Shinichi , Yoshizaki Ayumi 
Published: June 2024

Abstract

Objectives
IL-34 is a haematopoietic cytokine that promotes macrophage activation. Macrophage activation in interstitial lung disease (ILD) in patients with DM, especially in those with anti-melanoma differentiation-associated gene 5 (MDA5) antibody suggests the involvement of IL-34 in the disease. However, the association between IL-34 and DM is unknown. In this study, we aimed to determine serum IL-34 levels in DM patients and evaluate their association with DM-ILD.

Methods
We measured serum IL-34 levels in 56 DM patients and 14 age- and sex- matched healthy controls by ELISA, and examined their correlation with clinical parameters. In addition, pre- and post-treatment serum IL-34 levels were examined using serum samples from 7 anti-MDA5 antibody-positive DM patients.

Results
Serum IL-34 levels were significantly elevated in DM patients, especially in those with anti-MDA5 antibody, compared with healthy controls. In anti-MDA5-antibody-positive DM patients, serum IL-34 levels positively correlated with serum levels of ferritin and anti-MDA5 antibody, which are known biomarkers for rapidly progressive (RP)-ILD. Following combined immunosuppressive therapy, serum IL-34 levels decreased along with ferritin and anti-MDA5 antibody.

Conclusion
These data suggest that IL-34 may be involved in the development of RP-ILD in anti-MDA5 antibody-positive DM. Serum IL-34 levels can serve as a potential biomarker for RP-ILD in this clinical entity.
Are Invasive Group A Streptococcal Infections Preventable by Antibiotic Therapy?: A Collaborative Retrospective Study
Authors: Erlacher Rahel , Toepfner Nicole , Dressen Svenja , Berner Reinhard , Bösch Annemarie , Tenenbaum Tobias , Heininger Ulrich 
Published: June 2024

Background:
In winter 2022/2023, a resurgence of invasive group A streptococcal (iGAS) infections in children was observed in Europe, including Germany and Switzerland. While a simultaneous increase in consultations for scarlet fever and pharyngitis was reported in England, leading to the recommendation to treat any suspected GAS disease with antibiotics, guidelines in Germany and Switzerland remained unchanged. We aimed to investigate whether this policy was appropriate.

Methods:
We conducted a retrospective multicenter study of children hospitalized for invasive GAS disease between September 2022 and March 2023 in pediatric departments in Dresden and Berlin (Germany) and Basel (Switzerland). We reviewed medical records and conducted structured telephone interviews to analyze whether suspected GAS infections with or without antibiotic treatment were reported prehospitalization.

Results:
In total, 63 patients met the inclusion criteria (median age 4.2 years, 57% males); however, clinical information was not complete for all analyzed characteristics; 32/54 (59%) had ≥1 physician visit ≤4 weeks prehospitalization. In 4/32 (13%) patients, GAS disease, that is, tonsillitis or scarlet fever, was suspected; 2/4 of them received antibiotics, and a positive rapid antigen test for GAS was documented in 1 of them.

Conclusions:
A small minority of patients had suspected GAS infection within 4 weeks before iGAS disease. These data suggest that there is little opportunity to prevent iGAS disease by antibiotic therapy, because in most patients—even if seen by a physician—there was either no evidence of GAS disease or when GAS disease was suspected and treated with antibiotics, consecutive invasive GAS disease was not prevented.
Twenty-four Month Outcomes of Extended- Versus Standard-course Antibiotic Therapy in Children Hospitalized With Pneumonia in High-risk Settings: A Randomized Controlled Trial
Authors: Kok Hing C. , McCallum Gabrielle B. , Yerkovich Stephanie T. , Grimwood Keith , Fong Siew M. , Nathan Anna M. , Byrnes Catherine A. , Ware Robert S. , Nachiappan Nachal , Saari Noorazlina , Morris Peter S. , Yeo Tsin W. , Oguoma Victor M. , Masters I. Brent , de Bruyne Jessie A. , Eg Kah P. , Lee Bilawara , Ooi Mong H. , Upham John W. , Torzillo Paul J. , Chang Anne B. 
Published: June 2024

Background:
Pediatric community-acquired pneumonia (CAP) can lead to long-term respiratory sequelae, including bronchiectasis. We determined if an extended (13–14 days) versus standard (5–6 days) antibiotic course improves long-term outcomes in children hospitalized with CAP from populations at high risk of chronic respiratory disease.

Methods:
We undertook a multicenter, double-blind, superiority, randomized controlled trial involving 7 Australian, New Zealand, and Malaysian hospitals. Children aged 3 months to ≤5 years hospitalized with radiographic-confirmed CAP who received 1–3 days of intravenous antibiotics, then 3 days of oral amoxicillin-clavulanate, were randomized to either extended-course (8-day oral amoxicillin-clavulanate) or standard-course (8-day oral placebo) arms. Children were reviewed at 12 and 24 months. The primary outcome was children with the composite endpoint of chronic respiratory symptoms/signs (chronic cough at 12 and 24 months; ≥1 subsequent hospitalized acute lower respiratory infection by 24 months; or persistent and/or new chest radiographic signs at 12-months) at 24-months postdischarge, analyzed by intention-to-treat, where children with incomplete follow-up were assumed to have chronic respiratory symptoms/signs (“worst-case” scenario).

Results:
A total of 324 children were randomized [extended-course (n = 163), standard-course (n = 161)]. For our primary outcome, chronic respiratory symptoms/signs occurred in 97/163 (60%) and 94/161 (58%) children in the extended-courses and standard-courses, respectively [relative risk (RR) = 1.02, 95% confidence interval (CI): 0.85–1.22]. Among children where all sub-composite outcomes were known, chronic respiratory symptoms/signs between groups, RR = 1.10, 95% CI: 0.69–1.76 [extended-course = 27/93 (29%) and standard-course = 24/91 (26%)]. Additional sensitivity analyses also revealed no between-group differences.

Conclusion:
Among children from high-risk populations hospitalized with CAP, 13–14 days of antibiotics (versus 5–6 days), did not improve long-term respiratory outcomes.
Analysis of Antipsychotic Dosage in Patients With Tardive Dyskinesia: A Case-Control Study Using the Claims Database of the Corporate Health Insurance Association
Authors: Gouda Maki , Abe Michikazu , Watanabe Yumi , Kato Takahiro A. 
Published: June 2024

Abstract

Purpose
This study aimed to assess the association between antipsychotic doses and the risk of tardive dyskinesia (TD) in clinical practice using a Japanese claims database from 2010 to 2020.

Methods
The study population included patients 15 years or older with a diagnosis record of schizophrenia, depression, or bipolar disorder who were prescribed antipsychotics. Using a case-control design, we categorized patients newly diagnosed with TD as cases, with corresponding 1:10 matching in the control group. The primary endpoint was the relative risk of TD in the >median dose and ≤median dose groups, as determined using conditional logistic regression analysis adjusted for age.

Results
The analysis population included 58,452 patients, and the median daily antipsychotic dose was 75 mg/d of chlorpromazine equivalent (CPZE). Of these, 80 were identified as TD cases, and doses >75 mg/d were associated with a significantly increased risk of TD at the last prescription and the maximum dose, respectively, before the date of the first diagnosis of TD. Post-hoc analysis further showed a significant association between doses ≥300 mg/d and the risk of TD compared to doses ≤75 mg/d and doses >75 to <300 mg/d. Comparing ≥300 mg/d versus >75 to <300 mg/d, the odd ratios at the last prescription and maximum dose before the first diagnosis of TD were 3.40 and 3.50, respectively.

Conclusions
In the Japanese medical claims database of patients receiving relatively low doses of antipsychotics, doses >75 mg/d were associated with an increased risk of TD in a dose-dependent manner.
Low-value care: an evolutionary concept analysis
Authors: Guan Yushan , Song Suhang , Wu Huazhang , Meng Zhaolin 
Published: June 2024

Abstract

Background:
Low-value care is a significant contributor to health care waste and a threat to the viability and sustainability of health care systems. Low-value care has attracted increasing international attention in the last decade, but its precise conception remains elusive.

Objective:
To clarify the concept of low-value care.

Methods:
A systematic search was conducted of the Medline, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, Health Technology Assessment, Web of Science, and Cumulative Index to Nursing and Allied Health Literature databases from their inception to July 22, 2023 for articles written in English. Rodgers’ evolutionary method guided the narrative analysis. The attributes of low-value care, as well as its antecedents, consequences, and related terms were extracted and synthesized.

Results:
A total of 53 articles were included in this concept analysis. Defining attributes included being of little to no benefit or potentially harmful, not being cost-effective, occurring along a continuum, being relative, ignoring or disregarding patient wishes in certain circumstances, and involving multiple types of care. Low-value care antecedents were classified into 4 categories: demand-side factors, supply-side factors, social factors, and health care system factors, while consequences of low-value care were categorized into patient harms and health care system-related consequences.

Conclusions:
This in-depth analysis of attributes, antecedents, and consequences of low-value care promotes a better understanding of low-value care among health care providers, thus contributing to the identification and deimplementation of low-value care in practice and eventually contributing to reducing waste in health care spending and improving patient outcomes.
State Laws Governing the Hiring of Public Health Government Employees, 2023
Authors: Yeager Valerie A. , Demosthenidy Mollye , Burns Ashlyn 
Published: June 2024

Objective:
Governmental public health agencies have experienced longstanding challenges in recruiting individuals at the state and local level. Understanding civil service laws as they relate to the hiring processes is an important component of recruitment and increasing public health workforce capacity. This study presents state hiring laws and regulations governing the public health government workforce.

Methods:
Legal mapping techniques were employed to collect and code data on current hiring laws governing governmental public health employees across all 50 states. The review of laws included constitutions, statutes and regulations, and searches of administrative code.

Results:
In 12 states, the laws do not specify civil service exam criteria or they have no mention of civil service exams in the law. Almost a third of states have laws that establish civil service exam requirements without specifying conditions for when exams must be required, or which positions allow which types of exam/criteria. Similarly, almost all of the states that have civil service exams denoted in their laws have unspecified language about whether there are exam fees. Requirements for the maintenance/use of state hiring lists are in place in 36 states and 26 states have a non-public health agency managing this process. Nearly all states (n = 48, 96%) require hiring preferences for certain types of individuals, most commonly veterans (n = 48, 96%) and family members of veterans (n = 30, 60%). No state laws provide hiring preferences for individuals from public health fellowships or special training programs.

Conclusion:
Key findings suggest that the laws governing the merit system and civil service vary and often lack clarity, which may be difficult for public health agencies and for potential employees to understand, navigate, and successfully recruit key employees. The recruitment and hiring of new governmental public health staff are complicated by the management of hiring by other state agencies and the vague civil service exam requirements and process. Developing preferences for hiring individuals who have additional practical training in public health (eg, public health fellowships and AmeriCorps) should be considered.
scRNA-seq revealed the rules for CDR3 length pairing in TCR beta and alpha chains and BCR heavy and light chains in human and mice
Authors: Xiao Jiaping , Li Jun , Wu Yingjie , Zhu Lanwei , Peng Qi , Xu Yuanyuan , Yao Xinsheng 
Published: June 2024

AbstractThe binding of T cell receptor (TCR)/B cell receptor (BCR) CDR3 with linear or conformational epitopes is a prerequisite for the adaptive immune response. The rules for CDR3 length pairing and the amino acid (AA) distributions in the prioritized rearrangement of the β chain (or heavy chain) and subsequent rearrangement of the α chain (or light chain) during the process of germline V(D)J gene rearrangement and self-tolerance selection to form the T- or B-cell CDR3 repertoire are currently unknown. Single-cell VDJ sequencing can provide abundant information on CDR3 sequences in paired chains. In this study, the paired-chain CDR3 sequences of central and peripheral T and B cells in humans and mice were analyzed according to single-cell VDJ sequencing data. This is the first study to find that T cells with β chains longer than paired α chains and B cells with heavy chains longer than paired light chains have absolute advantages. The proportion of T cells with length differences of three or more AAs between paired chains in CDR3 in humans was significantly higher than that in mice, and the proportion of B cells with length differences of six or more AAs between paired chains in CDR3 in humans was significantly higher than that in mice. The CDR3 length range of the β chain was narrower than that of the α chain, while the heavy chain had a much wider range than the light chain. The CDR3 length in human TCRs and BCRs was greater than that in mice. Extreme length differences were found between paired chains in both human and mouse T and B cells. There were significant differences in the range of pairing length, AA distribution, hydrophobicity, and polarity of the paired-chain CDR3 region in 5 chains (β, α, H, κ, and λ). Human TCR and BCR paired CDR3 sequences exhibited greater plasticity than those of mice. This study reveals new ideas about the molecular mechanisms of TCR and BCR responses to different antigenic epitopes. Our innovative findings offer novel perspectives and techniques for examining V(D)J rearrangement and selection mechanisms in T and B cells. These advancements enable us to analyze antigenic epitopes targeted by TCRs and BCRs, and further, to explore the genetic evolution of T and B cell responses across diverse animal species.Graphical AbstractscRNA-seq the TCR and BCR CDR3 repertoires of 35 samples from the central and peripheral tissues of humans and mice. It provides an opportunity to reveal the rules for CDR3 length pairing in TCR beta and alpha chains and BCR heavy and light chains.
Beyond variability: a novel gene expression stability metric to unveil homeostasis and regulation
Authors: Chen Mengjie 
Published: June 2024

AbstractThe concept of gene expression stability within a homeostatic cell is explored through the gene homeostasis Z-index, a measure that highlights genes under active regulation in response to internal and external stimuli. This index reveals distinct regulatory activities and patterns in different organs, such as enhanced synaptic transmission in pancreatic islets. The research indicates that traditional mean-based methods may miss these nuances, underlining the significance of new metrics in identifying gene regulation specifics in cellular adaptation.
A PHOX2B+ PONTINE NUCLEUS ESSENTIAL FOR INGESTION
Authors: Sungeelee Selvee , Mailhes-Hamon Caroline , Chettouh Zoubida , Bokiniec Philip , Eymael Annaliese , Dempsey Bowen , Brunet Jean-François 
Published: June 2024

AbstractThe first phase of feeding consists in acquiring solid foods from the environment by biting, and their preparation for swallowing by chewing. These actions require the precise coordination of tens of orofacial muscles for the jaw and tongue. The siege for this motor patterning is known to be in the reticular formation, a complex and poorly mapped region of the hindbrain, but the neuron groups involved are still elusive. Here, we characterize a group of reticular interneurons located in the supratrigeminal area that express the homeodomain transcription factorPhox2b. This nucleus — Sup5Phox2b— is premotor to both jaw-closing and jaw-opener motoneurons and receives direct input from cranial sensory afferents, motor cortex and satiation related nuclei. Its activity differentially tracks lapping, biting and chewing movements, suggesting its involvement in the elaboration of distinct orofacial motor patterns in vivo. Acute global activation or inhibition of Sup5Phox2bby optogenetics both interrupt volitional feeding sequences. Thus, Sup5Phox2bis an obligatory subcortical node, topologically and genetically defined, in the neural circuits that control the oral phase of feeding.TeaserA genetically defined cluster of neurons in the hindbrain is an essential relay for biting and chewing food.