bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of Nucleotides Bearing the 2′‐O‐Trifluoromethyl Group and Their Application in RNA Analogs Preparation
Authors: Chen Xuan , Xie Long , Zhang Chenglong , Tian Shen , Tang Zeyu , Xiang Ming , Tian Weiwei , Lu Patrick , Yang Xianbin
Published: January 2024

The integration of fluorine atoms into biologically active organic compounds has proved to be a vital technique in small molecule drugs. This technique can substantially enhance crucial properties, including metabolic stability, lipophilicity, and bioavailability, often with a mere addition of a single fluorine atom or a trifluoromethyl group. Over the past few decades, this concept has also been applied in nucleic acid chemistry. A commonly employed 2′‐OH substitution is the introduction of a 2′‐deoxy‐2′‐fluoro (2′‐F) group. The strong electronegativity of fluorine prompts the modified siRNA to readily adopt a C3′‐endo conformation, resulting in significant advantages in terms of binding affinity. To enrich the toolbox of chemical modification of oligonucleotides, the replacement of the 2′‐OH with the 2′‐O‐trifluoromethyl group has been developed in RNA analog synthesis. Oligodeoxynucleotides containing the 2′‐O‐trifluoromethyl group can greatly increase the thermal stability of DNA/RNA duplexes depending on the position and amount of the modification. Moreover, 2′‐O‐trifluoromethylated oligodeoxynucleotide also exhibited a slightly higher resistance to snake venom phosphodiesterase than the unmodified oligodeoxynucleotide. The 2′‐O‐trifluoromethylated oligonucleotides can emerge as a label to study RNA structure and function as well, or to develop DNA/RNA‐based diagnostics. Hence, it is necessary to report an effective method for the synthesis, deprotection, purification, and characterization of oligonucleotides bearing a 2′‐O‐trifluoromethyl group. © 2024 Wiley Periodicals LLC.

Basic Protocol 1: Preparation of 6‐N‐benzoyl‐5′‐O‐dimethoxytrityl‐2′‐O‐trifluoromethyl adenosine 3′‐(2‐cyanoethyl N,N‐diisopropyl)phosphoramidite

Basic Protocol 2: Preparation of 4‐N‐acetyl‐5′‐O‐dimethoxytrityl‐2′‐O‐trifluoromethyl cytidine 3′‐(2‐cyanoethyl N,N‐diisopropyl)phosphoramidite

Basic Protocol 3: Preparation of 2‐N‐isobutyryl‐5′‐O‐dimethoxytrityl‐2′‐O‐trifluoromethyl guanine 3′‐(2‐cyanoethyl N,N‐diisopropyl)phosphoramidite

Basic Protocol 4: Preparation of 5′‐O‐dimethoxytrityl‐2′‐O‐2‐trifluoromethyl uridine 3′‐(2‐cyanoethyl N,N‐diisopropyl) phosphoramidite

Basic Protocol 5: Solid‐phase synthesis of 2′‐O‐trifluoromethylated RNA analogs

Basic Protocol 6: Deprotection and purification of 2′‐O‐trifluoromethyl‐RNAs
The cross‐cutting pursuit of family values: When and how do family firms engage in corporate environmental responsibility
Authors: Kim Sang‐Joon , Bae Jongwan , Kang SoHyeon
Published: January 2024

This study examines how family values in a firm can impact non‐market strategies. Given that family members on the board tend to pursue non‐economic, especially family related, values, we attempt to specify how the perspectives, values, and tastes of family members serving on the board can be infused into the firm's environmental performance. Since actions addressing environmental issues are less directly related to family values than other types of CSR actions, such as donations and services to the local community, the family‐value‐infused characteristics of boards that represent family firms' pursuit of socio‐emotional wealth, can make firms less committed to environmental issues. Using our comprehensive sample of large U.S. firms consisting of 15,086 firm‐year observations between 1998 and 2016, we find that when family values are treated as a critical factor for non‐market strategies, family dominated firms are less likely to pursue corporate environmental responsibility. We also find that both external and internal factors can positively moderate the family firm's environmental underperformance by diluting the family values.
Drug upgrade: A complete methodology from old drug to new chemical entities using Nematic Protein Organization Technique
Authors: Eschbach Judith , Wagner Alain , Beahr Corinne , Bekel Akkiz , Korganow Anne‐Sophie , Quartier Angelique , Peter Jean‐Christophe , Eftekhari Pierre
Published: January 2024

Drug repurposing is used to propose new therapeutic perspectives. Here, we introduce “Drug Upgrade”, that is, characterizing the mode of action of an old drug to generate new chemical entities and new therapeutics. We proposed a novel methodology covering target identification to pharmacology validation. As an old drug, we chose hydroxychloroquine (HCQ) for its well‐documented clinical efficacy in lupus and its side effect, retinal toxicity. Using the Nematic Protein Organization Technique (NPOT®) followed by liquid chromatography‐tandem mass spectrometry analyses, we identified myeloperoxidase (MPO) and alpha‐crystallin β chain (CRYAB) as primary and secondary targets to HCQ from lupus patients' peripheral blood mononuclear cells (PBMCs) and isolated human retinas. Surface plasmon resonance (SPR) and enzymatic assays confirmed the interaction of HCQ with MPO and CRYAB. We synthesized INS‐072 a novel analog of HCQ that increased affinity for MPO and decreased binding to CRYAB compared to HCQ. INS‐072 delayed cutaneous eruption significantly compared to HCQ in the murine MRL/lpr model of spontaneous lupus and prevents immune complex vasculitis in mice. In addition, long‐term HCQ treatment caused retinal toxicity in mice, unlike INS‐072. Our study illustrates a method of drug development, where new applications or improvements can be explored by fully characterizing the drug's mode of action.
Impact of mental disorders on unplanned readmissions for congestive heart failure patients: a population‐level study
Authors: Sa Zhisheng , Badgery‐Parker Tim , Long Janet C. , Braithwaite Jeffrey , Brown Martin , Levesque Jean‐Frederic , Watson Diane E. , Westbrook Johanna I. , Mitchell Rebecca
Published: January 2024

Aims

Reducing preventable hospitalization for congestive heart failure (CHF) patients is a challenge for health systems worldwide. CHF patients who also have a recent or ongoing mental disorder may have worse health outcomes compared with CHF patients with no mental disorders. This study examined the impact of mental disorders on 28 day unplanned readmissions of CHF patients.

Methods and results

This retrospective cohort study used population‐level linked public and private hospitalization and death data of adults aged ≥18 years who had a CHF admission in New South Wales, Australia, between 1 January 2014 and 31 December 2020. Individuals' mental disorder diagnosis and Charlson comorbidity and hospital frailty index scores were derived from admission records. Competing risk and cause‐specific risk analyses were conducted to examine the impact of having a mental disorder diagnosis on all‐cause hospital readmission. Of the 65 861 adults with index CHF admission discharged alive (mean age: 78.6 ± 12.1; 48% female), 19.2% (12 675) had at least one unplanned readmission within 28 days following discharge. Adults with CHF with a mental disorder diagnosis within 12 months had a higher risk of 28 day all‐cause unplanned readmission [hazard ratio (HR): 1.21, 95% confidence interval (CI): 1.15–1.27, P‐value < 0.001], particularly those with anxiety disorder (HR: 1.49, 95% CI: 1.35–1.65, P‐value < 0.001). CHF patients aged ≥85 years (HR: 1.19, 95% CI: 1.11–1.28), having ≥3 other comorbidities (HR: 1.35, 95% CI: 1.25–1.46), and having an intermediate (HR: 1.34, 95% CI: 1.28–1.40) or high (HR: 1.37, 95% CI: 1.27–1.47) frailty score on admission had a higher risk of unplanned readmission. CHF patients with a mental disorder who have ≥3 other comorbidities and an intermediate frailty score had the highest probability of unplanned readmission (29.84%, 95% CI: 24.68–35.73%) after considering other patient‐level factors and competing events.

Conclusions

CHF patients who had a mental disorder diagnosis in the past 12 months are more likely to be readmitted compared with those without a mental disorder diagnosis. CHF patients with frailty and a mental disorder have the highest probability of readmission. Addressing mental health care services in CHF patient's discharge plan could potentially assist reduce unplanned readmissions.
Application of an echocardiographic index to characterize right ventricular–pulmonary arterial coupling in heart failure
Authors: Chen Xin , Zhang Peige , Lou Jie , Zhao Ruohan , Zhang Siyi , Xie Mingxing , Lv Qing
Published: January 2024

Heart failure (HF), with its high morbidity and mortality, remains a global public health issue. Right ventricular (RV) dysfunction is a sign of deterioration in the natural history of HF, and a thorough evaluation of the relationship between RV contractility and its afterload through RV–pulmonary arterial (RV–PA) coupling can aid in accurately assessing overall RV function. The ratio of RV end‐systolic elastance (Ees) to pulmonary arterial elastance (Ea) invasively measured by right heart catheterization served as the gold standard for evaluating RV–PA coupling. An echocardiographic index termed tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) has been shown to correlate well with Ees/Ea. TAPSE/PASP is recognized as a non‐invasive surrogate of RV–PA coupling and has been extensively studied in patients with HF. This review briefly describes the methods of assessing RV–PA coupling, mainly discussing echocardiography, summarizes the clinical utility of TAPSE/PASP in patients with different HF types, and provides an overview of the available literature.
On the influence of bed roughness on saltation in inertial regime
Authors: Minster Gaspard , Floc'h France , Valance Alexandre , Le Dantec Nicolas , Nicolle Amandine , Zerr Benoit
Published: January 2024

In extreme tidal environment, occurrences of saltating pebbles have been observed. The ambition to instal hydrokinetic turbines in such environment requires knowledge on the presence of pebbles in saltation in the water column because they can damage the structures. An experimental study is realized in a free‐surface flume with no slope and different bed roughnesses as in marine environment. With fast camera the trajectories of hundreds of spherical particles are analysed. Our study deals with saltation in the inertial regime (i.e., large Stokes number) over fixed beds with various roughnesses. In inertial regime, the bed roughness has more influence on the collision process and the trajectory of the particles than for non‐inertial motion where viscous forces play a key role. Jump height and length increase with bed roughness, with height increasing quicker than length leading to a more vertical trajectory for higher bed roughness. The vertical restitution coefficient is shown to increase with bed roughness leading to higher jumps. The initiation of the motion is shown to depend on the bed roughness as well. Power laws of the excess shear stress are proposed for jump height and length, taking into account the bed roughness. The dataset and analysis proposed in this study is a key ingredient for developing quantitative models for particle transport.
Modeling Writing Traits in a Formative Essay Corpus
Authors: Deane Paul , Yan Duanli , Castellano Katherine , Attali Yigal , Lamar Michelle , Zhang Mo , Blood Ian , Bruno James V. , Li Chen , Cui Wenju , Ruan Chunyi , Appel Colleen , James Kofi , Long Rodolfo , Qureshi Farah
Published: January 2024

This paper presents a multidimensional model of variation in writing quality, register, and genre in student essays, trained and tested via confirmatory factor analysis of 1.37 million essay submissions to ETS' digital writing service, Criterion®. The model was also validated with several other corpora, which indicated that it provides a reasonable fit for essay data from 4th grade to college. It includes an analysis of the test‐retest reliability of each trait, longitudinal trends by trait, both within the school year and from 4th to 12th grades, and analysis of genre differences by trait, using prompts from the Criterion topic library aligned with the major modes of writing (exposition, argumentation, narrative, description, process, comparison and contrast, and cause and effect). It demonstrates that many of the traits are about as reliable as overall e‐rater® scores, that the trait model can be used to build models somewhat more closely aligned with human scores than standard e‐rater models, and that there are large, significant trait differences by genre, consistent with genre differences in trait patterns described in the larger literature. Some of the traits demonstrated clear trends between successive revisions. Students using Criterion appear to have consistently improved grammar, usage, and spelling after getting Criterion feedback and to have marginally improved essay organization. Many of the traits also demonstrated clear grade level trends. These features indicate that the trait model could be used to support more detailed scoring and reporting for writing assessments and learning tools.
Recent advances in reactive oxygen species scavenging nanomaterials for wound healing
Authors: Joorabloo Alireza , Liu Tianqing
Published: January 2024

Reactive oxygen species play a crucial role in cell signaling pathways during wound healing phases. Treatment strategies to balance the redox level in the deep wound tissue are emerging for wound management. In recent years, reactive oxygen species scavenging agents including natural antioxidants, reactive oxygen species (ROS) scavenging nanozymes, and antioxidant delivery systems have been widely employed to inhibit oxidative stress and promote skin regeneration. Here, the importance of reactive oxygen species in different wound healing phases is critically analyzed. Various cutting‐edge bioactive ROS nanoscavengers and antioxidant delivery platforms are discussed. This review also highlights the future directions for wound therapies via reactive oxygen species scavenging. This comprehensive review offers a map of the research on ROS scavengers with redox balancing mechanisms of action in the wound healing process, which benefits development and clinical applications of next‐generation ROS scavenging‐based nanomaterials in skin regeneration.
The effects of raspberry consumption on lipid profile and blood pressure in adults: A systematic review and meta‐analysis
Authors: Jazinaki Mostafa Shahraki , Bahari Hossein , Rashidmayvan Mohammad , Arabi Seyyed Mostafa , Rahnama Iman , Malekahmadi Mahsa
Published: January 2024

Research into the effects of raspberry on blood pressure and lipid profiles is inconclusive. This meta‐analysis was aimed to determine whether raspberry has beneficial effects in clinical practice and to what extent these effects are associated with blood pressure and lipid profiles. A systematic literature search up to September 2023 was completed in PubMed/Medline, Scopus, and Web of Science, to identify eligible RCTs. Heterogeneity tests of the selected trials were performed using the I2 statistic. Random effects models were evaluated based on the heterogeneity tests, and pooled data were determined as weighted mean differences with a 95% confidence interval. Eleven randomized controlled trials (with 13 arms) were eligible for this meta‐analysis. Our findings revealed that Raspberry consumption had no significant effects on the blood pressure and lipid profile markers, including systolic blood pressure (SBP) (WMD, −0.37 mm Hg; 95%CI: −2.19 to 1.44; p = .68), diastolic blood pressure (DBP) (WMD, −2.14 mm Hg; 95%CI: −4.27 to 0.00; p = .05), total cholesterol (TC) (WMD, −6.83 mg/dL; 95%CI: −15.11 to 1.44; p = .10), triglycerides (TG) (WMD, −5.19 mg/dL: 95%CI: −11.76 to 1.37; p = .12), low‐density lipoprotein‐cholesterol (LDL‐C) (WMD, −5.19 mg/dL; 95%CI: −11.58 to 1.18; p = .11), and high‐density lipoprotein‐cholesterol (HDL‐C) (WMD, 0.82 mg/dL; 95%CI: −1.67 to 3.32; p = .51), compared to control groups. Subgroup analysis showed that raspberry consumption significantly decreased total cholesterol and LDL‐C levels in people with elevated TC levels, metabolic syndrome, and andropause symptoms, as well as those older than 35, while the consumption of raspberries led to a significant increase in HDL‐C levels in females, obese, under 35, and healthy individuals. Raspberry can improve lipid profile and blood pressure, but it is important to keep in mind that further research is necessary to fully understand the exact mechanism of action and a definite conclusion in this regard.
Infant and early childhood teleconsultation and training: Program description and feasibility outcomes from a statewide implementation
Authors: Loomis Alysse M. , McLaughlin Rose X. , Lyon McCall , Mitchell Jennifer
Published: January 2024

To address high rates of mental health and developmental concerns facing young children ages 0–6 in the United States and internationally, providers across professional sectors need Infant and early childhood mental health (IECMH) training and support. The training and teleconsultation program (TTP) is a state‐funded program developed in one Mountain West state in the United States to provide free IECMH training and teleconsultation to any provider working with young children. The TTP included access to webinars and individual or group consultation with licensed mental health providers. Webinars focused on increasing awareness and knowledge related to attachment and child development, supporting parents and caregivers, trauma‐informed practice, supporting emotional health of staff and providers, and culturally responsive practices with infants, young children, and caregivers. Teleconsultation included case consultation, reflective individual and group supervision, and collaboration supports/referrals. During the 18‐month evaluation period, 1568 unique providers engaged in either training or teleconsultation services, an average of 9% growth in new providers each month, with representation from all professional sectors and all state counties. This program demonstrates the feasibility and need for statewide training and teleconsultation programs to help meet the needs of providers who interact with and support young children and caregivers.
Wick irrigation improves seed yield and water use efficiency in mung bean
Authors: Rezaei Mansoor , Heidari Hassan
Published: January 2024

Drought is a serious threat to crop growth, and finding new irrigation methods can save water. This study was conducted to investigate water use efficiency and seed yield in mung bean under wick irrigation. Irrigation treatments consisted of the wick irrigation method, surface irrigation (common irrigation) with water equivalent to wick irrigation, and surface irrigation with the double water use of wick irrigation. The results showed that the wick irrigation had a seed weight per plant, 100‐seed weight, seed number per pod, pod number per plant, seed yield, biological yield, water use efficiency of seed, water use efficiency of biomass and net income increase of 164, 14, 28, 80, 164, 128, 164, 128 and 300%, respectively, compared to surface irrigation with an equivalent water volume of wick irrigation. Wick irrigation resulted in increases in plant height, internode length, leaf number per plant, node number per plant, branch number per plant, leaf length and leaf width of 60, 59, 65, 91, 91, 52 and 52%, respectively, compared to surface irrigation with an equivalent water volume of wick irrigation. In conclusion, the wick irrigation method, as a new method, can save water and improve seed yield and net income.
Wnt signaling in cell adhesion, development, and colon cancer
Authors: Tejeda‐Muñoz Nydia , Mei Kuo‐Ching
Published: January 2024

Wnt signaling is essential for embryonic development, influencing processes such as axis formation, cell proliferation and differentiation, cell fate decisions, and axon guidance. It also plays a role in maintaining tissue homeostasis in adult organisms. The loss of normal cell polarity and adhesion caused by Wnt signaling activation is a fundamental step for tumor progression and metastasis. Activating the canonical Wnt pathway is a driving force in many human cancers, especially colorectal, hepatocellular, and mammary carcinomas. Wnt causes the stabilization and nuclear transport of newly synthesized transcriptional regulator β‐catenin. The generally accepted view is that the canonical effects of Wnt growth factors are caused by the transcription of β‐catenin target genes. Here, we review recent findings that indicate Wnt is a regulator of many other cellular physiological activities, such as macropinocytosis, endosome trafficking, protein stability, focal adhesions, and lysosomal activity. Some of these regulatory responses occur within minutes and do not require new protein synthesis, indicating that there is much more to Wnt beyond the well‐established transcriptional role of β‐catenin. The main conclusion that emerges from these studies is that in basal cell conditions, the activity of the key protein kinase GSK3, which is inhibited by Wnt pathway activation, normally represses the actin machinery that orchestrates macropinocytosis with implications in cancer. These contributions expand our understanding of the multifaceted roles of Wnt signaling in cellular processes, development, and cancer, providing insights into potential therapeutic targets and strategies.
Development of the Core Outcome Set for Psychiatric Pharmacists
Authors: Reinstatler Kristina , Payne Gregory H. , Lister Jonathan F. , Moore Tera D. , Parmentier Brittany L. , Santos Ranel Troy , Cobb Carla D.
Published: January 2024

Objective

The American Association of Psychiatric Pharmacists (AAPP) sought to develop a consensus‐based set of outcomes and measures to standardize psychiatric pharmacy practice and research. The measures in this Core Outcome Set for Psychiatric Pharmacists (COS‐PP) are designed to study the impact of psychiatric pharmacists caring for individuals living with psychiatric disorders.

Methods

The COS‐PP was developed using guidelines from the Core Outcome Measures in Effectiveness Trials (COMET) initiative. A committee systematically reviewed a catalog of 194 articles and 40 posters that referenced psychiatric disorders, patient‐level outcomes, and pharmacist interventions. From these initial 234 resources, 554 combinations of outcomes and measures were identified. Additional papers, guidelines, and feedback from experts increased the number to 592 combined outcomes and measures. The principal investigator consolidated the list to 46 potential outcomes. AAPP members were invited to complete a survey rating the 46 potential outcomes on five key factors: comprehensive, attributable to pharmacy, feasible, scientifically sound, and usable. These survey results were provided to the 18 Board‐Certified Psychiatric Pharmacists participating in a summit examining the potential outcomes and measures gleaned from literature review. Through discussion and refinement, consensus was achieved on the final COS‐PP.

Results

The final COS‐PP included 21 outcomes, 14 of which included at least 1 measure (84 total measures). The outcomes were grouped according to the quadruple health care aims: better care, reduced healthcare costs, improved patient experience, and improved clinician well‐being.

Conclusions

COS‐PP will help define psychiatric pharmacists' support of the interdisciplinary team in addressing the quadruple health care aims. Using standardized outcomes across practice sites will allow aggregation of data on the impact of psychiatric pharmacists on patient care.
Addressing sample selection bias for machine learning methods
Authors: Brewer Dylan , Carlson Alyssa
Published: January 2024

We study approaches for adjusting machine learning methods when the training sample differs from the prediction sample on unobserved dimensions. The machine learning literature predominately assumes selection only on observed dimensions. Common approaches are to weight or include variables that influence selection as solutions to selection on observables. Simulation results show that selection on unobservables increases mean squared prediction error using popular machine‐learning algorithms. Common machine learning practices such as weighting or including variables that influence selection into the training or prediction sample often worsen sample selection bias. We propose two control function approaches that remove the effects of selection bias before training and find that they reduce mean‐squared prediction error in simulations. We apply these approaches to predicting the vote share of the incumbent in gubernatorial elections using previously observed re‐election bids. We find that ignoring selection on unobservables leads to substantially higher predicted vote shares for the incumbent than when the control function approach is used.
Impact of formulation on solid oxygen‐entrapping materials to overcome tumor hypoxia
Authors: McGovern Megan K. , Witt Emily , Rhodes Ashley C. , Kim Jinhee , Feig Vivian R. , Bi Jianling , Cafi Arielle B. , Hatfield Sam , Nwosu Ikenna , Byrne James D.
Published: January 2024

Tumor hypoxia, resulting from rapid tumor growth and aberrant vascular proliferation, exacerbates tumor aggressiveness and resistance to treatments like radiation and chemotherapy. To increase tumor oxygenation, we developed solid oxygen gas‐entrapping materials (O2‐GeMs), which were modeled after clinical brachytherapy implants, for direct tumor implantation. The objective of this study was to investigate the impact different formulations of solid O2‐GeMs have on the entrapment and delivery of oxygen. Using a Parr reactor, we fabricated solid O2‐GeMs using carbohydrate‐based formulations used in the confectionary industry. In evaluating solid O2‐GeMs manufactured from different sugars, the sucrose‐containing formulation exhibited the highest oxygen concentration at 1 mg/g, as well as the fastest dissolution rate. The addition of a surface coating to the solid O2‐GeMs, especially polycaprolactone, effectively prolonged the dissolution of the solid O2‐GeMs. In vivo evaluation confirmed robust insertion and positioning of O2‐GeMs in a malignant peripheral nerve sheath tumor, highlighting potential clinical applications.
Ibuprofen‐loaded bilayer electrospun mesh modulates host response toward promoting full‐thickness abdominal wall defect repair
Authors: Liu Jiajie , Tang Rui , Zhu Xiaoqiang , Ma Qiaolin , Mo Xiumei , Wu Jinglei , Liu Zhengni
Published: January 2024

Pro‐inflammatory response impairs the constructive repair of abdominal wall defects after mesh implantation. Electrospinning‐aid functionalization has the potential to improve the highly orchestrated response by attenuating the over‐activation of foreign body reactions. Herein, we combined poly(L‐lactic acid‐co‐caprolactone) (PLLA‐CL) with gelatin proportionally via electrospinning, with Ibuprofen (IBU) incorporation to fabricate a bilayer mesh for the repair improvement. The PLLA‐CL/gelatin/IBU (PGI) mesh was characterized in vitro and implanted into the rat model with a full‐thickness defect for a comprehensive evaluation in comparison to the PLLA‐CL/gelatin (PG) and off‐the‐shelf small intestinal submucosa (SIS) meshes. The bilayer PGI mesh presented a sustained release of IBU over 21 days with degradation in vitro and developed less‐intensive intraperitoneal adhesion along with a histologically weaker inflammatory response than the PG mesh after 28 days. It elicited an M2 macrophage‐dominant foreign body reaction within the process, leading to a pro‐remodeling response similar to the biological SIS mesh, which was superior to the PG mesh. The PGI mesh provided preponderant mechanical supports over the SIS mesh and the native abdominal wall with similar compliance. Collectively, the newly developed mesh advances the intraperitoneal applicability of electrospun meshes by guiding a pro‐remodeling response and offers a feasible functionalization approach upon immunomodulation.
Clock gene Per2 modulates epidermal tissue repair in vivo
Authors: Yujra Veronica Quispe , Silveira Ericka Janine Dantas da , Ribeiro Daniel Araki , Castilho Rogerio Moraes , Squarize Cristiane Helena
Published: January 2024

Wound healing can be influenced by genes that control the circadian cycle, including Per2 and BMAL1, which coordinate the functions of several organs, including the skin. The aim of the study was to evaluate the role of PER2 during experimental skin wound healing. Two groups (control and Per2‐KO), consisting of 14 male mice each, were anesthetized by inhalation, and two 6 mm wounds were created on their dorsal skin using a punch biopsy. A silicone ring was sutured around the wound perimeter to restrict contraction. The wound healing process was clinically measured daily (closure index) until complete wound repair. On Day 6, histomorphometric analysis was performed using the length and thickness of the epithelial migration tongue, in addition to counting vessels underlying the lesion by immunofluorescence assay and maturation of collagen fibers through picrosirius staining. Bromodeoxyuridine (BrdU) incorporation and quantification were performed using the subcutaneous injection technique 2 h before euthanasia and through immunohistochemical analysis of the proliferative index. In addition, the qualitative analysis of myofibroblasts and periostin distribution in connective tissue was performed by immunofluorescence. Statistically significant differences were observed in the healing time between the experimental groups (means: 15.5 days for control mice and 13.5 days for Per2‐KO; p = 0.001). The accelerated healing observed in the Per2‐KO group (p < 0.05) was accompanied by statistical differences in wound diameter and length of the migrating epithelial tongue (p = 0.01) compared to the control group. Regarding BrdU immunoreactivity, higher expression was observed in the intact epithelium of Per2‐KO animals (p = 0.01), and this difference compared to control was also present, to a lesser extent, at the wound site (p = 0.03). Immunofluorescence in the connective tissue underlying the wound showed a higher angiogenic potential in the Per2‐KO group in the intact tissue area and the wound region (p < 0.01), where increased expression of myofibroblasts was also observed. Qualitative analysis revealed the distribution of periostin protein and collagen fibers in the connective tissue underlying the wound, with greater organization and maturation during the analyzed period. Our research showed that the absence of the Per2 gene positively impacts the healing time of the skin in vivo. This acceleration depends on the increase of epithelial proliferative and angiogenic capacity of cells carrying the Per2 deletion.
Different factors identified by stakeholder group for barriers and facilitators to measurement‐based care implementation in behavioral health clinics
Authors: Yule Amy M. , Youn Soo Jeong , Dean Kimberlye , Woodward Diana W. , Firmin Elizabeth S. , Kramer Joanna , Stone Mira , Marques Luana , Wilens Timothy E.
Published: January 2024

Introduction

Despite the benefits of measurement‐based care (MBC) in the behavioral health setting, there have been difficulties in implementation and low saturation. Although barriers and facilitators to MBC implementation have been identified, research has generally only included the perspective of one stakeholder group. The current study aims to examine the similarities and differences—by stakeholder group—in the identified barriers to and facilitators of implementing MBC in the behavioral health setting.

Method

A purposeful sampling approach was used to recruit and conduct interviews and focus groups with stakeholders (clinicians, clinic leaders, and administrative staff) from four behavioral health clinics at an academic medical center that is part of a larger healthcare system. The data coding process included a directed content analytic approach whereby the coding team used an iterative process to analyze deidentified transcripts starting with a codebook based on the Consolidated Framework for Implementation Research (CFIR) constructs.

Results

A total of 31 clinicians, 11 clinic leaders, and 8 administrative staff participated in the interviews and focus groups. There was convergence among all stakeholder regarding which CFIR constructs were identified as barriers and facilitators, but there were differences in the specific thematic factors identified by stakeholders as barriers and facilitators within each of these implementation constructs. The barriers and facilitators that stakeholders identified within each CFIR construct were often connected to their specific role in implementing MBC.

Conclusion

Collecting information on barriers and facilitators to MBC implementation from the multiple stakeholders involved in the process may enhance successful implementation of MBC given the variation between groups in identified thematic factors. Administrative staff perspectives, which have not been reported in the literature, may be of particular importance in planning for successful MBC implementation.
Locational and functional characterization of PI4KB in the mouse embryo
Authors: Zhao Haoyu , Kong Fengyun , Yu Weikai , Zhao Huijie , Zhang Jingjing , Zhou Jun , Meng Xiaoqian
Published: January 2024

Phosphatidylinositol 4‐kinase beta (PI4KB) is a member of the PI4K family, which is mainly enriched and functions in the Golgi apparatus. The kinase domain of PI4KB catalyzes the phosphorylation of phosphatidylinositol to form phosphatidylinositol 4‐phosphate, a process that regulates various sub‐cellular events, such as non‐vesicular cholesterol and ceramide transport, protein glycosylation, and vesicle transport, as well as cytoplasmic division. In this study, a strain of PI4KB knockout mouse, immunofluorescence, reverse transcription polymerase chain reaction and microinjection were used to characterize the cytological location and biological function of PI4KB in the mouse embryos. we found that knocking down Pi4kb in mouse embryos resulted in embryonic lethality at around embryonic day (E) 7.5. Additionally, we observed dramatic fluctuations in PI4KB expression during the development of preimplantation embryos, with high expression in the 4‐cell and morula stages. PI4KB colocalized with the Golgi marker protein TGN46 in the perinuclear and cytoplasmic regions in early blastomeres. Postimplantation, PI4KB was highly expressed in the epiblast of E7.5 embryos. Treatment of embryos with PI4KB inhibitors was found to inhibit the development of the morula into a blastocyst and the normal progression of cytoplasmic division during the formation of a 4‐cell embryo. These findings suggest that PI4KB plays an important role in mouse embryogenesis by regulating various intracellular vital functions of embryonic cells.
Investigating the role of Purkinje fibers and synaptic connectivity in balance regulation through comprehensive ultrastructural and immunohistochemical analysis of the donkey's (Equus asinus) cerebellum
Authors: Elarab Samar M. Ez , Alsafy Mohamed A.M. , El‐Gendy Samir A.A. , El‐Bakary Neveen E.R. , Elsayed Noreldin Ahmed , Rashwan Ahmed M.
Published: January 2024

The donkey's extraordinary capacity to endure substantial loads over long distances while maintaining equilibrium suggests a distinctive cerebellar architecture specialized in balance regulation. Consequently, our study aims to investigate the intricate histophysiology of the donkey's cerebellum using advanced ultrastructural and immunohistochemical methodologies to comprehend the mechanisms that govern this exceptional ability. This study represents the pioneering investigation to comprehensively describe the ultrastructure and immunohistochemistry within the donkey cerebellum. Five adult donkeys' cerebella were utilized for the study, employing stains such as hematoxylin, eosin, and toluidine blue to facilitate a comprehensive histological examination. For immunohistochemical investigation, synaptophysin (SP), calretinin, and glial fibrillary acidic protein were used and evaluated by the Image J software. Furthermore, a double immunofluorescence staining of SP and neuron‐specific enolase (NSE) was performed to highlight the co‐localization of these markers and explore their potential contribution to synaptic function within the donkey cerebellum. This investigation aims to understand their possible roles in regulating neuronal activity and synaptic connectivity. We observed co‐expression of SP and NSE in the donkey cerebellum, which emphasizes the crucial role of efficient energy utilization for motor coordination and balance, highlighting the interdependence of synaptic function and energy metabolism. The Purkinje cells were situated in the intermediate zone of the cerebellum cortex, known as the Purkinje cell layer. Characteristically, the Purkinje cell's bodies exhibited a distinct pear‐like shape. The cross‐section area of the Purkinje cells was 107.7 ± 0.2 µm2, and the Purkinje cell nucleus was 95.7 ± 0.1 µm2. The length and diameter of the Purkinje cells were 36.4 × 23.4 µm. By scanning electron microscopy, the body of the Purkinje cell looked like a triangular or oval with a meandrous outer surface. The dendrites appeared to have small spines. The Purkinje cells' cytoplasm was rich with mitochondria, rough endoplasmic reticulum, ribosomes, Golgi apparatus, multivesicular bodies, and lysosomes. Purkinje cell dendrites were discovered in the molecular layer, resembling trees. This study sheds light on the anatomical and cellular characteristics underlying the donkey's exceptional balance‐maintaining abilities.
Transitional care of adolescents with inflammatory bowel disease to adult services varies widely across Australia and New Zealand
Authors: Vernon‐Roberts Angharad , Chan Patrick , Christensen Britt , Day Andrew S , Havrlant Rachael , Giles Edward , Williams Astrid‐Jane
Published: January 2024

Background and Aim

Children and adolescents account for approximately 14% of inflammatory bowel disease (IBD) diagnoses. At an appropriate age and level of development adolescents with IBD have their care transferred from the pediatric to adult clinical team during a process termed “transition”. The study aim was to survey pediatric gastroenterologists throughout Australasia to identify commonality in the transition process to contribute to standardized guideline development.

Methods

A descriptive survey captured key variables: transition clinic format, process and infrastructure, transition assessments, and guidelines. The survey was distributed electronically to 59 Pediatric Gastroenterologists throughout Australasia in January 2023.

Results

Seventeen (29%) clinicians completed the survey: Australia 13 (76%). New Zealand 4 (24%). Thirteen (76%) respondents had access to a dedicated IBD transition clinic. Adolescents attended transition clinics 1–7 times, and the main processes transferred were: prescription provision, biologic appointments, and adult team contacts. Transition was first discussed age 13–15 years (53%), or 16–18 years (47%), with the main discussion topics including: continuing adherence (88%), smoking (59%), alcohol use (59%), recreational drug use (59%). Transition readiness assessments were done infrequently (24%). The minority (24%) used formal guidelines to inform the transition process, but 15 (88%) considered the development of a standardized Australasian guideline as beneficial/extremely beneficial.

Conclusions

This survey highlighted that transition care for adolescents with IBD is variable across Australasia. Australasian guideline development may optimize the transition process for adolescents with IBD and improve their longitudinal outcomes.
Dearomative [4 + 2] cycloaddition of 3‐nitroindoles with ortho‐amino Morita−Baylis−Hillman carbonates to forge indole‐fused quinolines
Authors: Wang Kai‐Kai , Li Yan‐Li , Li Lan‐Xin , Yao Wei‐Wei , Li Ya‐Fei , Wang Wen‐Fei , Chen Rongxiang , Hu Yi‐Fan , Sun Aili
Published: January 2024

A dearomative [4 + 2] cycloaddition of 3‐nitroindoles ortho‐amino Morita−Baylis−Hillman carbonates was established under mild conditions. This method provides an efficient and practical approach for delivering tetrahydro‐5H‐indolo[2,3‐b]quinolines containing three contiguous stereocenters, two tertiary and one quaternary, in high yield (up to 95%) with excellent diastereoselectivity (all cases >25:1 dr). The potential synthetic applications of this strategy were also highlighted by the scale‐up experiment and further synthetic transformation. Moreover, the structure and relative configuration of the cycloadduct was unequivocally confirmed by single‐crystal X‐ray diffraction.
North Atlantic atmospheric circulation indices: Links with summer and winter temperature and precipitation in north‐west Europe, including persistence and variability
Authors: Simpson Ian , Hanna Edward , Baker Laura , Sun Yiming , Wei Hua‐Liang
Published: January 2024

Variability in seasonal weather in north‐west Europe is substantially determined by jet stream variability. The North Atlantic Oscillation (NAO) has been well studied as a key representation of this jet stream variability, but other circulation indices are also important. Here the first three principal component empirical orthogonal functions (EOFs) of 500 hPa geopotential height (GPH), which broadly correspond to the NAO, the East Atlantic pattern (EA) and Scandinavian pattern (SCA), as well as jet speed and latitude, are correlated with temperature and precipitation anomalies over Europe with a focus on north‐west Europe, as well as measures of persistence and variability. In high summer (July and August), all three of the principal EOFs are significantly correlated with extreme temperatures in large areas of northern Europe. In winter, for much of north‐west Europe, both temperatures and precipitation are positively correlated with the jet speed, and precipitation is negatively correlated with EOF3. There is some non‐stationarity in some of the relationships, notably between winter precipitation and EOF1, and between July/August precipitation and EOF2. In addition to single variate correlations, multiple correlation coefficients are also used to determine areas of significant correlation when combining two or three of the circulation indices. The multiple correlation analyses show that combining the three EOFs produces significant correlations with temperature and precipitation over much of Europe. These analyses provide scope for using seasonal forecasts to predict likely temperature and precipitation anomalies based on predicting the atmospheric circulation anomalies and downscaling them. Improved seasonal forecasts of temperature and precipitation, including persistence and variability, will be useful to a number of users, such as agrifood, transport, energy supply and insurance.
Integrating destination positioning and identity salience to enhance childcare service experiences in family travel: An insight from Macau
Authors: Liu Jing , Mai Huiwen , Tao Ran , Wang Ziyan , Zhang Yuanhao
Published: January 2024

Addressing the lack of an integrated view of family travel destination positioning and experience design, this study focuses on examining how a new form of family travel experiences, that is, childcare service experiences available during the hospitality and tourism consumption, combined with destination positioning to trigger travelers' positive perceptions of the overall tourism experiences in Macau. Furthermore, using the lens of identity salience, this study is among the first to investigate how the salience of self‐ or family‐identity changes the impact of childcare service experiences on travelers' destination attitudes. The findings of the two scenario‐based experiments suggested that compared to family travel destination positioning, individual characteristics (i.e., identity salience) exerted a significant strengthening effect on the impact of childcare service experiences on family travelers. This study is informative for destination marketers and hospitality and tourism managers and will help them to effectively design tourism experiences that appeal to family travelers.
The influence of value perceptions on tourist souvenir purchase decisions
Authors: Wang Wei , Yaoyuneyong Gallayanee , Sullivan Pauline , Burgess Brigitte
Published: January 2024

Shopping is an important activity impacting the travel and tourism industry. This research explores the influence of value perceptions on tourists' souvenir purchase decisions. A convenience sample of 380 respondents from a southeastern US university completed a survey regarding value perception towards the destination visited, type of shopping venue, and souvenir purchase intention. Through structural equation modeling, results revealed that functional and social value significantly influenced tourists' purchase intentions. This result provides valuable insight suggesting destination marketers should focus on these two indicators in future planning and promotion strategies. Limitations and directions for future research are provided.
Easing of travel restrictions: Examining increased intention toward proximity tourism through quasi‐experiments
Authors: Zhang Yang , Fu Xiao‐Xiao , Yin Yue
Published: January 2024

The rise of proximity tourism since the onset of COVID‐19 has enabled individuals to assess their daily lives from new perspectives. Nevertheless, in studies of this change, scant attention has been given to the influence of government performance on the perception and behavior of proximity tourists. Drawing upon micro‐governance theory in conjunction with the two‐factor hygiene model, this study proposes a novel conceptual framework. The effects of pandemic‐related strict vs. relaxed travel restrictions on potential proximity tourists' intention to travel are examined alongside mortality salience as a moderator and perceived extraordinariness as a mediator. Two quasi‐experiments reveal a positive link between government performance and travel intention, especially when moderated by mortality salience. Relaxed travel restrictions, coupled with the performance of government protests, greater perceived extraordinariness, thus amplifying travel intention. This study offers pioneering empirical validation of government response and its impact on post‐disaster proximity tourism intention.
Paradoxical effects of tourism ethnocentrism on domestic tourism: The moderating effect of pandemic anxiety travel
Authors: Kim Haeok Liz , Hyun Sunghyup Sean
Published: January 2024

This research findings to study the impact of socio‐psychological, economic, and political antecedents on tourism and to study the relationship among tourism ethnocentrism (TE), civilized tourism behavioral intention, willingness to visit, and electronic‐word of mouth. Also, it examines the moderating role of pandemic anxiety variables. The results show that American socio‐psychological and political antecedents are factors that directly affect TE and have a significant effect on travelers who are insecure about traveling due to the pandemic. Travelers affected by socio‐psychological and political antecedents were found to have higher TE and higher travel anxiety due to the pandemic. Therefore, this study suggests the need to strengthen people's patriotism and pride in their country to activate domestic tourism, which should be used as a tourism marketing material to promote domestic travel post‐pandemic.