bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution of slip partitioning in a major continental margin strike-slip fault system during a transition to oblique plate-margin tectonics: Insight into the evolution of the Garlock fault zone, California (USA)
Authors: Andrew Joseph E. , Walker J. Douglas , Rittase William M.
Published: March 2023

The Walker Lane belt and Eastern California shear zone of California, USA, are active, plate boundary–related dextral systems with transtensional and transpressional deformation, respectively. They are separated by the sinistral Garlock fault, creating a complex system without an overall integrated formation and evolution model. We examine the deformation within the eastern segment of the Garlock fault zone over geologic timescales by determining the slip history of faults. We assess the progression of faulting and associated deformation along the WSW-striking Garlock fault zone and how it applies to the overall NNW-directed dextral system. Previous studies found that large synthetic fault strands take up 30% of the slip of the Garlock fault zone and have proposed multiple mechanisms to explore how to accommodate regional NNW-directed shear across the Garlock fault without cutting its trace.

We analyze an unstudied section of faulting in one of the more complex areas of regional deformation via compiled and reinterpreted published geologic data for an analysis of total and incremental slip on the main faults of the eastern Garlock fault zone. We identify geologic offset features to interpret total slip, timing, and deformation evolution. We find that 30% of the total slip of the Garlock zone occurs on strands other than the Garlock fault sensu stricto, with the locus of main slip sidestepping during the evolution of accommodation of throughgoing, regional dextral shear. Our results support ideas of the creation and evolution of the regional dextral system via stress concentration on a sub-Garlock lithospheric anisotropy with a resulting lowering of the plastic yield stress. Our results also show an eastward increase in fault system complexity, which may imply an underappreciated seismic hazard of the eastern Garlock fault zone.
Evaluating emergency department transfers from urgent care centres: insights for paramedic integration with subacute healthcare
Authors: Strum Ryan P , Mowbray Fabrice I , Mondoux Shawn E , Costa Andrew P
Published: March 2023

Objective

Paramedics redirecting non-emergent patients from emergency departments (EDs) to urgent care centres is a new and forthcoming strategy to reduce overcrowding and improve primary care integration. Which patients are likely not suitable for paramedic redirection are unknown. To describe and specify patients inappropriate for urgent care centres, we examined associations between patient characteristics and transfer to the ED after patients initially presented to an urgent care centre.

Methods

A population-based retrospective cohort study of all adult (≥18 years) visits to an urgent care centre from 1 April 2015 to 31 March 2020 in Ontario, Canada. Binary logistic regression was used to determine unadjusted and adjusted associations between patient characteristics and being transferred to an ED using OR and 95% CIs. We calculated the absolute risk difference for the adjusted model.

Results

A total of 1 448 621 urgent care visits were reported, with 63 343 (4.4%) visits transferred to an ED for definitive care. Being 65 years and older (OR 2.29, 95% CI 2.23 to 2.35), scored an emergent Canadian Triage and Acuity Scale of 1 or 2 (OR 14.27, 95% CI 13.45 to 15.12) and higher comorbidity count (OR 1.51, 95% CI 1.46 to 1.58) had added odds of association with being transferred out to an ED.

Conclusion

Readily available patient characteristics were independently associated with interfacility transfers between urgent care centres and the ED. This study can support paramedic redirection protocol development, highlighting which patients may not be best suited for ED redirection.
Dissonance in views between healthcare professionals and adults with a spinal cord injury with their understanding and interpretation of exercise intensity for exercise prescription
Authors: Jung Kyung Su , Hutchinson Mike J , Chotiyarnwong Chayaporn , Kusumawardani Martha K , Yoon Seung-Hyun , Mikami Yukio , Laohasinnarong Phairin , Tinduh Damayanti , Prachgosin Pannika , Narasinta Inggar , Chotiyarnwong Pojchong , Utami Ditaruni A , Umemoto Yasonori , Tajima Fumihiro , Goosey-Tolfrey Vicky L
Published: March 2023

Objectives

To evaluate the difference between healthcare professionals (HCPs) and adults with spinal cord injury (SCI) in Asia regarding knowledge and interpretation of ‘exercise intensity’ for aerobic exercise prescription.

Methods and study design

A survey was distributed to practising HCP and adults with SCI. It was completed in participants’ local language on topics related to the importance of exercise frequency, intensity, time and type; methods for monitoring and terms related to exercise intensity prescription. χ2analysis was used to detect differences in HCP or those with SCI.

Results

121 HCP and 107 adults with an SCI ≥1 years (C1–L4) participated. Responses revealed 61% of all HCP ranked ‘intensity’ being most important whereas only 38% respondents from the SCI group ranked it as high importance (p=0.008). For those with SCI, ‘frequency’ was most important (61%) which was significantly higher than the 45% selected by HCPs (p=0.030). Of the 228 respondents on average only 34% believed that the terms, ‘moderate’ and ‘vigorous’ provided enough information for aerobic exercise intensity prescription. HCP most often used HR methods compared with the SCI group (90% vs 54%; p<0.01). Both groups frequently used the subjective measures of exercise intensity, for example, Ratings of Perceived Exertion (8%3 vs 76% for HCP and SCI), HCP also frequently used speed (81%) and SCI also frequently relied on ‘the affect’ or feelings while exercising (69%).

Conclusions

These differences must be considered when developing clinical-practice exercise guidelines and health referral educational pathways for adults with SCI in Asia.
High burden of polypharmacy and comorbidity in persons with psoriatic arthritis: an analysis of claims data, stratified by age and sex
Authors: Albrecht Katinka , Regierer Anne Constanze , Strangfeld Anja , Marschall Ursula , Callhoff Johanna
Published: March 2023

Objective

To assess polypharmacy in women and men with psoriatic arthritis (PsA).

Methods

From the German BARMER health insurance database, 11 984 persons with PsA and disease-modifying antirheumatic drug therapy in 2021 were included and compared with sex-matched and age-matched controls without inflammatory arthritis. Medications were analysed by Anatomical Therapeutic Chemical (ATC) groups. Polypharmacy (≥5 concomitant drugs) was compared by sex, age and comorbidity using the Rheumatic Disease Comorbidity Index (RDCI) and the Elixhauser Score. The mean difference in the number of medications between persons with PsA and controls was estimated using a linear regression model.

Results

Compared with controls, all ATC drug classes were significantly more frequent in persons with PsA, most commonly musculoskeletal (81% vs 30%), immunomodulatory (56% vs 2.6%), cardiovascular (62% vs 48%), alimentary tract/metabolic (57% vs 31%) and nervous system (50% vs 31%) drugs. Polypharmacy was significantly higher in PsA (49%) compared with controls (17%), more frequent in women (52%) compared with men (45%) and strongly increased with age and comorbidity. For each unit increase of the RDCI, the age-adjusted number of medications increased by 0.98 (95% CI 0.95 to 1.01) units in men and 0.93 (95% CI 0.90 to 0.96) units in women. Compared with controls, the number of medications in PsA (mean 4.9 (SD 2.8)) was 2.4 (95%CI 2.34; 2.43) units higher in women and 2.3 (95% CI 2.21 to 2.35) units higher in men.

Conclusions

Polypharmacy is common in PsA and is composed of PsA-specific medication as well as frequent medications for comorbidities, equally affecting women and men.
IgG4-related disease administered dupilumab: case series and review of the literature
Authors: Kanda Masatoshi , Kamekura Ryuta , Sugawara Masanari , Nagahata Ken , Suzuki Chisako , Takano Kenichi , Takahashi Hiroki
Published: March 2023

Dupilumab (DUP) is a monoclonal antibody that acts on the interleukin (IL)-4 receptor alpha, which inhibits IL-4 and IL-13 signalling and is approved for type 2 inflammatory diseases such as asthma, chronic rhinosinusitis with nasal polyposis and atopic dermatitis; however, the efficacy of DUP to IgG4-related disease (IgG4-RD) is under discussion due to the controversial outcomes based on the several case reports. Here, we reviewed the efficacy of DUP in four consecutive patients with IgG4-RD in our institute and the previous literature.

All patients administered DUP fulfilled the 2019 ACR/EULAR classification criteria for IgG4-RD complicated with severe asthma and chronic rhinosinusitis with nasal polyposis. Two cases were administered DUP without systemic glucocorticoids (GCs), and in 6 months, the volume of swollen submandibular glands (SMGs) was reduced by approximately 70%. Two cases receiving GCs successfully reduced their daily dose of GCs (10 and 50% reduction, respectively) with dupilumab in 6 months. In all four cases, serum IgG4 concentration and IgG4-RD responder index decreased in 6 months.

DUP reduced the volume of the swollen SMGs, serum IgG4 levels, responder index and the daily dose of GCs in patients with IgG4-RD with severe asthma or eosinophilic rhinosinusitis in 6 months.

The efficacy of DUP to IgG4-RD is under discussion due to the limited case reports with controversial outcomes. Here, we demonstrated that two patients with IgG4-RD treated by DUP without systemic GCs, showed volume reduction of swollen SMGs and two cases showed GC-sparing effects by DUP. DUP can ameliorate the disease activity and be a steroid-sparing agent in patients with IgG4-RD.
Entropy bound and EGUP correction of d-dimensional Reissner–Nordström black hole in rainbow gravity
Authors: Roy Tanusree , Debnath Ujjal
Published: March 2023

Inspired by the pronounced effect of gravity’s Rainbow on black hole thermodynamics, entropy relations and bounds have been investigated for [Formula: see text]-dimensional Reissner–Nordström (RN) black hole in the framework of Rainbow gravity. Basic thermodynamic properties of the black hole have been derived for the event horizon and Cauchy horizon. Except for the horizon radius, they all crucially depend on the Rainbow functions. Bounds of the aforesaid thermodynamic quantities have been deduced for both horizons. Analyzing the specific heat capacity, stability conditions have been obtained. Also, the extremal phase of the black hole has been explored. Further, a comparative study has been carried out to distinguish between the effects of Rainbow gravity model parameters on the entropy bound by considering different Rainbow gravity functions. For massless scalar perturbation, quasinormal modes have been computed using modified WKB approach. We have investigated the quantum correction of the black hole in a Rainbow gravity background to obtain the effects of Extended Uncertainty Principle (EUP) and Generalized Uncertainty Principle (GUP) parameters. We have derived the Hawking temperature, specific heat, entropy and remnant masses of the black hole in the Extended General Uncertainty Principle (EGUP) framework, and with the help of graphical methods, we have compared our findings.
Path Generation for a Given Performance Evaluation Value Interval by Modifying Bat Algorithm with Heuristic
Authors: Wang Fujun , Cao Zining , Li Zhen , Xing Chao , Zong Hui
Published: March 2023

Path generation means generating a path or a set of paths so that the generated path meets specified properties or constraints. To our knowledge, generating a path with the performance evaluation value of the path within a given value interval has received scant attention. This paper subtly formulates the path generation problem as an optimization problem by designing a reasonable fitness function, adapts the Markov decision process with reward model into a weighted digraph by eliminating multiple edges and non-goal dead nodes, constructs the path by using a priority-based indirect coding scheme, and finally modifies the bat algorithm with heuristic to solve the optimization problem. Simulation experiments were carried out for different objective functions, population size, number of nodes, and interval ranges. Experimental results demonstrate the effectiveness and superiority of the proposed algorithm.
A Neutrosophic Decision-Making Model for Determining Young People’s Active Engagement
Authors: Colhon Mihaela , Tilea Monica , González-Marcos Ana , Reşceanu Alina , Smarandache Florentin , Navaridas-Nalda Fermín
Published: March 2023

Young people’s skills and attitudes must be observed, studied and evaluated in order to create appropriate models that would serve an educational purpose. In this paper, we propose a decision-making model with the aim to detect certain attitudinal and behavioral patterns of actively engaged young people. The data used in this research resulted from a questionnaire drawn up by a group of researchers from six European countries with the aim to investigate the youth’s awareness about the Sustainable Development Goals and their engagement as active agents of development and change at regional level. For the purpose of this study, we selected the regional results obtained from administering this questionnaire in Dolj County (Romania) and La Rioja (Spain). We developed a neutrosophic model that determines the Mindchanger profile of the respondents based on a minimal set of questions, which is dependent on the inclusion or exclusion of the nationality-specific traits. The resulting decisions were then compared with the respondents’ self-evaluations, yielding high precisions (more than 0.83) for all the investigated evaluation scenarios. Our results were significantly better than the ones provided by several machine learning models applied on the same set of data. A direct impact of our model is that it can be applied to questionnaires which include linguistic responses that express, among others, unclear or vague thoughts. Additionally, it offers the possibility to identify the minimal set of questions that impact the respondent’s answer choice to a target question.
Study of Equivalent Mechanical Properties and Energy Absorption of Composite Honeycomb Structures
Authors: Farrokhabadi Amin , Gharehbaghi Hussain , Malekinejad Hossein , Sebghatollahi Mohammad , Noroozi Zahra , Veisi Hossein
Published: March 2023

In this study, an analytical model based on classical laminate theory (CLT) is proposed to predict the equivalent mechanical characteristics of three-dimensional (3D) printed fiber-reinforced polylactic acid (PLA) honeycomb structures. Higher rigidity and strength in comparison with the structures made of pure isotropic materials are presented by employing fiber-reinforced PLA. Tensile tests and finite elements studies are conducted to verify the developed analytical relationships. A good agreement is found between the experimental, numerical, and analytical results. Consequently, the mechanical characteristics of the aforementioned structures can be properly predicted using the presented analytical relationships. Moreover, the study examines the impact of using commingled yarn instead of single yarn as a fiberglass strut and finds higher ultimate tensile strength. Compression tests are also conducted to examine the energy absorption capacity of polyurethane foam-filled and hollow honeycomb structures. Finally, a parametric study is conducted to evaluate the effects of geometry on the elastic modulus and Poisson’s ratio of the honeycomb structures.
Probability-Based Approach for Inverse Stochastic Structural Problems
Authors: Laudani Rossella , Falsone Giovanni
Published: March 2023

The topic of this paper is related to the inverse stochastic mechanic problems, in which it is necessary to estimate the unknown mechanical and geometrical random quantities of the structures once the external loads and displacement responses are probabilistically known. In particular, in this work, a probability-based approach for inverse stochastic problems, working directly in terms of probability density functions (PDFs), is presented. This approach has been possible thanks to the application of the probability transformation method (PTM), which has been recently introduced for the solution of many stochastic analysis problems.
Mathematical Modeling of Multiple-Li-Dendrite Growth in Li-ion Battery Electrodes
Authors: Takagishi Yoichi , Yamaue Tatsuya
Published: March 2023

Lithium dendrite growth in Li-ion batteries is one of the most dangerous phenomena because it can cause inner short circuits and thermal runaways. However, the nucleation and growth of the dendrites are difficult to predict because of their complex behaviors, which depend on several factors such as the charging conditions and electrode-design parameters. In this study, a comprehensive mathematical model has been developed for Li-deposition on Li-ion battery electrodes. The model is based on the Single Particle model (to evaluate the Li-ion concentration fields) combined with dendrite-growth models based on the electrochemical and crystal growth theory. The effect of the SEI thickness distribution, the charging C-rate and cut-off voltage on the growth of dendrite tips have been statistically evaluated, and the risk of short circuit is discussed. The study focuses on the effects of the SEI-thickness distribution on the timing of the SEI breaking and density of the dendrite formation.
Renal blood flow during exercise: understanding its measurement with Doppler ultrasound
Authors: Rocha Marcos P. , Mentetzides Sandro H. , Drew Rachel C.
Published: March 2023

The sympathetic nervous system (SNS) has a critical role in continuously coordinating responses to stimuli internal and external to the human body by appropriately modulating the activity of the organs it innervates. The SNS is activated in response to various physiological stressors, including exercise, which can involve a significant increase in SNS activity. An increase in SNS activity directed toward the kidneys causes vasoconstriction of afferent arterioles within the kidneys. This sympathetically mediated renal vasoconstriction decreases renal blood flow (RBF), causing significant blood flow redistribution toward active skeletal muscles during exercise. In research studies, different modes, intensities, and durations of exercise have been used to investigate the sympathetically mediated RBF response to exercise, and several methodological approaches have been used to quantify RBF. Doppler ultrasound provides noninvasive, continuous, real-time measurements of RBF and has emerged as a valid and reliable technique to quantify RBF during exercise. This innovative methodology has been applied in studies in which the RBF response to exercise has been examined in healthy young and older adults and patient populations such as those with heart failure and peripheral arterial disease. This valuable tool has enabled researchers to produce clinically relevant findings that have furthered our understanding of the effect of SNS activation on RBF in populations of health and disease. Therefore, the focus of this narrative review is to highlight the use of Doppler ultrasound in research studies that have provided important findings furthering our knowledge of the impact of SNS activation on RBF regulation in humans.
Effect of Exogenous Nitric Oxide on Enterocytozoon hepatopenaei Copy Numbers and Immunity of Exopalaemon carinicauda
Authors: Jiang Haiyi , Li Yongchuang , Xu Jing , Li Wanying , Baloch Wazir Ali , Yu Fei , Mu Hua , Gao Huan
Published: March 2023

To explore the effect of nitric oxide (NO) on Enterocytozoon hepatopenaei (EHP) invading the shrimp, sodium nitroprusside was used as an exogenous NO donor to investigate the effects of different concentrations (0 μg/L (control group), 0.3 μg/L, 0.6 μg/L, and 0.9 μg/L) of sodium nitroprusside on the EHP copy number and the structure in the hepatopancreas of Exopalaemon carinicauda infected by EHP. The results showed that the EHP copy number in the sodium nitroprusside group was significantly lower than that in the control group, and the hepatopancreas in the sodium nitroprusside injection group had less structure damage than the control group. Additionally, superoxide dismutase (SOD) activity in the control group and 0.3 μg/L groups increased and then decreased, while alkaline phosphatase (AKP) activity decreased and then increased, with the same trend, and, the inducible nitric oxide synthase (iNOS) activity in the haemolymph of the 0.3 μg/L group was significantly higher than that of the control group at 3 days (

P
<
0.05

). The NO content the 0.3 μg/L group was also higher from 1 to 4 days than that in the control group and significantly higher than that in the control group at 3 days (

P
<
0.05

). The injection of NO could reduce the EHP copy number in infected E. carinicauda and slow down the pathological changes in the hepatopancreas structure, which might be related to the increase in NO content.
Fractional Modeling of Non-Newtonian Casson Fluid between Two Parallel Plates
Authors: Qayyum Mubashir , Afzal Sidra , Ahmad Efaza
Published: March 2023

In this manuscript, fractional modeling of non-Newtonian Casson fluid squeezed between two parallel plates is performed under the influence of magneto-hydro-dynamic and Darcian effects. The Casson fluid model is fractionally transformed through mixed similarity transformations. As a result, partial differential equations (PDEs) are transformed to a fractional ordinary differential equation (FODE). In the current modeling, the continuity equation is satisfied while the momentum equation of the integral order Casson fluid is recovered when the fractional parameter is taken as

α
=
1

. A modified homotopy perturbation algorithm is used for the solution and analysis of highly nonlinear and fully fractional ordinary differential equations. Obtained solutions and errors are compared with existing integral order results from the literature. Graphical analysis is also performed at normal and radial velocity components for different fluid and fractional parameters. Analysis reveals that a few parameters are showing different behavior in a fractional environment as compared to existing integer-order cases from the literature. These findings affirm the importance of fractional calculus in terms of more generalized analysis of physical phenomena.
The SIX1/LDHA Axis Promotes Lactate Accumulation and Leads to NK Cell Dysfunction in Pancreatic Cancer
Authors: Ge Wanli , Meng Lingdong , Cao Shouji , Hou Chaoqun , Zhu Xiaole , Huang Dongya , Li Qiang , Peng Yunpeng , Jiang Kuirong
Published: March 2023

Background. Pancreatic cancer (PC) is a malignant cancer with poor prognosis and high mortality rate. Sine oculis homeobox homolog 1 (SIX1) participates in the development of many cancers. However, the function of SIX1 in PC is not fully understood. Methods. SIX1 expression was determined using immunohistochemistry in PC tissues and cell lines. Glucose consumption, lactate production, and ATP assays were used to detect the function of SIX1. PC cells and NK cells were cocultured to study the effect of SIX1 overexpression in PC cells on NK cell function. Chromatin immunoprecipitation (ChIP) assays were used to study the relationship between SIX1 and lactate dehydrogenase A (LDHA). A series of in vitro and in vivo assays were further applied to elucidate the important role of the SIX1/LDHA axis in metabolism and NK cell dysfunction in PC. Results. SIX1 was significantly upregulated in PC tissue; SIX1 overexpression promoted the glycolysis capacity of PANC-1 and CFPAC-1 cells and resulted in NK cell dysfunction after the NK cells had been cultured with PC cells. LDHA inhibitor partially restored the promotion of PC caused by SIX1 overexpression. According to ChIP assays, SIX1 directly binds to the LDHA promoter region. Moreover, LDHA inhibitor and lactate transporter blocker treatment promoted the function of NK cells cocultured with PC cells. In vivo experiments yielded the same results. Conclusion. The SIX1/LDHA axis promotes lactate accumulation and leads to NK cell dysfunction in PC.
Analgesic Efficacy of Intravenous Ibuprofen in the Treatment of Postoperative Acute Pain: A Phase III Multicenter Randomized Placebo-ControlledDouble-Blind Clinical Trial
Authors: Zhou Hong-Su , Li Ting-Ting , Pi Yu , Wang Ting-Hua , Liu Fei , Xiong Liu-Lin
Published: March 2023

Objective. To evaluate the analgesic efficacy and safety of different does of intravenous ibuprofen (IVIB) in the treatment of postoperative acute pain. Methods. Patients with an intravenous (IV) patient-controlled analgesia device after abdominal or orthopedic surgery were randomly divided into placebo, IVIB 400 mg, and IVIB 800 mg groups. The first dosage of study medicines was given intravenously 30 minutes (min) before surgery ended, followed by six hours (h) intervals for a total of eight doses following surgery. The demographic characteristics and procedure data, cumulative morphine consumption, the visual analog scale (VAS), the area under the curve (AUC) of VAS, patient satisfaction score (PSS), the rates of treatment failure (RTF), and adverse events (AEs) and serious adverse event (SAEs) were recorded during the period of trial. Result. A total of 345 patients were enrolled in the full analysis set (FAS), and of 326 participants were valid data set (VDS). Demographic characteristics, disease features, and medical history of patients were not significantly different between groups. Total morphine consumption of the IVIB 400 mg group (11.14 ± 7.14 mg;

P

 = 0.0011) and the IVIB 800 mg group (11.29 ± 6.45 mg;

P

 = 0.0014) was significantly reduced compared with the placebo group (14.51 ± 9.19 mg) for 24 h postoperatively, there was no significant difference between the IVIB 400 mg and IVIB 800 mg groups (

P

 = 0.9997). The placebo group had significantly higher VAS and the AUCs of VAS than those in the IVIB 400 mg and the IVIB 800 mg groups at rest and movement for 24 h postoperatively (

P

 < 0.05), and there was no significant difference between the IVIB 400 mg and IVIB 800 mg groups (

P

 > 0.05). RTF was slightly higher in the placebo group than IVIB 400 mg group and 800 mg group, and no statistical significance (

P

 < 0.690). PSS in the IVIB 400 mg (

P

 = 0.0092) and the IVIB 800 mg groups (

P

 = 0.0011) was higher than the placebo group for pain management, there was also no significant difference between the IVIB 400 mg and IVIB 800 mg groups (

P

 = 0.456). The incidence of RTF (

P

 = 0.690) and AEs (

P

 > 0.05) were not different among the three groups. Conclusion. Intermittent IV administration of ibuprofen 400 mg or 800 mg within 24 h after surgery in patients undergoing abdominal and orthopedic surgery significantly decreased morphine consumption and relieved pain, without increasing the incidence of AEs.
Endothelial Progenitor Cell Therapy for Fracture Healing: A Dose-Response Study in a Rat Femoral Defect Model
Authors: Ramnaraign David J. , Godbout Charles , Hali Kalter , Hegner Christian , Bates Brent D. , Desjardins Sarah , Peck Jonathan , Schemitsch Emil H. , Nauth Aaron
Published: March 2023

Endothelial progenitor cell (EPC) therapy has been successfully used in orthopaedic preclinical models to heal bone defects. However, no previous studies have investigated the dose-response relationship between EPC therapy and bone healing. This study aimed to assess the effect of different EPC doses on bone healing in a rat model to define an optimal dose. Five-millimeter segmental defects were created in the right femora of Fischer 344 rats, followed by stabilization with a miniplate and screws. Rats were assigned to one of six groups (control, 0.1 M, 0.5 M, 1.0 M, 2.0 M, and 4.0 M; n = 6), receiving 0, 1 × 105, 5 × 105, 1 × 106, 2 × 106, and 4 × 106 EPCs, respectively, delivered into the defect on a gelatin scaffold. Radiographs were taken every two weeks until the animals were euthanized 10 weeks after surgery. The operated femora were then evaluated using micro-computed tomography and biomechanical testing. Overall, the groups that received higher doses of EPCs (0.5 M, 1.0 M, 2.0 M, and 4.0 M) reached better outcomes. At 10 weeks, full radiographic union was observed in 67% of animals in the 0.5 M group, 83% of animals in the 1.0 M group, and 100% of the animals in the 2.0 M and 4.0 M groups, but none in the control and 0.1 M groups. The 2.0 M group also displayed the strongest biomechanical properties, which significantly improved relative to the control and 0.1 M groups. In summary, this study defined a dose-response relationship between EPC therapy and bone healing, with 2 × 106 EPCs being the optimal dose in this model. Our findings emphasize the importance of dosing considerations in the application of cell therapies aimed at tissue regeneration and will help guide future investigations and clinical translation of EPC therapy.
Regenerative Potential of Granulation Tissue in Periodontitis: A Systematic Review and Meta-analysis
Authors: Tan Naiwen , Sabalic Maja , Nguyen Linh , D’Aiuto Francesco
Published: March 2023

Background and Aim. Soft and hard periodontal tissues contain limited numbers of stem cells. This makes regeneration of the periodontium in patients with periodontitis challenging and unpredictable. Granulation tissue is traditionally removed during periodontal corrective therapy, but it is believed to contain multipotent stem cells which could be used for regenerative therapy. The aim of this research was to critically appraise the evidence on cellular components within granulation tissue in patients with periodontitis and its regenerative potential when compared to control healthy periodontal tissue. Methods. Electronic searches were conducted in five databases including CENTRAL, MEDLINE, EMBASE, Web of Science, and Dentistry & Oral Sciences Source using a combination of MeSH terms and keywords up to 21 June 2022. Human studies including patients aged over 18 years with all forms of periodontitis were included. Following the risk of bias assessment, both qualitative and quantitative analyses were performed. Results. A total of twelve studies were included in qualitative analysis and six of them in quantitative analyses. The evidence suggested that cells derived from periodontitis granulation tissue have osteogenic, adipogenic, chondrogenic, neurogenic, and angiogenic differentiation abilities as well as immunoregulatory properties. In particular, CD44+, CD73+, CD90+, CD105+, and CD146+ cells were found widely in granulation tissue whilst the only meta-analysis confirmed that CD90+ cells were present in lower numbers within the granulation tissue when compared with healthy periodontal tissue (

WMD
=
−
23.43
%

, 95% CI -30.43 to -16.44,

p
<
0.00001

). Conclusions. This review provided further evidence that granulation tissue from patients with periodontitis can be a potential stem cell source for regenerative therapy.
Spatiotemporal Variability of Extreme Rainfall in Southern Benin in the Context of Global Warming
Authors: Hounvou S. F. , Guedje K. F. , Kougbeagbede H. , Adechinan J. , Houngninou E. , Houeto A.
Published: March 2023

Changes in the frequency and timing of extreme precipitation in southern Benin are assessed in the context of global warming. The peak-over-threshold (POT) is used for this purpose, with the six (06) year return period daily rainfall as the threshold over seventeen (17) weather stations between 1960 and 2018. The results show that the South Benin experienced extreme rainfall on many occasions between 1960 and 2018 with a nonuniform spatiotemporal distribution of this category of rainfall. No statistically significant trend in the frequency and variation of extreme rainfall intensities is revealed over the study period. Despite the low rate of extreme rainfall, the monthly trend is consistent with the bimodal rainfall regime in southern Benin. The global warming highlighted in its last decades in southern Benin is accompanied by a slightly upward trend in extreme rainfall compared to the period before 1990.
Drug Shortage Concepts among Stakeholders in Saudi Arabia
Authors: Almutairi Malak , Almomen Salwa , Alhazzani Haya , Almutairi Bushra , Alenzi Arwa , Hafiz Radwan
Published: March 2023

Introduction: The SFDA internal records showed that several pharmaceutical entities (National Unified Procurement Company (NUPCO) and Saudi Food and Drug Authority (SFDA) are overlapping in their tasks within the system of drug availability in the Saudi market. This may have led to difficulties in terms of contacting which entity when drug shortages occur. This study aimed to identify stakeholders’ understanding of drug shortage, the internal process of reporting a drug shortage to the SFDA, and to evaluate the clarity of the communication channels and the stakeholder’s satisfaction regarding drug shortage reporting system at SFDA. Method: A cross-sectional study conducted between December 2020 and August 2021. The study consisted of three separate surveys targeting the main stakeholders including healthcare institution (hospitals and pharmacies), NUPCO, and registered pharmaceutical companies/storage) with a response rate of (68.07%). The survey consists of three main parts: knowledge, practice, and perception of drug shortage reporting system at SFDA. Results: Healthcare institution defined drug shortages as unavailability of the product after confirmation of unavailability by the agent by 65.3% and low stock generic product by 44.9%. Nonetheless, 67.3% of healthcare institutions planned for inventory stock based on several factors such as the need of the stock/product and consumption of the products per different periods. Moreover, NUPCO identified the drug shortages by two factors when the stock of brand drug is zero and after pharmaceutical companies confirm the unavailability of the product. Additionally, all of the stakeholders were aware of SFDA communication channels for drug shortages. Conclusion: Based on our results, the internal workflow of stakeholders on the issue of drug shortages was reviewed and most responses provided a general overview of the internal processes for handling drug shortages, reporting steps, and submitting drug shortage reports. Nonetheless, when it comes to choosing the right provider for a healthcare facility, price and delivery time are major factors that influence their decision. In addition, it is recommended that further investigation of internal workflows be conducted to measure aspects that may affect the clarity and quality of services provided by the SFDA.
Paternal Deprivation and Female Biparental Family Rearing Induce Dendritic and Synaptic Changes in Octodon degus: II. Nucleus Accumbens
Authors: de Schultz Tony , Braun Katharina , Bock Joerg
Published: March 2023

While the majority of studies on the importance of parental caregiving on offspring behavioral and brain development focus on the role of the mother, the paternal contribution is still an understudied topic. We investigated if growing up without paternal care affects dendritic and synaptic development in the nucleus accumbens of male and female offspring and if replacement of the father by a female caregiver “compensates” the impact of paternal deprivation. We compared (a) biparental rearing by father and mother, (b) monoparental care by a single mother, and (c) biparental rearing by two female caregivers. Quantitative analysis of medium-sized neurons in the nucleus accumbens revealed that growing up without father resulted in reduced spine number in both male and female offspring in the core region, whereas spine frequency was only reduced in females. In the shell region, reduced spine frequency was only found in males growing up in a monoparental environment. Replacement of the father by a female caregiver did not “protect” against the effects of paternal deprivation, indicating a critical impact of paternal care behavior on the development and maturation of neuronal networks in the nucleus accumbens.
Peripheral Ischemia Imprints Epigenetic Changes in Hematopoietic Stem Cells to Propagate Inflammation and Atherosclerosis
Authors: Coppin Emilie , Zhang Xinyi , Ohayon Lee , Johny Ebin , Dasari Ankush , Zheng Kang H. , Stiekema Lotte , Cifuentes-Pagano Eugenia , Pagano Patrick J. , Chaparala Srilakshmi , Stroes Erik S. , Dutta Partha
Published: March 2023

Background:

Peripheral ischemia caused by peripheral artery disease is associated with systemic inflammation, which may aggravate underlying comorbidities such as atherosclerosis and heart failure. However, the mechanisms of increased inflammation and inflammatory cell production in patients with peripheral artery disease remain poorly understood.

Methods:

We used peripheral blood collected from patients with peripheral artery disease and performed hind limb ischemia (HI) in
Apoe

−/−

mice fed a Western diet and C57BL/6J mice with a standard laboratory diet. Bulk and single-cell RNA sequencing analysis, whole-mount microscopy, and flow cytometry were performed to analyze hematopoietic stem and progenitor cell (HSPC) proliferation, differentiation, and relocation.

Results:

We observed augmented numbers of leukocytes in the blood of patients with peripheral artery disease and
Apoe

−/−

mice with HI. RNA sequencing and whole-mount imaging of the bone marrow revealed HSPC migration into the vascular niche from the osteoblastic niche and their exaggerated proliferation and differentiation. Single-cell RNA sequencing demonstrated alterations in the genes responsible for inflammation, myeloid cell mobilization, and HSPC differentiation after HI. Heightened inflammation in
Apoe

−/−

mice after HI aggravated atherosclerosis. Surprisingly, bone marrow HSPCs expressed higher amounts of the receptors for IL (interleukin)-1 and IL-3 after HI. Concomitantly, the promoters of
Il1r1
and
Il3rb
had augmented H3K4me3 and H3K27ac marks after HI. Genetic and pharmacological inhibition of these receptors resulted in suppressed HSPC proliferation, reduced leukocyte production, and ameliorated atherosclerosis.

Conclusions:

Our findings demonstrate increased inflammation, HSPC abundance in the vascular niches of the bone marrow, and elevated IL-3Rb and IL-1R1 (IL-1 receptor 1) expression in HSPC following HI. Furthermore, the IL-3Rb and IL-1R1 signaling plays a pivotal role in HSPC proliferation, leukocyte abundance, and atherosclerosis aggravation after HI.
Economic and Health Value of Delaying Atrial Fibrillation Progression Using Radiofrequency Catheter Ablation
Authors: Berman Adam E. , Kabiri Mina , Wei Tom , Galvain Thibaut , Sha Qun , Kuck Karl-Heinz
Published: March 2023

Background:

Radiofrequency catheter ablation (RFCA) is an established treatment for atrial fibrillation (AF) refractory to antiarrhythmic drugs. The economic value of RFCA in delaying disease progression has not been quantified.

Methods:

An individual-level, state-transition health economic model estimated the impact of delayed AF progression using RFCA versus antiarrhythmic drug treatment for a hypothetical sample of patients with paroxysmal AF. The model incorporated the lifetime risk of progression from paroxysmal AF to persistent AF, informed by data from the ATTEST (Atrial Fibrillation Progression Trial). The incremental effect of RFCA on disease progression was modeled over a 5-year duration. Annual crossover rates were also included for patients in the antiarrhythmic drug group to mirror clinical practice. Estimates of discounted costs and quality-adjusted life years asssociated with health care utilization, clinical outcomes, and complications were projected over patients’ lifetimes.

Results:

From the payer’s perspective, RFCA was superior to antiarrhythmic drug treatment with an estimated mean net monetary benefit per patient of $8516 ($148–$16 681), driven by reduced health care utilization, cost, and improved quality-adjusted life years. RFCA reduced mean (95% CI) per-patient costs by $73 (−$2700 to $2200), increased mean quality-adjusted life years by 0.084 (0.0–0.17) and decreased the mean number of cardiovascular-related health care encounters by 24%.

Conclusions:

RFCA is a dominant (less costly and more effective) treatment strategy for patients with AF, especially those with early AF for whom RFCA could delay progression to advanced AF. Increased utilization of RFCA—particularly among patients earlier in their disease progression—may provide clinical and economic benefits.
Ablation of Ventricular Preexcitation to Cure Preexcitation-Induced Dilated Cardiomyopathy in Infants: Diagnosis and Outcome
Authors: Zhang Yi , Jiang He , Cui Jian , Li Mei-ting , Zhou Hui-ming , Li Xiao-mei
Published: March 2023

Background:

To investigate the clinical features of preexcitation-induced dilated cardiomyopathy in infants and evaluate safety and efficacy of radiofrequency ablation (RFCA) in these patients.

Methods:

This study included 10 infants (4 males and 6 females) with mean age of 6.78±3.14 months, mean weight of 8.11±1.71 kg, and mean left ventricular ejection fraction (LVEF) was 32.6±10.34%. Tachycardiomyopathy has been excluded and all patients were refractory to the drugs. All of these 10 patients underwent RFCA.

Results:

All the accessory pathways in these patients were located on right free wall and the acute success rate was 100%. No complication associated with the procedure occurred. In one case preexcitation recurred and was ablated successfully during the second attempt. There were 3 patients with mild cardiac dysfunction (LVEF, 40≤LVEF<50%), 3 with moderate (30≤LVEF<40%), and 4 with severe cardiac dysfunction (LVEF<30%, the ages were 3, 6, 7, and 10 months, respectively). The time for LVEF normalization was 1 week, 1 to 3 months, and ≥3 months, respectively. In 3 of the 4 severe cardiac dysfunction patients, the LVEF normalized at 3, 6, and 12 months after ablation, the LVEF of the remaining case did not recover at 3 months and is still being followed.

Conclusions:

Ventricular preexcitation could lead to severe cardiac dysfunction during infancy. RFCA may be a safe and effective treatment option in right free wall accessory pathways, even in infants with cardiac dysfunction. Cases of more severe cardiac dysfunction might require a longer time for LVEF recovery after RFCA.
Preadmission Opioid Use and 1‐Year Mortality Following Incident Myocardial Infarction: A Danish Population‐Based Cohort Study (1997–2016)
Authors: Korsgaard Søren , Munch Troels , Horváth–Puhó Erzsébet , Adelborg Kasper , Christiansen Christian Fynbo , Pedersen Lars , Schmidt Morten , Sørensen Henrik Toft
Published: March 2023

Background

Opioid use has been linked to an increased risk of myocardial infarction and cardiovascular mortality, but the prognostic impact of opioid use before an incident myocardial infarction is largely unknown.

Methods and Results

We conducted a nationwide population‐based cohort study including all patients hospitalized for an incident myocardial infarction in Denmark (1997–2016). Based on their last redeemed opioid prescription before admission, patients were categorized as current users (0–30 days), recent users (31–365 days), former users (>365 days), and nonusers. One‐year all‐cause mortality was calculated using the Kaplan–Meier method. Hazard ratios (HRs) were computed using Cox proportional hazards regression analyses, adjusting for age, sex, comorbidity, any preceding surgery within 6 months before the myocardial infarction admission, and medication use before the myocardial infarction admission. We identified 162 861 patients with an incident myocardial infarction. Of these, 8% were current opioid users, 10% were recent opioid users, 24% were former opioid users, and 58% were nonusers of opioids. One‐year mortality was highest among current users (42.5% [95% CI, 41.7%–43.3%]) and lowest among nonusers (20.5% [95% CI, 20.2%–20.7%]). Compared with nonusers, current users had an elevated 1‐year all‐cause mortality risk (adjusted HR, 1.26 [95% CI, 1.22–1.30]). Following adjustment, neither recent users nor former users of opioids were at elevated risk.

Conclusions

Preadmission opioid use was associated with an increased 1‐year all‐cause mortality risk following an incident myocardial infarction. Opioid users thus represent a high‐risk subgroup of patients with myocardial infarction.
Association Between Risk Factors in Childhood and Sex Differences in Prevalence of Carotid Artery Plaques and Intima‐Media Thickness in Mid‐Adulthood in the Childhood Determinants of Adult Health Study
Authors: Shah Mohammad , Buscot Marie‐Jeanne , Tian Jing , Phan Hoang T. , Fraser Brooklyn J. , Marwick Thomas H. , Dwyer Terence , Venn Alison , Gall Seana
Published: March 2023

Background

The origins of sex differences in cardiovascular diseases are not well understood. We examined the contribution of childhood risk factors to sex differences in adult carotid artery plaques and intima‐media thickness (carotid IMT).

Methods and Results

Children in the 1985 Australian Schools Health and Fitness Survey were followed up when they were aged 36 to 49 years (2014–19, n=1085–1281). Log binomial and linear regression examined sex differences in adult carotid plaques (n=1089) or carotid IMT (n=1283). Childhood sociodemographic, psychosocial, and biomedical risk factors that might contribute to sex differences in carotid IMT/plaques were examined using purposeful model building with additional adjustment for equivalent adult risk factors in sensitivity analyses. Women less often had carotid plaques (10%) than men (17%). The sex difference in the prevalence of plaques (relative risk [RR] unadjusted 0.59 [95% CI, 0.43 to 0.80]) was reduced by adjustment for childhood school achievement and systolic blood pressure (RR adjusted 0.65 [95% CI, 0.47 to 0.90]). Additional adjustment for adult education and systolic blood pressure further reduced sex difference (RR adjusted 0.72 [95% CI, 0.49 to 1.06]). Women (mean±SD 0.61±0.07) had thinner carotid IMT than men (mean±SD 0.66±0.09). The sex difference in carotid IMT (β unadjusted −0.051 [95% CI, −0.061 to −0.042]) reduced with adjustment for childhood waist circumference and systolic blood pressure (β adjusted −0.047 [95% CI, −0.057 to −0.037]) and further reduced with adjustment for adult waist circumference and systolic blood pressure (β adjusted −0.034 [95% CI, −0.048 to −0.019]).

Conclusions

Some childhood factors contributed to adult sex differences in plaques and carotid IMT. Prevention strategies across the life course are important to reduce adult sex differences in cardiovascular diseases.