bluuebunny/crossref_metadata_2025_split huggingface dataset:
3-Hydroxykynurenine Regulates Lipopolysaccharide-Stimulated IL-6 Production and Protects against Endotoxic Shock in Mice
Authors: Hoshi Masato , Kubo Hisako , Ando Tatsuya , Tashita Chieko , Nakamoto Kentaro , Yamamoto Yasuko , Tezuka Hiroyuki , Saito Kuniaki 
Published: June 2021

Abstract
Despite advances in our understanding of endotoxic shock, novel therapeutic interventions that can reduce the burden of sepsis remain elusive. Current treatment options are limited, and it is only through refinements in the ways that we deliver supportive care that mortality has fallen over the years. In this study, the role of kynurenine 3-monooxygenase (KMO) in immune regulation was examined in LPS-induced endotoxemia using KMO−/− and KMO+/+ mice treated with the KMO inhibitor Ro61-8048. We showed that LPS-induced or cecal ligation and puncture–induced mortality and hepatic IL-6 production increased in the absence of KMO, possibly involving increased activating transcription factor 4 (ATF4) signaling in hepatic macrophages. Moreover, treatment of septic mice with 3-hydroxykynurenine reduced mortality rates and inflammatory responses regardless of the presence or absence of KMO. According to our results, the administration of 3-hydroxykynurenine as part of the treatment approach for sepsis or as an adjuvant therapy might reduce the overproduction of IL-6, which is responsible for severe endotoxemia, and ultimately improve the survival rates of patients with sepsis.
SARS-CoV-2 Proteins Induce Endotoxin Tolerance Hallmarks: A Demonstration in Patients with COVID-19
Authors: Avendaño-Ortiz José , Lozano-Rodríguez Roberto , Martín-Quirós Alejandro , Maroun-Eid Charbel , Terrón-Arcos Verónica , Montalbán-Hernández Karla , Valentín Jaime , Muñoz del Val Elena , García-Garrido Miguel A , del Balzo-Castillo Álvaro , Casalvilla-Dueñas José Carlos , Peinado María , Gómez Laura , Herrero-Benito Carmen , Rubio Carolina , Cubillos-Zapata Carolina , Pascual-Iglesias Alejandro , del Fresno Carlos , Aguirre Luis A , López-Collazo Eduardo 
Published: June 2021

Abstract
According to a large number of reported cohorts, sepsis has been observed in nearly all deceased patients with COVID-19. We and others have described sepsis, among other pathologies, to be an endotoxin tolerance (ET)–related disease. In this study, we demonstrate that the culture of human blood cells from healthy volunteers in the presence of SARS-CoV-2 proteins induced ET hallmarks, including impairment of proinflammatory cytokine production, low MHC class II (HLA-DR) expression, poor T cell proliferation, and enhancing of both phagocytosis and tissue remodeling. Moreover, we report the presence of SARS-CoV-2 blood circulating proteins in patients with COVID-19 and how these levels correlate with an ET status, the viral RNA presence of SARS-CoV-2 in plasma, as well as with an increase in the proportion of patients with secondary infections.
Genetic, Immunological, and Clinical Features of 32 Patients with Autosomal Recessive STAT1 Deficiency
Authors: Le Voyer Tom , Sakata Sonoko , Tsumura Miyuki , Khan Taushif , Esteve-Sole Ana , Al-Saud Bandar K , Gungor Hatice Eke , Taur Prasad , Jeanne-Julien Valentine , Christiansen Mette , Köhler Lisa-Maria , ElGhazali Gehad Eltayeb , Rosain Jérémie , Nishimura Shiho , Sakura Fumiaki , Bouaziz Matthieu , Oleaga-Quintas Carmen , Nieto-Patlán Alejandro , Deyà-Martinez Àngela , Altuner Torun Yasemin , Neehus Anna-Lena , Roynard Manon , Bozdemir Sefika Elmas , Al Kaabi Nawal , Al Hassani Moza , Mersiyanova Irina , Rozenberg Flore , Speckmann Carsten , Hainmann Ina , Hauck Fabian , Alzahrani Mohammed Hamdan , Alhajjar Sami Hussain , Al-Muhsen Saleh , Cole Theresa , Fuleihan Ramsay , Arkwright Peter D , Badolato Raffaele , Alsina Laia , Abel Laurent , Desai Mukesh , Al-Mousa Hamoud , Shcherbina Anna , Marr Nico , Boisson-Dupuis Stéphanie , Casanova Jean-Laurent , Okada Satoshi , Bustamante Jacinta 
Published: June 2021

Abstract
Autosomal recessive (AR) STAT1 deficiency is a severe inborn error of immunity disrupting cellular responses to type I, II, and III IFNs, and IL-27, and conferring a predisposition to both viral and mycobacterial infections. We report the genetic, immunological, and clinical features of an international cohort of 32 patients from 20 kindreds: 24 patients with complete deficiency, and 8 patients with partial deficiency. Twenty-four patients suffered from mycobacterial disease (bacillus Calmette–Guérin = 13, environmental mycobacteria = 10, or both in 1 patient). Fifty-four severe viral episodes occurred in sixteen patients, mainly caused by Herpesviridae viruses. Attenuated live measles, mumps, and rubella and/or varicella zoster virus vaccines triggered severe reactions in the five patients with complete deficiency who were vaccinated. Seven patients developed features of hemophagocytic syndrome. Twenty-one patients died, and death was almost twice as likely in patients with complete STAT1 deficiency than in those with partial STAT1 deficiency. All but one of the eight survivors with AR complete deficiency underwent hematopoietic stem cell transplantation. Overall survival after hematopoietic stem cell transplantation was 64%. A diagnosis of AR STAT1 deficiency should be considered in children with mycobacterial and/or viral infectious diseases. It is important to distinguish between complete and partial forms of AR STAT1 deficiency, as their clinical outcome and management differ significantly.
Jojoba oil-based microemulsion for transdermal drug delivery
Authors: Assaf Shereen Mashhour , Maaroof Khalid Taieb , Altaani Bashar Mohammad , Ghareeb Mowafaq Mohammed , Abu Alhayyal Amane Awad 
Published: June 2021

Background and purpose:
Microemulsions are gaining an increased interest in transdermal drug delivery. Microemulsions are stable, easy to prepare, and provide high solubilizing capacity for various drugs. The aim of this work was to prepare microemulsions from jojoba oil for transdermal delivery of ketorolac and lidocaine HCl with improved permeation.

Experimental approach:
Microemulsions based on jojoba oil as the oil phase were formulated for transdermal delivery of lidocaine HCl and ketorolac. Brij 97 was selected as surfactant and hexanol as cosurfactant. Pseudoternary phase diagrams were constructed. Selected microemulsion formulations were characterized for their physical properties and in vitro drug permeation.

Findings/Results:
Water-in-oil microemulsions were obtained with droplet sizes not more than 220 nm. The viscosity of the microemulsions was linked to the viscosity of the surfactant used. Improved drug permeation rates were observed for both model drugs. The significant increase in permeation rate in presence of hexanol was due to its impact on skin integrity as indicated by the histopathological study. Drug permeation enhancements were caused by the surfactant, the cosurfactant used, jojoba oil itself, and the microemulsion formulation. Higher surfactant content showed lower lag times and better flux.

Conclusion and implications:
Jojoba oil microemulsions are considered promising vehicles for transdermal delivery of ketorolac and lidocaine HCl with improved drug permeation. Jojoba oil-based microemulsion would present a safe and effective means for delivering drugs through the skin.
Cost-utility and budget impact analysis of adding-on apremilast to biologic therapy in the treatment of moderate to severe plaque psoriasis, an Iranian payer perspective
Authors: Zargaran Marzieh , Soleymani Fatemeh , Nasrollahi Saman Ahmad , Seyedifar Meysam , Rahaghi Mohammad Mehdi Ashrafian 
Published: June 2021

Background and purpose:
Plaque psoriasis is a chronic inflammatory disease with skin manifestations that affect the patients’ quality of life negatively. The prevalence of psoriasis is approximately 2-3% worldwide and appears to be still on the increase. Due to the stigma problems, psoriasis has a significant effect on one’s life that is often overlooked. The current study aimed to conduct the cost-utility evaluation and budget impact analysis of adding-on apremilast ahead of biologic therapy in the treatment of moderate to severe plaque psoriasis. The psoriatic patients who did not undergo the conventional systemic therapy were eligible to enter the defined sequences.

Experimental approach:
An excel-based Markov model with 40 cycles of 3 months, each of which was adopted to compare the outcomes of each exclusively administered sequence in the treatment of moderate to severe plaque psoriasis. Two exclusive therapeutic sequences were considered. In the first sequence, apremilast was followed by biologics and in the second one, biologics were administered initially without apremilast. The results were extrapolated up to 10 years. The designed Markov model was also used in budget impact analysis. The cost-saving potential of the new treatment was accounted for the next 5 years.

Findings/Results:
Incremental cost and incremental effect were reported in the base case scenario. Using the sequence consisting apremilast provided an additional 0.10 quality-adjusted life years and decreased total costs by about 11,100 USD per patient. These results were in line with the findings from sensitivity analysis. The cost-saving over 5 years is estimated to be around 30 million dollars for the Iran market following the use of the new treatment.

Conclusion and implications:
In the treatment of moderate to severe plaque psoriasis, apremilast supplementation prior to biological treatments is more cost-effective than biological treatment alone.
Thymoquinone abrogates methamphetamine-induced striatal neurotoxicity and hyperlocomotor activity in mice
Authors: Roohbakhsh Ali , Moshiri Mohammad , Salehi Kakhki Azam , Iranshahy Milad , Amin Fatemeh , Etemad Leila 
Published: June 2021

Background and purpose:
Methamphetamine (METH) abuse has devastating consequences on the nervous system. There are limited therapy choices in METH abuse with reduced effectiveness and elevated recurrence rates. Thymoquinone (TQ), the most bioactive constituent of Nigella sativa seeds exerts neuroprotective effects mainly via antioxidant properties. This study aimed to evaluate the effect of TQ against METH-induced striatal neurotoxicity and hyperlocomotor activity in mice.

Experimental approach:
Our groups of animals received METH (10 mg/kg) four times a day with 2 h intervals. Normal saline or TQ (5, 10, or 20 mg/kg) was injected intraperitoneally 30 min before METH administration. Control and sham groups received vehicle or TQ, respectively. The rectal temperature and behavioral tests including the open field for locomotor activity and rotarod for motor coordination were evaluated. The level of superoxide dismutase (SOD), as well as pathological changes, were also assessed in the striatum region.

Findings/Results:
No significant differences in rectal temperatures were observed among treated groups. Administration of METH increased locomotor activity and did not change motor coordination. TQ co-administration with METH significantly reduced the central and total locomotion and the mean latency to fall off the rotarod in a dose-dependent manner compared with the METH group. TQ also alleviated the METH-induced decrease in the activity of SOD.TQ, especially at the high dose, reduced the METH-induced reactive gliosis level.

Conclusion and implications:
In conclusion, TQ prevents the enhanced locomotor activity, antioxidant impairment, and morphological striatal damage caused by METH in mice. TQ may be a potential candidate for the treatment of specific METH-induced brain disorders or neurological diseases.
Protective effect of gallic acid on nicotine-induced testicular toxicity in mice
Authors: Jalili Cyrus , Korani Mastaneh , Pazhouhi Mona , Ghanbari Ali , Zhaleh Mohsen , Davoudi Samira , Rashidi Iraj 
Published: June 2021

Background and purpose:
Nicotine is an alkaloid found in many nutrients and tobacco that can cause infertility in men. Gallic acid is a powerful antioxidant that possesses antimutagenic and anticancer activities. This study aimed to determine the potential protective effect of gallic acid against nicotine-induced testicular toxicity in male mice.

Experimental approach:
In this in vivo study, forty-eight mice were equally divided into eight groups intraperitoneally receiving normal saline (control), nicotine (0.6 mg/kg), gallic acid (5, 10, and 15 mg/kg), and gallic acid (5, 10, and 15 mg/kg) plus nicotine. Nicotine was injected intraperitoneally for 14 days and gallic acid was administered concomitantly with nicotine and continued for 7 days later. Then, body and testicular weights, the sperm parameters (viability, number, motility, and morphology of sperm), and testicular histology were evaluated. Also, serum levels of nitric oxide, total antioxidant, superoxide dismutase, malondialdehyde, and testosterone were measured.

Findings/Results:
The results showed that the administration of nicotine significantly reduced testis and body weight, sperm count, viability, normal morphology and motility, seminiferous tubules diameter, testosterone levels, serum levels of total antioxidants, and superoxide dismutase compared to the control group (P < 0.05). It also significantly increased the level of nitric oxide and malondialdehyde (P < 0.05). Increasing the dose of gallic acid along with nicotine significantly increased body weight, sperm count, viability, normal morphology and motility, the diameter of seminiferous, testosterone concentration, total antioxidant levels (P < 0.05). This combination also significantly decreased malondialdehyde and nitric oxide levels compared to the nicotine-receiving group (P < 0.05).

Conclusion and implications:
Gallic acid had a protective effect on nicotine-induced testicular toxicity in mice. It can neutralize the harmful effect of nicotine on male fertility in smokers.
Integrin α6 β4 on Circulating Tumor Cells of Metastatic Breast Cancer Patients
Authors: Sharifi Mehran , Zarrin Bahareh , Bahri Najafi Majed , Hakimian Mohamad Reza , Hosseini Nastaran , Talebi Kasra , Javanmard Shaghayegh Haghjooy 
Published: June 2021

Background:
The detection of circulating tumor cells (CTCs) is prognostic during the disease in women with metastatic breast cancer. Integrins are key role players in nearly every step of cancer progression. In this study, we aimed to analyze integrin alpha6beta4 expression on CTCs isolated from blood samples of patients with advanced breast cancer.

Materials and Methods:
In this single-center study, peripheral blood samples from 23 breast cancer patients were obtained and analyzed for the presence of CTCs by EasySep™ Direct Human CTC Enrichment Kit combined with subsequent immunocytochemical staining of anti-cytokeratin and anti-epithelial cell adhesion molecules, and β4 integrin on CTCs. Data were correlated with clinicopathological parameters.

Results:
CTCs were detected in 100% of the patients. The ratio of integrin β4+ CTC was 61% ± 8% of total CTCs. No significant correlation between histopathological parameters and CTC detection was found.

Conclusion:
Our results demonstrated the importance of α6 β4 integrin expression on CTCs in distant metastasis.
Association between Behavioral Flexibility and Psychological Distress in Patients with Cardiovascular Disease
Authors: Habibovic Mirela , Widdershoven Jos , Wetzels Mart , Piera-Jimenez Jordi , Kop Willem J. 
Published: June 2021

Objective:
Being able to adapt to a changing environment has been associated with better mental and physical health. This adaptivity can be measured by behavioral flexibility assessment tools. However, the mental health consequences of behavioral flexibility have not been examined in patients with cardiovascular disease (CVD). The current study aims to examine if behavioral flexibility is associated with depression and anxiety in patients with CVD.

Methods:
A total of n = 387 patients with stable CVD were recruited as a part of the Do CHANGE study. At baseline, 3, and 6 months, data were collected. Depression (Patient Health Questionnaire-9) and anxiety (Generalized Anxiety Disorder Scale-7) were assessed at all time points.

Results:
The mean age of the sample was 61.9 ± 10.23 years, with 274 (71%) being male. An inverse association between behavioral flexibility and depression at baseline, 3, and 6 months was observed. The associations remained significant after adjusting for relevant demographic and medical variables and baseline depression. No longitudinal association between behavioral flexibility and anxiety was found in the multivariate models.

Conclusions:
Behavioral flexibility is associated with depression in cardiac patients. Future studies should focus on examining the pathways of this association and offering patients with low flexibility levels additional care if needed.
Hypnotic Communication in Interventional Electrophysiology Procedures in the COVID-19 Period
Authors: Maines Massimiliano , Peruzza Francesco , Angheben Carlo , Moggio Paolo , Catanzariti Domenico , Greco Maurizio Del 
Published: June 2021

Background:
Hypnotic communication is a validated technique for reducing procedural anxiety and pain. The aim of our work was to evaluate the additional utility of hypnotic communication during catheter ablation procedures in the COVID-19 period.

Materials and Methods:
Sixteen consecutive patients undergoing electrophysiological study and catheter ablation underwent: 8 to standard sedation procedure (Group B) and 8 to this with the addition of hypnotic communication (Group A). In these two groups, we measured and compared preprocedure and intraprocedure anxiety, compliance to the procedure, perceived pain, use of drugs, the procedural time perceived by the patient compared to real time in minutes, and radiological exposure, using validated scales.

Results:
Hypnotic communication resulted in a significant reduction in anxiety during the procedure (Group A: 1.1 ± 0.6 vs. Group B: 3.4 ± 2; P = 0.003); better procedural compliance (Group A: 4.8 ± 0.5 vs. Group B: 3.7 ± 0.8; P = 0.002) and showed a trend toward a reduction in procedural pain (Group A: 2.4 ± 2 vs. Group B: 4.3 ± 1.8; P = 0.08) compared to standard sedation. Midazolam was not used in Group A, while an average of 3 ± 1.3 mg was used in Group B. The use of local anesthetic and Fentanest was comparable. The real procedural durations (Group A: 167.5 ± 30.1 vs. Group B: 150 ± 27.8 min; P = not significant) and perceived (Group A: 78.8 ± 15.5 vs. Group B: 86.3 ± 29.9 min; P = not significant) and the difference between these was also comparable. The radiological exposure was 74.4 ± 65.5 s in Group A and 118 ± 119 s in Group B (P = not significant). There were no complications in the two groups.

Conclusions:
Hypnotic communication as an additional strategy during electrophysiological interventional procedures has made possible to eliminate the use of midazolam and reduce anxiety during the procedure, but above all, it has improved the patient's compliance with the procedure compared to traditional sedation approach.
Psychological Well-being in Adults with Congenital Heart Disease
Authors: Andonian Caroline , Freilinger Sebastian , Kaemmerer Harald , Beckmann Jurgen 
Published: June 2021

Background:
Due to advances in medical care and treatment of congenital heart disease (CHD), the number of adults with CHD (ACHD) is constantly growing. The psychological situation of ACHD has recently received increasing attention. There is evidence that adaptation to CHD may be affected by psychological factors, especially in how patients integrate their illness into their identities. The present study examined illness identity as a mediator of the association between a self-rated health and emotional distress among ACHD.

Materials and Methods:
The study used a cross-sectional design. A sample of 229 ACHD (38 ± 12.5 [18–73] years; 45% female) provided background data and completed three questionnaires on self-rated health (EuroQol group's visual analog scale), illness identity (Illness Identity Questionnaire), and emotional distress (Hospital Anxiety and Depression Scale) at the German Heart Center Munich. Serial multiple mediator models were tested using PROCESS macro for SPSS.

Results:
Perceived health had a direct and indirect effect on emotional distress which was mediated by illness identity (P < 0.05). Compared to all other dimensions of illness identity, engulfment fully mediated the relationship between self-rated health and emotional distress, when adjusted for sociodemographic and clinical confounders. The model explained 42% of variance in total emotional distress (R2 = 0.416). The extent of emotional distress did not differ as a function of CHD complexity.

Conclusions:
Illness identity emerged as a strong mediating factor between a patient's self-rated health and psychological outcomes. More importance needs to be directed toward assessing a patient's health perception and psychological state, independently of cardiac severity. Based on present findings, targeted psychocardiological interventions should include psychoeducational components and emotion-focused strategies.
Traumatic Dental Injuries in Schoolchildren and Adolescents of Rural and Urban Areas of Aligarh, India
Authors: Khan Mohammad Kamran , Jindal Mahendra Kumar , Khan Saima Yunus , Unnikrishnan Arjun 
Published: June 2021

Introduction:
Traumatic dental injury is becoming a public health problem and burden worldwide due to its higher prevalence, costly treatment procedures, and its sequelae.

Materials and Methods:
A cross-sectional epidemiological study was conducted among 1000 children aged 12 and 15 years of ten randomly selected schools of rural and urban areas of Aligarh, Uttar Pradesh, India, to evaluate the prevalence of traumatic dental injuries. The relevant findings of the study were collected by self-prepared pro forma and dental examination. Ellis and Davey's classification was used to record dental trauma in permanent teeth. SPSS 20 software was used to analyze the collected data from the study.

Results:
The overall prevalence of traumatic dental injuries in the present study was found to be as 13.5%. Children of 12 years of age (17.6%) were more affected with traumatic dental injuries as compared to adolescents of 15 years of age (12.8%). Schoolchildren of rural areas (15.2%) were traumatized greater than urban areas (11.8%) (P > 0.05).

Conclusions:
Dental trauma among schoolchildren was relatively higher in Aligarh and among which children of 12 years of age of rural areas were more traumatized with dental trauma than urban areas. Hence, preventive strategies must be implemented among children, adolescents, parents, and teachers to reduce the occurrence of such deleterious injuries.