bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of Patients With Severe Obstructive Sleep Apnea Who Maintain Slow-Wave Sleep
Authors: Kim Min Woo , Choi Myoung Su
Published: June 2023

Background and Objectives Obstructive sleep apnea (OSA) is a complex sleep-related respiratory disorder with various pathophysiology and clinical manifestations. Diagnosis and treatment considering only the number of respiratory events, such as sleep duration, may have limitations. The purpose of this study is to analyze the clinical and polysomnography (PSG) characteristics of patients with severe OSA in whom slow wave sleep (SWS) was well-maintained.Subjects and Method This study retrospectively analyzed 203 patients who underwent PSG due to suspected OSA. Severe OSA patients were classified into a SWS maintained group (SWS≥15%) and a SWS reduced group (SWS<15%), and their clinical records, PSG results, and heart rate variability (HRV) were compared.Results The SWS maintained group (n=27), compared to the SWS reduced group (n=58), had a significantly longer total sleep time (p=0.027) and lower wake after sleep onset (p=0.001), rapid eye movoement (REM) latency (p=0.007), non-supine apnea-hypopnea index (AHI, p=0.006), non-REM AHI (p<0.001), arousal index (p<0.001) and Epworth Sleepiness Scale (p=0.048). In addition, the SWS maintained group had a significantly low value in very low frequency in HRV than that of the SWS reduced group (p=0.046).Conclusion The SWS maintained group in the severe OSA showed better PSG and HRV results and reduced daytime sleepiness than those of the SWS reduced group.
Uzaktan Çalışmanın Bir Türü Olarak Tele Çalışmada İşçinin Dinlenme Hakkı
Authors: ERKANLI BAŞBÜYÜK Betül
Published: June 2023

Çalışma hayatında dijitalleşme, çalışanların çalışma sürelerini düzenleyebilmeleri ve iş-aile yaşamı arasındaki dengeyi sağlayabilmeleri açısından olumlu etkide bulunmakla birlikte, çeşitli potansiyel riskleri de içermektedir. Pek çok alanda işin zaman ve mekandan bağımsız olarak teknolojik iletişim araçları ile ifa edilebilmesinden doğan önemli sorunlardan biri, iş sınırlarının çizilmesinde ortaya çıkan güçlüktür. Uzaktan çalışma modeli, çalışanlara çalışma sürelerini esnek olarak belirleme imkanı tanırken, çalışma ve dinlenme sürelerinin iç içe geçmesine, işçinin dinlenme hakkından yararlanamamasına sebep olabilmektedir. Uzaktan çalışan işçinin kaynağını Anayasadan alan dinlenme hakkının güvence altına alınması, beden ve ruh sağlığı ile özel yaşamının korunması açısından önem taşımaktadır. Çalışmamızda genel olarak uzaktan çalışan işçinin dinlenme hakkı, konu ile ilgili uluslararası alanda ve Alman hukukunda mevcut bulunan düzenleme ve görüşlere de yer verilerek incelenmeye ve dinlenme hakkına ilişkin ortaya çıkan sorunlar tespit edilmeye çalışılacaktır.
Problems in the diagnosis of endogenous hypercorticism (a clinical case)
Authors:   S. I. Sergeev Regional Clinical Hospital No. 1 of the Ministry of Health of the Khabarovsk Krai, Khabarovsk, Russia, Ryabova T.I. , Yefimova E.V. ,   S. I. Sergeev Regional Clinical Hospital No. 1 of the Ministry of Health of the Khabarovsk Krai, Denisenko S.S. ,   S. I. Sergeev Regional Clinical Hospital No. 1 of the Ministry of Health of the Khabarovsk Krai, Khabarovsk, Russia
Published: June 2023

The article presents a clinical case of endogenous hypercortisolism, which was diagnosed on the basis of clinical observation and examination in a multidisciplinary hospital. The presumptive diagnosis was confirmed in the conditions of the National Research Center for Endocrinology of the Russian Ministry of Health
Antalya İli Finike İlçesinde Marul Üretim Alanlarında Marul Mozaik Virüsü'nün Belirlenmesi
Authors: ÇULAL KILIÇ Handan , ERDAŞ Emine
Published: June 2023

Bu çalışmada, Antalya ili Finike ilçesi marul üretim alanlarında Marul mozaik virüsü (Lettuce mosaic virüs: LMV)’nün belirlenmesi amacıyla yürütülmüştür. Virüsün tanılama çalışmalarında DAS-ELISA (Double Antibody Sandwich Enzyme Linked Immunosorbent Assay) ve IC-RT-PCR (Immunocapture Ters Transkripsiyon Polimeraz Zincir Reaksiyonu) yöntemleri kullanılmıştır. Bu amaçla araştırma alanından 92 marul örneği toplanmıştır. Örnekler LMV etmenine spesifik antibadiler kullanılarak DAS-ELISA testine tabi tutulmuştur. DAS-ELISA yöntemine göre; 5 örnek LMV ile enfekteli bulunmuştur. DAS-ELISA testinde pozitif çıkan 5 örnek IC-RT-PCR çalışmalarında kullanılmıştır. IC-RT-PCR çalışmalarında, LMV’ye özgü primer çiftleri (1196, 1087) kullanılmış ve LMV’nin 800 bp’lik bir kısmı çoğaltılarak agaroz jel elektroforezinde beklenen seviyede bant elde edilmiştir. Bu çalışma ile Antalya ili Finike ilçesinde LMV’nin varlığı ilk kez ortaya konulmuştur.
In Vitro Evaluation of Biofilm Forming Capacity and Antifungal Resistance of Yeast Isolated from Individuals Aged 18-25 Years
Authors: ÖZCAN ATEŞ Gülçin , OTKUN Müşerref
Published: June 2023

Microbiota studies are an increasingly important issue today. In the literature, there are limited studies on the antifungal resistance and biofilm formation capacity of yeasts isolated from the mouths of young individuals. For this reason, our study was carried out with 133 yeast isolates isolated from the mouths of 17 young individuals between the ages of 18-25 in 2018-2020. When the biofilm-forming capacities of 133 isolates were examined, it was determined that 99.25% were biofilm producers by tissue culture plate method and 66.92% by tube method. One hundred thirty-three yeast isolates and seven reference strains were first evaluated against fluconazole antifungal by agar disc diffusion method. The isolates were found to be susceptible to fluconazole. According to this result, 20 isolates with strong biofilm-forming capacity were selected from 133 yeast isolates. Antifungal resistance was evaluated with fluconazole, itraconazole, clotrimazole, amphotericin B and nystatin gradient test strips. It was determined that 20 isolates were resistant to amphotericin B, and 18 were resistant to nystatin antifungal. It was determined that the sensitivity of itraconazole to 14 isolates and clotrimazole to 3 isolates was dose-dependent. As a result, azole group antifungals can be used mainly in treating oral yeast infections.
HSV-2 Associated Meningitis Case: A Challenging Diagnosis in An Immunocompetent Woman
Authors: Baddal Buket , Bostancı Aysegul , Süer Kaya
Published: June 2023

Herpes simplex virus type-2 (HSV-2) associated aseptic meningitis is rarely seen in healthy individuals. Herein, we report a rare case of meningitis, associated with HSV-2, without the presence of genital lesions. A healthy, 40-year-old female was presented to the emergency service with unremitting headache, vomiting and nausea. Her cerebrospinal fluid (CSF) revealed elevated protein level of 308,2 mg/dL, high leukocyte cell count of 1,118,000 cells/µL with 98% lymphocytes and 2% polymorphonuclear neutrophils (PMNs). The bacterial culture and gram staining of CSF were negative. Real-time quantitative polymerase chain reaction (RT-qPCR) CSF analysis indicated the presence of HSV-2. The cranial MRI revealed meningeal contrast enhancement. The patient was administered acyclovir for 10 days during her hospital stay and she was discharged without any neurological sequela. The patient has a history of herpes infection. This case report shows that HSV-2 meningitis can occur in immunocompetent individuals via re-activation and should always be considered by the clinicians even in the absence of genital lesions.
Acute Emphysematous Cholecystitis Rarely Accompanied by Necrotized Cystic Duct: A Case Report
Authors: Sanalp Menekşe Tuğba , Menekşe Burak , Kişi Ömer
Published: June 2023

Emphysematous cholecystitis is an acute abdominal disease characterized by gas in the gallbladder lumen and wall. Emphysematous cholecystitis and related cystic duct necrosis are rare, but if not noticed, they can cause a mortal picture up to perforation and sepsis. In this article, we present a case of emphysematous cholecystitis involving gangrenous gallbladder and necrotizing cystic duct, which developed suddenly in an immunosuppressive patient who presented to the emergency department with abdominal pain and was treated with rapid emergency successful surgery.
Risk Analysis, Assessment and Management for Local Fishing Ports in North-Eastern Mediterranean, Türkiye
Authors: AKAR Özkan , DEMİRCİ Aydın
Published: June 2023

This study aimed to analyze the risks of activities in fishing ports in the province of Hatay. Due to these activities, the fishing port is under health, good, labor, and environmental risks. In this study, risks were identified and evaluated at the four fishing ports. For this purpose; (1) A preliminary survey was conducted with stakeholders on the current situation and the functions of the fishing ports (2) brainstorm meetings were organized in three sessions in one day- three sections with 12 invited participants throughout the year 2016, (3) as a result of these meetings, risk assessments were carried out in terms of the risks identified, loss of health, good, labor, and environment for each fishing port. The risk matrices were presented graphically in terms of the risk effect and the frequency value, and risk tables were created for each risk. Approximately 20 (17-22) risks were identified for each fishing port. The risks identified for the fishing port were found similar these were different impact levels and frequency values. These differences were generally related to the location. The differences in the settlement structure of the fishing port caused advantages and disadvantages to risks of the fishing port risk. When risks were grouped and classified as administrative, structural, pollution, and security, the lack of management and supervision was striking. Risk analysis outputs were evaluated by using the “L type matrix” method with issuing by numerical and statistical comparisons for different fishing ports. The reason for the risks was due to incompatible legal regulations and control mechanisms rather than a benefit for fishing ports than regional and personal shortfalls with the current situation and expected. Finally, these assessments were the result of a regional study, but they were important both nationally and internationally fishing port risk lack of management. This article attempts to provide a range of knowledge, which is compulsory for managers.
Evaluation of bacteriophage therapy of Aeromonas hydrophila infection in a freshwater fish, Pangasius buchanani
Authors: Kumari Ritu , Yadav Ragini , Kumar Deepak , Chaube Radha , Nath Gopal
Published: June 2023

Introduction

The present study aimed to optimize the doses and schedule of specific bacteriophage cocktails in freshwater fish infections as prophylactic and therapeutic measures.

Methods

The three most active phages against Aeromonas hydrophila (A. hydrophila) (φAHBHU12, φAHBHU16, and φAHBHU19) were characterized phenotypically and genotypically. Intramuscular and water immersion routes were used to calculate the absolute lethal dose of A. hydrophila in Pangasius buchanani. Phage therapy was given simultaneously and after 6, 12, and 24 h of bacterial challenge through intramuscular and water immersion routes.

Results

The prophylactic and early phage administration could save the fish. Furthermore, the dose of intramuscular 1.0 × 104 plaque-forming unit (PFU)/fish and water immersion 1.0 × 106 PFU mL–1 of the phage cocktail was optimal.

Discussion

The efficacy of bacteriophage therapy as preventive or curative measures practical when administered simultaneously or early hours of A. hydrophila infection in aquaculture systems. Phage-based approaches may be used as an alternative to antibiotics in aquaculture to reduce antibiotic use as a part of the “One Health” approach.
Plasma polymerized nanoparticles are a safe platform for direct delivery of growth factor therapy to the injured heart
Authors: Clayton Zoë E. , Santos Miguel , Shah Haisam , Lu Juntang , Chen Siqi , Shi Han , Kanagalingam Shaan , Michael Praveesuda L. , Wise Steven G. , Chong James J. H.
Published: June 2023

Introduction: Heart failure due to myocardial infarction is a progressive and debilitating condition, affecting millions worldwide. Novel treatment strategies are desperately needed to minimise cardiomyocyte damage after myocardial infarction and to promote repair and regeneration of the injured heart muscle. Plasma polymerized nanoparticles (PPN) are a new class of nanocarriers which allow for a facile, one-step functionalization with molecular cargo.

Methods: Here, we conjugated platelet-derived growth factor AB (PDGF-AB) to PPN, engineering a stable nano-formulation, as demonstrated by optimal hydrodynamic parameters, including hydrodynamic size distribution, polydisperse index (PDI) and zeta potential, and further demonstrated safety and bioactivity in vitro and in vivo. We delivered PPN-PDGF-AB to human cardiac cells and directly to the injured rodent heart.

Results: We found no evidence of cytotoxicity after delivery of PPN or PPN-PDGFAB to cardiomyocytes in vitro, as determined through viability and mitochondrial membrane potential assays. We then measured contractile amplitude of human stem cell derived cardiomyocytes and found no detrimental effect of PPN on cardiomyocyte contractility. We also confirmed that PDGF-AB remains functional when bound to PPN, with PDGF receptor alpha positive human coronary artery vascular smooth muscle cells and cardiac fibroblasts demonstrating migratory and phenotypic responses to PPN-PDGF-AB in the same manner as to unbound PDGF-AB. In our rodent model of PPN-PDGF-AB treatment after myocardial infarction, we found a modest improvement in cardiac function in PPN-PDGF-AB treated hearts compared to those treated with PPN, although this was not accompanied by changes in infarct scar size, scar composition, or border zone vessel density.

Discussion: These results demonstrate safety and feasibility of the PPN platform for delivery of therapeutics directly to the myocardium. Future work will optimize PPN-PDGF-AB formulations for systemic delivery, including effective dosage and timing to enhance efficacy and bioavailability, and ultimately improve the therapeutic benefits of PDGF-AB in the treatment of heart failure cause by myocardial infarction.
Determination of CAR T cell metabolism in an optimized protocol
Authors: Joaquina Sandy , Forcados Christopher , Caulier Benjamin , Inderberg Else Marit , Wälchli Sébastien
Published: June 2023

Adoptive transfer of T cells modified to express chimeric antigenic receptors (CAR) has emerged as a solution to cure refractory malignancies. However, although CAR T cell treatment of haematological cancers has now shown impressive improvement in outcome, solid tumours have been more challenging to control. The latter type is protected by a strong tumour microenvironment (TME) which might impact cellular therapeutic treatments. Indeed, the milieu around the tumour can become particularly inhibitory to T cells by directly affecting their metabolism. Consequently, the therapeutic cells become physically impeded before being able to attack the tumour. It is therefore extremely important to understand the mechanism behind this metabolic break in order to develop TME-resistant CAR T cells. Historically, the measurement of cellular metabolism has been performed at a low throughput which only permitted a limited number of measurements. However, this has been changed by the introduction of real-time technologies which have lately become more popular to study CAR T cell quality. Unfortunately, the published protocols lack uniformity and their interpretation become confusing. We herein tested the essential parameters to perform a metabolic study on CAR T cells and propose a check list of factors that should be set in order to draw sound conclusion.
3D geological modeling of deep fractured low porosity sandstone gas reservoir in the Kuqa Depression, Tarim Basin
Authors: Liu Zhaolong , Chen Dong , Gao Zhiyong , Wu Yongping , Zhang Yongzhong , Fan Kunyu , Chang Baohua , Zhou Peng , Huang Weigang , Hu Chunlei
Published: June 2023

The fractured reservoir is one of the significant petroleum reservoir types in China, representing over one-third of total reserves. The Kuqa Depression in the Tarim Basin is dominated by fractured low-porosity sandstone gas reservoirs with characteristic tight matrix, developed fractures, and edge and bottom water. However, the continued development of these reservoirs has led to various problems, including strong reservoir heterogeneity, low well control, complex gas-water relationships, and early water invasion. Addressing these issues requires a detailed understanding of the reservoir’s geological characteristics. One method for achieving a fine reservoir description is through the use of 3D geological modeling. This high-level, comprehensive characterization technique is widely used throughout the entire life cycle of oil and gas field development. A 3D geological model can accurately predict the actual underground reservoir characteristics and provide a geological basis for later numerical simulation work. Based on a study of the geological characteristics of the Kuqa Depression in the Tarim Basin, a 3D geological modeling technique was developed, which includes structural modeling, facies modeling, petrophysical modeling, and fracture modeling. This technology has been successfully applied to many deep gas reservoirs in the Kuqa Depression of the Tarim Basin, leading to enhanced gas recovery.
Emotional education for sustainable development: a curriculum analysis of teacher training in Portugal and Spain
Authors: Cristóvão Ana Maria , Valente Sabina , Rebelo Hugo , Ruivo Ana Francisca
Published: June 2023

The challenges before us indicate that the current model of societal development is creating problems for our planet, such as the climate crisis, the increase in inequalities, and the emergence of new phenomena of exclusion and social malaise. The 2030 Agenda for Sustainable Development presents 17 Sustainable Development Goals (SDGs) that define priorities for a more sustainable world. Education is one of the main ways to create a peaceful and sustainable world for the survival and prosperity of present and future generations. The literature highlights the importance of teachers’ socio-emotional skills and the promotion of socio-emotional skills in their students. The Emotional Education approach proposes a new pedagogical paradigm, in which the individual is encouraged to develop intra-and interpersonal skills, enabling them to deal creatively with their conflicts and those encountered in the environment, and increasing their self-confidence and emotional balance. These skills will contribute to the achievement of the objectives of the SDG. Based on these arguments, the study and systematization of social–emotional education is urgent. In this study, a documentary analysis was carried out of the programs of study offered as part of the degrees (undergraduate and master’s level) provided for the training of preschool and primary teachers in Portugal and Spain, with the aim of understanding whether these courses offer content relating to Emotional Education. Programs of study from 127 public and private higher education institutions across both countries were analyzed. The analysis revealed that in Portugal, despite an increase in interest in issues relating to emotional intelligence in schools, this interest is not yet reflected in the initial training of preschool and primary teachers (with only two universities, both private institutions, offering Emotional Education content). In Spain, there is already a considerable number of institutions (29) that offer Emotional Education, but this corresponds to only 30% of the universities listed. The results of this study indicate that there is still some distance to go to make Emotional Education an effective component of the curricula of future teachers and thus contribute to achievement of the SDGs.
Evidence of causality of low body mass index on risk of adolescent idiopathic scoliosis: a Mendelian randomization study
Authors: Otomo Nao , Khanshour Anas M. , Koido Masaru , Takeda Kazuki , Momozawa Yukihide , Kubo Michiaki , Kamatani Yoichiro , Herring John A. , Ogura Yoji , Takahashi Yohei , Minami Shohei , Uno Koki , Kawakami Noriaki , Ito Manabu , Sato Tatsuya , Watanabe Kei , Kaito Takashi , Yanagida Haruhisa , Taneichi Hiroshi , Harimaya Katsumi , Taniguchi Yuki , Shigematsu Hideki , Iida Takahiro , Demura Satoru , Sugawara Ryo , Fujita Nobuyuki , Yagi Mitsuru , Okada Eijiro , Hosogane Naobumi , Kono Katsuki , Nakamura Masaya , Chiba Kazuhiro , Kotani Toshiaki , Sakuma Tsuyoshi , Akazawa Tsutomu , Suzuki Teppei , Nishida Kotaro , Kakutani Kenichiro , Tsuji Taichi , Sudo Hideki , Iwata Akira , Inami Satoshi , Wise Carol A. , Kochi Yuta , Matsumoto Morio , Ikegawa Shiro , Watanabe Kota , Terao Chikashi
Published: June 2023

Introduction

Adolescent idiopathic scoliosis (AIS) is a disorder with a three-dimensional spinal deformity and is a common disease affecting 1-5% of adolescents. AIS is also known as a complex disease involved in environmental and genetic factors. A relation between AIS and body mass index (BMI) has been epidemiologically and genetically suggested. However, the causal relationship between AIS and BMI remains to be elucidated.

Material and methods

Mendelian randomization (MR) analysis was performed using summary statistics from genome-wide association studies (GWASs) of AIS (Japanese cohort, 5,327 cases, 73,884 controls; US cohort: 1,468 cases, 20,158 controls) and BMI (Biobank Japan: 173430 individual; meta-analysis of genetic investigation of anthropometric traits and UK Biobank: 806334 individuals; European Children cohort: 39620 individuals; Population Architecture using Genomics and Epidemiology: 49335 individuals). In MR analyses evaluating the effect of BMI on AIS, the association between BMI and AIS summary statistics was evaluated using the inverse-variance weighted (IVW) method, weighted median method, and Egger regression (MR-Egger) methods in Japanese.

Results

Significant causality of genetically decreased BMI on risk of AIS was estimated: IVW method (Estimate (beta) [SE] = -0.56 [0.16], p = 1.8 × 10-3), weighted median method (beta = -0.56 [0.18], p = 8.5 × 10-3) and MR-Egger method (beta = -1.50 [0.43], p = 4.7 × 10-3), respectively. Consistent results were also observed when using the US AIS summary statistic in three MR methods; however, no significant causality was observed when evaluating the effect of AIS on BMI.

Conclusions

Our Mendelian randomization analysis using large studies of AIS and GWAS for BMI summary statistics revealed that genetic variants contributing to low BMI have a causal effect on the onset of AIS. This result was consistent with those of epidemiological studies and would contribute to the early detection of AIS.
Total serum FGF-21 levels positively relate to visceral adiposity differently from its functional intact form
Authors: Crudele Lucilla , Garcia-Irigoyen Oihane , Cariello Marica , Piglionica Marilidia , Scialpi Natasha , Florio Marilina , Piazzolla Giuseppina , Suppressa Patrizia , Sabbà Carlo , Gadaleta Raffaella Maria , Moschetta Antonio
Published: June 2023

Objective

Increased Fibroblast Growth Factor-21 (FGF-21) circulating levels have been described in obesity. In this observational study, we analysed a group of subjects with metabolic disorders to unravel the putative link between visceral adiposity and FGF-21 serum levels.

Methods

Total and intact serum FGF-21 concentration was measured with an ELISA assay respectively in 51 and 46 subjects, comparing FGF-21 levels in dysmetabolic conditions. We also tested Spearman’s correlations between FGF-21 serum levels and biochemical and clinical metabolic parameters.

Results

FGF-21 was not significantly increased in high-risk conditions such as visceral obesity, Metabolic Syndrome, diabetes, smoking, and atherosclerosis. Waist Circumference (WC), but not BMI, positively correlated with total FGF-21 levels (r=0.31, p <0.05), while HDL-cholesterol (r=-0.29, p <0.05) and 25-OH Vitamin D (r=-0.32, p <0.05) showed a significant negative correlation with total FGF-21. ROC analysis of FGF-21 in prediction of increased WC, showed that patients with total FGF-21 level over cut-off value of 161.47 pg/mL presented with impaired FPG. Conversely, serum levels of the intact form of FGF-21 did not correlate with WC and other metabolic biomarkers.

Conclusion

Our newly calculated cut-off for total FGF-21 according to visceral adiposity identified subjects with fasting hyperglycemia. However, waist circumference correlates with total FGF-21 serum levels but does not correlate with intact FGF-21, suggesting that functional FGF-21 does not necessarily relate with obesity and metabolic features.
Azathioprine as an adjuvant therapy in severe Graves’ disease: a randomized controlled open-label clinical trial
Authors: Allam Magdy Mohamed , El-Zawawy Hanaa Tarek , Kader Okda Amr Abdel , Ali Alshaikh Ayoub , Ghazy Ramy Mohamed
Published: June 2023

Introduction

Azathioprine (AZA) interferes with the activation of T and B lymphocytes, which are the main cells involved in the pathogenesis of Graves’ disease (GD). The aim of this study was to investigate the effectiveness of AZA as an adjuvant therapy to antithyroid drugs (ATDs) for moderate and severe GD. In addition, we conducted an incremental cost-effectiveness analysis of AZA to determine its cost-effectiveness.

Methods

We conducted a randomized, open-label, and parallel-group clinical trial. We randomized untreated hyperthyroid patients with severe GD into three groups. All patients received 45-mg carbimazole (CM) as the starting dose and propranolol 40–120 mg daily. The first group (AZA1) received an additional 1 mg/kg/day AZA, the second group (AZA2) received an additional 2 mg/kg/day AZA, and the third group (control group) received only CM and propranolol. We measured thyroid-stimulating hormone (TSH) and TSH-receptor antibody (TRAb) levels at baseline and every 3 months, while free triiodothyronine (FT3) and free thyroxine (FT4) levels were measured at the time of diagnosis, 1 month after initiation of therapy, and every 3 months thereafter until 2 years after remission. Thyroid volume (TV) was assessed by ultrasound at baseline and 1 year after remission.

Results

A total of 270 patients were included in this trial. By the end of follow-up, there was higher remission rate in the AZA1 and AZA2 groups compared with controls (87.5% and 87.5% vs. 33.4%, p = 0.002). Throughout the course of follow-up, FT3, FT4, TSH, and TRAb were significantly different between the AZA groups and the control group, but there was no significant difference regarding TV. The decline in the concentrations of FT4, FT3, and TRAb was significantly faster in the AZA2 group than in the AZA1 group. The relapse rate during the 12-month follow-up was insignificantly higher in the control group than in either the AZA1 or AZA2 group (10, 4.4, and 4.4%, p = 0.05, respectively). The median relapse time was 18 months for the control group and 24 months for the AZA1 and AZA2 groups. The incremental cost-effectiveness ratio for the AZA group compared with the conventional group was 27,220.4 Egyptian pounds per remission reduction for patients using AZA as an adjuvant for ATDs.

Conclusion

AZA could be a novel, affordable, cost-effective, and safe drug offering hope for patients with GD to achieve early and long-lasting medical remission.

Trial registry

The trial is registered at the Pan African Clinical Trial Registry (Registration number: PACTR201912487382180).
Post hoc analysis of a randomized, double-blind, prospective trial evaluating a CXCR1/2 inhibitor in new-onset type 1 diabetes: endo-metabolic features at baseline identify a subgroup of responders
Authors: Sordi Valeria , Monti Paolo , Lampasona Vito , Melzi Raffaella , Pellegrini Silvia , Keymeulen Bart , Gillard Pieter , Linn Thomas , Bosi Emanuele , Rose Ludger , Pozzilli Paolo , Giorgino Francesco , Cossu Efisio , Piemonti Lorenzo
Published: June 2023

Aim

In a recent randomized, multicenter trial (NCT02814838) a short-term anti-inflammatory treatment with ladarixin (LDX; an inhibitor of the CXCR1/2 chemokine receptors) did not show benefit on preserving residual beta cell function in new-onset type 1 diabetes. We present a post hoc analysis of trial patients in the predefined subgroup analysis developed according to baseline daily insulin requirement (DIR) tertiles.

Method

A double-blind, randomized (2:1), placebo-controlled study was conducted in 45 men and 31 women (aged 18–46 years) within 100 days of the first insulin administration. Patients received LDX (400 mg twice daily) for three cycles of 14 days on/14 days off, or placebo. The primary endpoint was the area under the curve for C-peptide [AUC (0–120 min)] in response to a 2-h mixed meal tolerance test (MMTT) at week 13 ± 1. Seventy-five patients completed the week 13 MMTT and were divided into three groups according to the DIR tertiles: lower, ≤ 0.23U/kg/die (n = 25); middle, 0.24–0.40 U/kg/die (n = 24); upper, ≥ 0.41 U/kg/die (n = 26).

Results

When considering the patients in the upper tertile (HIGH-DIR), C-peptide AUC (0–120 min) at 13 weeks was higher in the LDX group (n = 16) than in the placebo (n = 10) group [difference: 0.72 nmol/L (95% CI 0.9–1.34), p = 0.027]. This difference reduced over time (0.71 nmol/L at 26 weeks, p = 0.04; 0.42 nmol/L at 52 weeks, p = 0.29), while it has never been significant at any time in patients in the lower and/or middle tertile (LOW-DIR). We characterized at baseline the HIGH-DIR and found that endo-metabolic (HOMA-B, adiponectin, and glucagon-to-C-peptide ratio) and immunologic (chemokine (C-C motif) ligand 2 (CCL2)/monocyte chemoattractant protein 1 (MCP1) and Vascular Endothelial Growth Factor (VEGF)) features distinguished this group from LOW-DIR.

Conclusion

While LDX did not prevent the progressive loss of beta-cell function in the majority of treated subjects, the post hoc analysis suggests that it could work in subjects with HIGH-DIR at baseline. As we found differences in endo-metabolic and immunologic parameters within this subgroup, this generates the hypothesis that the interactions between host factors and drug action can contribute to its efficacy. Further research is needed to evaluate this hypothesis.
MPPT control technology based on the GWO-VINC algorithm
Authors: Yan Chang , Lei Guoping , Cai Li , He Chao , Dai Nina , Jiang Zhou , Wu Jiacheng , Li Shenghao
Published: June 2023

It is a challenging task to accurately track the global maximum power point (GMPP) in a changing environment in widely used photovoltaic (PV) systems. So far, a variety of maximum power point (MPP) tracking algorithms have been used in solar PV power systems. The classical algorithm is simple and fast to track the speed effectively in a constant environment, but it can get stuck at an extreme point in a variable environment. In this paper, the variable-step incremental conductance (VINC) method is combined with the gray wolf optimization (GWO) algorithm. Firstly, GWO conducts a global search. When the search reaches the area near GMPP, the next step of the search process is carried out based on the iteration number conditions of GWO. Enter the search process of VINC and determine whether the current search process is on the left or right side of the vertex based on the current search value. And adjust the duty cycle during the VINC search process using different variable step size methods based on the left and right sides, and finally accurately locate the GMPP value. To verify the robustness of the proposed algorithm, simulation, and experimental comparisons were conducted between the proposed method in the article and GWO and VINC. The tracking efficiency of static shadows, simulated dynamic shadows, and experimental static and dynamic shadows is 99.80%, 98.82%, 99.43%, and 98.51%, respectively. The tracking time of simulation and experiment is 46.49% and 89.34% faster than GWO and VINC technologies, respectively. The results show that compared with the GWO and VINC methods, the proposed method has improved tracking speed and efficiency. Moreover, compared with the method that combines the two intelligent algorithms, this method has fewer algorithm parameters, a simple calculation process, lower complexity, lower hardware requirements, and better actual implementation performance.
m6A-related lncRNAs predict prognosis and indicate cell cycle in gastric cancer
Authors: Wan Dong , He Lingnan , Guo Cheng , Zhong Zishao , Yan Xiaohan , Cao Jia , Xu Qinwei , Zhang Haibin , Duan Bensong
Published: June 2023

Background: N6-methyladenosine (m6A) modification is a common epigenetic methylation modification of RNA, which plays an important role in gastric carcinogenesis and progression by regulating long non-coding RNA (lncRNA). This study is aimed to investigate the potential prognostic signatures of m6A -related lncRNAs in STAD.

Methods: The m6A-related lncRNAs with the most significant impact on gastric cancer prognosis in the TCGA database were identified by bioinformatics and machine learning methods. The m6A-related lncRNA prognostic model (m6A-LPS) and nomogram was constructed by Cox regression analysis with the minimum absolute contraction and selection operator (LASSO) algorithm. The functional enrichment analysis of m6A-related lncRNAs was also investigated. The miRTarBase, miRDB and TargetScan databases were utilized to establish a prognosis-related network of competing endogenous RNA (ceRNA) by bioinformatics methods. The correlation of AL391152.1 expressions and cell cycle were experimentally testified by qRT-PCR and flow cytometry.

Results: In total, 697 lncRNAs that were identified as m6A-related lncRNAs in GC samples. The survival analysis showed that 18 lncRNAs demonstrated prognostic values. A risk model with 11 lncRNAs was established by Lasso Cox regression, and can predict the prognosis of GC patients. Cox regression analysis and ROC curve indicated that this lncRNA prediction model was an independent risk factor for survival rates. Functional enrichment analysis and ceRNA network revealed that the nomogram was notably associated with cell cycle. qRT-PCR and flow cytometry revealed that downregulation of GC m6A-related lncRNA AL391152.1 could decrease cyclins expression in SGC7901 cells.

Conclusion: A m6A-related lncRNAs prognostic model was established in this study, which can be applied to predict prognosis and cell cycle in gastric cancer.
The role of extravillous trophoblasts and uterine NK cells in vascular remodeling during pregnancy
Authors: Wei Xiao-Wei , Zhang Yu-Chen , Wu Fan , Tian Fu-Ju , Lin Yi
Published: June 2023

Successful embryo implantation requires both a receptive endometrium and competent blastocysts. After implantation, the maternal decidua undergoes a series of changes, including uterine spiral artery (SA) remodeling to accommodate the fetus and provide nutrients and oxygen for the fetus to survive. Uterine spiral arteries transform from small-diameter, high-resistance arteries to large-diameter and low-resistance arteries during pregnancy. This transformation includes many changes, such as increased permeability and dilation of vessels, phenotypic switching and migration of vascular smooth muscle cells (VSMCs), transient loss of endothelial cells (ECs), endovascular invasion of extravillous trophoblasts (EVTs), and presence of intramural EVT, which are regulated by uterine NK (uNK) cells and EVTs. In this review, we mainly focus on the separate and combined roles of uNK cells and EVTs in uterine SA remodeling in establishing and maintaining pregnancy. New insight into related mechanisms will help us better understand the pathogenesis of pregnancy complications such as recurrent pregnancy loss (RPL) and preeclampsia (PE).
Incidence, persistence, and clearance of anogenital human papillomavirus among men who have sex with men in Taiwan: a community cohort study
Authors: Zhou Xinyi , Tian Tian , Lu Zhen , Yu Yi-Fang , Li Yuwei , Zhou Yiguo , Lin Yi-Fan , Strong Carol , Zou Huachun
Published: June 2023

Background

Men who have sex with men (MSM) have an increased risk of human papillomavirus (HPV) infection. This study aimed to assess the incidence, persistence, and clearance of anogenital HPV infections among MSM and the correlates in a 3-year community cohort study.

Methods

From 2015 to 2019, MSM were recruited and followed up at 6, 12, 24, and 36 months in Taiwan. Questionnaires and anogenital swabs were collected at baseline and each follow-up visit. Thirty-seven HPV genotypes were tested and genotyped using the linear array HPV genotyping test. The incidence, persistence, and clearance rates of anogenital HPV infection and 95% confidence intervals (CIs) were estimated through Poisson regression. Correlates of the incidence and clearance rates were examined using a generalized estimating equations (GEE) model.

Results

A total of 201 MSM were retained in the cohort study with a median age of 27 years (interquartile range [IQR]: 24–32) at baseline. The incidence, persistence, and clearance rates of any anal HPV infection among MSM were 43.6 (95% CI: 33.7–55.6), 23.4 (17.7–30.2), and 58.3 (45.1–74.1) per 1,000 person months (pms), respectively. The incidence, persistence, and clearance rates of any penile HPV infection among MSM were 26.8 (20.1–34.9), 13.4 (8.0–20.9), and 51.5 (37.8–68.5) pms, respectively. MSM who did not consistently use a condom in receptive sex (adjusted odds ratio [AOR]: 2.06, 95% CIs: 1.14–3.72) were more likely to acquire any anal HPV infection. Age at recruitment (1.05, 1.01–1.09) was positively associated with any penile HPV incidence. MSM with over one sex partner in receptive anal sex (0.53, 0.30–0.94) were less likely to clear any anal HPV infection. MSM who were unemployed/students (0.55, 0.30–0.98) were less likely to clear any penile HPV infection.

Conclusion

High incidence and low clearance of anogenital HPV infection among MSM in the study serve as a reminder that this population needs to be targeted for HPV vaccination. It is essential for MSM to scale up HPV screening and adhere to safe sex.
The structure of Leptospira interrogans GAPDH sheds light into an immunoevasion factor that can target the anaphylatoxin C5a of innate immunity
Authors: Navas-Yuste Sergio , de la Paz Karla , Querol-García Javier , Gómez-Quevedo Sara , Rodríguez de Córdoba Santiago , Fernández Francisco J. , Vega M. Cristina
Published: June 2023

Leptospirosis is a neglected worldwide zoonosis involving farm animals and domestic pets caused by the Gram-negative spirochete Leptospira interrogans. This bacterium deploys a variety of immune evasive mechanisms, some of them targeted at the complement system of the host’s innate immunity. In this work, we have solved the X-ray crystallographic structure of L. interrogans glyceraldehyde-3-phosphate dehydrogenase (GAPDH) to 2.37-Å resolution, a glycolytic enzyme that has been shown to exhibit moonlighting functions that potentiate infectivity and immune evasion in various pathogenic organisms. Besides, we have characterized the enzyme’s kinetic parameters toward the cognate substrates and have proven that the two natural products anacardic acid and curcumin are able to inhibit L. interrogans GAPDH at micromolar concentration through a noncompetitive inhibition modality. Furthermore, we have established that L. interrogans GAPDH can interact with the anaphylatoxin C5a of human innate immunity in vitro using bio-layer interferometry and a short-range cross-linking reagent that tethers free thiol groups in protein complexes. To shed light into the interaction between L. interrogans GAPDH and C5a, we have also carried out cross-link guided protein-protein docking. These results suggest that L. interrogans could be placed in the growing list of bacterial pathogens that exploit glycolytic enzymes as extracellular immune evasive factors. Analysis of the docking results indicates a low affinity interaction that is consistent with previous evidence, including known binding modes of other α-helical proteins with GAPDH. These findings allow us to propose L. interrogans GAPDH as a potential immune evasive factor targeting the complement system.
Skin-infiltrating T cells display distinct inflammatory signatures in lichen planus, bullous pemphigoid and pemphigus vulgaris
Authors: Schinner Jona , Cunha Tomas , Mayer Johannes U. , Hörster Stefan , Kind Peter , Didona Dario , Keber Corinna , Hertl Michael , Worzfeld Thomas , Juratli Hazem A.
Published: June 2023

Introduction

We here thought to dissect the inflammatory signature in lesions of three skin disorders, which show a common adaptive immune response against autoantigens of the skin but are characterized by diverging clinical phenotypes. Pemphigus vulgaris (PV) and bullous pemphigoid (BP) are type-2-dependent, IgG autoantibody-driven blistering disorders of mucous membranes and skin, which target desmoglein (Dsg)3 and bullous pemphigoid (BP)180, respectively. In contrast, lichen planus (LP) is a common chronic inflammatory disease of the skin and mucous membranes with a pronounced dermal T cell infiltrate. We previously identified peripheral type 1 and 17 T cell responses against Dsg3 and BP180 in a cohort of LP patients strongly suggesting that the underlying inflammatory T cell signature may drive the evolving phenotype.

Methods

Paraffin-embedded skin biopsies from well-characterized patients with LP (n=31), BP (n=19), PV (n=9), and pemphigus foliaceus (PF) (n=2) were analysed. Areas with the most prominent inflammatory infiltrate were excised with punch biopsies and tissue microarrays (TMA) containing multiple biopsies were created. Using multicolor immunofluorescence, the inflammatory infiltrate was stained with antibodies against multiple cellular markers, i. e. CD3ϵ, CD4, CD15, TCR-δ, the cytokine IL-17A, and the transcription factors, T-bet and GATA-3.

Results

In LP, there was a higher number of CD4+ T cells expressing T-bet compared to GATA-3. In contrast, CD4+ T cells in PV and BP skin lesions more frequently expressed GATA-3 than T-bet. IL-17A+ cells and IL-17A+ T cells were found to a similar extent in all the three disorders. IL-17A+ granulocytes were more predominant in BP than in LP or PV. Of note, the majority of IL-17A+ cells in LP were neither T cells nor granulocytes.

Discussion

Our findings in inflammatory skin infiltrates clearly show a predominant type 1 signature in LP in contrast to a preponderance of type 2 T cells in PV and BP. In contrast to LP, granulocytes and to a much lesser extent CD3+ T cells were a cellular source of IL-17A in BP and PV. These data strongly suggest that different inflammatory cell signatures drive evolving clinically diverse phenotypes of LP, PV and BP despite common target antigens of the skin.
Breaking bad: necroptosis in the pathogenesis of gastrointestinal diseases
Authors: Patankar Jay V. , Bubeck Marvin , Acera Miguel Gonzalez , Becker Christoph
Published: June 2023

A delicate balance between programmed cell death and proliferation of intestinal epithelial cells (IEC) exists in the gut to maintain homeostasis. Homeostatic cell death programs such as anoikis and apoptosis ensure the replacement of dead epithelia without overt immune activation. In infectious and chronic inflammatory diseases of the gut, this balance is invariably disturbed by increased levels of pathologic cell death. Pathological forms of cell death such as necroptosis trigger immune activation barrier dysfunction, and perpetuation of inflammation. A leaky and inflamed gut can thus become a cause of persistent low-grade inflammation and cell death in other organs of the gastrointestinal (GI) tract, such as the liver and the pancreas. In this review, we focus on the advances in the molecular and cellular understanding of programmed necrosis (necroptosis) in tissues of the GI tract. In this review, we will first introduce the reader to the basic molecular aspects of the necroptosis machinery and discuss the pathways leading to necroptosis in the GI system. We then highlight the clinical significance of the preclinical findings and finally evaluate the different therapeutic approaches that attempt to target necroptosis against various GI diseases. Finally, we review the recent advances in understanding the biological functions of the molecules involved in necroptosis and the potential side effects that may occur due to their systemic inhibition. This review is intended to introduce the reader to the core concepts of pathological necroptotic cell death, the signaling pathways involved, its immuno-pathological implications, and its relevance to GI diseases. Further advances in our ability to control the extent of pathological necroptosis will provide better therapeutic opportunities against currently intractable GI and other diseases.
Deciphering the contributions of cuproptosis in the development of hypertrophic scar using single-cell analysis and machine learning techniques
Authors: Song Binyu , Liu Wei , Zhu Yuhan , Peng Yixuan , Cui Zhiwei , Gao Botao , Chen Lin , Yu Zhou , Song Baoqiang
Published: June 2023

Hypertrophic scar (HS) is a chronic inflammatory skin disease characterized by excessive deposition of extracellular matrix, but the exact mechanisms related to its formation remain unclear, making it difficult to treat. This study aimed to investigate the potential role of cuproptosis in the information of HS. To this end, we used single-cell sequencing and bulk transcriptome data, and screened for cuproptosis-related genes (CRGs) using differential gene analysis and machine learning algorithms (random forest and support vector machine). Through this process, we identified a group of genes, including ATP7A, ULK1, and MTF1, as novel therapeutic targets for HS. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to confirm the mRNA expression of ATP7A, ULK1, and MTF1 in both HS and normal skin (NS) tissues. We also constructed a diagnostic model for HS and analyzed the immune infiltration characteristics. Additionally, we used the expression profiles of CRGs to perform subgroup analysis of HS. We focused mainly on fibroblasts in the transcriptional profile at single-cell resolution. By calculating the cuproptosis activity of each fibroblast, we found that cuproptosis activity of normal skin fibroblasts increased, providing further insights into the pathogenesis of HS. We also analyzed the cell communication network and transcription factor regulatory network activity, and found the existence of a fibroblast-centered communication regulation network in HS, where cuproptosis activity in fibroblasts affects intercellular communication. Using transcription factor regulatory activity network analysis, we obtained highly active transcription factors, and correlation analysis with CRGs suggested that CRGs may serve as potential target genes for transcription factors. Overall, our study provides new insights into the pathophysiological mechanisms of HS, which may inspire new ideas for the diagnosis and treatment.
Using fruit flies to delve into mosquito insecticide resistance
Authors: Hossain Kaniz Fatima Binte , Vimal Divya , Owusu-Ansah Edward
Published: June 2023

With more than 3,000 species and an almost ubiquitous presence, the economic importance of mosquitoes cannot be overemphasized. Anopheles mosquitoes are vectors for infectious diseases such as malaria – an endemic disease in tropical and sub-tropical regions of the world that infects more than 200 million people worldwide and causes over 400,000 deaths annually, with most casualties being infants or inhabitants of sub-Saharan Africa. The Aedes aegytpi and Culex quinquefasciatus species of mosquitoes are also vectors for arboviruses such as chikungunya virus, dengue virus, western equine encephalitis virus, and Zika virus. Consequently, insecticides are frequently used to stem the population of mosquitoes. Nevertheless, mosquito insecticide resistance has emerged as a major problem that has contributed to numerous failed eradication campaigns for the aforementioned diseases. In this mini-review, we expound on how fruit flies (Drosophila melanogaster) could be a complementary model system for studying mosquito insecticide resistance, with the ultimate goal of confirming any promising leads in mosquitoes.