bluuebunny/crossref_metadata_2025 huggingface dataset:
Model peningkatan kinerja dosen melalui penerapan Organizational Happiness Character dan Komitmen organisasi
Authors: Agustina Granit , Novedliani Riztrya , Febrian Feby
Published: December 2024

Kondisi kelembagaan merupakan aspek penting dalam peranannya mendongkrak peringkat perguruan tinggi dimana kondidi kelembagaan sanganlah mepengruhi kinerja dosen. Banyak factor yang diasumsikan dalam peningkatan kinerja dosen salah satunya adalah organizational happiness character (OHC). Penelitian ini bertujuan untuk mengetahui peran organizational happiness character dalam mempengaruhi kinerja dosen dimediasi oleh komitmen organisasi. Penelitian dilakukan keada para dosen dilingkungan perguruan tinggi swasta di wilayah Bandung timur. Jumlah sample penelitian sebanyak minimal 200 dosen yang diperoleh dari 5 perguruan tinggi swasta di Bandung timur. Data penelitian dikumpulkan dengan menggunakan kuesioner menggunakan skala semantic differensial. Teknik analisis data yang digunakan yaitu analis SEM-AMOS. Penelitian ini dilakukan untuk melihat persepsi dosen terhadap organizational happiness character, komitmen organisasi dan kinerja dosen dengan menguji 4 hipotesis penelitian. Dari hasil pengjuin hipotesis diperoehl hasil bahwa organizational happiness character memiliki ubungan positif signifikan terhadap kinerja dosen. organizational happiness character  (OHC) dan komitmen organisasi juga telah terbukti memberikan pengaruh positif dan signifikan dan komitmen organisasi juga memberikan pengaruh positif signifikan terhadap peningkatan kinerja dosen. Dari hasil penelitian ini juga dapat diperlihatkan bahwa komitmen organisasi memberikan pengaruh mediasi secara parsial dalam peningkatan kinerja dosen sehingga dapat dikatakan bahwa komitmen organisasi merupakan variable yang dapat memediasi organizational happiness character terhadap kinerja dosen
Kaçarlar Döneminde Ermeniler: Tumanyan Kardeşlerinin Ticari ve Finansal Faaliyetleri
Authors: Tuncer Tekin , Jafarov Ziyafat
Published: December 2024

Bu çalışma, Kaçarlar döneminde İran Ermenilerinin ticari ve finansal faaliyetlerini incelemeyi amaçlamıştır. Araştırma, İran Ermenilerinin ekonomik ve sosyal hayatlarına dair kaynakların dağınıklığı ve sınırlılığı nedeniyle literatürde eksik kalan bu alanı, özellikle Tumanyans Kardeşleri ve onların İran’daki ticari faaliyetleri merkezde yer alacak şekilde ele almıştır. Çalışmanın ana sorusu, Kaçarlar döneminde Ermeni tüccarların İran ticaret ve bankacılık sistemine olan etkilerini ve katkılarını ortaya koymak olmuştur. Bu doğrultuda, Ermeni tüccarların İran’da ve Rusya ile olan ticari ilişkileri, İran’ın kuzey ve güney bölgelerinde oynadıkları roller ve özellikle Nasıreddin Şah dönemindeki ekonomik dönüşümlere katkıları değerlendirilmiştir. Tumanyans Kardeşlerinin sarraflık ve bankacılık faaliyetleri üzerinden, Ermeni tüccarların İran ekonomisinde nasıl merkezi bir rol oynadığı açıklanmıştır. Çalışma, İran ve Ermeniler üzerine yapılan önceki araştırmalarda yeterince ele alınmamış ticari ve finansal ilişkiler üzerine yoğunlaşarak literatüre katkıda bulunmayı amaçlamıştır. Ağırlıklı olarak Farsça kaynaklara ve dönemin diplomatlarının seyahatnamelerine dayanan bu araştırma, İran Ermenileri üzerine yapılacak gelecek çalışmalar için bir zemin oluşturacaktır. Öncelikle Nasıreddin Şah döneminde Kaçarların ticari-ekonomik ve siyasi durumuna genel bir bakış sunulmuştur. Ardından, söz konusu dönemde İran’daki Ermenilerin nüfusları ele alınmıştır. Çalışmanın ana hattını, 1840’lı yıllardan başlayarak Kaçarların yıkılışına kadar İran’da birçok alanda ticari faaliyetler sürdüren, Rusya ile geniş ticari ilişkiler kuran ve Nasıreddin Şah saltanatının sonlarına doğru yabancı sermayedarların banka kurdukları dönemde sarraflık ve bankacılık faaliyetlerine başlayan Tumanyans Kardeşleri ve Ticarethanesi oluşturmaktadır.
Ağırlıklı olarak Farsça kaynaklara ve Farsçaya çevrilen yabancı seyyahların, diplomatların seyahatnamelerine dayanan bu çalışmanın, konuya dair kaynak tanıtımının yanı sıra şu ana kadar çalışılmamış olması dolayısıyla literatüre önemli katkılarda bulunacağı kanaatindeyiz.
TÜRK HAVACILIK TARİHİNDE MERZİFON
Authors: Taşdemir Serap
Published: December 2024

Uçmak ve sadece yer yüzüne değil, gökyüzüne de hâkim olma duygusu sonucu ortaya çıkan uçaklar kısa sürede orduların savaş gereçleri arasında yer aldı. Dünyadaki gelişmelere bağlı olarak 1 Haziran 1911 yılında Tayyare Komisyonunun kurulmasıyla faaliyete başlayan Türk Hava Kuvvetleri bu anlamda dünyada ilk kurulan askeri havacılık teşkilatları arasında yer alır. Bununla birlikte ard arda yaşanan Trablusgarp, Balkan ve Birinci Dünya Savaşları askeri havacılık konusunda önemli adımlar atılmasına izin vermedi. Milli Mücadele yıllarında Ankara Hükümeti’nin kurduğu ilk teşkilatlardan biri olan Türk Hava Teşkilatı, Cumhuriyetin ilanı sonrasında yaşanan her türlü ekonomik ve malî sıkıntılara rağmen desteklenmiş; şartlar elverdiğinde havacılıkla ilgili düzenlemeler yapılmış, havacılık millî birlik ve beraberliğin pekişmesine yardımcı güçler içinde önemli bir konumda yer almış; gerek 40 yıl önce savaş uçağı yapan ve bu uçakla Hava Kuvvetleri Komutanlığı’nın belkemiğini oluşturan TUSAŞ-TAİ-TEI-ASELSAN-HAVELSAN gibi dev kuruluşları ve yan sanayii ve gerekse günümüzde Bayraktar’ın insansız gözlem yapan ve/veya bomba atan yerli ve milli uçaklarıyla bu önemini devam ettirmektedir. Merzifon ilçesindeki havacılık faaliyetleri ise 1935-1936 yılları arası başladı. Hava Atış Okulu 1943 yılında Adana’ya taşınırken, 1941 yılına kadar Çorlu’da bulunan 4. Hava Atış Alayı’nın 1942 yılında Merzifon’a gelmesiyle Merzifon’da havacılık faaliyetleri devam etmiş; 1951 yılında ismi 4. Hava Üs Komutanlığı olarak değiştirilmiştir. Genelkurmay Başkanlığı’nın 1 Kasım 1961 ve Hava Kuvvetleri Komutanlığı’nın 14 Kasım 1961 tarihli emri ile 5. Hava Üs Komutanlığı üs teşkilatına geçildi. Karadeniz bölgesi hava savunmasından sorumlu olan 5. Ana Jet Üssü, Amasya iline bağlı Merzifon ilçesinde hizmet vermeye devam ederken; 16 Kasım 1986 tarihinde Genelkurmay Başkanlığı ile Ulaştırma Bakanlığı arasında imzalanan protokol ile sivil hava trafiğine de açıldı.
1939 YILINI “OKUYUCU MEKTUPLARI” IŞIĞINDA YENİDEN OKUMAK
Authors: Karabulut Sezen
Published: December 2024

1939 yılı Türk Tarihi’nde önemli bir dönüm noktasını oluşturmaktadır. Atatürk sonrası dünyanın İkinci Dünya Savaşı’nın eşiğinde olduğu bir süreçte Türkiye’de yeni bir siyasal başlamıştır. Türk milletinin bağımsızlığına kavuşmasını sağlayan liderinin ölümünün ardından devralınan sürecin ve cumhuriyet değerlerinin korunmasına adına da iç politika da önemli bir sürecin başlangıcıdır. “Milli Şef” olarak adlandırılan ve 12 yıl devam edecek olacak yeni bir dönemin de başlangıcıdır. Bu nedenle bu yılın siyasi, ekonomik ve uluslararası alanda yaşananların sıradan vatandaşlar üzerindeki etkilerinin de incelenmesi tarihe önemli ölçüde ışık tutacağı düşüncesi ile bu dönem yeni kaynak grubu ile ele alınmıştır. Aşağıdan tarihçilik anlayışı ile kaleme aldığım çalışmamda daha önce birkaç çalışma dışında kullanılmamış bir materyal olan “Okuyucu Mektupları” kullanılmıştır. Buradaki amaç; halkın bakışını keşfetmektir. Dönemin önemli yayın organları olan Cumhuriyet, Ulus ve Vakit gazeteleri taranmış, toplam da 112 tane okuyucu mektubu tespit edilmiştir. Ayrıca halkın sıkıntılarının daha iyi anlaşılabilmesi için TBMM arşivinden Arzuhal Encümeni Cedveli temin edilerek dilekçeler incelenmiş ve konu analizleri çıkarılmıştır. Temin edilen birincil kaynaklar, ikincil kaynaklar ile desteklenerek çalışma hazırlanmıştır.
The modulating role of uniaxial straining in the IL-1β and TGF-β mediated inflammatory response of human primary ligamentocytes
Authors: Heidenberger Johannes , Hangel Raphael , Reihs Eva I. , Strauss Jonathan , Liskova Petra , Alphonsus Jürgen , Brunner Cornelia , Döring Kevin , Gerner Iris , Jenner Florien , Windhager Reinhard , Toegel Stefan , Rothbauer Mario
Published: December 2024

Biomechanical (over-)stimulation, in addition to inflammatory and fibrotic stimuli, severely impacts the anterior cruciate ligament (ACL) biology, contributing to the overall chronic nature of desmopathy. A major challenge has been the lack of representative two-dimensional (2D) in vitro models mimicking inflammatory processes in the presence of dynamic mechanical strain, both being crucial for ligament homeostasis. Physiological levels of strain exert anti-inflammatory effects, while excessive strain can facilitate inflammatory mechanisms. Adhering to the 3Rs (Replacement, Reduction and Refinement) principles of animal research, this study aims to investigate the role of a dynamic biomechanical in vitro environment on inflammatory mechanisms by combining a Flexcell culture system with primary human ligamentocytes for the study of ligament pathology. Primary ligamentocytes from OA patients were cultured under animal-free conditions with human platelet lysate, and exposed to either IL-1β or TGF-β3 to simulate different inflammatory microenvironments. Cells were subjected to different magnitudes of mechanical strain. Results showed that cells aligned along the force axis under strain. This study highlights the critical role of the mechanical microenvironment in modulating inflammatory and fibrotic cellular responses in ligamentocyte pathology, providing valuable insights into the complex interplay between biomechanical stimuli and cytokine signaling. These findings not only advance our understanding of ligament biology but also can pave the way for the development of more targeted therapeutic strategies for ligament injuries and diseases, potentially improving patient outcomes in orthopedic medicine.
Identification of the factors influencing the liquid sloshing wave height in a sloped bottom tank under horizontal excitation using PCA approach
Authors: Ren Wenhao , Zhong Zuowei
Published: December 2024

The dynamic behavior of liquid storage tanks represents a pivotal research area concerning structural safety and reliability. Notably, sloped bottom tanks exhibit heightened sloshing with reduced liquid mass compared to rectangular counterparts. This study adopts a hybrid approach that seamlessly integrates the linear potential-flow theory, renowned for its analytical rigor in fluid dynamics modeling, with principal component analysis (PCA), a potent technique for dimensionality reduction and feature extraction. The hybrid methodology initially employs the linear potential-flow theory to simulate the fundamental fluid dynamics within sloped bottom tanks subjected to horizontal excitation. Subsequently, PCA is applied to the simulated data, identifying key components of liquid sloshing wave height variations. Through the analysis of these principal components, an accurate model of the maximum sloshing wave height is derived, achieving a close correlation with ANSYS simulation results, exhibiting a correlation coefficient of 0.98 and a mean absolute error of 2.5%. This approach uniquely facilitates the evaluation of the intricate interplay between multiple factors, including tank geometry and excitation frequency, on the dynamic characteristics of liquid sloshing waves in sloped bottom tanks. The findings emphasize the significant influence of tank height and tilt angle, with a sensitivity analysis indicating a 4.07% increase in maximum wave height per degree increase in tilt angle under specified experimental conditions. This comprehensive methodology not only enhances understanding of the complex liquid sloshing phenomenon but also provides precise theoretical and practical guidance for fluid sway control strategies. Future investigations will further expand the scope and elucidate the fundamental mechanisms governing liquid sloshing dynamics.
Comprehensive study of SNAREs involved in the post-Golgi transport in Drosophila photoreceptors
Authors: Ochi Yuka , Yamashita Hitomi , Sasaki Shogo , Ogawa Takumi , Yamada Yumi , Tago Tatsuya , Satoh Takunori , Satoh Akiko K.
Published: December 2024

Polarized transport is essential for the construction of multiple plasma membrane domains within cells. Drosophila photoreceptors serve as excellent model systems for studying the mechanisms of polarized transport. We conducted a comprehensive soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) screening of the fly genome using RNAi knockdown and CRISPR/Cas9 somatic knockout combined with the CoinFLP system to identify SNAREs involved in post-Golgi trafficking. The results suggest that in post-Golgi transport, no SNARE is exclusively responsible for transport to a single specific plasma membrane domain. However, each SNARE shows some preference for certain membrane domains: the loss of nSyb, Ykt6, and Snap24/25 results in severe defects in rhabdomere transport, while the loss of Syx1A and Snap29 leads to significant impairments in basolateral transport. Together with the function of Syx1A, Snap25, and nSyb in the fusion of synaptic vesicles with the synaptic plasma membrane, these results suggest that SNAREs are not the sole determinants for vesicles to specify their target subdomains in the plasma membrane. Furthermore, rhodopsin transport to the rhabdomere requires two kinds of R-SNAREs, Ykt6 and nSyb, suggesting that multiple sets of post-Golgi SNAREs contribute in tandem or in cooperation, rather than in parallel.
Recent advances in the treatment of non-small cell lung cancer with MET inhibitors
Authors: Zhang Dongna , Zhang Wenying , Liu He , Liu Pan , Li Chunxin , Liu Yangyang , Han Jicheng , Zhu Guangze
Published: December 2024

Recently, research into the oncogenic driver genes associated with non-small cell lung cancer (NSCLC) has advanced significantly, leading to the development and clinical application of an increasing number of approved therapeutic agents. Among these, small molecule inhibitors that target mesenchymal-epithelial transition (MET) have demonstrated successful application in clinical settings. Currently, three categories of small molecule MET inhibitors, characterized by distinct binding patterns to the MET kinase region, have been developed: types Ia/Ib, II, and III. This review thoroughly examines MET’s structure and its crucial role in NSCLC initiation and progression, explores discovery strategies for MET inhibitors, and discusses advancements in understanding resistance mechanisms. These insights are anticipated to enhance the development of a new generation of MET inhibitors characterized by high efficiency, selectivity, and low toxicity, thereby offering additional therapeutic alternatives for patients diagnosed with NSCLC.
The effect of educational intervention through sending emails on improving physical posture in female computer users of Eastern Iran: a quasi-experiment study
Authors: Hosseini Zahra , Ziapour Arash , Rahimi Seyyede Fateme , Dalake Fatemeh , Yıldırım Murat
Published: December 2024

Background

Musculoskeletal disorders are among the most common occupational injuries and disabilities in developing and industrialized countries. This study aims to determine the effectiveness of e-mail training to improve the physical posture of female computer users at Birjand University of Medical Sciences in Iran.

Methods

The present interventional research explores the effect of email-based training to correct the body posture of female computer users in Birjand, Iran. In this quasi-experiment, 120 women who worked in Birjand University of Medical Sciences using computers were selected through a census. 60 computer users were selected from the deputy of education and 60 from the deputy of development for the intervention group (IG) and control group (CG), respectively. A training program was developed on the ergonomics of office work (12 emails at an interval of 6 weeks). The data was collected using demographic, occupational information, and a knowledge assessment questionnaire. Nordic Musculoskeletal Questionnaire (NMQ) and Rapid Office Strain Assessment (ROSA) were used in both groups before the intervention and 6 months later.

Results

After the educational intervention, a significant increase was observed in the ergonomics knowledge of the IG compared to the control. The ROSA score was lowered from a high-risk to a low-and medium-risk level (p < 0.05). In the IG, 44 subjects (73.30%) who needed ergonomic intervention (a score above 5) were reduced to 10 subjects (16.70%) with a need for ergonomic intervention. According to NMQ, the highest frequency of pain in the IG and CG was related to the back (56.70% and 55%, respectively). The neck, shoulders, wrists, back and elbows were next.

Conclusions

This quasi-intervention study was conducted to determine the effect of email-based training on correcting female computer users’ body posture in 2022. Training ergonomics through email is a practical and acceptable way to improve ergonomic behaviors among computer users. It enables them to adapt to the workplace by applying the correct ergonomics, changing their work behavior to prevent occupational musculoskeletal disorders, and reduce risks and complications.
Fostering self-regulated learning using synchronous or asynchronous digital learning environments: a latent profile analysis of pre-service teachers’ individual differences
Authors: Barz Nathalie , Benick Manuela , Dörrenbächer-Ulrich Laura , Perels Franziska
Published: December 2024

Self-regulated learning (SRL) is positively associated with improved learning achievements during all educational phases. Despite playing an important role in conveying SRL strategies to their students, pre-service often lack knowledge about SRL and imparting it. Therefore, addressing SRL and teaching SRL strategies to students seems relevant to pre-service teacher training. The present study aims to analyze pre-service teachers’ SRL profiles in asynchronous and synchronous digital learning environments and compares their influence on training effectiveness. As part of a pre-post design, a total of N = 141 pre-service teachers participated in the study, and questionnaires on SRL strategy use and an SRL knowledge test were used. A latent profile analysis indicated a three-class solution (low, moderate, high SRL), revealing significant differences regarding SRL strategy use but not for SRL knowledge. These findings enable a person-centered approach to develop digital learning environments and provide insight into specific learner behavior.
Tracing the roots: understanding the factors that drive motivation and loyalty of scholars toward joining international academic conferences
Authors: Williady Angellie , Handani Narariya Dita , Wang Jue , Kim Hak-Seon
Published: December 2024

This study aims to examine the factors contributing to motivation and loyalty among scholars attending international academic conferences. Specifically, the study aims to understand what motivates scholars to participate actively in these events by investigating the interaction between academic skills, academic self-concept, support, motivation, and loyalty. Data were collected from 238 respondents to a structured questionnaire distributed at three international conferences in Indonesia, South Korea, and India. As a result of these findings, academic skills (β = 0.453, t-value = 5.128) and self-concept (β = 0.358, t-value = 3.963) significantly influence perceived support, which encourages motivation and fosters loyalty toward these conferences. Furthermore, motivation serves as a critical mediator, bringing together academic skills and self-esteem with loyalty, suggesting that nurturing these elements has a significant impact on scholars’ engagement and commitment to the academic community.
Clinical and neuroimaging characteristics of diabetic striatopathy: a case series report
Authors: Chen Yaning , Wu Chunliu , Ren Ming , Wang Qingjun , Wang Zhiwei , Zhang Yimo , Yu Yingxin
Published: December 2024

Background

Diabetic striatopathy (DS) is a rare disorder characterized by clinical manifestations of hemichorea, non-ketotic hyperglycemia, and high signal on T1-weighted MRI or high density on CT scan in basal ganglia, typically associated with poor glycemic control.

Objective

This study aimed to analyze clinical characteristics of patients with diabetic striatopathy to raise awareness amongst physicians, especially endocrinologists, about this rare neurological manifestation in patients with diabetes.

Methods

We retrospectively analyzed the data on clinical presentations, laboratory workups, and cranial CT and MRI of six patients with DS who were admitted to our hospital from October 2013 to June 2022.

Results

The mean age of onset among the six patients was 80.5 years, and the mean value of HbA1c was 13.65%. All six patients complained of involuntary movements, which primarily affected the arm and leg on one side of the body. Bilateral caudate nucleus hyperdensities were shown on the CT examination in Case 3,while the other 5 patients, unilateral caudate nucleus hyperdensity was shown. In addition, five patients (except Case 5) underwent MRI, all showing hypersignal lesions on the T1-weighted images. A low signal in the right basal ganglia was shown on MRI susceptibility weighted imaging (SWI) sequences in Case 6. All six patients exhibited carotid artery or cerebral artery stenosis. Following strict blood glucose control and symptomatic management, the symptoms of chorea improved significantly in all patients, and repeat images indicated that the lesions gradually disappeared.

Conclusion

Both poor vascular conditions and severe hyperglycemia contribute to the development of diabetic striatopathy. The prognosis is usually good by active treatment.
Case report: Duplication of the GCK gene is a novel cause of nesidioblastosis: evidence from a case with Silver-Russell syndrome-like phenotype related to chromosome 7
Authors: Shoji Takashi , Yamauchi Ichiro , Kawasaki Hidenori , Iwanaga Kogoro , Hakata Takuro , Tanaka Daisuke , Fujikura Junji , Masui Toshihiko , Suzuki Hisato , Yamada Mamiko , Kosaki Kenjiro , Kasai Yosuke , Hatano Etsuro , Inaba Akira , Wada Takahito , Kosugi Shinji , Ueda Yohei , Fujii Toshihito , Taura Daisuke , Inagaki Nobuya
Published: December 2024

Silver-Russell syndrome (SRS) is a syndrome characterized by prenatal and postnatal growth retardation, facial features, and body asymmetry. SRS is often complicated with hypoglycemia, whose etiology is unclear. We describe the clinical course of 25-year-old man with hypoglycemia. We diagnosed him with hyperinsulinemic hypoglycemia (HH) and treated him with laparoscopic distal pancreatectomy. Histological examination led to a diagnosis of nesidioblastosis. The juvenile onset of his nesidioblastosis and its slowly progressive course suggested a genetic etiology. Whole-exome sequencing (WES) identified the heterozygous NR0B2 Ala195Ser variant, which alone was unlikely to cause nesidioblastosis because this variant is sometimes detected in the Japanese population. Copy number analysis using WES data suggested duplication in chromosome 7, and subsequent G-banding chromosome analysis confirmed mos dup(7)(p11.2p14). We determined that the patient had SRS-like phenotype based on his clinical features and this duplication. Furthermore, we found that the duplicated region contained the GCK gene, whose gain-of function variants could cause HH. Taken together, the patient’s HH may have been caused by duplication of the GCK gene, which could be a novel cause of nesidioblastosis.
Traditional versus intensive blood glucose control: long-term target range duration and cardiovascular disease risk and all-cause mortality - a real-world cohort study
Authors: Zhang Jingdi , Li Liuxin , Luo Donglei , Huo Zhenyu , Zhang Xiaoxue , Xu Yiran , Jiang Jingyuan , Liu Tiantian , Wu Shouling , Huang Zhe
Published: December 2024

Objective

For a long time, the dispute about whether improved glycemic control can bring significant benefits has remained unresolved. We aimed to investigate the association of time spent in different fasting glucose target ranges with cardiovascular risk and all-cause mortality in a population with type 2 diabetes (T2DM).

Method

A total of 3460 T2DM patients in the Kailuan cohort were included in this study. The Time in Target Range (TITRE) was calculated as the proportion of time that fasting blood glucose (FBG) was within the usual glycemic control range and the intensive glycemic control range between 2006 and 2016. The Cox proportional hazards regression model analyzed the relationship between TITRE, defined by different glucose ranges, and cardiovascular disease and all-cause mortality.

Results

During a median follow-up of 4.23 years, a total of 360 CVDs and 238 deaths were recorded. After correcting for traditional risk factors, we observed that in the conventional blood glucose control group, each increase of 1 standard deviation in TITRE was associated with a 23% (HR, 0.77; 95%CI, 0.68-0.87) reduction in CVD risk and a 20% reduction in all-cause mortality (HR, 0.80; 95%CI, 0.69-0.92). Similar results were also observed in the intensified blood glucose control group. In the conventional blood glucose control group, participants with TITRE of 50% or more had an absolute incidence rate of CVD of 16.77%, whereas in the intensified blood glucose control group, participants with TITRE of 50% or more had an absolute incidence rate of CVD of 11.82%.

Conclusions

In patients with type 2 diabetes, achieving near-normal blood glucose levels appears to significantly reduce the risk of diabetes-related cardiovascular outcomes.
Bile acids as a key target: traditional Chinese medicine for precision management of insulin resistance in type 2 diabetes mellitus through the gut microbiota-bile acids axis
Authors: Wang Yu , Yu Jing , Chen Binqin , Jin Wenqi , Wang Meili , Chen Xuenan , Jian Mengqiong , Sun Liwei , Piao Chunli
Published: December 2024

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease caused by insulin resistance (IR) and insufficient insulin secretion. Its characteristic pathophysiological processes involve the interaction of multiple mechanisms. In recent years, globally, the prevalence of T2DM has shown a sharp rise due to profound changes in socio-economic structure, the persistent influence of environmental factors, and the complex role of genetic background. It is worth noting that most T2DM patients show significant IR, which further exacerbates the difficulty of disease progression and prevention. In the process of extensively exploring the pathogenesis of T2DM, the dynamic equilibrium of gut microbes and its diverse metabolic activities have increasingly emphasized its central role in the pathophysiological process of T2DM. Bile acids (BAs) metabolism, as a crucial link between gut microbes and the development of T2DM, not only precisely regulates lipid absorption and metabolism but also profoundly influences glucose homeostasis and energy balance through intricate signaling pathways, thus playing a pivotal role in IR progression in T2DM. This review aims to delve into the specific mechanism through which BAs contribute to the development of IR in T2DM, especially emphasizing how gut microbes mediate the metabolic transformation of BAs based on current traditional Chinese medicine research. Ultimately, it seeks to offer new insights into the prevention and treatment of T2DM. Diet, genetics, and the environment intricately sculpt the gut microbiota and BAs metabolism, influencing T2DM-IR. The research has illuminated the significant impact of single herbal medicine, TCM formulae, and external therapeutic methods such as electroacupuncture on the BAs pool through perturbations in gut microbiota structure. This interaction affects glucose and lipid metabolism as well as insulin sensitivity. Additionally, multiple pathways including BA-FXR-SHP, BA-FXR-FGFR15/19, BA-FXR-NLRP3, BA-TGR5-GLP-1, BAs-TGR5/FXR signaling pathways have been identified through which the BAs pool significantly alter blood glucose levels and improve IR. These findings offer novel approaches for enhancing IR and managing metabolic disorders among patients with T2DM.
Short-term effects of temperature and air pollution on mortality in Norway: a nationwide cohort-based study
Authors: Rao Shilpa , Zhang Siqi , Ahimbisibwe Ashley , Bekkevold Terese , Di Ruscio Francesco , Diz-Lois Palomares Alfonso , Frohn Lise Marie , Geels Camilla , Vázquez Fernández Liliana , Schneider Alexandra
Published: December 2024

Background

This time-stratified case-crossover study examined short-term associations of air temperature with cause-specific mortality (natural-cause, cardiovascular and respiratory) and potential effect modification by daily mean air pollution concentrations and individual characteristics in the Cohort of Norway (CONOR) cohort.

Methods

The CONOR cohort recruited ∼173,000 participants from 1994 to 2003. Participants’ vital status and the cause of death were collected from the Cause of Death Registry of Norway until 2018. Daily mean air temperatures and concentrations of fine particulate matter (PM2.5) and ozone (O3) estimated by spatial-temporal models were assigned to participants’ residences. We applied conditional logistic regression models with the distributed lag non-linear model approach to assess cold and heat effects on cause-specific mortality. The potential effect modification was analyzed by incorporating an interaction term between air temperature and the modifier in the regression model. The cold and heat effects were estimated for different subgroups of participants and at the low (5th percentile), medium (50th percentile), and high (95th percentile) levels of air pollution.

Results

We observed an increased risk of natural-cause mortality (OR: 1.26 95% CI: 1.09, 1.46) for a decrease in temperature from the minimum mortality temperature (MMT, 17.6°C) to the 1st percentile and an increased risk of cardiovascular mortality (OR: 1.32, 95% CI: 1.04, 1.67) for a decrease from MMT (16.1°C) to the 1st percentile. The cold effect on natural-cause mortality was more pronounced among women, former smokers, those aged below 75 years and people with a history of cardiovascular diseases. The cold effect on natural-cause mortality was stronger at higher levels of air pollution in winter, and the heat effect on cardiovascular mortality were stronger with elevated air pollution levels in summer.

Conclusion

We find adverse short-term cold effects on overall mortality in Norway. We further observe significant risk of cold related effects on natural and cardiovascular mortality in the wintertime and increased risk of respiratory mortality due to higher temperatures in the summer. We identified subpopulations who were likely to be more at risk for temperature-related mortality. We also see that increased air pollution impacts temperature related mortality in winter and summer time.
Evaluation of work distribution schedulers for heterogeneous architectures and scientific applications
Authors: Gonzalez Tallada Marc , Morancho Enric
Published: December 2024

This article explores and evaluates variants of state-of-the-art work distribution schemes adapted for scientific applications running on hybrid systems. A hybrid implementation (multi-GPU and multi-CPU) of the NASA Parallel Benchmarks - MutiZone (NPB-MZ) benchmarks is described to study the different elements that condition the execution of this suite of applications when parallelism is spread over a set of computing units (CUs) of different computational power (e.g., GPUs and CPUs). This article studies the influence of the work distribution schemes on the data placement across the devices and the host, which in turn determine the communications between the CUs, and evaluates how the schedulers are affected by the relationship between data placement and communications. We show that only the schedulers aware of the different computational power of the CUs and minimize communications are able to achieve an appropriate work balance and high performance levels. Only then does the combination of GPUs and CPUs result in an effective parallel implementation that boosts the performance of a non-hybrid multi-GPU implementation. The article describes and evaluates the schedulers static-pcf , Guided, and Clustered Guided to solve the previously mentioned limitations that appear in hybrid systems. We compare them against state-of-the-art static and memorizing dynamic schedulers. Finally, on a system with an AMD EPYC 7742 at 2.250GHz (64 cores, 2 threads per core, 128 threads) and two AMD Radeon Instinct MI50 GPUs with 32GB, we have observed that hybrid executions speed up from 1.1 × up to 3.5 × with respect to a non-hybrid GPU implementation.
Unraveling the impact of SARS-CoV-2 mutations on immunity: insights from innate immune recognition to antibody and T cell responses
Authors: Bayarri-Olmos Rafael , Sutta Adrian , Rosbjerg Anne , Mortensen Mie Mandal , Helgstrand Charlotte , Nielsen Per Franklin , Pérez-Alós Laura , González-García Beatriz , Johnsen Laust Bruun , Matthiesen Finn , Egebjerg Thomas , Hansen Cecilie Bo , Sette Alessandro , Grifoni Alba , da Silva Antunes Ricardo , Garred Peter
Published: December 2024

Throughout the COVID-19 pandemic, the emergence of new viral variants has challenged public health efforts, often evading antibody responses generated by infections and vaccinations. This immune escape has led to waves of breakthrough infections, raising questions about the efficacy and durability of immune protection. Here we focus on the impact of SARS-CoV-2 Delta and Omicron spike mutations on ACE-2 receptor binding, protein stability, and immune response evasion. Delta and Omicron variants had 3–5 times higher binding affinities to ACE-2 than the ancestral strain (KDwt = 23.4 nM, KDDelta = 8.08 nM, KDBA.1 = 4.77 nM, KDBA.2 = 4.47 nM). The pattern recognition molecule mannose-binding lectin (MBL) has been shown to recognize the spike protein. Here we found that MBL binding remained largely unchanged across the variants, even after introducing mutations at single glycan sites. Although MBL binding decreased post-vaccination, it increased by 2.6-fold upon IgG depletion, suggesting a compensatory or redundant role in immune recognition. Notably, we identified two glycan sites (N717 and N801) as potentially essential for the structural integrity of the spike protein. We also evaluated the antibody and T cell responses. Neutralization by serum immunoglobulins was predominantly mediated by IgG rather than IgA and was markedly impaired against the Delta (5.8-fold decrease) and Omicron variants BA.1 (17.4-fold) and BA.2 (14.2-fold). T cell responses, initially conserved, waned rapidly within 3 months post-Omicron infection. Our data suggests that immune imprinting may have hindered antibody and T cell responses toward the variants. Overall, despite decreased antibody neutralization, MBL recognition and T cell responses were generally unaffected by the variants. These findings extend our understanding of the complex interplay between viral adaptation and immune response, underscoring the importance of considering MBL interactions, immune imprinting, and viral evolution dynamics in developing new vaccine and treatment strategies.
The potential role of n-3 fatty acids and their lipid mediators on asthmatic airway inflammation
Authors: Tian Yuan , Sun JingMeng , Jiao DongMei , Zhang WeiYu
Published: December 2024

Asthma, is a common, significant and diverse condition marked by persistent airway inflammation, with a major impact on human health worldwide. The predisposing factors for asthma are complex and widespread. The beneficial effects of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) in asthma have increasingly attracted attention recently. In asthma therapy, n-3 PUFAs may reduce asthma risk by controlling on levels of inflammatory cytokines and regulating recruitment of inflammatory cells in asthma. The specialized pro-resolving mediators (SPMs) derived from n-3 PUFAs, including the E- and D-series resolvins, protectins, and maresins, were discovered in inflammatory exudates and their biosynthesis by lipoxygenase mediated pathways elucidated., SPMs alleviated T-helper (Th)1/Th17 and type 2 cytokine immune imbalance, and regulated macrophage polarization and recruitment of inflammatory cells in asthma via specific receptors such as formyl peptide receptor 2 (ALX/FPR2) and G protein-coupled receptor 32. In conclusion, the further study of n-3 PUFAs and their derived SPMs may lead to novel anti-inflammatory asthma treatments.
Case report: Low-dose interleukin-2: a treatment of bullous pemphigoid with predominantly perifollicular blistering caused by PD-1/PD-L1 inhibitor
Authors: Zhang Yingyue , Cao Xianwei , Tong Jianbo
Published: December 2024

Objectives

This study aimed to evaluate the efficacy of low-dose interleukin (IL-2) treatment for bullous pemphigoid (BP) caused by anti-programmed cell death protein 1/ligand 1 (PD-1/PD-L1) inhibitors.

Methods

Low-dose IL-2 treatment was standardized for BP. The Bullous Pemphigoid Disease Area Index (BPDAI), 5D-Itch Scale (5D-IS), and Dermatology Life Quality Index (DLQI) were recorded before and after treatment, and hexachromatic lymphocytes, regulatory T cells (Treg cells), and cytokines were measured.

Results

A significant decline in the BPDAI score, 5D-IS, and DLQI score was observed following treatment. The count of B-cells, CD4+ T-cells, CD8+ T-cells, Treg cells, and the levels of cytokines (IL-4, -8, and -10) were significantly downregulated in comparison to baseline measurements.

Conclusion

Low-dose IL-2 could be an effective therapeutic choice for treating BP caused by PD-1/PD-L1 inhibitors.
The impact of persistent organic pollutants on fertility: exposure to the environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin alters reproductive tract immune responses
Authors: Stephens Victoria R. , Horner Kensley B. , Avila Walter M. , Spicer Sabrina K. , Chinni Riya , Bernabe Emily B. , Hinton Antentor O. , Damo Steven M. , Eastman Alison J. , McCallister Monique M. , Osteen Kevin G. , Gaddy Jennifer A.
Published: December 2024

Exposure to environmental contaminants can result in profound effects on the host immune system. One class of environmental toxicants, known as dioxins, are persistent environmental contaminants termed “forever chemicals”. The archetype toxicant from this group of chemicals is 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), an immunotoxicant that activates the aryl-hydrocarbon receptor pathway leading to a variety of changes in immune cell responses. Immune cell functions are crucial to the development and maintenance of healthy reproduction. Immune cells facilitate tolerance between at the maternal-fetal interface between the parent and the semi-allogenic fetus and help defend the gravid reproductive tract from infectious assault. Epidemiological studies reveal that exposure to environmental contaminants (such as TCDD) are linked to adverse reproductive health outcomes including endometriosis, placental inflammation, and preterm birth. However, little is known about the molecular mechanisms that underpin how environmental toxicant exposures impact immune functions at the maternal-fetal interface or within the reproductive tract in general. This review presents the most recent published work that studies interactions between dioxin or TCDD exposure, the host immune system, and reproduction.
Psoriatic arthritis in psoriasis: optimizing the current screening system for psoriatic arthritis based on serum data from U.S. and Chinese populations
Authors: Lin Zheng , Pan Si-yi , Shi Yue-yi , Wu Xuan , Dou Yuan , Lin Ping , Cao Yi
Published: December 2024

Background

Psoriatic arthritis (PSA) is an inflammatory joint disease associated with psoriasis (PSO) that can be easily missed. Existing PSA screening tools ignore objective serologic indicators. The aim of this study was to develop a disease screening model and the Psoriatic Arthritis Inflammation Index (PSAII) based on serologic data to enhance the efficiency of PSA screening.

Method

A total of 719 PSO and PSA patients from the National Health and Nutrition Examination Survey (NHANES) (as training set and test set) and 135 PSO and PSA patients who were seen at The First Affiliated Hospital of Zhejiang Chinese Medical University (as external validation set) were selected, 31 indicators for these patients were collected as potential input features for the model. Least Absolute Shrinkage and Selection Operator (LASSO) was used to identify PSA-related features. Five models of logistic regression (LR), random forest, k-nearest neighbor, gradient augmentation and neural network were developed in the training set using quintuple cross validation. And we developed PSAII based on the results of LASSO regression and weights of logistic model parameters. All performance metrics are derived on the test set and the external validation set.

Results

Five variables were selected to build models, including age, lymphocyte percentage, neutrophil count, eosinophilic count, and C-reactive protein. In all established models, the LR model performed the best, with an Area Under Curve (AUC) of 0.87 (95% confidence interval (CI): 0.83-0.90) on the test set; on the external validation set the AUC was 0.82 (95%CI: 0.74-0.90). The PSAII formula was PSAII = percentage of lymphocytes × C-reactive protein/(neutrophil count × eosinophilic count × 10). The AUC of PSAII in the test is 0.93 (95%CI: 0.88-0.97), and the cutoff value is 18. The AUC of the external validation set is 0.81 (95%CI: 0.72-0.89).

Conclusions

This study developed and validated five models to assist screening for PSA by analyzing serum data from NHANES and Chinese populations. The LR model demonstrated the best performance. We created PSAII for PSA screening. However, the high false positive rate of PSAII makes it necessary to combine it with other PSA screening tools when applied.
Immune and physiological responses in Penaeus monodon to ammonia-N stress: a multi-omics approach
Authors: Luo Zhi , Zhou Falin , Jiang Song , Huang Jianhua , Yang Lishi , Yang Qibin , Shi Jianzhi , Li Erchao , Ma Zhenhua , Li Yundong
Published: December 2024

Ammonia-N stress is a significant environmental factor that adversely affects the health and productivity of aquaculture species. This study investigates the effects of ammonia-N stress on the shrimp Penaeus monodon through a combination of biochemical, histological, transcriptomic, and metabolomic analyses. Shrimp were exposed to ammonia-N stress for 12 and 96 hours, and key markers of oxidative stress, nitrogen metabolism, immune response, and overall health were assessed. The results showed that prolonged ammonia-N exposure causes significant hepatopancreatic damage, including atrophy and deformation. Transcriptomic analysis revealed significant changes in gene expression related to apoptosis, immune response, and key metabolic pathways, with particular emphasis on the disruption of innate immune signaling and defense mechanisms. Metabolomic analysis identified disruptions in nucleotide turnover, antioxidant defenses, and fundamental metabolic processes. These findings suggest that ammonia-N stress induces a multifaceted stress response in shrimp, involving oxidative stress, immune activation, and metabolic disturbances. Understanding these immune-related and metabolic mechanisms provides valuable insights into the molecular responses of crustaceans to environmental stress, laying the foundation for assessing the ecological risk of ammonia-N and identifying potential immunological biomarkers for monitoring and mitigating its adverse effects in aquaculture systems.
Pilot study on the dynamic interactions between cardiac activity and corneal biomechanics during eye movements
Authors: Shahiri Mohammadali , Kasprzak Henryk , Asejczyk Magdalena
Published: December 2024

Background and objective

The study examines the relationship between ocular rotations and cardiovascular functions through detailed biomechanical analysis. The study documents specific patterns of ocular movements and their synchronization with cardiovascular activity, highlighting significant correlations. These findings provide a basis for understanding the opto-biomechanical interplay between ocular and cardiovascular dynamics.

Methods

Authors employed a custom-designed prototype, integrating a camera and numerical pulse oximeter, to analyze the right eyeballs of participants. The corneal surface reflections were recorded, along with concurrent blood pulsation (BP) signal acquisition. Numerical analysis helped determine the reflection positions and orientations to study eye movements and corneal deformations. Time and frequency domain analyses, including coherence functions, were utilized.

Results

Significant correlations were found between variations in corneal curvature, selected fixational eye movements (FEM) parameters, and Pulsatile ocular blood flow (POBF), revealing synchronized expansions of the corneal surfaces with cardiovascular activity. Furthermore, FEM displayed spectral correlations with BP, indicating an interrelation between ocular rotations and cardiovascular functions.

Conclusion

These findings reveal the complex interactions between the cornea and Pulsatile Ocular Blood Flow (POBF), as well as between Fixational Eye Movements (FEM) and POBF. While the influence of POBF on both corneal dynamics and FEM is clear, further research is necessary to directly link corneal dynamics and FEM. These insights hold potential for non-invasive diagnostic applications and provide a deeper understanding of ocular biomechanics.
Trends and levels of the global, regional, and national burden of pulmonary arterial hypertension from 1990 to 2021: findings from the global burden of disease study 2021
Authors: Liu Le , Li Chen , Cai Jing , Kong Renjing , Wang Yanjiao , Wang Yi , Li Shuang , Zhan Junkun , Liu Youshuo
Published: December 2024

Background

Pulmonary arterial hypertension (PAH) is a severe and progressive lung disease that significantly impairs patients’ health and imposes heavy clinical and economic burdens. Currently, there is a lack of comprehensive epidemiological analysis on the global burden and trends of PAH.

Methods

We estimated the prevalence, mortality, disability-adjusted life years (DALYs) of PAH from 1990 to 2021 using the results of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). The average annual percentage changes were used to estimate the trends of PAH across 21 regions and 204 countries and territories.

Results

From 1990 to 2021, the number of prevalent cases and deaths associated with PAH worldwide increased by 81.5 and 48.4%. However, the age-standardized prevalence rate of PAH remained relatively stable, while the age-standardized mortality rate and DALYs declined. In 2021, the global age-standardized prevalence rate of PAH was 2.28 per 100,000, with 1.78 per 100,000 in males and 2.75 per 100,000 in females. The age-standardized mortality rate of PAH globally was 0.27 per 100,000, and the age-standardized DALYs was 8.24 per 100,000. Among the 21 regions, Western Europe had the highest age-standardized prevalence rate (3.56 per 100,000), while North Africa and the Middle East had the highest age-standardized mortality rate (0.44 per 100,000) and DALYs (14.81 per 100,000). Additionally, older individuals and females are at higher risk of PAH. The age-standardized mortality rate and DALYs associated with PAH increase with age, peaking in the 95+ age group. As the sociodemographic index increased, the age-standardized prevalence rates showed an upward trend, while both the age-standardized mortality rates and DALYs exhibited a downward trend.

Conclusion

From 1990 to 2021, the overall trend of PAH burden presents regional and national variations and differs by age, sex, and sociodemographic index. These findings emphasize the importance of implementing targeted interventions to alleviate the burden of PAH.