bluuebunny/crossref_metadata_2025 huggingface dataset:
19. YÜZYILDA NİŞ VE LESKOFÇA ÇİFTLİKLERİ’NDE MÜLKİYET VE “CEZA HUKUKU” SORUNLARI: SADRAZAM KIBRISLI MEHMED EMİN PAŞA’NIN TEFTİŞ RAPORLARI ÇERÇEVESİNDE
Authors: KARAGÖZ Fatma Gül
Published: July 2023

19. yüzyılda Tanzimat dönemi boyunca Osmanlı hükümeti taşrada pek çok müfettiş görevlendirmiştir. Müfettişlerin görevlendirilmesinin arka planında farklı sebepler vardır: Gülhane Hatt-ı Hümayunu’nun ilanının hemen akabinde, 1840 yılında, Ahmed Arif Hikmet Bey özellikle toprak rejimi hakkında bilgi toplamak ve halka Tanzimat sürecini anlatmak için Rumeli müfettişi olarak atanmıştır. Arif Hikmet Bey ayrıca halkın şikayetlerini de dinlemiştir. Bu teftişin amacı yerel düzlemde bilgi toplayarak tarımsal üretimi yeniden düzenlemektir. 1858 Kanunname-i Arazisi’nin yürürlüğe girmesinden sonra da teftişler benzer kaygılarla, bazen de dış müdahalenin önlenmesiyle amacıyla, devam etmiştir. Bu teftişlerden biri de 1860 yılında Sadrazam Kıbrıslı Mehmed Emin Paşa’nın Rumeli’de gerçekleştirdiği teftiştir. Bu araştırma sürecinde tutulan ve defter haline getirilmiş raporlar, 19. yüzyılın ikinci yarısında Bulgaristan ve Sırbistan’da toprak hukuku sorunları açısından önemli bir kaynak teşkil etmektedir. Ayrıca bu belgeler Osmanlı toplumunda yönetici sınıfıyla halk arasında ortaya çıkan cezai problemler hakkında önemli veri sunmaktadır. Bu makale Emin Paşa’nın teftişinde Niş ve Leskofça çiftliklerinde ortaya çıkan mülkiyet hukuku ve ceza hukukuna dair şikayetlerin ve çözüm sürecinin hukukî analizine dayanmaktadır.
TERÖR ÖRGÜTÜ VARLIĞININ HUKUKEN TESPİTİ
Authors: YILDIZ Furkan
Published: July 2023

Terör saldırıları ile karşı karşıya kalan devletler, varlıklarını sürdürebilmek için terörle mücadele etmek zorundadır. Bu mücadele saldırıları önleme, saldırılara karşılık verme ve uluslararası iş birliği yapma şeklinde olabilmektedir. Güçlü devlet yapıları, savunma yeteneği ve askeri müdahale kapasitesiyle bağlantılı olduğundan terörle mücadele sürecinde hayati öneme sahiptir. Sağlam ve etkili bir hukuk sistemi de güçlü devlet yapıları için olmazsa olmaz bir faktör olarak karşımıza çıkmaktadır. Zira etkin bir şekilde uygulanan hukuk kuralları terörizmle mücadele sürecindeki önleyici tedbirlerin başında gelmektedir. Uluslararası güvenliği her geçen gün daha fazla tehdit eden terörizm sorunu bu çalışmada hukuki boyutlarıyla incelenmiş, bu bağlamda bir organizasyonun hukuken terör örgütü olarak belirlenmesi sorunu ele alınmıştır. Bir organizasyonun terör örgütü niteliğinde olup olmadığının tespiti ve terör örgütü olarak tanıma yöntemleri hususunda Türk hukukunda yasal bir düzenleme bulunmamaktadır. Bu durumda terör örgütlerinin varlığı ceza davalarında, yargı organları tarafından dosyadaki deliller kapsamında yapılan değerlendirme sonucunda belirlenmekte, terör örgütünün varlığı kesinleşen mahkeme kararlarıyla tescillenmektedir.
KARŞILAŞTIRMALI ANAYASA HUKUKUNDA VE TÜRKİYE'DE TORBA KANUN
Authors: ESEN ARNWİNE Selin , YEŞİLIRMAK Bahadır
Published: July 2023

Yasaların yapılma usulü ve sahip olmaları gereken biçimsel ve maddi özellikleri demokratik hukuk devletinin önemli konularından biridir. Torba kanun, genellikle hızlandırılmış yasama usulü kullanarak birbiriyle ilgisi olmayan çok sayıda konuyu çok sayıda maddeden oluşan tek bir yasada düzenleyen bir yöntemdir. Bu usul, Türkiye de dâhil olmak üzere çok sayıda ülkede sıklıkla uygulanan ve çok eleştirilen yasa türlerinden biridir. Bu makalede demokratik hukuk devletinde olması gereken nitelikli yasa kavramı ve bunun temel özellikleri; torba kanun kavramı, torba kanunun konusu, özellikleri, olumlu ve olumsuz yönleri ve torba kanun uygulamasını sınırlamaya ya da kaldırmaya yönelik hukuki araçlar karşılaştırmalı olarak ele alınmaktadır.
THE DISAPPEARANCE OF THE "PRIVATE" ELEMENT FROM THE CONCEPT OF THEFT: A HISTORICAL EXPLANATION
Authors: ZHANG Xuewei
Published: July 2023

According to the unique public and private law division standards in Roman law, the concept of theft in Roman law has a dual nature of public and private. Ordinary theft is considered to reflect private legal relations and is a delictum, while aggravated theft reflects the legal relations dominated by the will of the state and is a public crime. The duality of this theft also affected the development of the concept of theft in the Middle Ages, both Canon law and Germanic law distinguished between ordinary theft and aggravated theft, but ordinary theft was no longer regarded as delictum. Germanic law upheld the idea of “public peace”, while Canon law legitimized the criminalization of theft based on the idea of “atonement” and finally integrated the concepts of theft in Roman law, Canon law and Germanic law through the promulgation of the Constitutio Criminalis Carolina at the end of the Middle Ages. Ultimately, Germanic jurists reinterpreted the conception of theft expounded by classical jurists and transmuted the notion of theft into one invested with the character of a public crime. This thereafter constituted the prototypical paradigm of modern German theft legislation.
A Cluster Analysis of Renewable Electricity Generation Policies in Asian Region Countries Using SPSS Software
Authors: HARAMEEN Huzaıfa Mohammed Adam , AKMAN Gulsen
Published: July 2023

The sector of renewable electricity generation in Asia region countries was comprehensively analyzed. A comparative study has been conducted with bar chart. A hierarchical clustering analysis was performed for the various renewable electricity generation types using SPSS software. The countries were clustered into 7 clusters based on the total renewable electricity generation. In hydroelectricity sector Asia Region countries were clustered into six groups in which India and Turkey are taking the lead. In Wind electricity sector four clusters were found in which India and Turkey lead. Countries were analyzed by dividing them into six clusters based on solar energy production. India and Japan is isolated in the first cluster followed by Turkey, while Arab Gulf countries were in the sixth cluster. In biomass electricity sector five clusters were founds in which India and japan in the first cluster. In geothermal electricity, Indonesia is isolated in the first. Four clusters were obtained in the wave-tide electricity sector in which Japan, South Korea and Turkey are isolated in the first cluster. Multiple Regression Model was created to estimate the amount of carbon dioxide emissions in Asia Region countries using the renewable electricity generation as an independent variable. However, the value of the intercept and the hydroelectricity factor were found 51.888 and 3.116 respectively. Moreover, a strong correlation between the GDP and the hydro, solar, wind, and biomass electricity generation was found.
The Effect of Human Resource Management Practices on Open Innovation: A Research on Blue Collar Employees in IT Business
Authors: KANDEMİR Hamza , YILDIRIM Duygu , TEZCAN Mehmet
Published: July 2023

Human resources management practices are carried out in order to ensure that people efficiently, effective and actively work and to maximize their contribution to the organization during the process from entering an organization to leaving that organization. Since the importance of innovation has been understood in terms of the competitiveness of businesses, it has been one of the topics of interest to manage employees and to understand human resource management practices to support their innovation capacities. This study, it has tried to determine the effect of human resources management practices carried out on the personnel working as a lower level (blue collar) in IT sector businesses on the open innovation climate of the organization. For this purpose, practices of human resource management including human resources planning, training and development, personnel empowerment, performance evaluation, wage management and reward system, recruitment and placement, worker health and safety have been revealed statistically impact on open innovation climate dimensions (innovation and flexibility, outward focus and insight). In conclusion, it has been determined to be effective human resources planning, which is one of the human resources management practices on all three of the open innovation climate dimensions. Also, the occupational health and safety practice has a positive effect on the external focus dimension.
Öz-Şefkat Konusunda Yayınlanan Makalelerin Bibliyometrik Analizi
Authors: KARAGÖZ Şerife , UZUNBACAK Hasan Hüseyin
Published: July 2023

Bu çalışmanın amacı Türkiye’de 2007-2023 yılları arasında öz-şefkat konusunda yapılmış olan çalışmaları sistematik bir şekilde incelemektir. Bu incelemede, nicel araştırma yöntem türlerinden birisi olan bibliyometrik analiz kullanılmıştır. Araştırma evrenini, DergiPark, TR Dizin ve SOBİAD gibi veri tabanlarında yapılan tarama sonucunda elde edilen toplam 168 çalışma (araştırma makalesi ve derleme) oluşturmaktadır. Araştırmada, amaçlı örnekleme yönteminden faydalanılmış olup verilerin analizinde MAXQDA 2020 programı kullanılmıştır. Makalelerde öz-şefkat kavramı 8 ana temaya (yayınlandığı yıl, makale türü, kullanılan dil, veri toplama araçları, kullanılan analiz programları, araştırma yöntemleri, ilişkili olduğu değişkenler, örneklem kitlesi) ayrılmış ve alt kodlamalar gerçekleştirilmiştir. Bazı analiz sonuçları değerlendirildiğinde öz-şefkat kavramına ilişkin araştırma makalelerinin 2022 yılında daha yüksek seviyede olduğu görülmektedir. Nicel araştırma yöntem ve tekniklerinin kullanıldığı makalelerde öğrenciler örnekleminin daha çok tercih edildiği saptanmıştır. Söz konusu kavramın en yoğun olarak psikolojik sağlamlık, depresyon, affetme kavramları ile ilişkilendirildiği belirlenmiştir. Sonuç olarak öz-şefkat kavramının yazında önemli bir yer kapladığı ve ilgili araştırmaların yıllar geçtikçe artmaya başladığı görülmektedir.
Nüfus Coğrafyası Açısından Bir Değerlendirme: İstanbul Gaziosmanpaşa İlçesi Örneği
Authors: YAĞIZ Zeynep , SERTKAYA DOĞAN Özlem
Published: July 2023

Nüfus, sınırları belirlenmiş bir sahada ve belli bir zaman diliminde yaşayan kişilerin toplam sayısını ifade eder. Nüfus coğrafyası ise nüfusun mekânsal dağılışını, bu dağılışta etkili olan coğrafi unsurları, nüfus ve mekân etkileşimini ortaya koyarak, nüfusun nicel ve nitel özelliklerini beşerî coğrafya ilkelerine uygun olarak araştırılmasını sağlayarak elde edilen bulguların bir sonuca ulaşılmasını amaçlar. Ülkelerin sosyal, ekonomik, kültürel, sanayi gibi nitel ve nicel alanlarda gelişmişlik durumunu ifade eden en önemli unsur nüfus yapısıdır. Kalkınma planlarının hazırlanmasında toplam nüfus miktarının yanı sıra nüfusun yaş, cinsiyet, doğum, ölüm, evlenme, boşanma, eğitim gibi nitel özelliklerinin de belirlenmesi ülkelerin mevcut ya da gelecekte uygulayacakları nüfus planlama çalışmalarını doğrudan etkiler. Bu kapsamda İstanbul Gaziosmanpaşa ilçesinde 1927-2022 yılları arasında nüfusun zaman içinde göstermiş olduğu nitel ve nicel özelliklerinde meydana gelen değişim ve gelişim, ilçe ile ilgili yapılan demografik yapı çalışmalarında büyük önem taşır. Gaziosmanpaşa’da nüfus, özellikle 1950’li yıllardan itibaren gerek dış göç gerekse iç göç sonucunda sürekli artmıştır ve hazırlanan nüfus projeksiyonları ile gelecekte de artacağı öngörülmektedir. Nüfusun sürekli artması beraberinde trafik, çevre kirliliği, işsizlik gibi birçok sorunu beraberinde getirdiğinden uygulanabilir bir nüfus politikasının ilçe bazında hazırlanmasını zorlaştırmıştır. Adını Plevne Kahramanı’ndan alan Gaziosmanpaşa, geçmişten günümüze kadar sürekli göç alarak nüfus bakımından kozmopolit bir yapıya dönüşmüştür.
Hz. Ömer’in Yönetim Anlayışında Emânet İlkesinin Önemi
Authors: KURT Eyüp
Published: July 2023

Hz. Peygamber’in vefatına yakın bir dönemde ortaya çıkan ve irtihalinden sonra giderek yaygınlaşan Ridde hâdiseleri, oluşturulan yönetime karşı ilk başkaldırı olmuştur. Bu durum, ana unsurunu Ensar destekli Muhâcirlerin oluşturduğu “Merkez”in, “Çevre” tarafından bir üst otorite olarak benimsenmekte zorlanıldığını göstermiştir. Bahsi geçen “Merkez-Çevre” rekabeti, özellikle Hz. Ömer liderliğinde sergilenen yönetim mekanizmasının işletilmesindeki anlayış sayesinde yeniden ortaya çıkmamıştır. Toplumun çok daha kozmopolit bir yapıya dönüşmesine rağmen bu dönemde herhangi bir tepkisel hareketin yaşanmamasını sağlayan yönetimin devleti algılayış biçiminin tespiti, bu çalışmanın vücuda getirilmesinin ana hedeflerindendir. Bu çalışmada selefleriyle aynı değerlere sahip olmasına rağmen özellikle devlet yönetiminde Hz. Ömer’i öne çıkaran hususlar irdelenmeye çalışılmıştır. Klasik kaynaklardan ve araştırmalardan istifade edilerek bahsi geçen hedeflere ulaşılmaya çalışılmıştır. Çalışmanın akademik yazına katkı sağlayacağı düşünülmektedir.
Positioning of pivot points in quadrupedal locomotion: limbs global dynamics in four different dog breeds
Authors: Andrada Emanuel , Hildebrandt Gregor , Witte Hartmut , Fischer Martin S.
Published: July 2023

Dogs (Canis familiaris) prefer the walk at lower speeds and the more economical trot at speeds ranging from 0.5 Fr up to 3 Fr. Important works have helped to understand these gaits at the levels of the center of mass, joint mechanics, and muscular control. However, less is known about the global dynamics for limbs and if these are gait or breed-specific. For walk and trot, we analyzed dogs’ global dynamics, based on motion capture and single leg kinetic data, recorded from treadmill locomotion of French Bulldog (N= 4), Whippet (N= 5), Malinois (N= 4), and Beagle (N= 5). Dogs’ pelvic and thoracic axial leg functions combined compliance with leg lengthening. Thoracic limbs were stiffer than the pelvic limbs and absorbed energy in the scapulothoracic joint. Dogs’ ground reaction forces (GRF) formed two virtual pivot points (VPP) during walk and trot each. One emerged for the thoracic (fore) limbs (VPPTL) and is roughly located above and caudally to the scapulothoracic joint. The second is located roughly above and cranially to the hip joint (VPPPL). The positions of VPPs and the patterns of the limbs’ axial and tangential projections of the GRF were gaits but not always breeds-related. When they existed, breed-related changes were mainly exposed by the French Bulldog. During trot, positions of the VPPs tended to be closer to the hip joint or the scapulothoracic joint, and variability between and within breeds lessened compared to walk. In some dogs, VPPPLwas located below the pelvis during trot. Further analyses revealed that leg length and not breed may better explain differences in the vertical position of VPPTLor the horizontal position of VPPPL. The vertical position of VPPPLwas only influenced by gait, while the horizontal position of VPPTLwas not breed or gait-related. Accordingly, torque profiles in the scapulothoracic joint were likely between breeds while hip torque profiles were size-related. In dogs, gait and leg length are likely the main VPPs positions’ predictors. Thus, variations of VPP positions may follow a reduction of limb work. Stability issues need to be addressed in further studies.
Cu-doped polypyrrole hydrogel with tumor catalyst activity for NIR-II thermo-radiotherapy
Authors: Wang Shile , Fei Haotian , Ma Yuhong , Zhu Daoming , Zhang Hongtao , Li Xiang , Huang Qinqin
Published: July 2023

Introduction: Radiotherapy (RT) is one of the key methods for treating breast cancer. However, the effect of single RT is often poor because of insufficient deposition of X-rays in tumor sites and radiation resistance induced by the abnormal tumor microenvironment (overexpression of glutathione (GSH)). The development of multifunctional RT sensitizers and synergetic therapeutic strategies is, therefore, a promising area for enhancing the anticancer effect of RT.

Methods: In this study, a multifunctional nanozyme hydrogel based on Cu-doped polypyrrole (CuP) was designed to work concertedly with a second near-infrared thermal RT. The CuP-based hydrogel (CH) reached the tumor site when injected in-situ and achieved long-term storage.

Results: Once stimulated with 1064-nm laser irradiation, the heated and softened hydrogel system released CuP nanozyme to provide photothermal therapy, thereby inhibiting the repair of DNA damage caused by RT. In addition, CuP with dual nanozyme activity depleted the intracellular GSH to reduce the antioxidant capacity of the tumor. Moreover, CuP converted H2O2 to produce ·OH to directly kill the tumor cells, thus enhancing the capability of low-dose RT to inhibit tumor growth. In vivo experiments showed that the CH system used in combination with a low-power 1064-nm laser and low-dose RT (4 Gy) exhibited good synergistic anticancer effects and biological safety.

Discussion: As a new light-responsive hydrogel system, CH holds immense potential for radio-sensitization.
Development of an antibacterial polypropylene/polyurethane composite membrane for invisible orthodontics application
Authors: Yang Feng , Wu Chenyi , Jiang Yuanzhang , Tan Lin , Shu Rui
Published: July 2023

In virtue of the advantages, such as aesthetics, designability, convenient removal, and comfortable experience, invisible orthodontics (IO) have been widely recognized and accepted by the public. However, most of the membranes currently used for IO only meet the requirement of shape retention. Other vital functions, like antibacterial and antifouling activities, are neglected. Herein, antibacterial composite membranes (ACMs) containing polypropylene (PP), thermoplastic polyurethane (TPU) and poly (hexamethylene guanidine) hydrochloride-sodium stearate (PHMG-SS) were facilely manufactured through the hot-pressing membrane forming technology. ACMs were conferred with favorable transparency (∼70% in the visible light range) and excellent antibacterial ability. Experiment results demonstrated that bactericidal rates of ACMs against Staphylococcus aureus, Escherichia coli and Streptococcus mutans were larger than 99.99%. Noticeably, the amount of protein adhered on the surface of ACMs was only 28.1 μg/cm2, showing ideal antifouling performance. Collectively, the mutifunctional ACMs in the study are expected to be prominent alternatives for existing IO.
Regulation of the Wnt signaling pathway during myogenesis by the mammalian SWI/SNF ATPase BRG1
Authors: Sharma Tapan , Olea-Flores Monserrat , Imbalzano Anthony N.
Published: July 2023

Skeletal muscle differentiation is a tightly regulated process, and the importance of the mammalian SWI/SNF (mSWI/SNF) chromatin remodeling family for regulation of genes involved in skeletal myogenesis is well-established. Our prior work showed that bromodomains of mSWI/SNF ATPases BRG1 and BRM contribute to myogenesis by facilitating the binding of mSWI/SNF enzymes to regulatory regions of myogenic and other target genes. Here, we report that pathway analyses of differentially expressed genes from that study identified an additional role for mSWI/SNF enzymes via the regulation of the Wnt signaling pathway. The Wnt pathway has been previously shown to be important for skeletal muscle development. To investigate the importance of mSWI/SNF enzymes for the regulation of the Wnt pathway, individual and dual knockdowns were performed for BRG1 and BRM followed by RNA-sequencing. The results show that BRG1, but not BRM, is a regulator of Wnt pathway components and downstream genes. Reactivation of Wnt pathway by stabilization of β-catenin could rescue the defect in myogenic gene expression and differentiation due to BRG1 knockdown or bromodomain inhibition using a specific small molecule inhibitor, PFI-3. These results demonstrate that BRG1 is required upstream of β-catenin function. Chromatin immunoprecipitation of BRG1, BRM and β-catenin at promoters of Wnt pathway component genes showed binding of BRG1 and β-catenin, which provides further mechanistic insight to the transcriptional regulation of these genes.
The interplay of common genetic variants NRG1 rs2439302 and RET rs2435357 increases the risk of developing Hirschsprung’s disease
Authors: Chi Shuiqing , Li Shuai , Cao Guoqing , Guo Jialing , Han Yunqiao , Zhou Yun , Zhang Xi , Li Yibo , Luo Zhibin , Li Xiangyang , Rong Liying , Zhang Mengxin , Li Linglu , Tang Shaotao
Published: July 2023

Introduction: As a congenital and genetically related disease, many single nucleotide polymorphisms (SNPs) have been reported to be associated with the risk of HSCR. Our previous research showed that SNP rs2439302 (NRG1) interacted with rs2435357 (RET) to increase the risk of HSCR development. However, the underlying molecular mechanism is still not well understood.

Methods: SNP rs2439302 (NRG1) and rs2435357 (RET) were genotyped in 470 HSCR cases. The expression of NRG1 and RET was investigated in the colon of HSCR patients. Knockdown of the NRG1 and RET homologs was performed in zebrafish to investigate their synergistic effect on ENS development. The effect of SNP rs2439302 and rs2435357 polymorphism on neuron proliferation, migration, and differentiation were investigated in SHSY-5Y cells and IPSCs.

Results: Significant downregulation of NRG1 and RET expression was noticed in the aganglionic segment of HSCR patients and SHSY-5Y cells with rs2439302 GG/rs2435357 TT genotype. NRG1 and RET double mutants caused the most severe reduction in enteric neuron numbers than NRG1 single mutant or RET single mutant in the hindgut of zebrafish. SHSY-5Y cells and IPSCs with rs2439302 GG/rs2435357 TT genotype exhibited a decreased proliferative, migration, and differentiative capacity. CTCF showed a considerably higher binding ability to SNP rs2439302 CC than GG. NRG1 reduction caused a further decrease in SOX10 expression via the PI3K/Akt pathway, which regulates RET expression by directly binding to rs2435357.

Discussion: SNP rs2439302 (NRG1) GG increases the risk of developing HSCR by affecting the binding of transcription factor CTCF and interacting with rs2435357 (RET) to regulate RET expression via the PI3K/Akt/SOX10 pathway.
CSK-mediated signalling by integrins in cancer
Authors: Maldonado Horacio , Leyton Lisette
Published: July 2023

Cancer progression and metastasis are processes heavily controlled by the integrin receptor family. Integrins are cell adhesion molecules that constitute the central components of mechanosensing complexes called focal adhesions, which connect the extracellular environment with the cell interior. Focal adhesions act as key players in cancer progression by regulating biological processes, such as cell migration, invasion, proliferation, and survival. Src family kinases (SFKs) can interplay with integrins and their downstream effectors. SFKs also integrate extracellular cues sensed by integrins and growth factor receptors (GFR), transducing them to coordinate metastasis and cell survival in cancer. The non-receptor tyrosine kinase CSK is a well-known SFK member that suppresses SFK activity by phosphorylating its specific negative regulatory loop (C-terminal Y527 residue). Consequently, CSK may play a pivotal role in tumour progression and suppression by inhibiting SFK oncogenic effects in several cancer types. Remarkably, CSK can localise near focal adhesions when SFKs are activated and even interact with focal adhesion components, such as phosphorylated FAK and Paxillin, among others, suggesting that CSK may regulate focal adhesion dynamics and structure. Even though SFK oncogenic signalling has been extensively described before, the specific role of CSK and its crosstalk with integrins in cancer progression, for example, in mechanosensing, remain veiled. Here, we review how CSK, by regulating SFKs, can regulate integrin signalling, and focus on recent discoveries of mechanotransduction. We additionally examine the cross talk of integrins and GFR as well as the membrane availability of these receptors in cancer. We also explore new pharmaceutical approaches to these signalling pathways and analyse them as future therapeutic targets.
Outcomes of covered stents versus bare-metal stents for subclavian artery occlusive disease
Authors: Wei Libing , Gao Xixiang , Tong Zhu , Cui Shijun , Guo Lianrui , Gu Yongquan
Published: July 2023

Objective

To compare the clinical efficacy of covered stents and bare-metal stents in the endovascular treatment of subclavian artery occlusive disease.

Methods

Between January 2014 and December 2020, 161 patients (112 males) underwent stenting of left subclavian arteries; CSs were implanted in 55 patients (34.2%) and BMSs in 106 (65.8%). Thirty-day outcomes, mid-term patency, and follow-up results were analyzed with Kaplan-Meier curves. Relevant clinical, anatomical, and procedural factors were evaluated for their association with patency in the two groups using Cox proportional hazards regression.

Results

Mean follow-up was 45 ± 18 months. The primary patency was 93.8% (95% CI, 81.9%–98.0%) in the covered stent group and 73.7% (95% CI, 63.2%–81.6%; P = 0.010) in the bare-metal stent group. The primary patency in the total occlusion subcategory was significant in favor of CS (93.3%, 95% CI, 61.26%–99.0%) compared with BMS (42.3%, 95% CI, 22.9%–60.5%; P = 0.005). Cox proportional hazards regression indicated that the use of BMSs [hazard ratio (HR), 4.90; 95% CI, 1.47–16.31; P = 0.010] and total occlusive lesions (HR, 7.03; 95% CI, 3.02–16.34; P < 0.001) were negative predictors of patency, and the vessel diameter (HR, 3.17; 95% CI, 1.04–9.71; P = 0.043)) was a positive predictor of patency.

Conclusion

Compared with bare stents, covered stents have a higher midterm primary patency in the treatment of subclavian artery occlusive disease.
Systemic immune-inflammation index is associated with coronary heart disease: a cross-sectional study of NHANES 2009–2018
Authors: Ma Jiwen , Li Ka
Published: July 2023

Background

Inflammation has been linked to the development of coronary heart disease (CHD). The systemic immune inflammation index (SII) is a useful biomarker of systemic inflammation. Our study aimed to explore the correlation between SII and CHD.

Methods

We conducted a multivariate logistic regression analysis, smoothing curve fitting, and segmented model comparison on 15,905 participants with a CHD prevalence of 3.31% and a mean age of 46.97 years.

Results

Adjusting for gender, age, and race, we found a negative association between SII and CHD [odds ratio (OR) 0.66; 95% confidence interval (CI) 0.48, 0.90]. There was an inverse trend where increasing SII was associated with decreasing odds of CHD (p for trend = 0.0017). After further adjustment, the association was strengthened, with a similar trend (p for trend = 0.0639). Smoothing curve fitting demonstrated a gender-specific association between SII and CHD.

Conclusions

Our findings suggest that higher SII values may be associated with a higher incidence of CHD, which varies by gender. SII may be a cost-effective and convenient method to detect CHD. Further studies are needed to confirm the causality of these findings in a larger prospective cohort.
A non-linear relationship between triglyceride glucose waist circumference and nonalcoholic fatty liver disease in a Japanese population: a secondary analysis
Authors: He Xiaojie , Huang Xinyue , Qian Yafang , Sun Ting
Published: July 2023

Introduction

Nonalcoholic fatty liver disease (NAFLD) is a common metabolic disorder associated with insulin resistance (IR). Triglyceride glucose waist circumference (TyG-WC) is a novel index of IR that reflects both visceral fat and hepatic steatosis. However, it is not known whether TyG-WC and NAFLD exhibit a nonlinear relationship in Japanese subjects with normal plasma glucose level. Thus, we examined the relationship between TyG-WC and NAFLD, in addition to determining the threshold level of TyG-WC associated with NAFLD.

Methods

A secondary analysis was performed based on a previous study that extracted medical examination records from Murakami Memorial Hospital between 2004 and 2015 in order to detect chronic diseases and their risk factors. TyG-WC was determined at baseline. NAFLD is the dependent variable. Univariate and multivariate logistic regression models were used to evaluate the risk of NAFLD incidence. Based on the smoothing plot, a two-piecewise linear regression model was used to examine the threshold effect of TyG-WC on NAFLD. A subgroup analysis was carried out in order to study other factors that may influence the association between TyG-WC and NAFLD.

Results

14,280 met the criteria for inclusion in the current secondary analysis. The adjusted OR (95% CI) for NAFLD in all subjects was 1.007 (95% CI 1.006–1.009, P < 0.001). The relationship between TyG-WC and NAFLD in Japanese subjects with normal plasma glucose level is nonlinear. TyG-WC is positively associated with NAFLD when TyG-WC is ranged between 480 and 800. In subgroup analyses, there was a significant interaction between BMI and TyG-WC associated NAFLD risk (P for interaction <0.001).

Discussion

The relationship between TyG-WC and NAFLD is nonlinear. TyG-WC is positively associated with NAFLD when TyG-WC is ranged between 480 and 800. There is potential clinical significance for the TyG-WC in identifying groups at high risk for NAFLD in subjects with normal plasma glucose level.
The role of m6A and m6Am RNA modifications in the pathogenesis of diabetes mellitus
Authors: Benak Daniel , Benakova Stepanka , Plecita-Hlavata Lydie , Hlavackova Marketa
Published: July 2023

The rapidly developing research field of epitranscriptomics has recently emerged into the spotlight of researchers due to its vast regulatory effects on gene expression and thereby cellular physiology and pathophysiology. N6-methyladenosine (m6A) and N6,2’-O-dimethyladenosine (m6Am) are among the most prevalent and well-characterized modified nucleosides in eukaryotic RNA. Both of these modifications are dynamically regulated by a complex set of epitranscriptomic regulators called writers, readers, and erasers. Altered levels of m6A and also several regulatory proteins were already associated with diabetic tissues. This review summarizes the current knowledge and gaps about m6A and m6Am modifications and their respective regulators in the pathophysiology of diabetes mellitus. It focuses mainly on the more prevalent type 2 diabetes mellitus (T2DM) and its treatment by metformin, the first-line antidiabetic agent. A better understanding of epitranscriptomic modifications in this highly prevalent disease deserves further investigation and might reveal clinically relevant discoveries in the future.
Assessing ecotoxicity of an innovative bio-based mulch film: a multi-environmental and multi-bioassay approach
Authors: Barbir J. , Arato E. , Chen C-Y. , Granberg M. , Gutow L. , Krång A-S. , Kröger S. D. , Leal Filho W. , Liwarska-Bizukojc E. , Miksch L. , Paetz K. , Prodana M. , Saborowski R. , Silva Rojas R. , Witt G.
Published: July 2023

Among the highly diverse range of biobased polymers, polylactic acid (PLA) received vast attention in recent years due to its versatility for different applications and being the first commercially used polymer produced from renewable sources. Production and application of bio-based, biodegradable plastics will have one of the most crucial roles in tackling worldwide plastic pollution.

Methods: This study is based on integrative ecotoxicological assessment of an innovative PLA-based agricultural mulch film (BPE-AMF-PLA), developed under the H2020 EU project “BIO-PLASTICS EUROPE”, towards organisms from different environmental compartments (soil, fresh water and marine) and from different trophic levels. Such comprehensive evaluation has an overarching goal to promote environmentally safe and sustainable use of these PLA-based plastics for agricultural and other potential applications.

Results: Low-to-no phytotoxicity was obtained in both single-species standardized bioassays, and in a multi-species microcosms experiment. Earthworm reproduction was negatively affected at the lowest test concentration of 0.1% w/w of PLA-based plastic particles. For freshwater Daphnia, reproduction was found a sensitive endpoint, upon exposure to the leachates of the PLA-based plastic. However, the reported toxicity seemed to be caused by the presence of 2-methylnaphthalene, which can be avoided in the production process. As for the marine organisms, algae growth was inhibited with a LOEC = 25 g L−1, whereas test with brine shrimp only revealed stimulation of lipase upon digestion of micro-sized PLA-based plastics. Marine lugworm ingested pristine and UV pre-treated micro-sized plastics, yet without impact either on biological activity, or on the health of the test individuals.

Discussion: The approach used in the present work will contribute to product development, environmental safety and sustainable applications of the PLA-based mulch film BPE-AMF-PLA, in the scope of project BIO-PLASTICS EUROPE. Furthermore, the tools and results obtained in this work are a relevant contribution in the framework development for additional support in the certification of the bio-based polymers, being aligned with European zero waste and non-toxicity strategies, certification, and regulations.
Construction and application of a new index for root architecture quantification in arid and semi-arid regions
Authors: Li Qiang , Ai Feng , Kang Furen , Zhang Zheng , Tuo Dengfeng
Published: July 2023

During the restoration of degraded vegetation, the mutual matching of underground root systems is crucial for the formation and effective function of the future plant community. In this study, the Amoeba graphic method was integrated to comprehensively establish a root framework index (RFI), based on the three dimensions of root morphology, as well as quantitative and spatial connection characteristics, to quantify the root system architecture. The root development characteristics of alfalfa (T-type), switchgrass (F-type), and mixed planting with alfalfa and switchgrass (T+F-type) were monitored at the test positions. The RFI parameters comprise the acting coefficient of the root framework, root density, root framework degree, and soil bulk density. The RFI values of T-, F-, and T + F-type were 0.38, 0.86, and 1.68, respectively, and were found to provide a well representation of the root structure characteristics. The findings obtained in this study provide scientific support for the ecological construction and evaluation of degraded vegetation.
Warming promoted CH4 absorption compared with precipitation addition in typical steppe in Inner Mongolia
Authors: Chen Xuemeng , Wan Zhiqiang , Gu Rui , Ganjurjav Hasbagan , Hu Guozheng , Gao Qingzhu , Chun Xi , Zhou Haijun , Hai Chunxing
Published: July 2023

Introduction

Climate change, characterized by rising temperatures and changing precipitation patterns, has emerged as a significant global concern. Particularly, the warming potential of CH4 is 28 times greater than that of CO2, leading to an increased focus on its impact. Among various ecosystems, grasslands exhibit a high vulnerability to climate change. Grassland in Inner Mongolia is an important component of the typical grassland in Eurasian, and there was evidence that warmer and more precipitation in this area in future.

Methods

In this study, we utilized an open-top chamber (OTC) to conduct warming and precipitation experiments on a representative steppe located in Inner Mongolia in 2011. From 2017 to 2019, we monitored various factors, including soil temperature, moisture, CH4 flux, community characteristics, soil carbon nitrogen content. Subsequently, we analyzed the response of CH4 flux and its influencing factors to warming and precipitation in this typical steppe.

Results

The soil in the typical steppe acted as a CH4 sink. In 2018, CH4 flux during the growing season and t during the non-growing season were −59.31 and −21.21 under C, −56.55 and −31.17 under T, −41.34 and −24.93 under P, −50.09 and −26.51 ug C·m−2·h−1 under TP respectively. Warming stimulated absorption of CH4 during the non-growing season (25.8%), while the addition of precipitation hindered CH4 absorption during the growing season (76.37%). Warming and precipitation addition decreased the percentage of CH4 absorbed in growing season and increased that in non-growing season which account 67.66% and 32.34% under C, 59.81% and 40.19% under T, 62.71% and 37.29% under P, 62.03% and 37.97% under TP respectively. Soil temperature exhibited a positive correlation with CH4 flux (P<0.001), while the dominance of Leymus chinensis (IV-L.c.) exhibited a negative correlation with CH4 flux (P<0.01). Moreover, NH4+-N displayed a positive correlation with CH4 flux (P<0.05).

Conclusion

The findings suggest that CH4 absorption in a typical steppe may increase in a warmer future, and warming is conducive to the absorption of CH4 in the non-growing season. Not only abiotic factors had an impact on CH4 absorption, but also changes in community composition. Consequently, further exploration of the underlying mechanisms is warranted.
Functional identification of two novel variants and a hypomorphic variant in ASS1 from patients with Citrullinemia type I
Authors: Liu Jing , Wang Zhongjie , Yan Huiming , Teng Yanling , Shi Qingxin , Chen Jing , Tang Wanglan , Yu Wenxian , Peng Ying , Xi Hui , Ma Na , Liang Desheng , Li Zhuo , Wu Lingqian
Published: July 2023

Background: Citrullinemia type I (CTLN1) is a rare autosomal recessive inborn error of the urea cycle caused by mutations in the gene encoding the arginosuccinate synthetase (ASS1) enzyme. Classic CTLN1 often manifests with acute hyperammonemia and neurological symptoms. Molecular genetic testing is critical for patient diagnosis.

Methods: Three unrelated families with clinically suspected CTLN1 were included in this study. Potential pathogenic variants were identified using whole exome sequencing (WES) and validated using Sanger sequencing. Western blotting, quantitative PCR, immunofluorescent staining, and ELISA were used to assess functional changes in candidate ASS1 variants.

Results: Five variants were identified, two of which were novel, and one has been reported, but its pathogenicity was not validated. The novel variant c.649-651del (p.P217del) and the 5′UTR variant (c.-4C>T) resulted in a decrease in ASS1 expression at both the protein and transcription levels. The other novel variant, c.1048C>T (p.Q350*), showed a marked decrease in expression at the protein level, with the formation of truncated proteins but an increased transcription. Both c.649_651del (p.P217del) and c.1048C>T (p.Q350*) showed a highly significant reduction in enzyme activity, while c.-4C>T had no effect.

Conclusion: We identified two novel variants and a hypomorphic non-coding variant in ASS1 and validated the pathogenicity using functional studies. Our findings contribute to expanding the spectrum of ASS1 variants and understanding the genotype-phenotype relationships of CTLN1.
NK cells from COVID-19 positive patients exhibit enhanced cytotoxic activity upon NKG2A and KIR2DL1 blockade
Authors: Lee Grace , Schauner Robert , Burke Juanita , Borocz Jade , Vasana Smitha , Sobieraj Lukasz , Giraudo Maria , Jackson Zachary , Ansari Qasim , Navas Maria , Sakr Hany , Wald David
Published: July 2023

SARS CoV-2 has caused a global pandemic leading to significant morbidity and mortality. There is a need to elucidate and further understand the implications of COVID-19 disease on the immune system to develop improved therapeutic strategies. In particular, Natural Killer (NK) cells play an essential role in mediating the innate immune response against viral infections. To better understand the role of innate immunity in COVID-19, we characterized the phenotype of circulating NK cells from 74 COVID-19 patients and 25 controls. Through evaluating the protein expression of activating and inhibitory NK cell surface molecules using dimension reduction analysis and clustering, we identified 4 specific clusters of NK cells specific to disease state (COVID-19 positive or COVID-19 negative) and characterized COVID-19 positive NK cells as: NGK2A+KIR2DL1+NKG2C-. Utilizing blocking antibodies specific for receptors NKG2A and KIR2DL1, we found that both NKG2A and KIR2DL1 blockade markedly enhances the ability of NK cells from COVID-19 positive patients to lyse SARS-Cov-2 infected cells. Overall, this study reveals new insights into NK cell phenotypes during SARS-CoV-2 infection and suggests a therapeutic approach worthy of further investigation to enhance NK cell-mediated responses against the virus.
Immune responses in the uterine mucosa: clues for vaccine development in pigs
Authors: Choudhary Pooja , Magloire Donaldson , Hamonic Glenn , Wilson Heather L.
Published: July 2023

The immune system in the upper reproductive tract (URT) protects against sexually transmitted pathogens, while at the same time providing immune tolerance responses against allogenic sperm and the developing fetus. The uterine environment is also responsive to hormonal variations during the estrus cycle, although the most likely timing of exposure to pathogens is during estrus and breeding when the cervix is semi-permissive. The goal for intrauterine immunization would be to induce local or systemic immunity and/or to promote colostral/lactogenic immunity that will passively protect suckling offspring. The developing fetus is not the vaccine target. This minireview article focuses on the immune response induced in the pig uterus (uterine body and uterine horns) with some comparative references to other livestock species, mice, and humans.
γδ T cell-intrinsic IL-1R promotes survival during Staphylococcus aureus bacteremia
Authors: Wang Yu , Ahmadi Michael Z. , Dikeman Dustin A. , Youn Christine , Archer Nathan K.
Published: July 2023

Staphylococcus aureus is a leading cause of bacteremia, further complicated by the emergence of antibiotic-resistant strains such as methicillin-resistant S. aureus (MRSA). A better understanding of host defense mechanisms is needed for the development of host-directed therapies as an alternative approach to antibiotics. The levels of IL-1, IL-17, and TNF-α cytokines in circulation have been associated with predictive outcomes in patients with S. aureus bacteremia. However, their causative role in survival and the cell types involved in these responses during bacteremia is not entirely clear. Using a mouse model of S. aureus bacteremia, we demonstrated that IL-17A/F and TNF-α had no significant impact on survival, whereas IL-1R signaling was critical for survival during S. aureus bacteremia. Furthermore, we identified that T cells, but not neutrophils, monocytes/macrophages, or endothelial cells were the crucial cell type for IL-1R-mediated survival against S. aureus bacteremia. Finally, we determined that the expression of IL-1R on γδ T cell, but not CD4+ or CD8+ T cells was responsible for survival against the S. aureus bacteremia. Taken together, we uncovered a role for IL-1R, but not IL-17A/F and TNF-α in protection against S. aureus bacteremia. Importantly, γδ T cell-intrinsic expression of IL-1R was crucial for survival, but not on other immune cells or endothelial cells. These findings reveal potential cellular and immunological targets for host-directed therapies for improved outcomes against S. aureus bacteremia.
NAIR: Network Analysis of Immune Repertoire
Authors: Yang Hai , Cham Jason , Neal Brian Patrick , Fan Zenghua , He Tao , Zhang Li
Published: July 2023

T cells represent a crucial component of the adaptive immune system and mediate anti-tumoral immunity as well as protection against infections, including respiratory viruses such as SARS-CoV-2. Next-generation sequencing of the T-cell receptors (TCRs) can be used to profile the T-cell repertoire. We developed a customized pipeline for Network Analysis of Immune Repertoire (NAIR) with advanced statistical methods to characterize and investigate changes in the landscape of TCR sequences. We first performed network analysis on the TCR sequence data based on sequence similarity. We then quantified the repertoire network by network properties and correlated it with clinical outcomes of interest. In addition, we identified (1) disease-specific/associated clusters and (2) shared clusters across samples based on our customized search algorithms and assessed their relationship with clinical outcomes such as recovery from COVID-19 infection. Furthermore, to identify disease-specific TCRs, we introduced a new metric that incorporates the clonal generation probability and the clonal abundance by using the Bayes factor to filter out the false positives. TCR-seq data from COVID-19 subjects and healthy donors were used to illustrate that the proposed approach to analyzing the network architecture of the immune repertoire can reveal potential disease-specific TCRs responsible for the immune response to infection.
Efficacy and safety of Lenvatinib-based combination therapies for patients with unresectable hepatocellular carcinoma: a single center retrospective study
Authors: Huang Jian , Wang Zhen-Guang , Tao Qi-Fei , Yang Yun , Yuan Sheng-Xian , Gu Fang-Ming , Liu Hui , Pan Ze-Ya , Jiang Bei-Ge , Lau Wan Yee , Zhou Wei-Ping
Published: July 2023

Background

Reports on Lenvatinib-based therapies show promising treatment outcomes for patients with unresectable hepatocellular carcinoma (uHCC). However, the effect and safety of Lenvatinib-based therapies still need to be further studies.

Methods

This was a retrospective, single-center study on the safety and treatment efficacy of Lenvatinib-based combination therapies for uHCC Patients. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary endpoints were progressive disease (PD), stable disease (SD), partial response (PR), and complete response (CR).

Results

Of 91 patients, there were 16 females and 75 males with uHCC who received systemic therapies based on Lenvatinib in our center. Forty-six patients (50.5%) received Lenvatinib combined with PD-1 antibody treatment. All these patients also received local therapy with the exception of 2 patients. The remaining 36 patinets received Lenvatinib combined with transcatheter arterial chemoembolization (TACE), 1 patient treated Lenvatinib combined with radiotherapy, 8 patients received Lenvatinib alone. At a median treatment time of 8 months, the objective response rate (ORR) of the entire cohort was 58.2% (53 patients), including 7 patients with CR and 46 patients with PR. 21 patients (23.1%) had SD. The disease control rate (DCR) of all patients was 81.3% (74 patients). However, 17 patients (18.7%) developed PD. The 1- and 2-year cumulative OS rates for the entire cohort were 66.8% and 39.3%, while the corresponding PFS rates were 38.0% and 17.1%, respectively. Univariate and multivariate Cox regression analysis revealed multiple tumor sites to be an independent OS risk factor for uHCC patients (HR=2.204, 95% CI=1.104-4.399, P=0.025). The most frequently reported adverse events in all patients were AST elevation (51.6%), followed by hypertension (33.0%), ALT elevation (26.4%), and decreased appetite (25.3%). After a combination treatment of Lenvatinib-based therapies, 15 patients met the criteria for salvage liver resection and underwent down-staging hepatectomy with a curative intent. The combination of PD-1 treatment was not very effective in improving the prognosis of uHCC patients treated with Lenvatinib combined with TACE.

Conclusion

Our study demonstrated that a proportive of patients benefited from Lenvatinib-based combination therapies with manageable safety profiles, allowing these patients to undergo downstaging surgery with curative intent.