bluuebunny/crossref_metadata_2025 huggingface dataset:
Erken Çocuklukta Öz Düzenleme ile Bilişsel Tempo Arasındaki İlişki
Authors: Yıldız Ezgi , Koçyiğit Sezai
Published: September 2021

Bu araştırmada, çocukların öz düzenleme beceri düzeyi ile bilişsel tempo boyutu arasındaki ilişkiyi incelemek amaçlanmıştır. Araştırma ilişkisel tarama modelinde gerçekleştirilmiştir. Araştırmanın örneklemine, oransız kademeli örnekleme yöntemiyle belirlenen 2018-2019 eğitim öğretim yılında Uşak merkez ilçesine bağlı anasınıflarında eğitim alan 124, özel anaokulunda eğitim alan 91, resmi anaokullarında eğitim alan 137 okul öncesi dönem çocuğu olmak üzere 352 çocuk dahil edilmiştir. Çalışmada veri toplama aracı olarak Kansas Okul öncesi Çocuklar İçin Düşünsellik-İçtepisellik Ölçeği A formu ve Okul Öncesi Öz Düzenleme Ölçeği kullanılmıştır. Araştırma sonucunda; öz düzenleme becerisi ile bilişsel tempo arasında pozitif yönde anlamlı bir ilişki bulunmuştur. Çocukların öz düzenleme beceri düzeylerindeki artışla birlikte reflektif olma olasılıkları artarken impulsif olma olasılıklarının azalmakta olduğu saptanmıştır.
Eğitim Konulu Filmlerin Sınıf Yönetiminin Boyutları Açısından İncelenmesi
Authors: Akcan Emrullah , Kara Mevlüt
Published: September 2021

Bu araştırmada Millî Eğitim Bakanlığı’nın (MEB) Eylül 2018 dönemi mesleki çalışma programı kapsamında öğretmenlerin izlemesi için önerdiği filmlerin sınıf yönetiminin boyutları açısından incelenmesi amaçlanmıştır.  Bu amaç doğrultusunda MEB tarafından önerilen 50 film arasından sınıf içi uygulamaların en yoğun sahnelendiği dört film ölçüt örnekleme tekniği ile seçilmiştir. Nitel olarak tasarlanan bu araştırmada verilerin elde edilmesinde doküman incelemesi; çözümünde betimsel analiz tekniğinden yararlanılmıştır. Araştırma sonucunda, filmlerde sınıf yönetimi açısından öğrencilerin tek kişilik sıralarda oturması, öğretmenlerin derse hazırlıklı ve öğrenciden önce gelmesi, öğrencilere ismi ile hitap etmesi ve sakin, samimi, nezaket kurallarına dikkat eden bir yapıda olmaları gibi olumlu özelliklerin ön plana çıktığı belirlenmiştir. Diğer yandan öğretmen tarafından sınıfın seviyesine uygun olmayan bir metnin okutulması, dersin plansız bir şekilde işlenmesi ve tepkisel sınıf yönetimi modelinin benimsenerek ceza yöntemine başvurulması ise sınıf yönetimini olumsuz etkileyen davranışlar olarak tespit edilmiştir. Filmlerde sınıf yönetimi açısından ortaya çıkan olumlu ve olumsuz davranışlar, öğretmenlik grubu lisans öğrencilerine “Sınıf Yönetimi” derslerinde uygulamalı örnekler olarak sunulabilir.
Stone icon from Belz in the context of Christian cult products of Upper Bug region
Authors: Petehyrych Volodymyr , Lazurko Ostap
Published: September 2021

Recently discovered stone icon from annalistic Belz is presented for scientific use. This scapular is considered in the context of other stone icons and metal crosses-encolpions, which are concentrated in the oldest annalistic cities of the Upper Bug region – Volodymyr, Cherven, Belz, Volhyn, Zvenyhorod or near them, forming a distinct cluster of Christian cult products. Circumstances and place of discovery of the Belz icon are analyzed, its connection with dytynets of the ancient city is proved. The icon from Belz is dedicated to the great martyr brothers Borys and Glib – first Old Rus’ canonized saints, sons of grand knyaz Volodymyr Svyatoslavovych. Iconographic type of image from the icon, where knyazs are represented in full growth as martyrs and warriors with crosses and swords, was created in Byzantium. From here, it could be moved to Kyiv Rus’ state directly or through South Slavic and European culture. Very few icons with such iconographic scheme have been found. According to artistic value and elements of iconography, the stone icon from the Solotchinskyi cloister near Old Ryazan was the closest. Its production is associated with activities of South Rus’ Kyiv craftsmen. The Belz scapular probably can be dated back to XIII century, perhaps the first third of it, characterized by activity of the Kyiv school, which is associated with a series of wonderful works of small stone plastic. Borys-and-Glib cult was quite active on the territory of Upper Bug region during this period, as evidenced by encolpions with images of Borys and Glib and data on the possibility of their local production. Tradition of worshiping this cult in Volhyn’ in the second half of XIII century can be associated with active religious efforts of knyaz Volodymyr Vasylkovych (1249/1250–1288). The same tradition continued during following centuries, as evidenced by Church of Borys and Glib in Potelych near Belz, mentioned in the chronicle in 1262. The Belz scapular is characterized by an artistically perfect depiction of figures of Borys and Glib, rich decoration of their clothes and headgear, realistic images of soft leather shoes, clothing details, distinctive highlight of the sword and cross – symbols of martyrdom. It can be placed in line with the best stone icons of a whole Rus’.
Key words: Upper Bug region, Christian symbols, icon, Belz, Borys and Glib.
Rescuing archeological researches in Krakow suburb of Lviv
Authors: Voitovych Nazariy , Voitovych Maria
Published: September 2021

Results of rescuing archeological researches carried out by the expedition of SRC “Rescuing archaeological service” of IA of NAS of Ukraine led by N. Voitovych on the territory of building of private medical centre are presented at the article. During field season of 2013 archeological researches in Pidmurna Street, 5 were focused on the southern part of examined locality, where trench 2 with an area of 26.2 м² was dug. Through archeological researches remains of the foundation of Austrian building was discovered and also part of interior of basement (stone pavement) was found. In addition, wooden construction of residential use was discovered. It was destroyed in a fire in the second half of XVII century. A significant amount of mobile material in a good taphonomic condition was recorded in the infill of the building. It consisted of ceramic, glass and metal ware, tiles, metal products (stirrups, coins, crossbow arrowhead). At the southern wall of the trench, a cluster of wood was discovered, which served as a strengthening of the slope to prevent falling. The last one can be dated back to XVII–XVIII centuries. Another wooden construction was found in the cultural layers of XV–XVI centuries. It was also discovered anthropogenic layers that can be dated back from VIII century B.C. to XVIII–XIX centuries A. D. inclusively. Archaeological material, dated back from VIII century B.C. to XVIII century A. D. inclusively was found in the trench. It is established that the bedrock was found on the depth of 4.3–4.9 m, with a decrease to the north-eastern direction. A significant amount of mobile material was collected. The largest number of finds is represented by artifacts from Late Middle Ages (ceramic, glass and wooden ware, building ceramics, leather footwear, products made of metal), which indicates that population of the former Old Rus' suburbs not finished after the capture of Lviv by Kazimierz III and relocation of the city inside the walls, but on the contrary – obtained a new momentum to its further development, this time as a Krakow suburb of Lviv.
Key words: Lviv, Pidmurna Street, archeological researches, wooden construction, ceramic ware, leather footwear, metal products.
Large-scale comparison of biomass and reproductive phenology among native and non-native populations of the seagrass Zostera japonica
Authors: Ito MA , Lin HJ , O’Connor MI , Nakaoka M
Published: September 2021

Large-scale analysis along latitude or temperature gradients can be an effective method for exploring the potential roles of light and temperature in controlling seagrass phenology. In this study, we investigated effects of latitude and temperature on seagrass biomass and reproductive seasonality.Zostera japonicais an intertidal seagrass with a wide latitudinal distribution expanding from tropical to temperate zones in its native range in Asia, with an additional non-native distribution in North America. We collated available data on phenological traits (timings of peak biomass or reproduction, durations of biomass growth and reproductive season, and maximum biomass or reproductive ratio) from publications and our own observations. Traits were compared among geographic groups: Asia-tropical, Asia-temperate, and North America-temperate. We further examined relationships between traits and latitude and temperature for 3 population groups: Asian, North American, and all populations. Our analysis revealed significant variation among geographic groups in maximum biomass, peak reproductive timing, and maximum reproductive ratio, but not in other traits. Maximum biomass and peak reproductive timing for Asian and all populations were significantly correlated with latitude and temperature. Maximum biomass was highest at mid-latitudes or intermediate temperatures and decreased toward distribution range limits, and peak reproductive timing occurred later in the year at higher latitudes or cooler sites. North American populations showed shorter growth durations and greater reproductive ratios at higher latitude. Different responses observed for North American populations may reflect effects of introduction. Our study demonstrates potential variation among geographic regions and between native and non-native populations.
The Effects of the Intrinsic Motivation and Extrinsic Motivation on Employee Performance with Job Satisfaction as an Intervening Variable at PT. Alwi Assegaf Palembang
Authors: Yusuf Muhammad
Published: September 2021

This study aimed to examine and analyze the effects of intrinsic motivation and extrinsic motivation on the performance of employees with job satisfaction as an intervening variable at PT. Alwi Assegaf Palembang. The number of respondents was 51 people. The data were collected using a questionnaire method with a Likert scale. They were examined and analyzed using the Smart-partial least square. Furthermore, the intrinsic motivation variable showed a significant positive influence on employee performance, but the extrinsic motivation variable did not have a significant influence on the performance of the employees. Job satisfaction was not an intervening influence between intrinsic motivation and employee performance and between extrinsic motivation and employee performance. The results showed that intrinsic motivation and extrinsic motivation had a significant positive effect on employee job satisfaction. The effect of the intrinsic motivation on the performance was significantly positive, while the extrinsic motivation was not significantly positive on the performance. In this study, job satisfaction was not an intervening variable between the intrinsic and extrinsic motivations on the performance.

 

Abstrak

Penelitian ini bertujuan untuk menguji dan menganalisis pengaruh motivasi intrinsik dan motivasi ekstrinsik terhadap kinerja karyawan dengan kepuasan kerja sebagai variable intervening pada PT. Alwi Assegaf Palembang. Responden dalam penelitian ini berjumlah 51 orang. Data dalam penelitian ini diperoleh dengan menyebarkan kuisioner berupa pertanyaan dengan menggunakan skala Likert. Data dianalisis dengan smart-partial least square. Hasil penelitian menunjukkan bahwa motivasi intrinsic dan motivasi ekstrinsik berpengaruh positif signifikan terhadap kepuasan kerja karyawan. Pengaruh motivasi intrinsik terhadap kinerja adalah positif signifikan, sedangkan motivasi ekstrinsik menunjukkan tidak ada pengaruh signifikan positif terhadap kinerja. Kepuasan kerja bukan merupakan variabel intervening antara motivasi intrinsik dan ekstrinsik terhadap kinerja dalam penelitian ini.

Kata kunci: Motivasi Intrinsik, Motivasi Ekstrinsik, Kepuasan Kerja, Kinerja
The use of Platelet-Rich Plasma in the Gynaecological Clinical Setting. A review
Authors: Sanoulis Vasileios , Nikolettos Nikolaos , Vlahos Nikolaos
Published: September 2021

Reports on clinical use of platelet-rich plasma (PRP) have dramatically increased in the last decade. PRP is a natural product where a high level of platelets is concentrated with growth factors concentration 3 to 5 times greater than plasma. In their alpha granules, platelets contain a cocktail of chemical mediators that trigger tissue regeneration, both through the promotion of angiogenesis and the initiation of cell regeneration. Such bioactive factors include platelet derived growth factor (PDGF), transforming growth factor-beta (TGF-β), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), fibroblast growth factor (FGF), insulin growth factor (IGF). In the gynaecological setting, PRP has been shown to facilitate wound healing and has been proposed as an effective treatment for the treatment of disorders such as Lichen Sclerosus (LS) or cervical ectopy. Evidence of PRP effectiveness in conditions of pelvic organ prolapse and urinary incontinence has also been reported. Recent publications have shown its positive effects in promoting endometrial and follicular growth and gestation in assisted reproduction cycles. PRP administration in the ovarian tissue has resulted in rejuvenation as evaluated by the relevant biochemical markers as well as reactivation of folliculogenesis. Other researchers have showed effective use in improving pregnancy outcomes in patients with repeated implantation failure. For managing repeated failures, several methods have been attempted, but recently PRP appears as effective in inducing endometrial development in patients with thin, poor endometrium. Another possible mechanism of PRP to endometrium is through its anti-inflammatory actions. PRP is an innovative therapeutic modality, as it is simple, easily performed, and effective, with minimal risk as it is an autologous product. The employment of regenerative medicine approaches will continue to grow in the gynaecological setting and the future trials should be carefully designed in order to facilitate the clinical translation.
PI3K/PDK1/Akt pathways and their fundamental role in Gynecological Cancer
Authors: Stavros Sofoklis , Pappa Kalliopi , Drakakis Peter
Published: September 2021

The PI3K/PDK1/Akt pathway can regulate a large variety of cellular processes such as cell growth, proliferation and survival. Moreover, it is one of the most frequently altered networks in cancer though. The dysregulation of these pathways has been reported in several human cancers, as well as in diabetes, neurological diseases and cardiovascular diseases. Cervical carcinogenesis seems to be associated with increased levels of activated AKT kinase. Moreover, PTEN inactivation is the most common genetic alteration in type1 endometrial cancer. In addition, the PI3K /AKT pathway is related to ovarian carcinomas cell motility and adhesion. This pathway plays an imperative role in cell survival and except for that, it may lead to metastatic and invasive phenotypes of a large variety of malignant cells. A battery of cancerous types has been associated with PI3K/AKT hyperactivation; inhibition of this pathway has been described as a treatment option of malignancy. The role of PI3K-PDK-AKT signaling pathway in gynecological malignancy seems to play a pivotal role, but it necessitates further investigation, which could lead to novel therapeutic strategies of eventual robust advantages to many cancer patients. The aim of that review is to highlight and underline the role of those pathways paving the way of gynecological malignancy.
Laser treatment of twin-to-twin transfusion syndrome (TTTS): preliminary findings from a tertiary center in Greece
Authors: Papaioannou Georgios , Evangelinakis Nikolaos , Papantoniou Nikolaos
Published: September 2021

Background: Twin- to-twin transfusion syndrome (TTTS) affects approximately 15% of monochorionic twin pregnancies with an estimated incidence of 1 in 1,600 pregnancies. The gold standard of care is considered to be Fetoscopic Laser Photocoagulation Therapy (FLPT). Objective: To present our experience with FLPT in a preliminary prospective observational study. Materials and methods: Fourteen patients who underwent FLPT in the Fetal Maternal Medicine Unit of Attikon University Hospital, between January 2017 and August 2018. Fetoscopic laser photocoagulation was offered to all patients with pregnancies complicated by TTTS (Quintero stage >2), before the completion of 26 weeks of gestation. Results: The mean gestational age at diagnosis was 22.2 ± 2.6 weeks, at surgery 23.1±1.9 weeks and at birth 29.8±3.3 weeks. Mean interval from surgery to delivery was 6.6±3.1 weeks and mean neonatal birthweight was 1426±408 grams. Mean recipient’s weight at delivery was 1652±283gr, whereas mean donor’s weight at delivery was 1299 ± 402gr. Concerning fetal viability, ten (71,4%) donor fetuses survived to full term whereas 4 (28,6%) donor fetuses died in utero. The survival rate of recipient fetuses reached 85,7% which is very good according to the literature. In total 22 fetuses (78,6%) were alive at birth and survived the first 6 months of life and in 6 cases an intrauterine demise occurred (21,4%). In 10 pregnancies (71,4%) both fetuses survived, in 2 (14,3%) both died and in 12 pregnancies (85,7%) there was at least one survivor. Conclusion: These preliminary results support the use of FPLT in Greece as the percentage of live neonates that was reached is comparable to those published in larger studies in the international literature. We are confident that with increasing experience and new instrumentation, these results will become even better and this service will accept more cases all over Greece.
Prenatal diagnosis of a large suprasellar arachnoid cyst
Authors: Asimakopoulos George , Antsaklis Panagiotis , Theodora Mariana , Sindos Michael , Rodolakis Alexandros , Loutradis Dimitrios , Daskalakis George
Published: September 2021

Arachnoid cysts represent 1% of all intracranial lesions and appear on the arachnoid membrane (subarachnoid space). The etiology and pathogenesis of arachnoid cysts remain unclear and in their majority they are asymptomatic. Due to the developmental origin of arachnoid cysts, these formations can be identified on prenatal fetal imaging. In this report we presented a case of an enlarged suprasellar arachnoid cyst detected incidentally during a routine fetal sonographic examination at 33 weeks of gestation. The cyst remained stable in size prenatally and postnatally without compressive symptoms and signs and the patient has been set under expectant management with serial clinical evaluation and serial imaging of the cyst.
Post Partum Hemorrhage – Mini Review
Authors: Voros Charalampos , Pappa Kalliopi
Published: September 2021

Postpartum hemorrhage (PPH) is an obstetric emergency. It is one of the top causes of maternal mortality in both high and low income countries, although the absolute risk of death from PPH is much lower in high-income countries. Several risk factors predispose to the development of PPH including prolonged labor, precipitous labor, uterine distension. In 2017, the American College of Obstetricians and Gynecologists revised the definition of PPH to help guide its management. In the present mini-review we focus on specific medical and minimally invasive interventions, and surgical interventions at laparotomy.
Smoking during pregnancy was negatively associated with physical fitness in childhood
Authors: Tambalis Konstantinos D. , Mourtakos Stamatis , Panagiotakos Demosthenes D. , Sidossis Labros S.
Published: September 2021

Background: To explore the potential relationship of several prenatal predictors with physical fitness (PF) components among children. Material and Methods: Α random sample of 5,125 dyads children (8 to 9 years old) and their mothers was evaluated. Mothers were asked to provide information contained in their medical booklets and pregnancy ultrasound records. With the use of a standardized questionnaire, telephone interviews were carried out for the collection of maternal factors in order to assess the potential association between several prenatal factors (preterm birth, maternal age, parity before, mode of delivery, gestational diabetes, hypertensive disorders of pregnancy, alcohol consumption and smoking during pregnancy) and child’s PF. Data from five PF tests were used to assess cardiorespiratory fitness (CRF), speed, and lower and upper body strength. Results: Children born to mothers with adequate physical activity (PA) levels during pregnancy, parity before and higher education presented higher performances in PF components (all p-values<0.05) in childhood. Also, mother’s smoking during pregnancy was unfavorably associated with CRF (b=-0.04), lower body strength (b=-0.02), upper body strength (b=-0.02), and speed (b=0.10), after adjusting for several covariates. Conclusion: Among prenatal factors considered, parity before, educational level and PA and smoking during pregnancy had an important influence on PF in childhood.
Default Solution on Sharia Housing in The View of Private Law and Islamic Law
Authors: Khoirrani Tri Lestari , Arifah Risma Nur
Published: September 2021

Sharia housing with sharia developer system using cash and in house method without involving the bank is thriving, because in the advert mentioned no fines and confiscations. While every financing there is a possibility of contract breach, such as La Tansa Cluster Malang Housing, there are several users doing breach of contract. This breach of contract can cause problems between developer and user so that solution is needed. The goals of this research are determining factors that led to the breach of contract and the efforts to resolve trade breach of contract in La Tansa Cluster Malang in terms of civil code and Islamic laws. This research uses empirical legal research with a sociological juridical approach, a concept approach, and a legislative approach. Data collected by interviews with developer of La Tansa Cluster Malang and the user, and then analyzed using qualitative descriptive analysis methods. The results showed that breach of contract occurred in La Tansa Cluster Malang due to lack of user candidate analysis, postpone payments, family deaths, business failures, serious illness, and inaccurate financial predictions. According to civil code, the efforts to resolve contract breach of sharia housing trade in La Tansa Cluster Malang are doing deliberation, communication, time extension, PPJB canceling (according to the Article 1338 paragraph (2) of Civil Code), and money returning (according to Article 1267 and Article 1248 of Civil Code). While the efforts to resolve the breach of contract in La Tansa Cluster Malang according to Islamic laws are doing deliberation or reconciliation (shulh), communication, time extension (according to surah al-Baqarah (2): 280), PPJB canceling (based on fasakh iqalah), and money returning (based on dhaman al ‘aqdi).
The Essence of Mysticism in The Study of Tasawwuf
Authors: Hanifiyah Fitriyatul
Published: September 2021

Sufism is another name for mysticism in Islam. the western orientalists it is known as Sufism, which is a special term for Islamic mysticism. Then the word Sufism does not exist in the mysticism of other religions. Sufism or mysticism in Islam is inherent in life and develops from zuhudan life, in the f amali Sufism, then philosophical Sufism. Sufism is the most important aspect of Islamic teachings, because the role of Sufism is the key to the perfection of the practice of Islamic teachings. In addition to the aspect of Sufism, in Islam there are other aspects, namely faith and sharia, or in other words what is meant by religion is consisting of Islam, faith and ihsan, where these three aspects are a unity. To know Islamic law, we have to refer to sharia / fiqih, to know the pillars of faith we have to refer to ushuludin / faith and to know the perfection of ihsan we enter into Sufism. The research method used in this research is literature review. For the results of this study that overall the science of Sufism can be grouped into two, namely tasawuf ilmi or nadhari, which is theoretical Sufism. The second part is Sufism amali or tathbiqi, which is applied Sufism, which is practical Sufism. It is not just a theory, but demands practice to achieve the goals of Sufism. As for what is meant by human relations and spirituality, namely humans think more deeply. Self-reflection will be awakened along with life's problems. Political, cultural and other problems will be resolved well with a cool head. A clean soul will radiate a clean implementation too. Meanwhile, the meaning of man's closeness to his God is based on some of the words of Allah SWT which are contained in the Al-Qur'an explaining that Allah is one with his servant (Al-Hulul / Wahdatul-Wujud).
Characterization and Evaluation of Biofilm Formation by Klebsiella pneumonia MBB9 Isolated from Epilithic Biofilms of the Porter Brook River, Sheffield
Authors: Ghazay Alotaibi , Mamdouh Bukhari
Published: September 2021

Microbes generally attach to surfaces and produce an Extracellular Polymeric Substance (EPS) matrix. The exopolysaccharide production plays a role in biofilm protection against environmental stress factors. Biofilm-forming bacteria exhibit different physiological properties in their response to environmental influences compared with their planktonic counterparts. This study aimed to investigate the impact of changing the concentrations of glucose, peptone, and yeast extract and environmental parameters, such as temperature, pH, anaerobic conditions, osmotic stresses, and growth media on biofilm formation by K. pneumonia MBB9 recovered from river-stones collected from the Porter Brook, Sheffield using crystal violet and resazurin assays in microtiter plates. The different concentrations of glucose (0.25, 0.5 and 1 g L-1), peptone (0.25, 0.5 and 1 g L-1) and yeast extract (0.25, 0.5 and 1 g L-1) as carbon and nitrogen sources found to have an impact on biofilm formation by K. pneumonia MBB9. The greatest biomass level being at 0.25 g L-1 for glucose whereas the density of biofilm increased significantly with increasing the concentration of peptone and yeast extract until 1 g L-1 of peptone and yeast extract, suggesting that higher levels of peptone and yeast extract can be beneficial for biofilm formation by K. pneumonia MBB9 in microtiter plates. The amount of biofilm was high at pH 4.5 and 0.6% NaCl; however, the significant reduction at pH 10.5 and 10.6% NaCl could be as a result of the slow growth under higher NaCl concentrations and highly alkaline condition. High-density biofilm produced at 40 °C; however, a temperature of 50 °C reduced the amount of biofilm by K. pneumonia MBB9, suggesting that more extreme temperatures might affect the formation of biofilm by inhibiting growth. Besides, biofilm production under anaerobic conditions was significantly lower (83% less) than under aerobic environments. Klebsiella pneumonia MBB9 possessed a high capacity to form biofilms on the surface of glass slide coupons.
Microfluidic Preparation of Janus Microparticles With Temperature and pH Triggered Degradation Properties
Authors: Feng Zi-Yi , Liu Tao-Tao , Sang Zhen-Tao , Lin Zhen-Sheng , Su Xin , Sun Xiao-Ting , Yang Hua-Zhe , Wang Ting , Guo Shu
Published: September 2021

Based on the phase separation phenomenon in micro-droplets, polymer-lipid Janus particles were prepared on a microfluidic flow focusing chip. Phase separation of droplets was caused by solvent volatilization and Janus morphology was formed under the action of interfacial tension. Because phase change from solid to liquid of the lipid hemisphere could be triggered by physiological temperature, the lipid hemisphere could be used for rapid release of drugs. While the polymer we selected was pH sensitive that the polymer hemisphere could degrade under acidic conditions, making it possible to release drugs in a specific pH environment, such as tumor tissues. Janus particles with different structures were obtained by changing the experimental conditions. To widen the application range of the particles, fatty alcohol and fatty acid-based phase change materials were also employed to prepare the particles, such as 1-tetradecanol, 1-hexadecanol and lauric acid. The melting points of these substances are higher than the physiological temperature, which can be applied in fever triggered drug release or in thermotherapy. The introduction of poly (lactic-co-glycolic acid) enabled the formation of multicompartment particles with three distinct materials. With different degradation properties of each compartment, the particles generated in this work may find applications in programmed and sequential drug release triggered by multiple stimuli.
MCL-1 Inhibition Overcomes Anti-apoptotic Adaptation to Targeted Therapies in B-Cell Precursor Acute Lymphoblastic Leukemia
Authors: Manzano-Muñoz Albert , Alcon Clara , Menéndez Pablo , Ramírez Manuel , Seyfried Felix , Debatin Klaus-Michael , Meyer Lüder H. , Samitier Josep , Montero Joan
Published: September 2021

Multiple targeted therapies are currently explored for pediatric and young adult B-cell precursor acute lymphoblastic leukemia (BCP-ALL) treatment. However, this new armamentarium of therapies faces an old problem: choosing the right treatment for each patient. The lack of predictive biomarkers is particularly worrying for pediatric patients since it impairs the implementation of new treatments in the clinic. In this study, we used the functional assay dynamic BH3 profiling (DBP) to evaluate two new treatments for BCP-ALL that could improve clinical outcome, especially for relapsed patients. We found that the MEK inhibitor trametinib and the multi-target tyrosine kinase inhibitor sunitinib exquisitely increased apoptotic priming in an NRAS-mutant and in a KMT2A-rearranged cell line presenting a high expression of FLT3, respectively. Following these observations, we sought to study potential adaptations to these treatments. Indeed, we identified with DBP anti-apoptotic changes in the BCL-2 family after treatment, particularly involving MCL-1 – a pro-survival strategy previously observed in adult cancers. To overcome this adaptation, we employed the BH3 mimetic S63845, a specific MCL-1 inhibitor, and evaluated its sequential addition to both kinase inhibitors to overcome resistance. We observed that the metronomic combination of both drugs with S63845 was synergistic and showed an increased efficacy compared to single agents. Similar observations were made in BCP-ALL KMT2A-rearranged PDX cells in response to sunitinib, showing an analogous DBP profile to the SEM cell line. These findings demonstrate that rational sequences of targeted agents with BH3 mimetics, now extensively explored in clinical trials, may improve treatment effectiveness by overcoming anti-apoptotic adaptations in BCP-ALL.
Differentiation of Human Pluripotent Stem Cells Into Definitive Endoderm Cells in Various Flexible Three-Dimensional Cell Culture Systems: Possibilities and Limitations
Authors: Bogacheva Mariia S. , Harjumäki Riina , Flander Emilia , Taalas Ara , Bystriakova Margarita A. , Yliperttula Marjo , Xiang Xiaoqiang , Leung Alan W. , Lou Yan-Ru
Published: September 2021

The generation of human stem cell-derived spheroids and organoids represents a major step in solving numerous medical, pharmacological, and biological challenges. Due to the advantages of three-dimensional (3D) cell culture systems and the diverse applications of human pluripotent stem cell (iPSC)-derived definitive endoderm (DE), we studied the influence of spheroid size and 3D cell culture systems on spheroid morphology and the effectiveness of DE differentiation as assessed by quantitative PCR (qPCR), flow cytometry, immunofluorescence, and computational modeling. Among the tested hydrogel-based 3D systems, we found that basement membrane extract (BME) hydrogel could not retain spheroid morphology due to dominant cell–matrix interactions. On the other hand, we found that nanofibrillar cellulose (NFC) hydrogel could maintain spheroid morphology but impeded growth factor diffusion, thereby negatively affecting cell differentiation. In contrast, suspension culture provided sufficient mass transfer and was demonstrated by protein expression assays, morphological analyses, and mathematical modeling to be superior to the hydrogel-based systems. In addition, we found that spheroid size was reversely correlated with the effectiveness of DE formation. However, spheroids of insufficient sizes failed to retain 3D morphology during differentiation in all the studied culture conditions. We hereby demonstrate how the properties of a chosen biomaterial influence the differentiation process and the importance of spheroid size control for successful human iPSC differentiation. Our study provides critical parametric information for the generation of human DE-derived, tissue-specific organoids in future studies.
The Diagnostic Value of Metagenomic Next–Generation Sequencing in Lower Respiratory Tract Infection
Authors: Zheng Yan , Qiu Xiaojian , Wang Ting , Zhang Jie
Published: September 2021

Lower respiratory tract infections are associated with high morbidity and mortality and significant clinical harm. Due to the limited ability of traditional pathogen detection methods, anti-infective therapy is mostly empirical. Therefore, it is difficult to adopt targeted drug therapy. In recent years, metagenomic next-generation sequencing (mNGS) technology has provided a promising means for pathogen-specific diagnosis and updated the diagnostic strategy for lower respiratory tract infections. This article reviews the diagnostic value of mNGS for lower respiratory tract infections, the impact of different sampling methods on the detection efficiency of mNGS, and current technical difficulties in the clinical application of mNGS.
AKR1C3 and Its Transcription Factor HOXB4 Are Promising Diagnostic Biomarkers for Acute Myocardial Infarction
Authors: Liang Jingjing , Cao Yue , He Mingli , Li Weiwen , Huang Guolin , Ma Tianyi , Li Meijun , Huang Yuli , Huang Xiaohui , Hu Yunzhao
Published: September 2021

Background: A recent study disclosed that ferroptosis was an important myocyte death style in myocardial infarction (MI). However, the diagnostic value of ferroptosis regulators and correlated underlying mechanisms in acute myocardial infarction (AMI) remain unknown.

Methods: Bioinformatical analyses were conducted to identify the candidate biomarkers for AMI, and the collected local samples were used to validate the findings via real-time quantitative PCR. Bioinformatical analysis and luciferase reporter assay were implemented to identify the transcriptional factor. Transient transfection and ferroptosis characteristic measurement, including glutathione peroxidase 4, malondialdehyde, iron, and glutathione, was performed to verify the ability of the candidate gene to regulate the ferroptosis of cardiomyocytes. A meta-analysis was conducted in multiple independent cohorts to clarify the diagnostic value.

Results: A total of 121 ferroptosis regulators were extracted from previous studies, and aldo-keto reductase family 1 member C3 (AKR1C3) was significantly downregulated in the peripheral blood samples of AMI cases from the analysis of GSE48060 and GSE97320. HOXB4 served as a transcriptional activator for AKR1C3 and could suppress the ferroptosis of the H9C2 cells treated with erastin. Besides this, peripheral blood samples from 16 AMI patients and 16 patients without coronary atherosclerotic disease were collected, where AKR1C3 and HOXB4 both showed a high diagnostic ability. Furthermore, a nomogram including HOXB4 and AKR1C3 was established and successfully validated in six independent datasets. A clinical correlation analysis displayed that AKR1C3 and HOXB4 were correlated with smoking, CK, CK-MB, and N-terminal-pro-B-type natriuretic peptide.

Conclusion: Taken together, this study demonstrates that AKR1C3 and HOXB4 are promising diagnostic biomarkers, providing novel insights into the ferroptosis mechanisms of AMI.
Case Report: A Cluster of Complications During Carotid Artery Stenting Managed With Peripheral, Coronary, and Imaging Techniques
Authors: Montorsi Piero , Galli Stefano , Teruzzi Giovanni , Troiano Sarah , Caputi Luigi , Gili Sebastiano , Trabattoni Daniela
Published: September 2021

We describe the case of a 72-year-old man with severe, asymptomatic in-stent restenosis detected 4 years after index carotid artery stenting (CAS). The patient was deemed at low risk and scheduled for re-angioplasty with a drug-coated balloon as per institution protocol. What at first seemed a simple case suddenly turned into a series of cerebral and vascular complications that were successfully managed with a mix of peripheral, coronary, and imaging techniques.
Association Between Cardiovascular Risk Factors and the Severity of Coronavirus Disease 2019: Nationwide Epidemiological Study in Korea
Authors: Kong Kyoung Ae , Jung Sodam , Yu Mina , Park Junbeom , Kang In Sook
Published: September 2021

Background: Acute respiratory viral infections can result in cardiovascular involvement, with such patients having a significantly higher mortality rate than those without cardiovascular involvement. Due to the ongoing coronavirus disease 2019 (COVID-19) pandemic, it is important to determine whether cardiovascular risk factors are associated with the severity of COVID-19.

Methods: These nationwide data were provided by the Korea Disease Control and Prevention Agency. We defined a patient as having a “critical illness” if they required more than invasive mechanical ventilation and “fatal illness” if they died.

Results: Among the total 5,307 patients, 2,136 (40.8%) were male. The critical illness rate was 5.1% (males: 6.7, females: 4.0%) and the fatality rate was 4.54%. The multivariable analysis showed that age ≥60 years, male sex, diabetes mellitus, hypertension, heart failure, chronic kidney disease, cancer, and dementia were independent risk factors for critical illness. The risk scoring model showed the significance of multiple risk factors. Patients with four risk factors; old age (≥60 years), male sex, hypertension, and diabetes mellitus had a more than a 100 times higher risk for severe COVID-19 than those without these risk factors (OR; 95% confidence interval, 104; 45.6–240.6 for critical, 136.2; 52.3–3547.9 for fatal illness).

Conclusions: This study demonstrated that cardiovascular risk factors are also significant risk factors for severe COVID-19. In particular, patients who have multiple cardiovascular risk factors are more likely to progress to severe COVID-19. Therefore, early and appropriate treatment of these patients is crucial.
A New Insight Into Seawater-Basalt Exchange Reactions Based on Combined δ18O—Δ′17O—87Sr/86Sr Values of Hydrothermal Fluids From the Axial Seamount Volcano, Pacific Ocean
Authors: Zakharov D. O. , Tanaka R. , Butterfield D. A. , Nakamura E.
Published: September 2021

The δ18O values of submarine vent fluids are controlled by seawater-basalt exchange reactions, temperature of exchange, and to a lesser extent, by phase separation. These variations are translated into the δ18O values of submarine hydrothermal fluids between ca. 0 and + 4‰, a range defined by pristine seawater and equilibrium with basalt. Triple oxygen isotope systematics of submarine fluids remains underexplored. Knowing how δ17O and δ18O change simultaneously during seawater-basalt reaction has a potential to improve i) our understanding of sub-seafloor processes and ii) the rock-based reconstructions of ancient seawater. In this paper, we introduce the first combined δ17O-δ18O-87Sr/86Sr dataset measured in fluids collected from several high-temperature smoker- and anhydrite-type vent sites at the Axial Seamount volcano in the eastern Pacific Ocean. This dataset is supplemented by measurements of major, trace element concentrations and pH indicating that the fluids have reacted extensively with basalt. The salinities of these fluids range between 30 and 110% of seawater indicating that phase separation is an important process, potentially affecting their δ18O. The 87Sr/86Sr endmember values range between 0.7033 and 0.7039. The zero-Mg endmember δ18O values span from -0.9 to + 0.8‰, accompanied by the Δ′17O0.528 values ranging from around 0 to −0.04‰. However, the trajectory at individual site varies. The endmember values of fluids from focused vents exhibit moderate isotope shifts in δ′18O up to +0.8‰, and the shifts in Δ′17O are small, about −0.01‰. The diffuse anhydrite-type vent sites produce fluids that are significantly more scattered in δ′18O—Δ′17O space and cannot be explained by simple isothermal seawater-basalt reactions. To explain the observed variations and to provide constraints on more evolved fluids, we compute triple O isotope compositions of fluids using equilibrium calculations of seawater-basalt reaction, including a non-isothermal reaction that exemplifies complex alteration of oceanic crust. Using a Monte-Carlo simulation of the dual-porosity model, we show a range of possible simultaneous triple O and Sr isotope shifts experienced by seawater upon reaction with basalt. We show the possible variability of fluid values, and the causal effects that would normally be undetected with conventional δ18O measurements.
Analysis of Microorganism Diversity in Haemaphysalis longicornis From Shaanxi, China, Based on Metagenomic Sequencing
Authors: Cao Runlai , Ren Qiaoyun , Luo Jin , Tian Zhancheng , Liu Wenge , Zhao Bo , Li Jing , Diao Peiwen , Tan Yangchun , Qiu Xiaofei , Zhang Gaofeng , Wang Qilin , Guan Guiquan , Luo Jianxun , Yin Hong , Liu Guangyuan
Published: September 2021

Ticks are dangerous ectoparasites of humans and animals, as they are important disease vectors and serve as hosts for various microorganisms (including a variety of pathogenic microorganisms). Diverse microbial populations coexist within the tick body. Metagenomic next-generation sequencing (mNGS) has been suggested to be useful for rapidly and accurately obtaining microorganism abundance and diversity data. In this study, we performed mNGS to analyze the microbial diversity of Haemaphysalis longicornis from Baoji, Shaanxi, China, with the Illumina HiSeq platform. We identified 189 microbial genera (and 284 species) from ticks in the region; the identified taxa included Anaplasma spp., Rickettsia spp., Ehrlichia spp., and other important tick-borne pathogens at the genus level as well as symbiotic microorganisms such as Wolbachia spp., and Candidatus Entotheonella. The results of this study provide insights into possible tick-borne diseases and reveal new tick-borne pathogens in this region. Additionally, valuable information for the biological control of ticks is provided. In conclusion, this study provides reference data for guiding the development of prevention and control strategies targeting ticks and tick-borne diseases in the region, which can improve the effectiveness of tick and tick-borne disease control.
Systems-Level Proteomics Evaluation of Microglia Response to Tumor-Supportive Anti-Inflammatory Cytokines
Authors: Ahuja Shreya , Lazar Iulia M.
Published: September 2021

Background

Microglia safeguard the CNS against injuries and pathogens, and in the presence of certain harmful stimuli are capable of inducing a disease-dependent inflammatory response. When exposed to anti-inflammatory cytokines, however, these cells possess the ability to switch from an inflammatory to an immunosuppressive phenotype. Cancer cells exploit this property to evade the immune system, and elicit an anti-inflammatory microenvironment that facilitates tumor attachment and growth.

Objective

The tumor-supportive biological processes that are activated in microglia cells in response to anti-inflammatory cytokines released from cancer cells were explored with mass spectrometry and proteomic technologies.

Methods

Serum-depleted and non-depleted human microglia cells (HMC3) were treated with a cocktail of IL-4, IL-13, IL-10, TGFβ, and CCL2. The cellular protein extracts were analyzed by LC-MS/MS. Using functional annotation clustering tools, statistically significant proteins that displayed a change in abundance between cytokine-treated and non-treated cells were mapped to their biological networks and pathways.

Results

The proteomic analysis of HMC3 cells enabled the identification of ~10,000 proteins. Stimulation with anti-inflammatory cytokines resulted in the activation of distinct, yet integrated clusters of proteins that trigger downstream a number of tumor-promoting biological processes. The observed changes could be classified into four major categories, i.e., mitochondrial gene expression, ECM remodeling, immune response, and impaired cell cycle progression. Intracellular immune activation was mediated mainly by the transducers of MAPK, STAT, TGFβ, NFKB, and integrin signaling pathways. Abundant collagen formation along with the expression of additional receptors, matrix components, growth factors, proteases and protease inhibitors, was indicative of ECM remodeling processes supportive of cell-cell and cell-matrix adhesion. Overexpression of integrins and their modulators was reflective of signaling processes that link ECM reorganization with cytoskeletal re-arrangements supportive of cell migration. Antigen processing/presentation was represented by HLA class I histocompatibility antigens, and correlated with upregulated proteasomal subunits, vesicular/viral transport, and secretory processes. Immunosuppressive and proangiogenic chemokines, as well as anti-angiogenic factors, were detectable in low abundance. Pronounced pro-inflammatory, chemotactic or phagocytic trends were not observed, however, the expression of certain receptors, signaling and ECM proteins indicated the presence of such capabilities.

Conclusions

Comprehensive proteomic profiling of HMC3 cells stimulated with anti-inflammatory cytokines revealed a spectrum of microglia phenotypes supportive of cancer development in the brainviamicroenvironment-dependent biological mechanisms.
Minimizing Ischemia Reperfusion Injury in Xenotransplantation
Authors: Patel Parth M. , Connolly Margaret R. , Coe Taylor M. , Calhoun Anthony , Pollok Franziska , Markmann James F. , Burdorf Lars , Azimzadeh Agnes , Madsen Joren C. , Pierson Richard N.
Published: September 2021

The recent dramatic advances in preventing “initial xenograft dysfunction” in pig-to-non-human primate heart transplantation achieved by minimizing ischemia suggests that ischemia reperfusion injury (IRI) plays an important role in cardiac xenotransplantation. Here we review the molecular, cellular, and immune mechanisms that characterize IRI and associated “primary graft dysfunction” in allotransplantation and consider how they correspond with “xeno-associated” injury mechanisms. Based on this analysis, we describe potential genetic modifications as well as novel technical strategies that may minimize IRI for heart and other organ xenografts and which could facilitate safe and effective clinical xenotransplantation.