bluuebunny/crossref_metadata_2025 huggingface dataset:
Politeness Strategies Used by Mario Teguh in Handling Questions in MTGW Program
Authors: Al Arief Yusuf
Published: February 2022

Mario Teguh was one of the motivators in Indonesia whose fans are considered the most. He was also issued as the most expensive motivator in Indonesia at this time being. As a great motivator, he must have some strategies to be close and motivate his Audience. This research aimed to figure out the strategies he used, focusing on handling questions. The data was collected by observation method and documentation technique. The data was analyzed based on the politeness strategy of Brown and Levinson. From the analysis, The researcher found that at least there were ten strategies used by Mario to share the motivation. These made the audience did not feel to be lectured when he shared it. They feel like a friend to him.
The Component of Variation Skill Apllied by a Teacher in “Freedom Writers” Film
Authors: Norliani
Published: February 2022

Teacher as an educator is one of essential factors to support the success of education in the class, so a teacher must have teaching skills. This research was conducted to find and describe the component of variation skill applied by a teacher in “Freedom Writers “Film This research used descriptive qualitative approach. The data was taken from the movie. Component of variation skill theory used was Turney’s theory (1983). The result of data analysis reveal that the teacher in the movie applied all the component of variation skills, they were variation in teacher’s manner, there are six in this variations, voice variation, focusing, pausing, eyes contact, gesturing and movement.  variation in media and material instruction, such as, the use of visual, aural and tactile and also the use   of interaction variation.
An Analysis of learning difficulties faced by first year students of STMIK Palangkaraya in English Subject as General Course
Authors: Elmayantie Catharina , Norhayati Norhayati
Published: February 2022

At the College of Informatics and Computer Management (STMIK) Palangka Raya, English course appear in the curriculum of each study programs. This course is divided into English I and English II, for both undergraduate and diploma levels. One of the goals of learning English here is so that students have the ability to speak English both verbally and in writing. The mastery level of English skill will be very beneficial for the students to comprehend their major subject; technology informatics and computers. As in the perspective of academic achievement for English courses, the students can be categorized at good level. As for the final assessment of a student, it is assessed by the level of attendance for each lecture, individual and group assignments, and test scores taken form midterm test and final test. One of the problem faced both teachers and students in teaching learning English  that the lecturers have not been able to provide learning and assessment comprehensively for listening skill mastery. As the impact the students get less opportunity to practice listening skill. It is caused that  the college does not yet have adequate supporting facilities such as language laboratory.
A Critical Discourse Analysis of Gender Disparity in Taskmaster
Authors: Prasadini Nauka Nayana
Published: February 2022

British comedy panel show is the television comedy genre that is known for spontaneous banters and humour. Despite the popularity, the shows in this genre are often criticized as "male-dominated" and heavily gender-biased. As one of the most popular comedy panel shows, Taskmaster also shows the same problems, despite having more women in the future series. Therefore, the study analyses the gender disparity as showed in Taskmaster through the perspective of Critical Discourse Analysis (CDA). The study uses a qualitative approach, focusing on CDA. Moreover, the data was taken from the Series 2 of Taskmaster using open coding technique and analysed with Fairclough’s Critical Discourse Analysis framework. The results show that throughout the series, the only woman panellist is often being underestimated and interrupted by men, confirming gender disparity in Taskmaster. She is also constantly being objectified while defending her attempts, as this occurrence increases throughout the episodes. Interestingly, some of the men panellists and presenters try to diminish the male-dominated nature by helping in weighing sexist-sounding tasks or decisions. This also confirmed the opinions that men often hold more power in comedy panel show than women.
A RARE CASE OF HYPERLACTATEMIA IN THE EMERGENCY DEPARTMENT
Authors: Stumpf Matheo , Simões Ademar , Alencar Julio
Published: February 2022

Introduction: Glycogen storage disease type 1a is a rare autosomal recessive syndrome characterized by hypoglycemia, hyperuricemia, hyperlipidemia, hepatomegaly, among other features. Case report: A 31-year-old woman genetically diagnosed with this disease in childhood was admitted to the Emergency Department with tachypnea. Her lactate was 179 mg/dL, and her arterial bicarbonate was 2 mmol/L, with a pH of 7.0 and pCO2 of 2.2 mmHg. She received IV glucose, isotonic bicarbonate, and antibiotics. Her urine culture was positive for Escherichia coli. She had a complete recovery from acidosis in 12 hours and was discharged three days later. Conclusion: This case highlights a rare differential of lactic acidosis that can, sometimes, be present in the emergency department.
COVID-19 Cases With Acute Necrotizing Pancreatitis
Authors: Bilir Özlem , Ayaz Teslime , Ünlü Alpaslan , Taşçı Filiz , Ersunan Gökhan
Published: February 2022

Introduction: COVID-19 is a multisystemic condition that presents with different signs and symptoms. Studies conducted have shown that it shows its effect on different tissues through Angiotensin Converting Enzyme 2 receptors. In particular, gastrointestinal system symptoms have started to attract more attention.
Case Report: We present two COVID-19 cases, aged 82 and 70, presenting with acute pancreatitis without any other risk factors. An 82-year-old female patient had a fatal outcome despite the treatment, while a 70-year-old female patient was discharged for outpatient follow-up.
Conclusion: While COVID-19 patients are typically admitted with symptoms of respiratory system, some patients may have symptoms such as nausea-vomiting, diarrhoea and abdominal pain.
Üniversite Tercihlerinin Yansımaları: Bilgi ve Belge Yönetimi Programları Üzerine Bir Çalışma
Authors: AL Umut
Published: February 2022

Yaklaşık 2,5 milyon öğrencinin girdiği Yükseköğretim Kurumları Sınavı sonucunda adayların çoğunluğu herhangi bir programa yerleşememektedir. Yerleşilen programların adayların gerçekten istedikleri yerler olup olmadığı ise tartışmalıdır. Çoğunluğun istediği yere giremediği yönünde genel bir kabul bulunmakla birlikte, çok fazla paydaşı ve ilgilisi olan konunun gerektiği ölçüde incelenmediği değerlendirilmektedir. Bu çalışmada yükseköğretim sisteminin kamuoyu ile paylaştığı veriler üzerinden, bilgi ve belge yönetimi programları özelinde öğrencilerin üniversite sınav performansı ve tercihleri mercek altına alınmaktadır. Bilgi ve belge yönetimi programlarının doluluk oranları, öğretim elemanı sayıları, adayların tercih eğilimleri gibi konular, kimi zaman yıllara göre, kimi zaman da daha önce yapılan bazı çalışmaların bulguları ile karşılaştırılarak sunulmaktadır. Çalışmanın sonuçları bilgi ve belge yönetimi programlarını bekleyen potansiyel tehlikeler olduğunu göstermektedir. Bu tehlikelerin en başında ise bilgi ve belge yönetimi programlarının adaylar tarafından tercih edilmeyen programlar haline dönüşebilme riski gelmektedir. Konunun ilgililerinin, programların geleceği konusunda hızlı ve gerçekçi şekilde hareket etmeleri gerektiği açıktır. Bu bağlamda çok boyutu olan konunun elde edilen nicel bulgular temelinde nitel verilerle desteklenerek ele alınması ve uzlaşma sonucunda ulaşılan sonuçlara göre eyleme geçilmesi önerilmektedir.
Art in Slovakia in Prehistoric Times
Authors:   Academy of Arts in Banská Bystrica, Strenacikova Sr. Maria , Strenacikova Jr. Maria ,   Academy of Arts in Banská Bystrica
Published: February 2022

Archaeological research in the territory of today’s Slovakia has revealed rare artifacts from the oldest period in human history, from prehistory. Two unique female figures of Venus represent them. This article presents a statuette from the Paleolithic Era — the Venus of Moravany, which is made from a mammoth tusk and is an artistic expression of fertility in the matriarchy. The article also describes a gem from the Neolithic period, the Venus of Hrádok, Magna Mater, as the goddess of harvest, success, the giver of life and well-being.
Fujianese Provincial Brass Band Traditions of Chinese Immigrant Musicians in New York City: The Chinese Voices
Authors:   College of Staten Island of the City University of New York, Kaminski Joseph S.
Published: February 2022

This article focuses on the Chinese Voices Wind Orchestra. Fujianese brass band musicians immigrated to New York and changed Chinatown’s musical soundscape. The bands perform mainly inside or on the street outside of funeral parlors on Canal and Mulberry Streets. Their profession is mainly that of a funeral musician. They also travel to Philadelphia or Washington, D.C. for rites. They accompany families and decedents to cemeteries to play special repertoire. After the burial they perform songs of prosperity at receptions in restaurants. They maintain a wide repertoire of funeral songs and national marches. Funeral performances are a hidden music tradition performed at a sacred place for a sacred function, not intended for the public. Passers-by though observe bands performing outdoors when a coffin is brought to the hearse. There is a display of music and drama at this moment, for bands’ sounds transform the Downtown neighborhood into a Taoist aura. Bands came to perform adjacent to traditional Chinese instruments and at funerals as early as 1908, during the late Qing Dynasty influenced by the European imperial tradition. Today Chinese brass bands are transnational, and Fujianese bands bring the genre of a European brass band to New York in a Chinese interpretation of nationalism.
Political Posters, the Soviet Enlightenment and the Construction of a Learning Society, 1917-1928
Authors: Ignatovich Elena , Walter Pierre
Published: February 2022

This paper explores the construction of a Soviet learning society represented in Soviet political posters during the first decade after the 1917 Socialist Revolution. The theoretical framework is based on studies of learning societies, lifelong education and learning, Soviet education, and the theory of multiple modernities. We employed a post-structuralist discourse analysis that allowed us to explore verbal and non-verbal poster elements to identify key domains in the construction of the Soviet learning society. Our study identified six main discursive visual and textual messages in political posters as educational devices in the development of the Socialist learning state. Findings show that learning was embedded in broader social, political, economic and cultural practices and took multiple forms. Political posters served multiple functions: they were motivators for learning, learning devices, means to communicate the Soviet party-state agenda, and part of the social-political and cultural curriculum of the learning society to come.
Sustainable Waste Management Strategies for Effective Energy Utilization in Oman: A Review
Authors: Okedu Kenneth E. , Barghash Hind F. , Al Nadabi Husam A.
Published: February 2022

Due to the adverse effect of energy production from traditional fossil fuels, the move toward renewable and sustainable energy has become imperative. The waste disposal sector offers hope toward environmental sustainability and potential to generate strong income for any economy. The region of the Gulf Cooperation Council (GCC) member countries in the Middle East generates the highest quantity of municipal waste per capita, compared to other countries globally. In the GCC region, waste is usually just dumped at different landfill stations. Effective waste management is imperative for environmental protection and sustainable development. This article presents a review of the sustainable waste management strategies in Oman, in line with the United Nations goal on environmental management of waste. The current waste management strategies in Oman were discussed, and various waste-to-energy (WTE) technologies were proposed. These proposed WTE strategies would help in effective waste management in Oman and also in increasing the power grid capability. The salient part of this article is an overview of the ability of using landfill leachate as feedstock to produce clean and green hydrogen gas using different photo-fermentation processes. The production of hydrogen using single photo-fermentation process using landfill leachate alone, with leachate and addition of inoculum such as sewage sludge, and with substrates such as sucrose, glucose, and landfill leachate was investigated by utilizing a batch bioreactor and anaerobic conditions at controlled temperature, different initial pH, and heat treatment temperature range. Furthermore, a prototype model for the optimization of the inoculum size and the substrate was proposed with 2-level factorial design using Design Expert. The data gathering for this study was carried out by investigating different regions in Oman having the lowest and highest waste produce, the average annual waste for the different governorates, and the total amount of waste for five consecutive years (2015–2020), for the various engineered landfills. The cost of managing waste in the different governorates of Oman was presented, considering the average annual waste produced, in various regions of the country for the duration of the study. Furthermore, some challenges and opportunities in carrying out effective waste management in Oman were addressed.
Synthesis of Star 6-Arm Polyethylene Glycol-Heparin Copolymer to Construct Anticorrosive and Biocompatible Coating on Magnesium Alloy Surface
Authors: Hong Qingxiang , Zhou Hualan , Cheng Yuxin , Yang Minhui , Zhang Qiuyang , Liu Sen , Xiong Qingping , Pan Changjiang
Published: February 2022

Magnesium alloy has become a research hotspot of the degradable vascular stent materials due to its biodegradability and excellent mechanical properties. However, its rapid degradation rate after implantation and the limited biocompatibility restrict its application in clinic. Constructing a multifunctional bioactive polymer coating on the magnesium alloys represents one of the popular and effective approaches to simultaneously improve the corrosion resistance and biocompatibility. In the present study, the copolymer of 6-arm polyethylene glycol and heparin (PEG-Hep) was successfully synthesized and then immobilized on the surface of chitosan (Chi)-modified magnesium alloy surface through electrostatic interaction to improve the corrosion resistance and biocompatibility. The results of attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy showed that a dense and compact coating was created on the magnesium alloy surface. The coating displayed excellent hydrophilicity. At the same time, the as-prepared coating can significantly not only improve the corrosion potential, reduce the corrosion current and the pH changes of the immersion solution, but also keep a relatively intact surface morphology after immersing in simulated body fluid solution for 14 days, demonstrating that the coating can significantly improve the corrosion resistance of the magnesium alloy. Moreover, the magnesium alloy with PEG-Hep coating exhibited excellent hemocompatibility according to the results of the hemolysis rate and platelet adhesion and activation. In addition, the modified magnesium alloy had a good ability to promote the endothelial cell adhesion and proliferation. Therefore, the PEG-Hep multifunctional coating can be applied in the surface modification of the biodegradable magnesium alloy stent to simultaneously improve the corrosion resistance and biocompatibility.
Essential Functions of MLL1 and MLL2 in Retinal Development and Cone Cell Maintenance
Authors: Sun Chi , Zhang Xiaodong , Ruzycki Philip A. , Chen Shiming
Published: February 2022

MLL1 (KMT2A) and MLL2 (KMT2B) are homologous members of the mixed-lineage leukemia (MLL) family of histone methyltransferases involved in epigenomic transcriptional regulation. Their sequence variants have been associated with neurological and psychological disorders, but little is known about their roles and mechanism of action in CNS development. Using mouse retina as a model, we previously reported MLL1’s role in retinal neurogenesis and horizontal cell maintenance. Here we determine roles of MLL2 and MLL1/MLL2 together in retinal development using conditional knockout (CKO) mice. Deleting Mll2 from Chx10+ retinal progenitors resulted in a similar phenotype as Mll1 CKO, but removal of both alleles produced much more severe deficits than each single CKO: 1-month double CKO mutants displayed null light responses in electroretinogram; thin retinal layers, including shorter photoreceptor outer segments with impaired phototransduction gene expression; and reduced numbers of M-cones, horizontal and amacrine neurons, followed by fast retinal degeneration. Despite moderately reduced progenitor cell proliferation at P0, the neurogenic capacity was largely maintained in double CKO mutants. However, upregulated apoptosis and reactive gliosis were detected during postnatal retinal development. Finally, the removal of both MLLs in fated rods produced a normal phenotype, but the CKO in M-cones impaired M-cone function and survival, indicating both cell non-autonomous and autonomous mechanisms. Altogether, our results suggest that MLL1/MLL2 play redundant roles in maintaining specific retinal neurons after cell fate specification and are essential for establishing functional neural networks.
The Rising of “Alblish” (Albanian + English)—Data Collection and Analysis of Anglicisms in the Albanian Language
Authors: Kapo Irena
Published: February 2022

This paper investigates the impact of English on the Albanian language, a language contact phenomenon hitherto largely unexamined by Albanian and non-Albanian linguists alike. This contact mainly started as an indirect one at the beginning of the twentieth century, primarily via translations, the establishment of several educational institutions with the support of American and British associations and Albanian immigration into English-speaking countries. Several newspapers introduced a considerable number of Anglicisms into Albanian during the first half of the twentieth century, a good quantity of which “survived” even during the communist years of isolation. Those Anglicisms which made their way into the Albanian language until the 1990s and which have established themselves in the Albanian of today are mainly from the domains of culture and sports. The fall of the communist regime exposed the Albanian language to external linguistic and social factors, bringing about a flood of Anglicisms in different lexical fields other than culture and sport, such as business, information technology, politics, and medicine. The current database of Anglicisms in Albanian used for the purpose of this Brief Research Report was collected in the framework of the GLAD (Global Anglicism Database Network) project,http://gladnetwork.org. It includes 1,895 Anglicisms from newspapers and dictionaries, all integrated in a single file. The report first provides background information regarding the growing impact of English on the Albanian language during the three time periods under review (early twentieth century until 1960, 1960 to 1990, and 1990 to the present day). This is followed by an account of the data and the methods applied in the research. Subsequently, the findings and results are presented and discussed from a morphological, lexical, and syntactical perspective. The final outcomes are then used as a basis for the identification of Albanian language structures or patterns the English borrowings have managed to penetrate as well as of the level of adaptation English borrowings have in Albanian.
Incident Stroke and Its Influencing Factors in Patients With Type 2 Diabetes Mellitus and/or Hypertension: A Prospective Cohort Study
Authors: Chang Wei-Wei , Fei Shi-Zao , Pan Na , Yao Ying-Shui , Jin Yue-Long
Published: February 2022

Objective

To understand the incidence of stroke in patients with type 2 diabetes mellitus (T2DM) and/or hypertension (HTN), and provide a basis for the prevention of stroke in these patients.

Methods

A prospective cohort study was performed for adults with T2DM and/or HTN. The follow-up period was 1 year. The incidence and recurrence rate of stroke was calculated and a multivariate Cox proportional hazard was used to analyze influencing factors of stroke occurrence and recurrence in the follow-up of patients with T2DM and/or HTN.

Results

Of the 1,650 patients with T2DM and/or HTN, 1,213 patients had no history of stroke. After 1 year of follow-up, 147 new stroke cases occurred, and the incidence rate of stroke was 12.1%. Among the patients who had stroke history (413), there were 116 cases of stroke with a recurrence rate of 26.5%. Seven risk factors were independently associated with stroke occurrence among patients without stroke history, included smoking, abnormal total cholesterol abnormal low-density lipoprotein patients with comorbid T2DM with HTN, physical inactivity, carotid artery stenosis (CAS), and higher scores of National Institutes of Health Stroke Scale (NIHSS). Higher scores of NHISS and CAS were independent risk factors for the recurrence of stroke among patients with stroke history.

Conclusions

Patients with T2DM and/or HTN have a higher rate of new stroke and recurrence after 1-year follow-up. Actively identifying the controllable risk factors, such as smoking and physical inactivity, will help reduce the risk of stroke and recurrence in patients with T2DM and HTN.
Effects of Different Aerosols on the Air Pollution and Their Relationship With Meteorological Parameters in North China Plain
Authors: Zhao Hujia , Gui Ke , Ma Yanjun , Wang Yangfeng , Wang Yaqiang , Wang Hong , Dou Yuanyuan , Zheng Yu , Li Lei , Zhang Lei , Zhang Yuqi , Che Huizheng , Zhang Xiaoye
Published: February 2022

Located in East Asia, the North China Plain (NCP) has a severe air pollution problem. In this study, variations in visibility, particulate matter (PM), gaseous pollutants, vertical meteorological parameters, and different types of aerosols and their optical properties were evaluated during an air pollution episode that occurred from 10 to 15 January 2019 in Tianjin over the NCP. The visibility was <10 km for approximately 96 h, and the concentrations of PM with an aerodynamic diameter of <2.5 μm (PM2.5) and <10 μm (PM10) increased to 300 and 400 μg/m3, respectively. Because of the conversion of SO2 to sulphate aerosol particles, the sulphur dioxide (SO2) concentration decreased to a minimum of 10 μg/m3. The continual deterioration of visibility was related to the high relative humidity and the boundary layer of <0.1 km. The southwest airflow (3.0–4.0 m/s) transported various pollutants from Hebei Province to the NCP. Higher mixing ratios of sulphate aerosols, organic aerosols, and black carbon aerosols were distributed over a 0.5-km-diameter area, and the maximum concentrations were approximately 90, 250–300, and 20 μg/kg, respectively. Higher mixing ratios of dust aerosols and sea salt aerosols were distributed within 1.5 km and 1.0–2.5 km, respectively, and their maximum concentrations were approximately 15 and 9 μg/kg, respectively. The findings are valuable for analysing the relationship between air quality and pollutant transport in the NCP.
Imaging With the Past: Revealing the Complexity of Chimaeroid Pelvic Musculature Anatomy and Development
Authors: Pears Jacob B. , Tillett Carley , Tahara Rui , Larsson Hans C. E. , Boisvert Catherine A.
Published: February 2022

Chondrichthyans are now widely adopted as models for examining the development and evolution of the stem gnathostome body plan. The fins of some cartilaginous fish are recognized for their plesiomorphic form and mode of muscular development, i.e., epithelial extension. Despite detailed molecular and descriptive examinations of these developmental mechanisms, there has been little contemporary examination of the ontogeny and morphology of the musculature in chondrichthyans including that of the paired fins. This gap represents a need for further examination of the developmental morphology of these appendicular musculatures to gain insight into their evolution in gnathostomes. The elephant shark is a Holocephalan, the sister group of all other chondrichthyans (Holocephali: Callorhinchus milii). Here, we use nano-CT imaging and 3D reconstructions to describe the development of the pelvic musculature of a growth series of elephant shark embryos. We also use historical descriptions from the nineteenth century and traditional dissection methods to describe the adult anatomy. This combined approach, using traditional methods and historical knowledge with modern imaging techniques, has enabled a more thorough examination of the anatomy and development of the pelvic musculature revealing that chimaeroid musculatures are more complex than previously thought. These data, when compared to extant and extinct sister taxa, are essential for interpreting and reconstructing fossil musculatures as well as understanding the evolution of paired fins.
Genome Editing for Improving Crop Nutrition
Authors: Nagamine Ai , Ezura Hiroshi
Published: February 2022

Genome editing technologies, including CRISPR/Cas9 and TALEN, are excellent genetic modification techniques and are being proven to be powerful tools not only in the field of basic science but also in the field of crop breeding. Recently, two genome-edited crops targeted for nutritional improvement, high GABA tomatoes and high oleic acid soybeans, have been released to the market. Nutritional improvement in cultivated crops has been a major target of conventional genetic modification technologies as well as classical breeding methods. Mutations created by genome editing are considered to be almost identical to spontaneous genetic mutations because the mutation inducer, the transformed foreign gene, can be completely eliminated from the final genome-edited hosts after causing the mutation. Therefore, genome-edited crops are expected to be relatively easy to supply to the market, unlike GMO crops. On the other hand, due to their technical feature, the main goal of current genome-edited crop creation is often the total or partial disruption of genes rather than gene delivery. Therefore, to obtain the desired trait using genome editing technology, in some cases, a different approach from that of genetic recombination technology may be required. In this mini-review, we will review several nutritional traits in crops that have been considered suitable targets for genome editing, including the two examples mentioned above, and discuss how genome editing technology can be an effective breeding technology for improving nutritional traits in crops.
B Cells Adapt Their Nuclear Morphology to Organize the Immune Synapse and Facilitate Antigen Extraction
Authors: Ulloa Romina , Corrales Oreste , Cabrera-Reyes Fernanda , Jara-Wilde Jorge , Saez Juan José , Rivas Christopher , Lagos Jonathan , Härtel Steffen , Quiroga Clara , Yuseff María-Isabel , Diaz-Muñoz Jheimmy
Published: February 2022

Upon interaction with immobilized antigens, B cells form an immune synapse where actin remodeling and re-positioning of the microtubule-organizing center (MTOC) together with lysosomes can facilitate antigen extraction. B cells have restricted cytoplasmic space, mainly occupied by a large nucleus, yet the role of nuclear morphology in the formation of the immune synapse has not been addressed. Here we show that upon activation, B cells re-orientate and adapt the size of their nuclear groove facing the immune synapse, where the MTOC sits, and lysosomes accumulate. Silencing the nuclear envelope proteins Nesprin-1 and Sun-1 impairs nuclear reorientation towards the synapse and leads to defects in actin organization. Consequently, B cells are unable to internalize the BCR after antigen activation. Nesprin-1 and Sun-1-silenced B cells also fail to accumulate the tethering factor Exo70 at the center of the synaptic membrane and display defective lysosome positioning, impairing efficient antigen extraction at the immune synapse. Thus, changes in nuclear morphology and positioning emerge as critical regulatory steps to coordinate B cell activation.
Immunotherapy in Lung Cancer: Current Landscape and Future Directions
Authors: Mamdani Hirva , Matosevic Sandro , Khalid Ahmed Bilal , Durm Gregory , Jalal Shadia I.
Published: February 2022

Over the past decade, lung cancer treatment has undergone a major paradigm shift. A greater understanding of lung cancer biology has led to the development of many effective targeted therapies as well as of immunotherapy. Immune checkpoint inhibitors (ICIs) have shown tremendous benefit in the treatment of non-small cell lung cancer (NSCLC) and are now being used as first-line therapies in metastatic disease, consolidation therapy following chemoradiation in unresectable locally advanced disease, and adjuvant therapy following surgical resection and chemotherapy in resectable disease. Despite these benefits, predicting who will respond to ICIs has proven to be difficult and there remains a need to discover new predictive immunotherapy biomarkers. Furthermore, resistance to ICIs in lung cancer is frequent either because of a lack of response or disease progression after an initial response. The utility of ICIs in the treatment of small cell lung cancer (SCLC) remains limited to first-line treatment of extensive stage disease in combination with chemotherapy with modest impact on overall survival. It is thus important to explore and exploit additional targets to reap the full benefits of immunotherapy in the treatment of lung cancer. Here, we will summarize the current state of immunotherapy in lung cancer, discuss novel targets, and explore the intersection between DNA repair defects and immunotherapy.
Case Report: A Peculiar Case of Inflammatory Colitis After SARS-CoV-2 Infection
Authors: Rutigliani Mariangela , Bozzo Matteo , Barberis Andrea , Greppi Marco , Anelli Emanuela , Castellaro Luca , Bonsignore Alessandro , Azzinnaro Antonio , Pesce Silvia , Filauro Marco , Rollandi Gian Andrea , Castagnola Patrizio , Candiani Simona , Marcenaro Emanuela
Published: February 2022

We report a case of inflammatory colitis after SARS-CoV-2 infection in a patient with no additional co-morbidity who died within three weeks of hospitalization. As it is becoming increasingly clear that SARS-CoV-2 infection can cause immunological alterations, we investigated the expression of the inhibitory checkpoint PD-1 and its ligand PD-L1 to explore the potential role of this axis in the break of self-tolerance. The presence of the SARS-CoV-2 virus in colon tissue was demonstrated by qRT-PCR and immunohistochemical localization of the nucleocapsid protein. Expression of lymphocyte markers, PD-1, and PD-L1 in colon tissue was investigated by IHC. SARS-CoV-2-immunoreactive cells were detected both in the ulcerated and non-ulcerated mucosal areas. Compared to healthy tissue, where PD-1 is weakly expressed and PD-L1 is absent, PD-1 and PD-L1 expression appears in the inflamed mucosal tissue, as expected, but was mainly confined to non-ulcerative areas. At the same time, these markers were virtually undetectable in areas of mucosal ulceration. Our data show an alteration of the PD-1/PD-L1 axis and suggest a link between SARS-CoV-2 infection and an aberrant autoinflammatory response due to concomitant breakdown of the PD-1/PD-L1 interaction leading to early death of the patient.
Quality-Reliability Coupled Network Modeling and Importance Measure of Multi-Stage Manufacturing Systems via Network Controllability Analysis
Authors: Zhang Ding , Pei Yu , Liu Qiang
Published: February 2022

The fluctuation of product quality is closely related to the degradation of the equipment in multi-stage manufacturing systems. This paper proposes a critical measure approach for a quality-reliability coupled network of multi-stage manufacturing systems via network controllability. The impact of component degradation will be transmitted, expanded, and accumulated in multiple manufacturing stages, leading to quality flaws or even shutdowns of the entire system. An important measurement method via controllability analysis is provided by quantifying the impact of attacking the quality-reliability coupled network. By quantifying the control ability of the fault source node on the key quality attribute node, the weakness that affects the processing accuracy of a production line is identified. Case studies of real production lines are applied to verify the effectiveness, and comparative results show the method can guide the quality-reliability improvement of manufacturing systems.
Efficacy of Initial vs. Delayed Photodynamic Therapy in Combination With Conbercept for Polypoidal Choroidal Vasculopathy
Authors: Sun Zuhua , Gong Yuanyuan , Yang Yating , Huang Ying , Yu Suqin , Pei Junqing , Lin Bing , Zhou Rong , Li Yingzi , Li Yumin , Zhang Junyan , Liu Xiaoling
Published: February 2022

Purpose

To compare the efficacy of initial vs. delayed photodynamic therapy (PDT) in combination with intravitreal injection of conbercept (IVC) for polypoidal choroidal vasculopathy (PCV).

Design

Multicenter, randomized, non-inferiority clinical trial.

Subjects

Naïve PCV patients.

Methods

Patients were randomized 1:1 into two groups: initial PDT with IVC and delayed PDT with IVC. At baseline, patients in the initial combination group were treated with PDT and IVC within 1 week, while patients in the delayed combination group were treated with IVC alone. PDT and IVC was given PRN during the follow-up in each group.

Main Outcome Measures

Non-inferiority of delayed PDT with IVC to initial PDT with IVC for mean change in best-corrected visual acuity from baseline to month 12 (95% CI of the difference entirely above −5 letters).

Results

Eighty-six patients were enrolled, with 43 in each group. At month 12, the change of BCVA in initial combination group was equivalent to that in the delayed combination group, with gains of 6.42 ± 1.89 and 7.49 ± 2.14 (mean ± standard error) letters, respectively [delayed group minus initial group: 1.07 letters; 95% confidence interval (CI): −4.62 to 6.76; Pnon−inferiority = 0.0198]. The rates of complete polyp regression were 66.67 and 45.83% in the initial and delayed combination groups, respectively. The difference was not statistically significant (P = 0.386). The mean reductions of CRT were 204.77 ± 28.79 and 84.14 ± 30.62 μm in each group respectively. The difference was statistically significant (P = 0.005). In addition, the mean injection numbers were 3.47 ± 2.39 and 4.91 ± 2.65 in each group respectively. The differences were statistically significant (P = 0.010).

Conclusions

There was effective in both groups in patients with PCV. The initial combination group showed a more efficient decrease in CRT and polyp regression, along with fewer injections. However, the delayed combination group was non-inferior compared with the initial combination group in terms of the improvement of BCVA.

Trial Registration

https://ClinicalTrials.gov, Identifier: NCT02821520.
Influence of Deep Invasive Tumor Thrombus on the Surgical Complexity and Prognosis of Patients With Non-Metastatic Renal Cell Carcinoma Combined With Venous Tumor Thrombus
Authors: Zhao Xun , Yan Ye , Dong Jing-han , Liu Zhuo , Zhang Hong-xian , Liu Cheng , Ma Lu-lin
Published: February 2022

Background

To evaluate the impact of deep invasive tumor thrombus (DITT) on the surgical complexity and prognosis of patients with renal cell carcinoma with venous tumor thrombus.

Methods

We retrospectively reviewed clinical data of 138 patients with non-metastatic renal cell carcinoma combined with venous tumor thrombus, who underwent surgical treatment in Peking University Third Hospital from January 2015 to June 2020. Patients were divided into the DITT group (84 patients) and non-invasive tumor thrombus (NITT) group (54 patients). Chi-square, t-test and Mann–Whitney U test were used for categorical and continuous variables, respectively. Kaplan–Meier plots were performed to evaluate the influence of DITT. Univariable and multivariable Cox regressions were conducted to determine independent prognostic factors and then assembled to make a nomogram to predict the survival. The performance of the nomogram was evaluated by Harrell’s consistency index (C-index) and calibration plot.

Results

Deep invasive tumor thrombus significantly increased the difficulty of surgery for patients with renal cell carcinoma with venous tumor thrombus, which is mainly reflected in longer operation time (p < 0.001), more surgical bleeding (p  < 0.001), a higher proportion of perioperative blood transfusion (p  = 0.006), a higher proportion of open surgery (p = 0.001), a longer postoperative hospital stay (p = 0.003), and a higher proportion of postoperative complications (p = 0.001). DITT (hazard ratio [HR] = 2.781, p = 0.040) was one of the independent risk factors for worse prognosis. Multivariate analysis showed that sarcoma-like differentiation (p = 0.040), tumor thrombus invasion (p = 0.040), low hemoglobin (p = 0.003), and pathological type (p < 0.001) were independent prognostic factors. The nomogram, combining all these predictors, showed powerful prognostic ability with a C-index of 78.8% (CI: 71.2%–86.4%). The predicted risk closely matches the observed recurrence probability.

Conclusion

Deep invasive tumor thrombus significantly increased the difficulty of surgeries for patients of renal cell carcinoma with venous tumor thrombus, and may lead to poor prognosis.
Recurrence of Congenital Diaphragmatic Hernia: Risk Factors, Management, and Future Perspectives
Authors: Macchini Francesco , Raffaeli Genny , Amodeo Ilaria , Ichino Martina , Encinas José Luis , Martinez Leopoldo , Wessel Lucas , Cavallaro Giacomo
Published: February 2022

Recurrence is one of the most common surgical complications in Congenital Diaphragmatic Hernia (CDH). It could remain clinically silent for a long time or present as an acute complication week, months, or even years after the primary surgery. Several risk factors have been identified so far. An extended diaphragmatic defect represents one of the leading independent risk factors, together with indirect signs of large defect such as the liver position related to the diaphragm and the use of the prosthetic patch and with the use of a minimally invasive surgical (MIS) approach. However, the exact contribution of each factor and the overall risk of recurrence during the life span still need to be fully understood. This mini-review aims to give an overview of the current knowledge regarding CDH recurrence, focusing on predisposing factors, clinical presentation, management and follow-up of high-risk patients, and future perspectives.
Resveratrol: Potential Application in Sepsis
Authors: Li Jiajia , Zeng Xiaoting , Yang Fuxun , Wang Lan , Luo Xiaoxiu , Liu Rongan , Zeng Fan , Lu Sen , Huang Xiaobo , Lei Yu , Lan Yunping
Published: February 2022

Sepsis is a life-threatening organ dysfunction syndrome caused by host response disorders due to infection or infectious factors and is a common complication of patients with clinical trauma, burns, and infection. Resveratrol is a natural polyphenol compound that is a SIRT-1 activator with anti-inflammatory, antiviral, antibacterial, antifungal inhibitory abilities as well as cardiovascular and anti-tumor protective effects. In recent years, some scholars have applied resveratrol in animal models of sepsis and found that it has an organ protective effect and can improve the survival time and reduce the mortality of animals with sepsis. In this study, Medline (Pubmed), embase, and other databases were searched to retrieve literature published in 2021 using the keywords “resveratrol” and “sepsis,” and then the potential of resveratrol for the treatment of sepsis was reviewed and prospected to provide some basis for future clinical research.
High-Intensity Inspiratory Muscle Training Improves Scalene and Sternocleidomastoid Muscle Oxygenation Parameters in Patients With Weaning Difficulties: A Randomized Controlled Trial
Authors: Van Hollebeke Marine , Poddighe Diego , Clerckx Beatrix , Muller Jan , Hermans Greet , Gosselink Rik , Langer Daniel , Louvaris Zafeiris
Published: February 2022

Background

Critically ill patients who have difficulties weaning from the mechanical ventilator are prone to develop respiratory muscle weakness. Inspiratory muscle training (IMT) can improve respiratory muscle strength. Whether IMT can improve scalene and sternocleidomastoid muscle oxygenation parameters is unknown.

Aim

To compare changes in muscle oxygenation parameters of scalene and sternocleidomastoid inspiratory muscles during a standardized task between patients with weaning difficulties who received either high-intensity IMT (intervention) or sham low-intensity IMT (control).

Method

Forty-one patients performed daily IMT sessions (4 sets, 6–10 breaths) until weaning success or for 28 consecutive days. The training load was progressively adjusted in the intervention group (n = 22) to the highest tolerable load, whilst the control group (n = 19) kept training at 10% of their baseline maximal inspiratory pressure (PImax). Breathing characteristics (i.e., work and power of breathing, PoB), respiratory muscle function [i.e., PImax and forced vital capacity (FVC)] were measured during a standardized loaded breathing task against a load of 30% of baseline PImax before and after the IMT period. In addition, during the same loaded breathing task, absolute mean and nadir changes from baseline in local scalene and sternocleidomastoid muscle oxygen saturation index (Δ%StiO2) (an index of oxygen extraction) and nadir Δ%StiO2 normalized for the PoB were measured by near-infrared spectroscopy.

Results

At post measures, only the intervention group improved mean PoB compared to pre measures (Pre: 0.42 ± 0.33 watts, Post: 0.63 ± 0.51watts, p-value < 0.01). At post measures, both groups significantly improved nadir scalene muscles StiO2% normalized for the mean PoB (ΔStiOnadir%/watt) compared to pre measurements and the improvement was not significant different between groups (p-value = 0.40). However, at post measures, nadir sternocleidomastoid muscle StiO2% normalized for the mean PoB (ΔStiOnadir%/watt) was significantly greater improved in the intervention group (mean difference: +18.4, 95%CI: −1.4; 38.1) compared to the control group (mean difference: +3.7, 95%CI: −18.7; 26.0, between group p-value < 0.01). Both groups significantly improved PImax (Intervention: +15 ± 13 cmH2O p-value < 0.01, Control: +13 ± 15 cmH2O p-value < 0.01). FVC only significantly improved in the intervention group (+0.33 ± 0.31 L p < 0.01) report also change in control group.

Conclusion

This exploratory study suggests that high-intensity IMT induces greater improvements in scalene and sternocleidomastoid muscle oxygenation parameters attributed for oxygen delivery, utilization and oxygen saturation index compared to low-intensity IMT in patients with weaning difficulties.
Recurrence Quantitative Analysis of Wavelet-Based Surrogate Data for Nonlinearity Testing in Heart Rate Variability
Authors: Calderón-Juárez Martín , González Gómez Gertrudis Hortensia , Echeverría Juan C. , Pérez-Grovas Héctor , Quintanar Eduardo , Lerma Claudia
Published: February 2022

Exploring the presence of nonlinearity through surrogate data testing provides insights into the nature of physical and biological systems like those obtained from heart rate variability (HRV). Short-term HRV time series are of great clinical interest to study autonomic impairments manifested in chronic diseases such as the end stage renal disease (ESRD) and the response of patients to treatment with hemodialysis (HD). In contrast to Iterative Amplitude Adjusted Fourier Transform (IAAFT), the Pinned Wavelet Iterative Amplitude Adjusted Fourier Transform (PWIAAFT) surrogates preserve nonstationary behavior in time series, a common characteristic of HRV. We aimed to test synthetic data and HRV time series for the existence of nonlinearity. Recurrence Quantitative Analysis (RQA) indices were used as discriminative statistics in IAAFT and PWIAAFT surrogates of linear stationary and nonstationary processes. HRV time series of healthy subjects and 29 ESRD patients before and after HD were tested in this setting during an active standing test. Contrary to PWIAAFT, linear nonstationary time series may be erroneously regarded as nonlinear according to the IAAFT surrogates. Here, a lower proportion of HRV time series was classified as nonlinear with PWIAAFT, compared to IAAFT, confirming that the nonstationarity condition influences the testing of nonlinear behavior in HRV. A contribution of nonlinearity was found in the HRV data of healthy individuals. A lower proportion of nonlinear time series was also found in ESRD patients, but statistical significance was not found. Although this proportion tends to be lower in ESRD patients, as much as 60% of time series proved to be nonlinear in healthy subjects. Given the important contribution of nonlinearity in HRV data, a nonlinear point of view is required to achieve a broader understanding of cardiovascular physiology.
Genome-Wide Analysis of U-box E3 Ubiquitin Ligase Family in Response to ABA Treatment in Salvia miltiorrhiza
Authors: Chen Chengan , Wang Can , Li Junbo , Gao Xiankui , Huang Qikai , Gong Yifu , Hao Xiaolong , Maoz Itay , Kai Guoyin , Zhou Wei
Published: February 2022

Plant U-box (PUB) proteins are ubiquitin ligases (E3) involved in multiple biological processes and in response to plant stress. However, the various aspects of the genome and the differences in functions between the U-box E3 (UBE3) ubiquitin ligases remain quite obscure in Salvia miltiorrhiza. The 60 UBE3 genes in the S. miltiorrhiza genome were recognized in the present study. The phylogenetic analysis, gene structure, motifs, promoters, and physical and chemical properties of the genes were also examined. Based on the phylogenetic relationship, the 60 UBE3 genes were categorized under six different groups. The U-box domain was highly conserved across the family of UBE3 genes. Analysis of the cis-acting element revealed that the UBE3 genes might play an important role in a variety of biological processes, including a reaction to the abscisic acid (ABA) treatment. To investigate this hypothesis, an ABA treatment was developed for the hairy roots of S. miltiorrhiza. Thirteen out of the UBE3 genes significantly increased after the ABA treatment. The co-expression network revealed that nine UBE3 genes might be associated with phenolic acids or tanshinone biosynthesis. The findings of the present study brought fresh and new understanding to the participation of the UBE3 gene family in plants, specifically in their biological responses mediated by the ABA. In S. miltiorrhiza, this gene family may be crucial during the ABA treatment. Significantly, the results of this study contribute novel information to the understanding of the ubiquitin ligase gene and its role in plant growth.