bluuebunny/crossref_metadata_2025 huggingface dataset:
Nietzsche and Luther: Reading, Counter-Text, Hermeneutics
Authors: Cummings Brian
Published: April 2021

In what way is Nietzsche's infamous late aphorism, ‘God is dead’, related to a general attack on theology and its intellectual practices? In Twilight of the Idols, he remarks: ‘I'm afraid we're not rid of God because we still believe in grammar.’ Reason, he decries, has become mired in linguistic rules long determined by the requirements of scholastic philosophy, whether of medieval theology or of Immanuel Kant. Nietzsche dismisses these as die Sprach-Metaphysik (‘metaphysics of language’). In this essay I examine Nietzsche's attack on theology via his long-term struggle with the ideas of Luther, once the idol of Goethe's German enlightenment, and now, Nietzsche insists, its arch-enemy. To do this, I re-examine Luther's theology of language, especially in the early Lectures on Romans (1515–1516). Luther's own attack on scholasticism is founded on a theology of reading which has unexpected affinities with Nietzsche. By placing this in a revised genealogy of hermeneutics from Nietzsche to Heidegger, it is possible to see theology as less deterministic and metaphysical.
Don't Say Practical Criticism, Say Fuck the Police
Authors: Rose Marika
Published: April 2021

This article responds to John Wilkinson's piece, ‘Moreover: Reading Alfred Starr Hamilton’. Opening with a consideration of the connections between language, law, economy, and freedom, it draws attention to Wilkinson's discussion of letters Hamilton wrote to the Montclair Police Department in 2020. These letters suggest that Hamilton's work might be usefully read as emerging from the economy of racial capitalism, and indicate the limits of his poetic search for freedom.
Eğitimde Artırılmış Gerçeklik Konulu Uluslararası Yayınların İçerik Analizi: 2011-2019 Dönemi
Authors: Akkuş İlyas , Güzel Yasin , Özhan Uğur
Published: April 2021

Bu çalışmada 2011-2019 yılları arasında artırılmış gerçeklik alanında yapılan uluslararası çalışmalar farklı kategorilere göre analiz edilmiştir. Bu amaçla, eğitim teknolojileri alanında uluslararası 10 SSCI dergideki son 9 yıllık “Artırılmış Gerçeklik” konulu toplam 77 akademik çalışma incelenmiştir. Araştırmaya dâhil edilen yayınlar, makale sınıflama formu kullanılarak 8 farklı kategoride analiz edilmiştir. Bu kategoriler doğrultusunda yapılan betimsel istatistikler tablolar halinde sunulmuş ve sonuçlar yorumlanmıştır. Yapılan çalışma sonucunda artırılmış gerçeklik çalışmalarında araştırma değişkeni olarak eğilimin akademik başarı, motivasyon ve tutum üzerine olduğu görülmüştür. Bunun yanında, çalışmalarda ilkokul ve lisans düzeyinin örneklem grubu olarak daha sık kullanıldığı görülmüştür. Bu çalışma, genel hatlarıyla artırılmış gerçeklik alanında araştırma yapanlar için güncel akademik çalışmalar hakkında detaylı analizler içermektedir.
Exploring the Correlation between Thinking Styles and Social and Academic Integration in English Major Students
Authors: Kırmızı Özkan , Güneş Uçar Nur
Published: April 2021

In educational psychology, individual differences have always received remarkable attention, with attention increasing in mental aspects such as thinking styles in recent years and with implications for teaching and learning. The aim of the present study is to investigate the possible connection between thinking styles and academic and social integration. It is well-known that psychological constructs like thinking styles play a role in certain behaviors or preferences and studying them can shed light on the educational process. The present study was conducted with 79 pre-service EFL teachers, all of whom are 4th grade learners. One reason for having 4th grade learners is that they have well-established ideas and attitudes towards academic and social integration. In order to collect data, two questionnaires were used. The first one is the Thinking Styles Inventory (TSI), developed by Sternberg and Wagner (1991). It is a comprehensive tool containing 104 items. There are 13 subscales, with 8 items each. The second tool is the Academic and Social Integration Scale, developed by Pascarella & Terenzini (1980). It contains 5 sub-dimensions, peer-group interaction, interactions with faculty, faculty concern for student development & teaching, academic & intellectual development, and institutional and goal commitments. The findings of the study indicate that the most common thinking styles are oligarchic, executive, and liberal thinking style while the least common thinking styles are conservative and hierarchical thinking style and it was the liberal thinking styles that mostly correlated with academic and social integration.
Süreli Görevlendirme Uygulamasının Okul Yöneticilerinin Performanslarını Yordama Düzeyi
Authors: Kurtul Erdal , Özgenel Mustafa
Published: April 2021

Bu çalışmanın amacı, okul yöneticilerinin rotasyon/süreli görevlendirme uygulamasının yöneticilerin performanslarını yordama düzeyini incelemektir. Araştırma nicel araştırma yöntemine ve ilişkisel tarama modeline göre yürütülmüştür. Araştırmanın örneklemini İstanbul Avcılar, Başakşehir, Beylikdüzü, Büyükçekmece ve Esenyurt İlçelerinin devlet okullarında görev yapan 390 okul yöneticisi oluşturmuştur. Örneklem kolay ulaşılır örnekleme yöntemi ile belirlenmiştir. Veri toplama aracı olarak; Kişisel Bilgi Formu, Yönetici Süreli Görevlendirme Ölçeği ve Performans Ölçeği kullanılmıştır. Verilerin çözümü sürecinde bağımsız grup t-testi, tek yönlü varyans analizi (ANOVA), korelasyon analizi ve regresyon analiz tekniklerinden yararlanılmıştır. Okul yöneticilerinin süreli görevlendirmeye yönelik görüşleri görev türü, eğitim düzeyi, yöneticilik kıdemi ve görev süresi değişkenlerine göre anlamlı olarak farklılaştığı belirlenmiştir. Okul müdürlerinin performansları ise cinsiyetlerine, eğitim düzeylerine, yöneticilik kıdemlerine ve okuldaki görev süresi değişkenine göre anlamlı olarak farklılaşmaktadır. Araştırma sonucunda, okul yöneticilerin süreli görevlendirmeye ilişkin görüşleri ile performansları arasında pozitif yönde ve orta düzeyde anlamlı ilişki tespit edilmiştir. Okul yöneticilerinin performanslarının %46’sı, süreli görevlendirmeye yönelik görüşleri tarafından açıklanmaktadır. Süreli görevlendirme uygulamasının etkili bir şekilde yürütülmesi için gözlem ve görüşme gibi nitel yaklaşımlardan yararlanılarak uygulama hakkında derinlemesine bilgi elde edinilebilir.
GeoGebra Destekli Matematik Öğretiminin Altıncı Sınıf Öğrencilerinin Başarılarına Etkisi: Alan ve Hacim Ölçme
Authors: Zengin Ali , Akçakın Veysel
Published: April 2021

Bu çalışmanın amacı, GeoGebra destekli matematik öğretiminin 6. sınıf öğrencilerinin alan ve hacim ölçme konularındaki akademik başarılarındaki rolünü incelemektir. Bu çalışmada, ön test-son test kontrol gruplu yarı deneysel desen kullanılmıştır. Araştırma, 2017-2018 eğitim öğretim yılının II. döneminde Afyonkarahisar ilinde bulunan bir devlet okulunda gerçekleştirilmiştir. Araştırmaya katılan üç sınıftan iki tanesi deney ve bir tanesi kontrol grubu olarak seçkisiz belirlenmiştir. Her bir grupta 21 öğrenci araştırmaya katılmıştır. Çalışmada deney I ve deney II grubunda GeoGebra destekli matematik öğretimine göre, kontrol grubunda ise ders kitabına dayalı olarak dersler işlenmiştir. Çalışmanın verileri akademik başarı testi ile toplanmıştır. Çalışma altı hafta sürmüştür ve toplanan veriler uygun istatistik yöntemler kullanılarak analiz edilmiştir. Çalışmaya başlamadan önce grupların denklikleri başarı testine göre kontrol edilmiştir. Araştırmadan elde edilen verilerin analizi sonucunda, her bir grupta uygulanan öğretim yönteminin öğrencilerin başarılarını son test lehine anlamlı bir şekilde geliştirdiği gözlenmiştir. Deney I, deney II ve kontrol gruplarının son test başarı testi puanlarının karşılaştırılmasından elde edilen sonuçlara göre, deney I grubu ile deney II grubunun kontrol grubundan daha başarılı oldukları görülmüştür. Bu sonuçlara göre GeoGebra destekli matematik öğretiminin öğrencilerin alan ve hacim ölçme konularındaki başarılarını artırmada etkili bir yöntem olduğu söylenebilir.
A Data-Driven Analysis of Youth Turnout Impact on U.S. Presidential Elections
Authors: Zhu Claire
Published: April 2021

Youth voters between 18 and 29 years of age have consistently had the lowest turnout among all age groups in U.S. presidential elections. This research was designed to study whether the number of votes from this age group would make a difference on the election results, had young voters participated more actively. An original method was devised to do so by simulating higher-than-actual youth voter turnout using various voting scenarios – combinations of voting rates and voter choices derived from past elections. The findings are: When 18- to 29-year olds participate in the election as actively as the entire voting population, they are definitely a formidable force in influencing the presidential election results. If either party energizes those young voters to participate and earns their votes with the margin it saw in its past wins in key states, the party stands a much better chance to win the election.
KOMPARASI KEKERASAN BAJA ST 60 SETELAH MENGALAMI PREHETING DAN PENGELASAN TERHADAP KEKERASAN
Authors: Gumono  , Bambang Irawan  , Nila Aulia
Published: April 2021

Pengelasan adalah proses penyambungan dua atau lebih logam atau lebih dengan tekanan atau tanpa tekanan, Untuk mendapatkan sifat mekanik yang bak maka saat awal proses pengelasan harus diperhatiak agar tidak terjadi penurunan sifat mekanik. Tujuan penelitian ini untuk mengetahui berapa besar perubahan kekerasan baja st 60 yang mengalami pengelasan dengan arus 100, 110 dan 120 amp dan di preheating dengan suhu 200, 300 dan 400°C. Metoda pembentukan spesimen sesuai standart jis Z 3121 . Data selanjutnya disajikan dalam bentuk grafik untuk dikomparasikan. Hasil saat preheating 400°C terhadap 200°C di daerah HAZ, sedang di weld metal 10,40HV Yang terjadi saat preheating 400°C.
PREDIKSI NILAI BATAS ELASTISITAS BAJA KONSTRUKSI DENGAN UJI KEKERASAN BRINELL DAN VICKERS
Authors: Vinan Viyus  , Khambali  , Bambang Hertomo
Published: April 2021

This study aimed to determine the correlation value against the value of hard carbon steel with elasticity it. This is done by determining the formula formulation in the form of the regression equation Y = AX1 + BX2. Data taken from the sample used in the form of a cylindrical rod test specimens and the steel plate. Severity using the Brinell test, whereas withdrawal using tensile testing machine. The results were obtained for cylindrical steel Y = 2,41 X1 – 0,4347X2 and for specimens of steel plate (flat) Y = 2,35 X1 – 0,534X2. Y is the value of the rigidity, and X1 is hardness of steel. While X2 arises from material stretch factor. Probability influence of workmanship and style fluctuate respectively 0,4347 and 0,534 is much larger than 0.05 (a standard which is commonly used). This means that the regression coefficient is not significantly different effect. Decrease in strength may be due to the loss of influence of the stress concentration occurs. In addition it could also be due to the configuration of the carbon forming constituents uneven in areas experiencing strain due to the with drawalprocess
PEMANFAATAN LIMBAH PLASTIK SEBAGAI MATERIAL TAMBAHAN PADA KONSTRUKSI TIMBUNAN RINGAN
Authors: Gerard Aponno  , Yunaefi  , Moch. Sholeh
Published: April 2021

Permasalahan terkait limbah saat ini telah menjadi isu yang mendapat perhatian serius baik secara nasional bahkan internasional. Berbagai macam limbah dihasilkan dari setiap sektor kehidupan, salah satunya berupa limbah plastik. Pada bidang konstruksi, limbah plastik diharapkan bisa menjadi salah satu alternatif material untuk timbunan ringan karena berat volume plastik yang lebih ringan daripada tanah. Tujuan penelitian ini yaitu menganalisis perubahan nilai CBR akibat penambahan limbah plastik, dan mengkaji pengaplikasian sebagai material timbunan ringan pada konstruksi jalan. Penelitian ini dilakukan di laboratorium dengan menggunakan butiran limbah Poly Propylene (PP) yang ditambahkan pada tanah dengan persentase sebesar 0 %, 12,5 %, 22,5 %, dan 32,5 % terhadap berat isi kering tanah. Hasil penelitian menunjukkan nilai CBR standard berturut-turut sesuai komposisi dalam kondisi unsoaked yaitu sebesar 17,73 %, 13,35 %, 9,66 %, dan 7,76 %. Pada kondisi soaked nilai yang dihasilkan sebesar 6,86 %, 5,13 %, 3,89 %, dan 2,69 %. Ditinjau dari pengujian CBR modified, nilai CBR yang dihasilkan untuk kondisi unsoaked yaitu 22,63 %, 18,31 %, 15,67 %, dan 10,93 %. Pada kondisi soaked nilai CBR sebesar 11,97 %, 10,49 %, 9,04 %, dan 8,14 %. Secara keseluruhan limbah plastik yang dicampurkan pada tanah menyebabkan penurunan nilai CBR
ANALISIS PERBANDINGAN PRODUKTIVITAS PRODUKSI BETON READYMIX METODE WETMIX DAN DRYMIX
Authors: Sunarto Suryanto  , Sugiharti  , Fauzi Akbar R.
Published: April 2021

Terdapat dua metode produksi beton readymix yang digunakan saat ini yaitu wetmix dan drymix. Pencampuran wetmix merupakan metode pencampuran beton yang memiliki produktivitas yang lebih tinggi dibandingkan drymix. Tingginya produktivitas tipe wetmix dikarenakan pan pengaduk pada pencampuran wetmix memiliki putaran mixing yang lebih cepat dari pada tipe drymix sehingga durasi pengadukan lebih cepat. Adapun perbaikan yang dapat dilakukan untuk meningkatkan produktivitas produksi beton readymix adalah dengan merubah bentuk batching plant serta memperbesar kapasitas hooper agregat agar dapat mengurangi waktu tunggu alat lain pada operasi penggunaan loader, sebab produksi beton pada aktivitas produksi berasal dari penggunaan loader untuk transportasi agregat.
Iterative Exponential Growth of Oxygen-Linked Aromatic Polymers Driven by Nucleophilic Aromatic Substitution Reactions
Authors: Jaynes Tyler J. , Sharafi Mona , Campbell Joseph P. , Bocanegra Jessica , McKay Kyle T. , Little Kassondra , Osadchey Brown Reilly , Gray Danielle L. , Woods Toby J. , Li Jianing , Schneebeli Severin T.
Published: April 2021

This work presents the first transition metal-free synthesis of oxygen-linked aromatic polymers by integrating iterative exponential polymer growth (IEG) with nucleophilic aromatic substitution (SNAr) reactions. Our approach applies methyl sulfones as the leaving groups, which eliminate the need for a transition metal catalyst, while also providing flexibility in functionality and configuration of the building blocks used. As indicated by 1) 1H-1H NOESY NMR spectroscopy, 2) single-crystal X-ray crystallography, and 3) density functional theory (DFT) calculations, the unimolecular polymers obtained are folded by nonclassical hydrogen bonds formed between the oxygens of the electron-rich aromatic rings and the positively polarized C–H bonds of the electron-poor pyrimidine functions. Our results not only introduce a transition metal-free synthetic methodology to access precision polymers but also demonstrate how interactions between relatively small, neutral aromatic units in the polymers can be utilized as new supramolecular interaction pairs to control the folding of precision macromolecules.
Multi-Modality Imaging for the Identification of Arrhythmogenic Substrates Prior to Electrophysiology Studies
Authors: Gimelli Alessia , Ernst Sabine , Liga Riccardo
Published: April 2021

Noninvasive cardiac imaging is crucial for the characterization of patients who are candidates for cardiac ablations, for both procedure planning and long-term management. Multimodality cardiac imaging can provide not only anatomical parameters but even more importantly functional information that may allow a better risk stratification of cardiac patients. Moreover, fusion of anatomical and functional data derived from noninvasive cardiac imaging with the results of endocavitary mapping may possibly allow a better identification of the ablation substrate and also avoid peri-procedural complications. As a result, imaging-guided electrophysiological procedures are associated with an improved outcome than traditional ablation procedures, with a consistently lower recurrence rate.
Optimal Degree of Hypothermia in Total Arch Replacement for Type A Aortic Dissection
Authors: Wu Jinlin , Qiu Juntao , Fang Zhongrong , Luo Qipeng , Huang Yao , Yu Cuntao , Wang Guyan
Published: April 2021

Background: We sought to investigate the best degree of hypothermic cardiac arrest (HCA) in type A aortic dissection (TAAD) with a cohort of 1,018 cases receiving total arch replacement from 2013 to 2018 in Fuwai Hospital.

Method: The cohort was divided by DHCA (≤24°C, n = 580) vs. MHCA (>24°C, n = 438), and interquartile range (Q1–Q4). Primary endpoints included mortality, stroke, paraplegia, and continuous renal replacement therapy (CRRT), which were summarized as composite major outcomes (CMO).

Results: The Odds Ratio (OR) of CMO for MHCA was 0.7 (95% CI: 0.5–1.0, p = 0.06) (unadjusted) and 0.6 (95% CI: 0.4–1.0, p = 0.055) (adjusted). DHCA group tended to have a significantly longer CPB time (175.6 ± 45.6 vs. 166.8 ± 49.8 min, p = 0.003), longer hospital stay (16.0 ± 13.6 vs. 13.5 ± 6.8 days, p < 0.001), and ICU stay [5.0 (3.9–6.6) vs. 3.8 (2.0–5.6) days]. A significantly greater blood loss was observed in DHCA group, with a greater requirement for RBC and platelet transfusion. Of note, MHCA showed a significant protective effect (60% risk reduction) for older patients (above 60 years) (OR 0.4; 95% CI: 0.2–0.8; p = 0.009). By quartering, Q1 had significantly higher mortality (10.9%) than Q4 (5.2%) (p = 0.035). For other comparisons, the gap was significantly widened in quartering between Q1 and Q4, i.e., the lower the temperature, the worse the outcomes, and vice versa. Propensity score matching and sensitivity analyses confirmed the above findings.

Conclusions: A paradigm change from DHCA to MHCA may be encouraged in TAAD arch operation, especially for the elderly.
Design and Validation of a Questionnaire for University Students’ Generic Competencies (COMGAU)
Authors: Regueiro Bibiana , Rodríguez-Fernández José Eugenio , Crespo Julia , Pino-Juste Margarita Rosa
Published: April 2021

University, as a social institution as defined in the European Higher Education Area, must be a benchmark in the preparation for beginning employment and education for the exercise of active citizenship. Therefore its functions include the development of knowledge and skills needed for appropriate personal performance in various social and professional arenas. This education is complex and requires bringing together specific and generic (or transversal) competencies. The fundamental aim of this study is to present the construction and validation of a questionnaire for evaluating generic competencies acquired via practical service-learning education and the potential employability of university students. Empirical analysis of the reliability and validity of the instrument was performed with a sample of 564 university students (67.2% women), aged between 18 and 59 years old, although with the majority between 18 and 22 (M = 20.96). Following exploratory and confirmatory factor analysis, as well as analysis of the items and the internal consistency of the scale, the results allow us to conclude that the internal consistency and validity of the Questionnaire on University Students’ Generic Competencies are satisfactory. The proposed measurement model incorporates various prior theoretical contributions, and offers a complementary scale that may contribute to advancing research into service-learning and employability.
The Interaction of Insulin and Pituitary Hormone Syndromes
Authors: Schernthaner-Reiter Marie Helene , Wolf Peter , Vila Greisa , Luger Anton
Published: April 2021

Pituitary hormone axes modulate glucose metabolism and exert direct or indirect effects on insulin secretion and function. Cortisol and growth hormone are potent insulin-antagonistic hormones. Therefore impaired glucose tolerance, elevated fasting glucose concentrations and diabetes mellitus are frequent in Cushing’s disease and acromegaly. Also prolactinomas, growth hormone (GH) deficiency, hypogonadism and hypothyroidism might be associated with impaired glucose homeostasis but usually to a lesser extent. Therefore glucose metabolism needs to be closely monitored and treated in patients with pituitary adenomas. Correction of the pituitary dysfunction is frequently followed by improvement of glucose homeostasis.
A Nomogram Based on Clinical and Ultrasound Characteristics to Predict Central Lymph Node Metastasis of Papillary Thyroid Carcinoma
Authors: Feng Jia-Wei , Hong Li-Zhao , Wang Fei , Wu Wan-Xiao , Hu Jun , Liu Sheng-Yong , Jiang Yong , Ye Jing
Published: April 2021

Background

The status of lymph nodes in the central compartment is crucial to determining the surgical strategies for papillary thyroid carcinoma (PTC). We aimed to develop a nomogram for predicting central lymph node metastasis (CLNM).

Methods

A total of 886 PTC patients who underwent total thyroidectomy or lobectomy with central neck dissection (CND) from July 2019 to June 2020 were retrospectively retrieved. Clinical and ultrasound features were collected. Univariate and multivariate analysis were performed to determine risk factors of CLNM. A nomogram for predicting CLNM was developed, internal and external calibration was performed for the established model.

Results

Variables (sex, chronic lymphocytic thyroiditis, tumor size, the number of foci, tumor location, margin) significantly associated with CLNM were included in the nomogram. The nomogram showed excellent calibration in the training group and validation group, with area under curves of 0.806 (95% CI, 0.771 to 0.825), and 0.799 (95% CI, 0.778–0.813) respectively.

Conclusion

Through this accurate and easy-to-use nomogram, the possibility of CLNM can be objectively quantified preoperatively. Clinicians can use this nomogram to evaluate the status of lymph nodes in PTC patients and consider prophylactic CND for those with high scores.
Prediction of the Minimum Film Boiling Temperature of Quenching Vertical Rods in Water Using Random Forest Machine Learning Algorithm
Authors: Alotaibi Sorour , Ebrahim Shikha , Salman Ayed
Published: April 2021

A great amount of research is focused, nowadays, on experimental, theoretical, and numerical analysis of transient pool boiling. Knowing the minimum film boiling temperature (Tmin) for rods with different substrate materials that are quenched in distilled water pools at various system pressures is known to be a complex and highly non-linear process. This work aims to develop a new correlation to predict theTminin the above process: Random forest machine learning technique is applied to predict theTmin. The approach trains a machine learning algorithm using a set of experimental data collected from the literature. Several parameters such as liquid subcooling temperature (Tsub), fluid to the substrate material thermophysical properties (βf/βw), and system saturated pressure (Psat) are collected and used as inputs, whereasTminis measured and used as the output. Computational results show that the algorithm achieves superior results compared to other correlations reported in the literature.
A Powerful Bio-Inspired Optimization Algorithm Based PV Cells Diode Models Parameter Estimation
Authors: Sun Liming , Wang Jingbo , Tang Lan
Published: April 2021

Accurate and reliable photovoltaic (PV) cell parameter identification is critical to simulation analysis, maximum output power harvest, and optimal control of PV systems. However, inherent high-nonlinear and multi-modal characteristics usually result in thorny obstacles to hinder conventional optimization methods to obtain a fast and satisfactory performance. In this study, a novel bio-inspired grouped beetle antennae search (GBAS) algorithm is devised to effectively identify unknown parameters of three different PV models, i.e., single diode model (SDM), double diode model (DDM), and triple diode model (TDM). Compared against beetle antennae search (BAS) algorithm, optimization efficiency of GBAS algorithm is markedly enhanced based on a cooperative searching group that consists of multiple individuals rather than a single beetle. Besides, a dynamic balance mechanism between local exploitation and global exploration is designed to increase the probability for a higher quality optimum. Comprehensive case studies demonstrate that GBAS algorithm can outperform other advanced meta-heuristic algorithms in both optimization precision and stability for estimating PV cell parameters, e.g., standard deviation (SD) of root mean square error (RMSE) obtained by GBAS algorithm is 64.34% smaller than the best value obtained by other algorithms in SDM, 61.86% smaller than that in DDM.
Case Report: Further Delineation of Neurological Symptoms in Young Children Caused by Compound Heterozygous Mutation in the PIEZO2 Gene
Authors: Klaniewska Magdalena , Jedrzejowska Maria , Rydzanicz Malgorzata , Paprocka Justyna , Biela Mateusz , Wolanska Ewelina , Pollak Agnieszka , Debek Emilia , Sasiadek Maria , Ploski Rafal , Gos Monika , Smigiel Robert
Published: April 2021

PIEZO2 protein is a unique ion channel that converts mechanical impulses into cellular signals in somatosensory neurons and is involved in various mechanotransduction pathways. The recessive PIEZO2 loss-of-function pathogenic variants are associated with distal arthrogryposis with impaired proprioception and touch (DAIPT). Here we present three new DAIPT patients. The genetic diagnosis was established by exome sequencing and let us to identify 6 novel loss-of-function PIEZO2 variants: four splicing (c.1080+1G>A, c.4092+1G>T, c.6355+1G>T, and c.7613+1G>A), one nonsense (c.6088C>T) and one frameshift variant (c.6175_6191del) for which mosaic variant was identified in proband's mother. All patients presented typical symptoms at birth, with congenital contractures, bilateral hip dislocation/dysplasia, generalized hypotonia, transient feeding and difficulties. Two were afflicted by transient respiratory insufficiency. In all children motor development was severely delayed. In one patient, severe cognitive delay was also observed. Moreover, among the cases described by us there is the youngest diagnosed child to date.
Cytokine Storm: The Primary Determinant for the Pathophysiological Evolution of COVID-19 Deterioration
Authors: Chen Ruirong , Lan Zhien , Ye Jujian , Pang Limin , Liu Yi , Wu Wei , Qin Xiaohuan , Guo Yang , Zhang Peidong
Published: April 2021

The coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing major threat to global health and has posed significant challenges for the treatment of severely ill COVID-19 patients. Several studies have reported that cytokine storms are an important cause of disease deterioration and death in COVID-19 patients. Consequently, it is important to understand the specific pathophysiological processes underlying how cytokine storms promote the deterioration of COVID-19. Here, we outline the pathophysiological processes through which cytokine storms contribute to the deterioration of SARS-CoV-2 infection and describe the interaction between SARS-CoV-2 and the immune system, as well as the pathophysiology of immune response dysfunction that leads to acute respiratory distress syndrome (ARDS), multi-organ dysfunction syndrome (MODS), and coagulation impairment. Treatments based on inhibiting cytokine storm-induced deterioration and occurrence are also described.
Immune Phenotyping of Patients With Acute Vogt-Koyanagi-Harada Syndrome Before and After Glucocorticoids Therapy
Authors: Jiang Han , Li Zhaohui , Yu Long , Zhang Ying , Zhou Li , Wu Jianhua , Yuan Jing , Han Mengyao , Xu Tao , He Junwen , Wang Shan , Yu Chengfeng , Pan Sha , Wu Min , Liu Hangyu , Zeng Haihong , Song Zhu , Wang Qiangqiang , Qu Shen , Zhang Junwei , Huang Yafei , Han Junyan
Published: April 2021

Previous studies have established that disturbed lymphocytes are involved in the pathogenesis of Vogt-Koyanagi-Harada (VKH) syndrome. Accordingly, glucocorticoids (GCs), with their well-recognized immune-suppressive function, have been widely used for treatment of VKH patients with acute relapses. However, the systemic response of diverse immune cells to GC therapy in VKH is poorly characterized. To address this issue, we analyzed immune cell subpopulations and their phenotype, as well as cytokine profiles in peripheral blood from VKH patients (n=25) and health controls (HCs, n=21) by flow cytometry and luminex technique, respectively. For 16 patients underwent GC therapy (methylprednisolone, MP), the aforementioned measurements as well as the transcriptome data from patients before and after one-week’s GC therapy were also compared to interrogate the systemic immune response to GC therapy. Lymphocyte composition in the blood was different in VKH patients and HCs. VKH patients had significantly higher numbers of T cells with more activated, polarized and differentiated phenotype, more unswitched memory B cells and monocytes, as compared to HCs. MP treatment resulted in decreased frequencies of T cells and NK cells, inhibited NK cell activation and T cell differentiation, and more profoundly, a marked shift in the distribution of monocyte subsets. Collectively, our findings suggest that advanced activation and differentiation, as well as dysregulated numbers of peripheral lymphocytes are the major immunological features of VKH, and GC therapy with MP not only inhibits T cell activation directly, but also affects monocyte subsets, which might combinatorically result in the inhibition of the pathogenic immune response.
High Levels of Common Cold Coronavirus Antibodies in Convalescent Plasma Are Associated With Improved Survival in COVID-19 Patients
Authors: Greenbaum Uri , Klein Kimberly , Martinez Fernando , Song Juhee , Thall Peter F. , Ramdial Jeremy L. , Knape Cristina , Aung Fleur M. , Scroggins Jamie , Knopfelmacher Adriana , Mulanovich Victor , Borjan Jovan , Adachi Javier , Muthu Mayoora , Leung Cerena , Medina Mayrin Correa , Champlin Richard , Olson Amanda , Alousi Amin , Rezvani Katayoun , Shpall Elizabeth J.
Published: April 2021

Background

COVID-19 Convalescent plasma (CCP) is safe and effective, particularly if given at an early stage of the disease. Our study aimed to identify an association between survival and specific antibodies found in CCP.

Patients and Methods

Patients ≥18 years of age who were hospitalized with moderate to severe COVID-19 infection and received CCP at the MD Anderson Cancer Center between 4/30/2020 and 8/20/2020 were included in the study. We quantified the levels of anti-SARS-CoV-2 antibodies, as well as antibodies against antigens of other coronavirus strains, in the CCP units and compared antibody levels with patient outcomes. For each antibody, a Bayesian exponential survival time regression model including prognostic variables was fit, and the posterior probability of a beneficial effect (PBE) of higher antibody level on survival time was computed.

Results

CCP was administered to 44 cancer patients. The median age was 60 years (range 37-84) and 19 (43%) were female. Twelve patients (27%) died of COVID-19-related complications. Higher levels of two non-SARS-CoV-2-specific antibodies, anti-HCoV-OC43 spike IgG and anti-HCoV-HKU1 spike IgG, had PBE = 1.00, and 4 SARS-CoV-2-specific antibodies had PBEs between 0.90 and 0.95. Other factors associated with better survival were shorter time to CCP administration, younger age, and female sex.

Conclusions

Common cold coronavirus spike IgG antibodies anti-HCoV-OC43 and anti-HCoV-HKU1 may target a common domain for SARS-CoV-2 and other coronaviruses. They provide a promising therapeutic target for monoclonal antibody production.
The Interplay of HIV and Autophagy in Early Infection
Authors: Cabrera-Rodríguez Romina , Pérez-Yanes Silvia , Estévez-Herrera Judith , Márquez-Arce Daniel , Cabrera Cecilia , Espert Lucile , Blanco Julià , Valenzuela-Fernández Agustín
Published: April 2021

HIV/AIDS is still a global threat despite the notable efforts made by the scientific and health communities to understand viral infection, to design new drugs or to improve existing ones, as well as to develop advanced therapies and vaccine designs for functional cure and viral eradication. The identification and analysis of HIV-1 positive individuals that naturally control viral replication in the absence of antiretroviral treatment has provided clues about cellular processes that could interact with viral proteins and RNA and define subsequent viral replication and clinical progression. This is the case of autophagy, a degradative process that not only maintains cell homeostasis by recycling misfolded/old cellular elements to obtain nutrients, but is also relevant in the innate and adaptive immunity against viruses, such as HIV-1. Several studies suggest that early steps of HIV-1 infection, such as virus binding to CD4 or membrane fusion, allow the virus to modulate autophagy pathways preparing cells to be permissive for viral infection. Confirming this interplay, strategies based on autophagy modulation are able to inhibit early steps of HIV-1 infection. Moreover, autophagy dysregulation in late steps of the HIV-1 replication cycle may promote autophagic cell-death of CD4+T cells or control of HIV-1 latency, likely contributing to disease progression and HIV persistence in infected individuals. In this scenario, understanding the molecular mechanisms underlying HIV/autophagy interplay may contribute to the development of new strategies to control HIV-1 replication. Therefore, the aim of this review is to summarize the knowledge of the interplay between autophagy and the early events of HIV-1 infection, and how autophagy modulation could impair or benefit HIV-1 infection and persistence, impacting viral pathogenesis, immune control of viral replication, and clinical progression of HIV-1 infected patients.
Transcriptional Profiling of Myceliophthora thermophila on Galactose and Metabolic Engineering for Improved Galactose Utilization
Authors: Wang Hanyu , Sun Tao , Zhao Zhen , Gu Shuying , Liu Qian , Wu Taju , Wang Depei , Tian Chaoguang , Li Jingen
Published: April 2021

Efficient biological conversion of all sugars from lignocellulosic biomass is necessary for the cost-effective production of biofuels and commodity chemicals. Galactose is one of the most abundant sugar in many hemicelluloses, and it will be important to capture this carbon for an efficient bioconversion process of plant biomass. Thermophilic fungus Myceliophthora thermophila has been used as a cell factory to produce biochemicals directly from renewable polysaccharides. In this study, we draw out the two native galactose utilization pathways, including the Leloir pathway and oxido-reductive pathway, and identify the significance and contribution of them, through transcriptional profiling analysis of M. thermophila and its mutants on galactose. We find that galactokinase was necessary for galactose transporter expression, and disruption of galK resulted in decreased galactose utilization. Through metabolic engineering, both galactokinase deletion and galactose transporter overexpression can activate internal the oxido-reductive pathway and improve the consumption rate of galactose. Finally, the heterologous galactose-degradation pathway, De Ley–Doudoroff (DLD) pathway, was successfully integrated into M. thermophila, and the consumption rate of galactose in the engineered strain was increased by 57%. Our study focuses on metabolic engineering for accelerating galactose utilization in a thermophilic fungus that will be beneficial for the rational design of fungal strains to produce biofuels and biochemicals from a variety of feedstocks with abundant galactose.
Diagnostic, Therapeutic, and Prognostic Value of the Thrombospondin Family in Gastric Cancer
Authors: Lu Yi , Kong Xianhe , Zhong Weijie , Hu Minhui , Li Chujun
Published: April 2021

Background: Gastric cancer (GC) is the fifth leading cancer in the world. The dysregulated expressions of the thrombospondin (THBS) family were reported to associate with GC, but their relations with tumor stage, prognosis, and correlations with tumor immunity have not been systematically reported.

Methods: We used versatile public databases such as Oncomine, GEPIA, UALCAN, Kaplan–Meier Plotter, LinkedOmics, STRING, cBioPortal, TIMER, and TISIDB to analyze the expression and mutations of different THBSs in GC, along with their functional networks, survival analysis, and tumor–immune interactions.

Results: The mRNA levels of THBS2, THBS4, and COMP were significantly higher in the tumor tissues; the expression levels of THBS1, THBS2, and THBS4 were higher in stages 2–4 than that of stage 1; patients with high expression of THBS1, THBS2, THBS4, and COMP had poor OS; the genes correlated with THBSs were enriched in focal adhesion, glycosaminoglycan biosynthesis, ECM-receptor interaction, and hedgehog signaling pathway; THBS1 and THBS4 expression had significant correlations with tumor purity, and all the THBSs expression correlated with macrophage and dendritic cells infiltration.

Conclusions: THBS2, THBS4, and COMP were potentially diagnostic markers for GC; THBS1, THBS2, THBS4, and COMP were potentially prognostic markers for GC; investigating the relations of THBSs and tumor immunology might help in immunotherapy of GC, while more studies are needed to confirm these results.
Identification of a Potential miRNA–mRNA Regulatory Network Associated With the Prognosis of HBV-ACLF
Authors: Ma Shanshan , Xie Zhongyang , Zhang Lingjian , Yang Ya , Jiang He , Ouyang Xiaoxi , Zhao Yalei , Liu Qiuhong , Xu Xiaowei , Li Lanjuan
Published: April 2021

Background

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a life-threatening disease with a high mortality rate; the systemic inflammatory response plays a vital role in disease progression. We aimed to determine if a miRNA–mRNA co-regulatory network exists in the peripheral blood mononuclear cells (PBMCs) of HBV-ACLF patients, which might be important for prognosis.

Methods

Transcriptome-wide microRNA (miRNA) and mRNA microarrays were used to define the miRNA and mRNA expression profiles of the PBMCs of HBV-ACLF patients in a discovery cohort. The targets of the miRNAs were predicted. We built a miRNA-mRNA regulatory network through bioinformatics analysis, and used quantitative real-time polymerase chain reaction (qRT-PCR) to assess the importance of candidate miRNAs and mRNAs. We also assessed the direct and transcriptional regulatory effects of miRNAs on target mRNAs using a dual-luciferase reporter assay.

Results

The miRNA/mRNA PBMC expression profiles of the discovery cohort, of whom eight survived and eight died, revealed a prognostic interactive network involving 38 miRNAs and 313 mRNAs; this was constructed by identifying the target genes of the miRNAs. We validated the expression data in another cohort, of whom 43 survived and 35 died; miR-6840-3p, miR-6861-3p, JADE2, and NR3C2 were of particular interest. The levels of miR-6840-3p and miR-6861-3p were significantly increased in the PBMCs of the patients who died, and thus predicted prognosis (areas under the curve values = 0.665 and 0.700, respectively). The dual-luciferase reporter assay indicated that miR-6840-3p directly targeted JADE2.

Conclusion

We identified a prognostic miRNA-mRNA co-regulatory network in the PBMCs of HBV-ACLF patients. miR-6840-3p-JADE2 is a potential miRNA–mRNA pair contributing to a poor prognosis.
The Electronic Bee Spy: Eavesdropping on Honeybee Communication via Electrostatic Field Recordings
Authors: Paffhausen Benjamin H. , Petrasch Julian , Greggers Uwe , Duer Aron , Wang Zhengwei , Menzel Simon , Stieber Peter , Haink Karén , Geldenhuys Morgan , Čavojská Jana , Stein Timo A. , Wutke Sophia , Voigt Anja , Coburn Josephine , Menzel Randolf
Published: April 2021

As a canary in a coalmine warns of dwindling breathable air, the honeybee can indicate the health of an ecosystem. Honeybees are the most important pollinators of fruit-bearing flowers, and share similar ecological niches with many other pollinators; therefore, the health of a honeybee colony can reflect the conditions of a whole ecosystem. The health of a colony may be mirrored in social signals that bees exchange during their sophisticated body movements such as the waggle dance. To observe these changes, we developed an automatic system that records and quantifies social signals under normal beekeeping conditions. Here, we describe the system and report representative cases of normal social behavior in honeybees. Our approach utilizes the fact that honeybee bodies are electrically charged by friction during flight and inside the colony, and thus they emanate characteristic electrostatic fields when they move their bodies. These signals, together with physical measurements inside and outside the colony (temperature, humidity, weight of the hive, and activity at the hive entrance) will allow quantification of normal and detrimental conditions of the whole colony. The information provided instructs how to setup the recording device, how to install it in a normal bee colony, and how to interpret its data.
Resting-State Theta Oscillations and Reward Sensitivity in Risk Taking
Authors: Azanova Maria , Herrojo Ruiz Maria , Belianin Alexis V. , Klucharev Vasily , Nikulin Vadim V.
Published: April 2021

Females demonstrate greater risk aversion than males on a variety of tasks, but the underlying neurobiological basis is still unclear. We studied how theta (4–7 Hz) oscillations at rest related to three different measures of risk taking. Thirty-five participants (15 females) completed the Bomb Risk Elicitation Task (BRET), which allowed us to measure risk taking during an economic game. The Domain-Specific Risk-Taking Scale (DOSPERT) was used to measure self-assessed risk attitudes as well as reward and punishment sensitivities. In addition, the Barratt Impulsiveness Scale (BIS11) was included to quantify impulsiveness. To obtain measures of frontal theta asymmetry and frontal theta power, we used magnetoencephalography (MEG) acquired prior to task completion, while participants were at rest. Frontal theta asymmetry correlated with average risk taking during the game but only in the female sample. By contrast, frontal theta power correlated with risk taking as well as with measures of reward and punishment sensitivity in the joint sample. Importantly, we showed that reward sensitivity mediated a correlation between risk taking and the power of theta oscillations localized to the anterior cingulate cortex. In addition, we observed significant sex differences in source- and sensor-space theta power, risk taking during the game, and reward sensitivity. Our findings suggest that sensitivity to rewards, associated with resting-state theta oscillations in the anterior cingulate cortex, is a trait that potentially contributes to sex differences in risk taking.
Valproic Acid Induces Autism-Like Synaptic and Behavioral Deficits by Disrupting Histone Acetylation of Prefrontal Cortex ALDH1A1 in Rats
Authors: Liu Huan , Tan Mei , Cheng Boli , Wang Si , Xiao Lu , Zhu Jiang , Wu Qionghui , Lai Xi , Zhang Qian , Chen Jie , Li Tingyu
Published: April 2021

Objectives

This study aimed to investigate the impact of valproic acid (VPA) on the histone acetylation of acetaldehyde dehydrogenase 1A1 (ALDH1A1) and the mechanism underlying VPA-induced autism-like behavior.

Methods

Female Sprague-Dawley rats were intraperitoneally injected with VPA during gestation to establish an autism model in their offspring. Some offspring prenatally exposed to VPA were randomly treated with MS-275, one histone deacetylase (HDAC) inhibitor, or retinoic acid (RA) after birth. Behavioral tests were conducted on the offspring 6 weeks after birth. Electrophysiological experiments were performed to investigate long-term potentiation (LTP) in the prefrontal cortex (PFC). The expression levels of AMPA receptors (GluA1 and 2), NMDA receptors (GluN1 and 2), synapsin 1 (SYN1), HDAC, acetylated histone 3 (AcH3), RA receptor alpha (RARα), and ALDH1A1 in the PFC were measured by Western blotting and quantitative polymerase chain reaction. ALDH enzyme activity in PFC tissue was detected using a Micro ALDH Assay Kit. The RA level in the PFC was measured using ultrahigh-performance liquid chromatography/tandem mass spectrometry. A chromatin immunoprecipitation (ChIP) experiment explored the interaction between the ALDH1A1 gene and AcH3.

Results

Offspring prenatally exposed to VPA showed autism-like behavior, upregulated the levels of LTP and GluN2A, GluA1, and SYN1 proteins relevant to synaptic plasticity in the PFC. The expression levels of HDAC3 mRNA and protein were increased. On the other hand, there was a significant reduction in the levels of AcH3, RARα, RA, ALDH1A1 mRNA and protein, the level of ALDH activity and AcH3 enrichment in the ALDH1A1 promoter region in VPA-induced offspring. Administration of MS-275 in VPA offspring significantly elevated the levels of AcH3, ALDH1A1 mRNA and protein, ALDH activity, RA, the level of RARα protein and the binding of AcH3 to the ALDH1A1 promoter. In addition, the GluA1 protein level and LTP were reduced, and most behavioral deficits were reversed. After RA supplementation in the VPA-treated offspring, the RA and RARα protein levels were significantly upregulated, GluA1 protein and LTP were downregulated, and most autism-like behavioral deficits were effectively reversed.

Conclusion

These findings suggest that VPA impairs histoneacetylation of ALDH1A1 and downregulates the RA-RARα pathway. Such epigenetic modification of ALDH1A1 by VPA leads to autism-like synaptic and behavioral deficits.
Individualized Prediction of Colorectal Cancer Metastasis Using a Radiogenomics Approach
Authors: Liu Qin , Li Jie , Xu Lin , Wang Jiasi , Zeng Zhaoping , Fu Jiangping , Huang Xuan , Chu Yanpeng , Wang Jing , Zhang Hong-Yu , Zeng Fanxin
Published: April 2021

Objectives: To evaluate whether incorporating the radiomics, genomics, and clinical features allows prediction of metastasis in colorectal cancer (CRC) and to develop a preoperative nomogram for predicting metastasis.

Methods: We retrospectively analyzed radiomics features of computed tomography (CT) images in 134 patients (62 in the primary cohort, 28 in the validation cohort, and 44 in the independent-test cohort) clinicopathologically diagnosed with CRC at Dazhou Central Hospital from February 2018 to October 2019. Tumor tissues were collected from all patients for RNA sequencing, and clinical data were obtained from medical records. A total of 854 radiomics features were extracted from enhanced venous-phase CT of CRC. Least absolute shrinkage and selection operator regression analysis was utilized for data dimension reduction, feature screen, and radiomics signature development. Multivariable logistic regression analysis was performed to build a multiscale predicting model incorporating the radiomics, genomics, and clinical features. The receiver operating characteristic curve, calibration curve, and decision curve were conducted to evaluate the performance of the nomogram.

Results: The radiomics signature based on 16 selected radiomics features showed good performance in metastasis assessment in both primary [area under the curve (AUC) = 0.945, 95% confidence interval (CI) 0.892–0.998] and validation cohorts (AUC = 0.754, 95% CI 0.570–0.938). The multiscale nomogram model contained radiomics features signatures, four-gene expression related to cell cycle pathway, and CA 19-9 level. The multiscale model showed good discrimination performance in the primary cohort (AUC = 0.981, 95% CI 0.953–1.000), the validation cohort (AUC = 0.822, 95% CI 0.635–1.000), and the independent-test cohort (AUC = 0.752, 95% CI 0.608–0.896) and good calibration. Decision curve analysis confirmed the clinical application value of the multiscale model.

Conclusion: This study presented a multiscale model that incorporated the radiological eigenvalues, genomics features, and CA 19-9, which could be conveniently utilized to facilitate the individualized preoperatively assessing metastasis in CRC patients.