bluuebunny/crossref_metadata_2025 huggingface dataset:
EVALUASI SINERESIS DAN SENSORI YOGURT DENGAN PENAMBAHAN STABILIZER PATI TALAS LOKAL (Colocasia esculenta) PADA MASA INKUBASI 18 JAM SUHU RUANG
Authors: Krisnaningsih Aju Tjatur Nugroho , Kustyorini Tri Ida Wahyu , Selviana Revi
Published: June 2021

Tujuan dari penelitian untuk mengetahui pengaruh penambahan stabilizer pati talas lokal (Colocasia esculenta) terhadap sineresis dan sensori yogurt pada masa inkubasi 18 jam suhu ruang.Materi yang digunakan dalam penelitian ini adalah susu sapi segar, pati talas, susu skim, dan starter (Lactobacillus bulgaricus,Streptococcus thermophillus dan Lactobacillus acidhopilus). Metode penelitian yang digunakan adalah percobaan Laboratorium  dengan menggunakan Rancangan Acak Lengkap (RAL). Perlakuan penelitian yakni penambahan pati talas, yaitu: P0 (0%), P1 (0,50%), P2 (1%), P3 (1,50%), P4 (2%) masing-masing perlakuan diulang sebanyak 4 kali. Data yang diperoleh dianalisis dengan analisis ragam, apabila terdapat perbedaan maka dilanjutkan dengan uji duncan. Variabel yang diamati meliputi: Sineresis dan Sensori yogurt. Hasil penelitian menunjukan bahwa penambahan level pati talas lokal (Colocasia esculenta) yang berbeda sebagai stabilizer memberikan pengaruh perbedaan yang sangat nyata (P<0,01) terhadap sineresis dan tekstur yogurt. Nilai Sineresis tertinggi dengan penambahan pati P0 (0%) sebesar 4,5% kemudian berturut-turut P1 (0,50%), P2 (1%), P3 (1,50%), P4 (2%) sebesar 4,23%, 4%, 3,72%, 3,48%. Pada kesukaan tekstur yogurt nilai tertinggi pada P3 dengan skor 3,8% dan nilai terendah yaitu P0 dengan skor nilai 3,13%. Penambahan pati tidak memberikan pengaruh (P>0,05) terhadap warna, rasa dan aroma yogurt. Berdasarkan hasil penelitian dapat disimpulkan bahwa penambahan pati talas 1,50% pada masa inkubasi 18 jam suhu ruang dapat menghasilkan yogurt yang optimal ditinjau dari sineresis dan sensori yogurt.
ANALISIS PENDAPATAN USAHA TERNAK AYAM PETELUR DI DESA TEGALHARJO KECAMATAN TRANGKIL KABUPATEN PATI
Authors: Cahyono Eko Budi , Suharyono Eko , Prayitno Ryantoko Setyo
Published: June 2021

The livestock sector is expected to make a real contribution to the development of the nation's economy. Livestock development is also directed at increasing the quality of production, increasing income, expanding employment opportunities and providing business opportunities for people in rural areas. Layer are one of the poultry commodities that have an important role as egg producers to support the availability of cheap and easy to obtain animal protein. The population of layer in Pati Regency in 2018 was 265,020 birds (BPS, 2020). Layer are increasingly in demand in the village of Tegalharjo as a profitable poultry business opportunity. Many breeders choose the business of layer as a side business or as their main income. The objectives of this study are 1). To determine the business income of layer, 2) To determine the business feasibility of layer, 3) To determine the effect of pullets, feed costs, medicines and labor on the income of layer. The research material was in the form of layer in Tegalharjo Village, Trangkil District, Pati Regency. Data collection for 3 months (March - May). The results of the research on layer in the village of Tegalharjo are feasible to work with an income of IDR 11,784,946.17 / ST / period and simultaneously there is an effect of the cost of pullets (X1), feed (X2), medicines (X3) and labor ( X4) to income.
Importance and prospects for design of selective muscarinic agonists
Authors: Jakubík J , Michal P , Machová E , Doležal V
Published: June 2021

There are five subtypes of muscarinic receptors that serve various important physiological functions in the central nervous system and the periphery. Mental functions like attention, learning, and memory are attributed to the muscarinic M1 subtype. These functions decline during natural aging and an early deficit is typical for Alzheimer s disease. In addition, stimulation of the M1 receptor increases non-amyloidogenic processing of the amyloid precursor protein and thus prevents accumulation of noxious beta-amyloid fragments. The selectivity of classical muscarinic agonists among receptor subtypes is very low due to the highly conserved nature of the orthosteric binding site among receptor subtypes. Herein we summarize some recent studies with the functionally-selective M1 agonist xanomeline that indicate complex pharmacological profile of this drug that includes interactions with and activation of receptor from both orthosteric and ectopic binding sites, and the time-dependent changes of ligand binding and receptor activation. These findings point to potential profitability of exploitation of ectopic ligands in the search for truly selective muscarinic receptor agonists.
Extracellular space diffusion and extrasynaptic transmission
Authors: Vargová L , Syková E
Published: June 2021

The diffusion of neuroactive substances in the extracellular space (ECS) plays an important role in short- and long-distance communication between nerve cells and is the underlying mechanism of extrasynaptic (volume) transmission. The diffusion properties of the ECS are described by three parameters: 1. ECS volume fraction alpha (alpha=ECS volume/total tissue volume), 2. tortuosity lambda (lambda2=free/apparent diffusion coefficient), reflecting the presence of diffusion barriers represented by, e.g., fine neuronal and glial processes or extracellular matrix molecules and 3. nonspecific uptake k'. These diffusion parameters differ in various brain regions, and diffusion in the CNS is therefore inhomogeneous. Moreover, diffusion barriers may channel the migration of molecules in the ECS, so that diffusion is facilitated in a certain direction, i.e. diffusion in certain brain regions is anisotropic. Changes in the diffusion parameters have been found in many physiological and pathological states in which cell swelling, glial remodeling and extracellular matrix changes are key factors influencing diffusion. Changes in ECS volume, tortuosity and anisotropy significantly affect the accumulation and diffusion of neuroactive substances in the CNS and thus extrasynaptic transmission, neuron-glia communication, transmitter "spillover" and synaptic cross-talk as well as cell migration, drug delivery and treatment.
Keputusan Santri Dalam Membeli Di Online Shop: Antara Lifestyle, Trust Dan Price
Authors: Umma Eri Shofa Rohmatul , Qomar Moh. Nurul , Arifin Jaenal
Published: June 2021

This study aims to determine the influence of Lifestyle Trust and Prices on Purchasing Decisions in Onlineshop at Raudlatul Falah Islamic Boarding School Students in Pati Patis. This type of research is quantitative, with a total sample of 81 respondents. Data analysis techniques include validity test, reliability test, classic assumption test, multiple linear regression analysis, coefficient of determination, and t- test. The results of this study indicate that lifestyle and trust have a positive and significant effect, while price does not significantly influence purchasing decisions online at Raudlatul Falah boarding school students in Gembong Pati. With a lifestyle significance test of 0, 000 with a t- count of 6. 374, a significance level of confidence of 0. 002 with a t- count of 2. 350, and a price significance level of- 0. 786 with t- count of- 0. 273. It can be concluded that H1 and H2 in this study were accepted and H3 was rejected.
Faktor Ekonomi yang Mempengaruhi Minat Konsumen Untuk Menggunakan Sistem Pembangkit Listrik Tenaga Surya (PLTS) Atap di Kota Palembang
Authors: Frastuti Melia , Royda
Published: June 2021

The purpose of this study is to determine whether there is an influence of economic factors that affect people's interest in using the Solar Roofing Power Generation System (PLTS) in Palembang. Data analysis methods used are qualitative and quantitative, with primary and secondary data sources in the form of questionnaires and interviews. The population in this study were all consumers of PT. PLN in the city of Palembang which has power> 2200 VA. Sampling using the Slovin formula obtained as many as 400 respondents, the sampling technique using proportionate stratified random sampling with the location of rayon into sub-populations. The results showed that there was a significant influence between economic factors on people's interest in using the PLTS Roof system with Sig 0,000.
Imagens do feminino: uma análise sob a perspectiva da história das mulheres e do livro didático como história pública
Authors: Dala Zen Daiane
Published: June 2021

O objetivo é analisar a representação do feminino em fotografias selecionadas a partir de livros didáticos de história, que abordem o tema da história da primeira metade do século XX. A metodologia tem como base a leitura de imagens proposta por Barbosa (2006), na perspectiva da história cultural e nas contribuições de Scott (1994), Burke (2004) e Chartier (2014). A pesquisa fundamenta-se em apontamentos teóricos sobre o livro didático, as imagens selecionadas, as questões de gênero e a história das mulheres. Os resultados apontam para a importância da exploração das imagens por professores/as e estudantes, conduzindo a reflexões sobre a mulher e sua história. Conclui também que essas fotografias, revelam a presença das mulheres na história, mas evidenciando sua fragilidade, passividade e submissão, ao lado ou atrás de um homem.
Entrevista com Ana Carolina Eiras
Authors: Medeiros Kenia Gusmão , Rovai Marta Gouveia de Oliveira
Published: June 2021

Entrevista para dosssiê
Vozes urbanas: narrando experiências nas e sobre as cidades
Authors: Oliveira Pedro Vagner Silva
Published: June 2021

Resenha
Refletindo sobre os estudos de gênero, feministas e a história pública: possibilidades epistêmicas na fronteira
Authors: Nichnig Cláudia Regina , Amorim Anna Carolina Horstmann
Published: June 2021

Quais seriam as propostas epistêmicas que uma experiência de ensino e pesquisa realizada em espaços marginais, permitem para a produção do conhecimento cientí­fico realizado fora do centro? A partir dos estudos de gênero e feministas, duas professoras de humanas propõem dialogar sobre suas propostas de intervenção como professoras que participam de atividades realizadas no Programa ProfHistória – Mestrado Profissional em História, mas também em outros espaços na universidade. Em diálogo com a História Pública, o artigo busca refletir sobre o impacto da aproximação com as alunas e alunos na produção do conhecimento pela própria professora/pesquisadora, que ao se reconhecerem como outsider within, uma forasteira de dentro (Collins, 2016), percebem transformações em suas pesquisas e em suas próprias subjetividades.
АМИШИ СТАРОГО ПОРЯДКА: КОНСЕРВАТИВНАЯ РЕЛИГИОЗНОСТЬ, ОСТАНОВИВШАЯ ВРЕМЯ
Authors: Казьмина Ольга Евгеньевна
Published: June 2021

В статье исследуются механизм формирования и сохранения очень своеобразной конфессиональной группы – амишей старого порядка и влияние религиозного учения на их повседневные практики. По существу, весь жизненный уклад амишей старого порядка определяется Орднунгом – сводом правил, позволяющим сохранять самобытность и приверженность традициям. В Орднунге выделяется письменная часть (составленные религиозными лидерами документы, содержащие основные догматические положения, обусловившие особенности религиозной и повседневной жизни) и устная (неписанные правила, постепенно складывавшиеся и определяющие отдельные детали быта). Устная часть Орднунга может несколько различаться в разных общинах и меняться с течением времени. Однако к любым переменам амиши старого порядка подходят очень осторожно – изменения могут касаться лишь незначительных частностей. Вся жизнь этой группы предполагает жесткую регламентацию норм поведения внутри общины и отношений с внешним миром; определены не только допустимые технологии, но и конкретные предметы хозяйства, быта и личного пользования. Амиши старого порядка верят, что Орднунг наставляет их на праведный путь и оберегает от грехов внешнего мира. Следование своему религиозному учению и своим традициям обеспечило формирование и воспроизводство амишей старого порядка как особой группы, сильно отличающейся от своего окружения не только религиозной принадлежностью. The article studies the formation and conservation of a very specific religious group – Old Order Amish, and how their religious doctrine affected their everyday practices. In fact, the whole life style of Old Order Amish is determined by Ordnung – a scope of rules that allowed them to preserve their distinctiveness and devotion to traditions. Ordnung consists of its written part (documents written by religious leaders that contain dogmatic statements determining specifics of religious and daily life) and oral part (unwritten rules that gradually developed in each community and determined particular details of daily life, not recorded in the written documents). Unwritten rules of the Ordnung may lightly vary in different communities and change over time. Yet, Old Order Amish are very cautious about any changes, which can only affect minor details. All their life is strictly regulated by the rules of conduct inside and outside the community and permitted technologies, tools and personal use items. Old Order Amish believe that Ordnung sets them on the right path and helps them not to let sins of the outside world into their lives. Following both religious doctrine and traditions determined by the oral part of Ordnung ensured the formation and reproduction of Old Order Amish as a particular group that dramatically differs from its neighboring population.
Рецензия на: Зубова А.В., Моисеев В.Г., Кульков А.М., Ободовский А.В. Новые результаты изучения краниологических и одонтологических материалов верхнепалеолитической стоянки Костенки 15 // Camera praehistorica, 2020. 2 (5): 147–155*
Authors: Герасимова Маргарита Михаайловна
Published: June 2021

Рецензия на: Зубова А.В., Моисеев В.Г., Кульков А.М., Ободовский А.В. Новые результаты изучения краниологических и одонтологических материалов верхнепалеолитической стоянки Костенки 15 // Camera praehistorica, 2020. 2 (5): 147–155*
Review: Zubova, Alisa V., Moiseyev, Vyacheslav G., Kulkov Aleksandr M. and Anatoliy V. Obodovskiy. Reassessment of the cranial and dental data from the Upper Paleolithic site of Kostenki 15. Camera praehistorica 2 (5): 147–155
Emerging Roles of Ubiquitin-Specific Protease 25 in Diseases
Authors: Zhu Wenjing , Zheng Dandan , Wang Dandan , Yang Lehe , Zhao Chengguang , Huang Xiaoying
Published: June 2021

The balance of ubiquitination and deubiquitination plays diverse roles in regulating protein stability and cellular homeostasis. Deubiquitinating enzymes catalyze the hydrolysis and removal of ubiquitin chains from target proteins and play critical roles in various disease processes, including cancer, immune responses to viral infections and neurodegeneration. This article aims to summarize roles of the deubiquitinating enzyme ubiquitin-specific protease 25 (USP25) in disease onset and progression. Previous studies have focused on the role of USP25 in antiviral immunity and neurodegenerative diseases. Recently, however, as the structural similarities and differences between USP25 and its homolog USP28 have become clear, mechanisms of action of USP25 in cancer and other diseases have been gradually revealed.
Cardiomyocyte Proliferative Capacity Is Restricted in Mice With Lmna Mutation
Authors: Onoue Kenji , Wakimoto Hiroko , Jiang Jiangming , Parfenov Michael , DePalma Steven , Conner David , Gorham Joshua , McKean David , Seidman Jonathan G. , Seidman Christine E. , Saito Yoshihiko
Published: June 2021

LMNA is one of the leading causative genes of genetically inherited dilated cardiomyopathy (DCM). Unlike most DCM-causative genes, which encode sarcomeric or sarcomere-related proteins, LMNA encodes nuclear envelope proteins, lamin A and C, and does not directly associate with contractile function. However, a mutation in this gene could lead to the development of DCM. The molecular mechanism of how LMNA mutation contributes to DCM development remains largely unclear and yet to be elucidated. The objective of this study was to clarify the mechanism of developing DCM caused by LMNA mutation.

Methods and Results: We assessed cardiomyocyte phenotypes and characteristics focusing on cell cycle activity in mice with Lmna mutation. Both cell number and cell size were reduced, cardiomyocytes were immature, and cell cycle activity was retarded in Lmna mutant mice at both 5 weeks and 2 years of age. RNA-sequencing and pathway analysis revealed “proliferation of cells” had the most substantial impact on Lmna mutant mice. Cdkn1a, which encodes the cell cycle regulating protein p21, was strongly upregulated in Lmna mutants, and upregulation of p21 was confirmed by Western blot and immunostaining. DNA damage, which is known to upregulate Cdkn1a, was more abundantly detected in Lmna mutant mice. To assess the proliferative capacity of cardiomyocytes, the apex of the neonate mouse heart was resected, and recovery from the insult was observed. A restricted cardiomyocyte proliferating capacity after resecting the apex of the heart was observed in Lmna mutant mice.

Conclusions: Our results strongly suggest that loss of lamin function contributes to impaired cell proliferation through cell cycle defects. The inadequate inborn or responsive cell proliferation capacity plays an essential role in developing DCM with LMNA mutation.
A Narrative Inquiry Into Indigenizing School Mathematics Through Miyō-pimōhtēwin and Kamskénow
Authors: Stavrou Stavros Georgios
Published: June 2021

In Canadian mathematics education, dominant colonial narratives highlight an achievement disparity between Indigenous and non-Indigenous students in a way that often re-inscribes perceived deficits of Indigenous students, ignores the educational aspirations of Indigenous peoples, and sidelines Indigenous cultural and linguistic representations of knowledge in the classroom. Intentions of Indigenizing curriculum include challenging and reversing racist and colonial ideologies that hinder Indigenous education, providing meaningful alternatives within school cultures that foreground essential aspects of Indigenous education, and supporting the dynamic learning of Indigenous students. In my research described in this article, I used a narrative inquiry to describe how two Cree elementary school teachers shared promising practices of holistic assessments in school mathematics that centered their Cree language,miyō-pimōhtēwin, andkamskénow.
Tumor Mutation Burden Predicts Relapse in Papillary Thyroid Carcinoma With Changes in Genes and Immune Microenvironment
Authors: Guo Mengli , Chen Zhen , Li Yayi , Li Sijin , Shen Fei , Gan Xiaoxiong , Feng Jianhua , Cai Wensong , Liu Qingzhi , Xu Bo
Published: June 2021

Background

The risk factors of papillary thyroid carcinoma (PTC) recurrence are meaningful for patients and clinicians. Tumor mutation burden (TMB) has been a biomarker for the effectiveness of immune checkpoint inhibitor (ICI) and prognosis in cancer. However, the role of TMB and its latent significance with immune cell infiltration in PTC are still unclear. Herein, we aimed to explore the effect of TMB on PTC prognosis.

Material and Methods

RNA-seq and DNA-seq datasets of PTC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The Gene Ontology (GO) and gene set enrichment analysis (GSEA 4.0.1) were applied further to explore potential differences in PTC patients’ biological functions. The differentially expressed genes (DEGs) and immune microenvironment between the high and low TMB groups were determined.

Results

TMB had the highest AUC score than other clinical indicators in ROC analysis on recurrence-free survival, and a higher TMB score was related to a worse prognosis. Further, GSEA showed a higher level of oxidative phosphorylation (OXPHOS) in the high TMB group, and four genes correlated with recurrence-free survival rate were identified. The abundance of CD8+ T cells and M1 macrophages in the high TMB group was significantly lower than that in the low TMB group.

Conclusions

Our study found that TMB was a better predictor variable at evaluating the risk of PTC recurrence. Moreover, TMB-related genes conferred dramatically correlated prognosis, which was worth exploring in guiding postoperative follow-up and predicting recurrence for PTC patients.
Progress in Demand Response and It’s Industrial Applications
Authors: Siddiquee S. M. Shahnewaz , Howard Bianca , Bruton Ken , Brem Alexander , O'Sullivan Dominic T. J.
Published: June 2021

Achieving energy flexibility is becoming a key concern for energy system planners that manage intermittent and variable generations. Industries have enormous potential to deliver large-scale energy flexibility through demand response (DR) programs. This industrial demand flexibility achieved through the demand response programs will enable widespread adoption of renewable sources in the electricity grid network. This paper aims to provide a comprehensive review of demand response and it’s industrial application by addressing: 1) Current research status, 2) Current stages of demand response applications in industries, and 3) Barriers in the deployment of DR programs. This study shows that there is significant research progress in recent years in the field of DR. It also shows potential applications of DR programs in industries. However, the study found several technical, policy, and financial barriers still exist, limiting the widespread adoption of DR. Thus, this paper offers recommendations on technical, policy, and financial measures needed to over-come the barriers and help facilitate the utilization of demand response potential, especially in industries.
Transient Thermal Analysis of a Solar-Assisted AHU by Focusing on Heat Recovery and Nanoparticles: Jeddah Climate Zone
Authors: Khetib Yacine
Published: June 2021

In the Jeddah climate region, a lot of energy is assigned to the air handling unit (AHU) sector, which should be reduced by using energy-efficient solutions. As the air passes through the cooling coil, a lot of energy is consumed to reduce the temperature along with humidity so that if the air is precooled in the previous stages, energy consumption in this energy-intensive section will be diminished. Using the coldness of the return air in the heat recovery unit (HRU), the incoming air is precooled. Based on the thermodynamic calculations, in June, July, and August, the cooling coil power demand reduces by 11.6, 13.3, and 12%, respectively. In summer, owing to using HRU, an energy-saving by 76.08 MWh is achieved (12.34% reduction in energy demand). By the incorporation of the solar collectors in the AHU, heating coil demand diminishes by 1,206, 1,399, and 1,367 kWh in June, July, and August, respectively. To improve the solar-assisted AHU effectiveness, the MWCNT nanoparticles are injected into the collectors, and it is found that the saving-energy capability improves by 17.7% using MWCNT-water at 0.1 vol.%.
Comparison of Landfill Leachate Properties by LPI and Phytotoxicity-A Case Study
Authors: Wdowczyk Aleksandra , Szymańska-Pulikowska Agata
Published: June 2021

The formation of leachate is one of the inevitable consequences associated with the operation of landfills. In addition to the study of physicochemical composition, toxicity is an important parameter taken into account, among others because of the need to subject leachate to treatment before discharge into the environment. The aim of this study was to determine the degree of leachate contamination using LPI and toxicity index. An analysis of the relationship between the toxic effect on plants and the calculated LPI values was also carried out to assess whether they could provide a measure of leachate toxicity when selecting a treatment method. The research conducted was to determine the degree of leachate contamination using LPI and toxicity index. An analysis of the relationship between the toxic effect on plants and the calculated LPI values was also carried out to assess whether they could provide a measure of leachate toxicity when selecting a treatment method. Calculated values of the leachate pollution index showed that leachates from selected Polish landfills are characterized by low and medium levels of LPI values. The variation in index values obtained was particularly evident between active and closed landfills and was related to the physicochemical composition of leachates. In closed landfills this value ranged from 7.4 to 11.1, while in active landfills from 12.9 to 15.9. The variation in index values obtained was particularly evident between active and inactive landfills and was related to the physicochemical composition of leachates. Phytotoxicity tests showed that leachate at low concentrations can promote plant growth. At higher concentrations (50 and 100%), leachates caused inhibition of root and shoot growth, which correlated with high LPI values. The results confirmed the relationship between the toxic effect on plants and the LPI values, so it can be considered as a reliable indicator of leachate toxicity.
Boron Isotopic Analysis of Representative Atmospheric Aerosols Derived From Long-Range Transported/Local Emission on an Islet Offshore NE Taiwan
Authors: Lin Yen-Po , You Chen-Feng , Kao Tsung-Yu , Chung Chuan-Hsiung , Hung Chung-Chieh Gary
Published: June 2021

To identify pollutant origins and their potential sources from either long-range transported (LRT) or local emissions, the Boron (B) concentrations and the B isotopic compositions (δ11B) in the water-soluble fraction of aerosols were determined. These aerosols were collected from an islet offshore in northeastern Taiwan, Peng Chia Yu (PCY), a non-residential islet, from January 1998 to March 2000. This islet may be influenced by various pollutants or chemical transport during monsoon periods, but suffers minimal human perturbation locally. The B in the specimens falls to 0.3–1.63 ng m−3 during the SW monsoon seasons when compared to 0.46–2.56 ng m−3 in the NE monsoon. However, the δ11B results show no clear variations in both monsoon seasons (10.7–24.3‰), regardless of differences in air mass origin. A two end-member mixing scenario is proposed to explain our observations using the obtained δ11B and 1/[B] results. The ocean endmember is characterized by high 1/[B] and high δ11B; while other endmember is from continental endmember or anthropogenic contributions that are characterized by of 1/[B] and lowδ11B (δ11B < 10‰). Based on these chemical and isotopic results, we found aerosol emissions in northern Taiwan are characterized as low B with nearly constant δ11B, when compared with long-range transported continental endmembers derived from nearby regions. This study provides preliminary B and δ11B levels in aerosols derived from LRT/local emissions and discusses potential monsoonal effects on aerosols offshore of NE Taiwan.
Polymorphism in INSR Locus Modifies Risk of Atrial Fibrillation in Patients on Thyroid Hormone Replacement Therapy
Authors: Soto-Pedre Enrique , Siddiqui Moneeza K. , Maroteau Cyrielle , Dawed Adem Y. , Doney Alex S. , Palmer Colin N. A. , Pearson Ewan R. , Leese Graham P.
Published: June 2021

Aims

Atrial fibrillation (AF) is a risk for patients receiving thyroid hormone replacement therapy. No published work has focused on pharmacogenetics relevant to thyroid dysfunction and AF risk. We aimed to assess the effect of L-thyroxine on AF risk stratified by a variation in a candidate gene.

Methods and Results

A retrospective follow-up study was done among European Caucasian patients from the Genetics of Diabetes Audit and Research in Tayside Scotland cohort (Scotland, United Kingdom). Linked data on biochemistry, prescribing, hospital admissions, demographics, and genetic biobank were used to ascertain patients on L-thyroxine and diagnosis of AF. A GWAS-identified insulin receptor-INSR locus (rs4804416) was the candidate gene. Cox survival models and sensitivity analyses by taking competing risk of death into account were used. Replication was performed in additional sample (The Genetics of Scottish Health Research register, GoSHARE), and meta-analyses across the results of the study and replication cohorts were done. We analyzed 962 exposed to L-thyroxine and 5,840 unexposed patients who were rs4804416 genotyped. The rarer G/G genotype was present in 18% of the study population. The total follow-up was up to 20 years, and there was a significant increased AF risk for patients homozygous carriers of the G allele exposed to L-thyroxine (RHR = 2.35, P = 1.6e–02). The adjusted increased risk was highest within the first 3 years of exposure (RHR = 9.10, P = 8.5e–04). Sensitivity analysis yielded similar results. Effects were replicated in GoSHARE (n = 3,190).

Conclusion

Homozygous G/G genotype at the INSR locus (rs4804416) is associated with an increased risk of AF in patients on L-thyroxine, independent of serum of free thyroxine and thyroid-stimulating hormone serum concentrations.
A Mix of Old British and Modern European Breeds: Genomic Prediction of Breed Composition of Smallholder Pigs in Uganda
Authors: Babigumira Brian Martin , Sölkner Johann , Mészáros Gábor , Pfeiffer Christina , Lewis Craig R. G. , Ouma Emily , Wurzinger Maria , Marshall Karen
Published: June 2021

Pig herds in Africa comprise genotypes ranging from local ecotypes to commercial breeds. Many animals are composites of these two types and the best levels of crossbreeding for particular production systems are largely unknown. These pigs are managed without structured breeding programs and inbreeding is potentially limiting. The objective of this study was to quantify ancestry contributions and inbreeding levels in a population of smallholder pigs in Uganda. The study was set in the districts of Hoima and Kamuli in Uganda and involved 422 pigs. Pig hair samples were taken from adult and growing pigs in the framework of a longitudinal study investigating productivity and profitability of smallholder pig production. The samples were genotyped using the porcine GeneSeek Genomic Profiler (GGP) 50K SNP Chip. The SNP data was analyzed to infer breed ancestry and autozygosity of the Uganda pigs. The results showed that exotic breeds (modern European and old British) contributed an average of 22.8% with a range of 2–50% while “local” blood contributed 69.2% (36.9–95.2%) to the ancestry of the pigs. Runs of homozygosity (ROH) greater than 2 megabase (Mb) quantified the average genomic inbreeding coefficient of the pigs as 0.043. The scarcity of long ROH indicated low recent inbreeding. We conclude that the genomic background of the pig population in the study is a mix of old British and modern pig ancestries. Best levels of admixture for smallholder pigs are yet to be determined, by linking genotypes and phenotypic records.
Optimizing Fertility in Primary Ovarian Insufficiency: Case Report and Literature Review
Authors: Piedade Kensuly C. , Spencer Hillary , Persani Luca , Nelson Lawrence M.
Published: June 2021

Primary ovarian insufficiency (POI) is a clinical spectrum of ovarian dysfunction. Overt POI presents with oligo/amenorrhea and hypergonadotropic hypogonadism before age 40 years. Overt POI involves chronic health problems to include increased morbidity and mortality related to estradiol deficiency and the associated osteoporosis and cardiovascular disease as well as psychological and psychiatric disorders related to the loss of reproductive hormones and infertility. Presently, with standard clinical testing, a mechanism for Overt POI can only be identified in about 10% of cases. Now discovery of new mechanisms permits an etiology to be identified in a research setting in 25–30% of overt cases. The most common genetic cause of Overt POI is premutation in FMR1. The associated infertility is life altering. Oocyte donation is effective, although many women prefer to conceive with their own ova. Surprisingly, the majority who have Overt POI still have detectable ovarian follicles (70%). The major mechanism of follicle dysfunction in Overt POI has been histologically defined by a prospective NIH study: inappropriate follicle luteinization due to the tonically elevated serum LH levels. A trial of physiologic hormone replacement therapy, clinically proven to suppress the elevated LH levels in these women, may improve follicle function and increase the chance of ovulation. Here, we report the case of a woman with Overt POI diagnosed at age 35 years. To attempt pregnancy, she elected a trial of intrauterine insemination (IUI) in conjunction with follicle monitoring and physiologic hormone replacement therapy. She conceived on the eighth cycle of treatment and delivered a healthy baby. Our report calls for a concerted effort to define the best methods by which to optimize fertility for women who have POI.
Unitarism vs. Individuality and a New Digital Agenda: The Power of Decentralized Web
Authors: Lauterbach Anastassia
Published: June 2021

Discussions around Covid-19 apps and models demonstrated that primary challenges for AI and data science focused on governance and ethics. Personal information was involved in building data sets. It was unclear how this information could be utilized in large scale models to provide predictions and insights while observing privacy requirements. Most people expected a lot from technology but were unwilling to sacrifice part of their privacy for building it. Conversely, regulators and policy makers require AI and data science practitioners to ensure optimal public health, national security while avoiding these privacy-related struggles. Their choices vary largely from country to country and are driven more by cultural aspects, and less by machine learning capabilities. The question is whether current ways to design technology and work with data sets are sustainable and lead to a good outcome for individuals and their communities. At the same time Covid-19 made it obvious that economies and societies cannot succeed without far-reaching digital policies, touching every aspect of how we provide and receive education, live, and work. Most regions, businesses and individuals struggled to benefit from competitive capabilities modern data technologies could bring. This opinion paper suggests how Germany and Europe can rethink their digital policy while recognizing the value of data, introducing Data IDs for consumers and businesses, committing to support innovation in decentralized data technologies, introducing concepts of Data Trusts and compulsory education around data starting from the early school age. Besides, it discusses advantages of data-tokens to shape a new ecosystem for decentralized data exchange. Furthermore, it emphasizes the necessity to develop and promote technologies to work with small data sets and handle data in compliance with privacy regulations, keeping in mind costs for the environment while bidding on big data and large-scale machine learning models. Finally, innovation as an integral part of any data scientist's job will be called for.
Reduced Energy Metabolism Impairs T Cell-Dependent B Cell Responses in Patients With Advanced HBV-Related Cirrhosis
Authors: Huang Chunhong , Shao Junwei , Lou Congcong , Wu Fengtian , Ge Tiantian , Gao Hainv , Zheng Xiaoping , Dong Xuejun , Xu Lichen , Chen Zhi
Published: June 2021

Background and Aims

Patients with decompensated HBV-related liver cirrhosis (HBV D-LC) showed compromised immune responses, which manifested as a proneness to develop infections and hyporesponsiveness to vaccines, resulting in accelerated disease progression. The alterations in T cell-dependent B cell responses in this pathophysiological process were not well understood. This study aimed to investigate T cell-dependent B cell responses in this process and discuss the mechanism from the perspective of metabolism.

Methods

Changes in phenotypes and subsets of peripheral B cells between HBV D-LC patients and healthy controls (HCs) were compared by flow cytometry. Isolated B cells were activated by coculture with circulating T follicular (cTfh) cells. After coculture, the frequencies of plasmablasts and plasma cells and immunoglobin levels were analyzed. Oxidative phosphorylation (OXPHOS) and glycolysis were analyzed by a Seahorse analyzer. Mitochondrial function and the AKT/mTOR pathway were analyzed by flow cytometry.

Results

The proliferation and differentiation capacities of B cells after T cell stimulation were impaired in D-LC. Furthermore, we found that B cells from D-LC patients showed reductions in OXPHOS and glycolysis after activation, which may result from reduced glucose uptake, mitochondrial dysfunction and attenuated activation of the AKT/mTOR pathway.

Conclusions

B cells from HBV D-LC patients showed dysfunctional energy metabolism after T cell-dependent activation. Understanding the regulations of B cell metabolic pathway and their changes may provide a new direction to rescue B cell hyporesponsiveness in patients with HBV D-LC, preventing these patients be infected and improving sensitivity to vaccines.
Transfer of PBMC From SSc Patients Induces Autoantibodies and Systemic Inflammation in Rag2-/-/IL2rg-/- Mice
Authors: Yue Xiaoyang , Petersen Frank , Shu Yaqing , Kasper Brigitte , Magatsin Junie D. Tchudjin , Ahmadi Marjan , Yin Junping , Wax Jacqueline , Wang Xiaoqing , Heidecke Harald , Lamprecht Peter , Müller Antje , Yu Xinhua , Riemekasten Gabriela
Published: June 2021

Objective

The contribution of sustained autologous autoantibody production by B cells to the pathogenesis of systemic sclerosis (SSc) and granulomatosis with polyangiitis (GPA) is not fully understood. To investigate this, a humanized mouse model was generated by transferring patient-derived peripheral blood mononuclear cells (PBMC) into immunocompromised mice.

Methods

PBMC derived from patients with SSc and GPA as well as healthy controls (HD) were isolated, characterized by flow cytometry, and infused into Rag2-/-/IL2rg-/- mice. In addition, PBMC from SSc patients treated with rituximab were transferred into mice. Twelve weeks later, human autoantibodies were determined in blood of the recipient mice and affected tissues were analyzed for pathological changes by histology and immunohistochemistry.

Results

Mice engrafted with PBMC derived from SSc patients developed autoantibodies such as antinuclear antibodies (ANA) mimicking the pattern of the respective donors. Moreover, cellular infiltrates dominated by B cells were observed in lung, kidney and muscles of the recipient mice. By contrast, PBMC derived from HD or GPA patients survived in recipient mice after transfer, but neither human autoantibodies nor inflammatory infiltrates in tissues were detected. Furthermore, these pathological changes were absent in mice transferred with PBMC from rituximab-treated SSc patients.

Conclusion

This humanized mouse model is indicative for cross-reactivity of human lymphocytes to murine autoantigens and argues for a pivotal role of B cells as well as of sustained autoimmunity in the pathogenesis of SSc. It provides a powerful tool to study interstitial lung disease and so far, under-recognized disease manifestations such as myositis and interstitial nephritis.
Murepavadin, a Small Molecule Host Defense Peptide Mimetic, Activates Mast Cells via MRGPRX2 and MrgprB2
Authors: Amponnawarat Aetas , Chompunud Na Ayudhya Chalatip , Ali Hydar
Published: June 2021

Pseudomonas aeruginosa is a frequent cause of hospital-acquired wound infection and is difficult to treat because it forms biofilms and displays antibiotic resistance. Previous studies in mice demonstrated that mast cells (MCs) not only contribute to P. aeruginosa eradication but also promote wound healing via an unknown mechanism. We recently reported that host defense peptides (HDPs) induce human MC degranulation via Mas-related G protein-coupled receptor-X2 (MRGPRX2). Small molecule HDP mimetics have distinct advantages over HDPs because they are inexpensive to synthesize and display high stability, bioavailability, and low toxicity. Murepavadin is a lipidated HDP mimetic, (also known as POL7080), which displays antibacterial activity against a broad panel of multi-drug-resistant P. aeruginosa. We found that murepavadin induces Ca2+ mobilization, degranulation, chemokine IL-8 and CCL3 production in a human MC line (LAD2 cells) endogenously expressing MRGPRX2. Murepavadin also caused degranulation in RBL-2H3 cells expressing MRGPRX2 but this response was significantly reduced in cells expressing missense variants within the receptor’s ligand binding (G165E) or G protein coupling (V282M) domains. Compound 48/80 induced β-arrestin recruitment and promoted receptor internalization, which resulted in substantial decrease in the subsequent responsiveness to the MRGPRX2 agonist. By contrast, murepavadin did not cause β-arrestin-mediated MRGPRX2 regulation. Murepavadin induced degranulation in mouse peritoneal MCs via MrgprB2 (ortholog of human MRGPRX2) and caused increased vascular permeability in wild-type mice but not in MrgprB2-/- mice. The data presented herein demonstrate that murepavadin activates human MCs via MRGPRX2 and murine MCs via MrgprB2 and that MRGPRX2 is resistant to β-arrestin-mediated receptor regulation. Thus, besides its direct activity against P. aeruginosa, murepavadin may contribute to bacterial clearance and promote wound healing by harnessing MC’s immunomodulatory property via the activation of MRGPRX2.
Severe COVID-19 Recovery Is Associated with Timely Acquisition of a Myeloid Cell Immune-Regulatory Phenotype
Authors: Trombetta Amelia C. , Farias Guilherme B. , Gomes André M. C. , Godinho-Santos Ana , Rosmaninho Pedro , Conceição Carolina M. , Laia Joel , Santos Diana F. , Almeida Afonso R. M. , Mota Catarina , Gomes Andreia , Serrano Marta , Veldhoen Marc , Sousa Ana E. , Fernandes Susana M.
Published: June 2021

After more than one year since the COVID-19 outbreak, patients with severe disease still constitute the bottleneck of the pandemic management. Aberrant inflammatory responses, ranging from cytokine storm to immune-suppression, were described in COVID-19 and no treatment was demonstrated to change the prognosis significantly. Therefore, there is an urgent need for understanding the underlying pathogenic mechanisms to guide therapeutic interventions. This study was designed to assess myeloid cell activation and phenotype leading to recovery in patients surviving severe COVID-19. We evaluated longitudinally patients with COVID-19 related respiratory insufficiency, stratified according to the need of intensive care unit admission (ICU, n = 11, and No-ICU, n = 9), and age and sex matched healthy controls (HCs, n = 11), by flow cytometry and a wide array of serum inflammatory/immune-regulatory mediators. All patients featured systemic immune-regulatory myeloid cell phenotype as assessed by both unsupervised and supervised analysis of circulating monocyte and dendritic cell subsets. Specifically, we observed a reduction of CD14lowCD16+ monocytes, and reduced expression of CD80, CD86, and Slan. Moreover, mDCs, pDCs, and basophils were significantly reduced, in comparison to healthy subjects. Contemporaneously, both monocytes and DCs showed increased expression of CD163, CD204, CD206, and PD-L1 immune-regulatory markers. The expansion of M2-like monocytes was significantly higher at admission in patients featuring detectable SARS-CoV-2 plasma viral load and it was positively correlated with the levels of specific antibodies. In No-ICU patients, we observed a peak of the alterations at admission and a progressive regression to a phenotype similar to HCs at discharge. Interestingly, in ICU patients, the expression of immuno-suppressive markers progressively increased until discharge. Notably, an increase of M2-like HLA-DRhighPD-L1+ cells in CD14++CD16− monocytes and in dendritic cell subsets was observed at ICU discharge. Furthermore, IFN-γ and IL-12p40 showed a decline over time in ICU patients, while high values of IL1RA and IL-10 were maintained. In conclusion, these results support that timely acquisition of a myeloid cell immune-regulatory phenotype might contribute to recovery in severe systemic SARS-CoV-2 infection and suggest that therapeutic agents favoring an innate immune system regulatory shift may represent the best strategy to be implemented at this stage.
Immunological Responses to Transgene-Modified Neural Stem Cells After Transplantation
Authors: Wei Naili , Sun Zhenxing , Yu Jimei , Jia Yanfei , Zheng Peiqi , Tang Hailiang , Chen Jian
Published: June 2021

Neural stem cell (NSC) therapy is a promising therapeutic strategy for stroke. Researchers have frequently carried out genetic modification or gene editing of stem cells to improve survival or therapeutic function. However, NSC transplantation carries the risk of immune rejection, and genetic modification or gene-editing might further increase this risk. For instance, recent studies have reported on manipulating the stem cell genome and transplantationviathe insertion of an exogenous gene derived from magnetotactic bacteria. However, whether transgene-modified stem cells are capable of inducing immunological reactions has not been explored. Although NSCs rarely express the major histocompatibility complex (MHC), they can still cause some immunological issues. To investigate whether transgene-modified NSCs aggravate immunological responses, we detected the changes in peripheral immune organs and intracerebral astrocytes, glial cells, and MHC-I and MHC-II molecules after the injection of GFP-labeled ormms6-GFP-labeled NSCs in a rat model. Xenogeneic human embryonic kidney (HEK-293T) cells were grafted as a positive control group. Our results indicated that xenogeneic cell transplantation resulted in a strong peripheral splenic response, increased astrocytes, enhanced microglial responses, and upregulation of MHC-I and MHC-II expression on the third day of transplantation. But they decreased obviously except Iba-1 positive cells and MHC-II expression. When injection of bothmms6-GFP-labeled NSCs and GFP-labeled NSCs also induced similar responses as HEK-293T cells on the third days, but MHC-I and MHC-II expression decreased 3 weeks after transplantation. In addition,mms6transgene-modified NSCs did not produce peripheral splenic response responses as well as astrocytes, microglial cells, MHC-I and MHC-II positive cells responses when compared with non-modified NSCs. The present study provides preliminary evidence that transgenic modification does not aggravate immunological responses in NSC transplantation.
A Rapid Assessment of the Marine Megafauna Biodiversity Around South Bali, Indonesia
Authors: Mustika Putu Liza Kusuma , Williams Rob , Kadarisman Hanggar Prasetio , Purba Andri Oktapianus , Maharta I Putu Ranu Fajar , Rahmadani Deny , Faiqoh Elok , Dewantama I Made Iwan
Published: June 2021

A low-cost, small-boat, rapid assessment survey was conducted on the waters off the southern Peninsula of Bali. The objectives were: (1) to conduct an inventory of cetacean species in the study area; (2) to map cetacean distribution to inform the design of the Badung MPA; (3) to estimate relative abundance of cetaceans and record information on presence and distribution of other marine megafauna; and (4) to train observers in the use of distance sampling methods. The survey adopted a “training while doing” approach to build local capacity for marine biodiversity monitoring, while collecting a snapshot of data to assess species richness and distribution. The survey accomplished its first two objectives, but due to violation of underlying assumptions, had mixed success with the third objective. Our survey revealed that the waters off the southern Peninsula of Bali support a rich cetacean fauna, with at least seven cetacean species, other marine megafauna, and avian species. Seven cetacean species found on our survey include: spinner dolphin (Stenella longirostris), pantropical spotted dolphin (Stenella attenuata), Fraser’s dolphin (Lagenodephis hosei), Risso’s dolphin (Grampus griseus), bottlenose dolphin (Tursiopssp.), Bryde’s whale (Balaenoptera edeni), and sperm whale (Physeter macrocephalus). Density estimates were low for all whales combined, but seem implausibly high for dolphins; likely due to violation of assumptions of distance sampling methods. Future surveys should include sufficient time for training to generate reliable abundance estimates. A dedicated bycatch study is needed to understand sustainability of bycatch mortality relative to reliable abundance estimates.