bluuebunny/crossref_metadata_2025 huggingface dataset:
Penegakan Hukum terhadap Tindakan Penyalahgunaan Kekuasaan dalam Kondisi Darurat Covid-19
Authors: Mulkan Hasanal
Published: October 2021

This study will look at the government's policy of handling Covid-19 from a prophetic legal point of view based on three main pillars, namely humanization, liberation and transcendence. In this study, the authors use normative research by using the approach to legislation, the prophetic legal concept approach and the case approach. The results of the study show that the Covid-19 handling policy carried out by the government still contains inaccurate recipient data, the distribution of basic needs assistance is not carried out in stages from the Central Government to the Regional Government but is carried out simultaneously, there is a legal basis that opens space abuse of authority due to legal immunity for officials. Keywords: Policies, handling of covid-19, prophetic lawThe government has issued several legal products such as Government Regulation in Lieu of Law Number 1 of 2020 concerning State Financial Policy and Financial System Stability for Handling the Corona Virus Disease 2019 (COVID-19) Pandemic and/ Or in the context of Facing Threats That Endanger the National Economy and/or Financial System Stability and Government Regulation Number 21 of 2020 concerning Large-Scale Social Restrictions (PSBB) in the Context of Accelerating Handling of Corona Virus Disease 2019 (COVID-19). The government has also implemented PSBB and Physical Distancing policies, but these policies are not effective in breaking the chain of spread of COVID-19, it can be seen that the number of COVID-19 cases in Indonesia on January 28, 2021 has reached 1 million cases, the highest in Southeast Asia.
Analisis Sistem Dan Prosedur Akuntansi dalam Pemberian Kredit Produktif pada PT. Bank Pembangunan Daerah Jambi Cabang Muara Bulian
Authors: Fauziah Fauziah , Albetris Albetris
Published: October 2021

Know the accounting system and procedures clearly and accurately so that the implementation of credit disbursement is selective and on target, especially productive credit to debtors at PT. Jambi Regional Development Bank Muara Bulian Branch, is the purpose of this research. The implementation of credit disbursement effectively and efficiently can be carried out properly in accordance with the standards and regulations that apply in general and in particular. Comparing the opinions of experts or references that are used as guidelines or technical instructions with the implementation in this research, and describe in detail the chronological details of the results of this research with qualitative descriptive methods. So that clear and detailed results are obtained from this research which shows that the systems and procedures that are run by PT. Jambi Regional Development Bank Muara Bulian Branch in the implementation of lending, especially productive credit, can be carried out properly in accordance with applicable principles and standards. Until the goal is to provide the best service and be able to choose the right debtors so that the provision of productive credit can be carried out effectively and efficiently, as expected.
PERAN SOCIOLOGICAL JURISPRUDENCE DALAM MENCIPTAKAN KEEFEKTIVITASAN HUKUM MELALUI LIVING LAW
Authors: Hernowo Wempy Setyabudi , Zaid Zaid , Erawan M. Aufar Saputra Pratama
Published: October 2021

The concept of Sociological jurisprudence has the view that as a product created by society, law also aims to protect the interests and satisfy society, which in turn becomes a means of controlling society itself. The purpose of the study or research in this article is to achieve these goals effectively. Through doctrinal research methods with a conceptual and statutory approach, the results and findings of this study indicate that effective law is the law that carries out its functions properly and correctly. And to achieve that, the effectiveness of the law can be realized through four things, namely by the values prevailing in society, social facts, the aspirations of the community and also the interests of society in the making, interpretation, and application of legal regulations against Public
ANALISIS KESALAHAN SISWA DALAM MENYELESAIKAN SOAL CERITA MATERI BARISAN DAN DERET ARITMATIKA
Authors: Handayani Tuti , Hartatiana Hartatiana , Muslimahayati Muslimahayati
Published: October 2021

Tujuan penelitian ini adalah untuk menganalisis kesalahan siswa dalam menyelesaikan soal cerita materi barisan dan deret aritmatika dan untuk mengetahui faktor internal penyebab siswa melakukan kesalahan dalam menyelesaikan soal cerita materi barisan dan deret aritmatika. Metode penelitian yang digunakan dalam penelitian ini adalah metode deskriptif dengan pendekatan kualitatif. Subjek penelitian terdiri dari 6 siswa. Data penelitian diperoleh dari tes tertulis, angket dan wawancara. Analisis data pada penelitian adalah analisis data kualitatif yang terdiri dari reduksi data, penyajian data, dan penarikan kesimpulan. Hasil penelitian diperoleh kesalahan yang dilakukan siswa yaitu kesalahan konsep, kesalahan menggunakan data, kesalahan interpretasi bahasa, kesalahan teknis dan kesalahan penarikan kesimpulan. Adapun penyebab kesalahan tersebut adalah karena kurangnya minat siswa dan kurangnya intelegensi siswa dalam menyelesaikan soal cerita materi barisan dan deret aritmatika. Kata kunci : Barisan dan deret aritmetika; Kesalahan siswa; Soal cerita
Perencanaan Baja Ringan Sebagai Salah Satu Alternatif Pengganti Kayu Pada Struktur Rangka Atap Bangunan
Authors: Primadani M Riza , Suhendra Suhendra , Dahlan Eri
Published: October 2021

Seiring perkembangan jaman, kebutuhan akan kayu sebagai ibahan idasar irangka iatap isemakin imeningkat, namun tidak diiringi dengan kualitasidan kuantitas kayu itu sendiri. Semakin langkanya pohon terutama pohonidenganikualitasikayu baik menyebabkan hargaikayuimenjadiirelatifimahal.iHaliini menjadi dasar pemikiran produseniuntukimenciptakaniinovasi baru berupa baja ringan untukimembuat rangkaiatap.iBajairinganidipilih sebagaiialternatifipenggantiikayuisebagaiirangka atap ikarena ibaja iringan imemiliki ifaktor ikeawetan, itahan irayap idan itahan ikarat. Tujuan idari ipenelitian iini iuntuk imenganalisis irangka ikuda-kuda ibaja iringan idan ikuda-kuda ikayu, serta membandingkan ibesarnya ibiaya iatap iyang imenggunakan ikonstruksi irangka ibajairingan idan ikonstruksi irangka ikayu.iMaterial istruktur ikayu imenggunakan imaterial ikayu ikelas iII idan imaterial ibaja imenggunakan iBaja iRingan iC75.75.iBangunan iyang idi ijadikan iobjek iadalah ibangunan i72 im2 idengan iluas iarea ibangunan i8 im ix i9 im. Pada ipenelitian iini idiperoleh iPersentase iharga ipada ikuda-kuda ibaja iringan i101,93% ikali iharga ipada ikuda-kuda ikayu.iDan ipersentase iberat ikuda-kuda ibaja iringan i11,25% idari iberat ikuda-kuda ikayu.iTerdapat iperbedaan ibiaya ipada irangka iatap iyaitu ipada ipembangunan irangka iatap ibaja iringan idengan iluas i72m2 ididapatkan itotal ibiaya iyang idikeluarkan isebesar iRp.63.278.178, iSedangkan imenggunakan irangka iatap ikayu itotal ibiaya iyang idikeluarkan isebesar iRp.62.082.444.iPerbandingan ibiaya ipada ipembangunan irangka iatap iatap ibaja iringan idan irangka iatap ikayu iadalah isebesar iRp.1.195.734.iJadi ikesimpulan iyang ibisa idiambil idari ikedua iperbandingan ibiaya itersebut iadalah ipembuatan irangka iatap imenggunakan irangka iatap ibaja iringan ilebih imahal idari ipada ibiaya imenggunakan irangka iatap ikayu.
ENVIRONMENTAL CRIMINAL LAW IN THE EUROPEAN UNION
Authors: OKUYUCU ERGÜN Güneş
Published: October 2021

Over the past decades, environmental offences have increasingly extended beyond the borders of the Member States. It has been observed that the existing systems of penalties have not been sufficient, and the availability of criminal penalties was required, to achieve complete compliance with the laws for the protection of the environment. As a result, the European environmental criminal law has gone through a remarkable development over the past decades at both EU and Member State levels. This paper suggests that, although the Directive 2008/99/EC, which is the main legal instrument of the EU environmental criminal law, was an important step forward in the protection of environment through criminal law, it may be criticised for its administrative dependence and lack of autonomous or independent approach both in terms of offences and their sanctions.
COAL PROJECTS IN THE ARCTIC RUSSIAN ZONE: EFFICIENCY AND ORIENTATION
Authors: Churashev Victor N. , Markova Vitalya M.
Published: October 2021

"The program for the development of the coal industry in the Russian Federation until 2035" provides for an increase in coal production to 484-670 million tons and exports to 400 million tons. Among new projects, the possibility of developing Arctic coal deposits is being considered, which generate both positive (growth in the NSR cargo turnover, employment in the territory, development of the Arctic infrastructure) and negative effects (environmental burden, non-transparency of tax revenues of projects outside the implementation area, rotational management, government subsidies, etc.). The perspectives of the coal markets in the conditions of carbon neutrality are analyzed. It is shown that the coking coal market has prospects for expansion, which creates a niche for Russian exports. The development of deposits in the Arctic competes with both global suppliers and other Russian projects (Yakutia, Tyva, Kuzbass).
ANALYSIS OF RELATIONSHIP BETWEEN SOCIO-ECONOMIC SITUATION AND RELIGIOUS COMPOSITION OF RUSSIA
Authors: Gravchikova Alina A.
Published: October 2021

In the modern world, globalization leads to the active interaction of representatives of different cultures, however, there are questions of how this is reflected in the well-being level of society. This article raises the problem of the cultural heterogeneity consequences as a result of globalization. For the analysis, religion was chosen as a cultural feature (criterion of heterogeneity), which is an institution of norms and values of the population, as well as a reflection of the historical past of population. The object of research is the regions of Russia. The analysis used data from the Atlas of Religions and Nationalities of Russia «Arena» (Non-profit research based consulting "Sreda") and the Federal Agency for Ethnic Affairs. The study analyzed the influence of religious heterogeneity on the level of scientific activity of organizations in the regions of the Russian Federation. The negative influence of religious heterogeneity on the level of research activity of organizations in the regions of the Russian Federation was revealed. It is shown that the impact is not direct. Religious heterogeneity is associated with the level of migration of young scientists, which, in turn, has an impact on the activities of scientific organizations in the country.
COMBI LANGUAGE - A MEANS OF PRESENTING OPTIMIZATION MODELS IN THE IPC OF ANALYSIS AND FORECASTING OF SPATIAL ECONOMY
Authors: Ibragimov Naimdzhon M. , Kostin Vitaly S.
Published: October 2021

One of the effective tools for solving applied problems of analysis and modeling of the spatial economy are optimization interregional intersectoral models. Currently, IEIE SB RAS has developed and implemented several versions of the Model-Program Complex of the Optimization Interregional Interindustry Model "MPK OMMM", which are used to coordinate macroeconomic, sectoral and regional long-term forecasts on a regular basis and for experimental calculations of forecast options for the development of the national economy of the Russian Federation . This paper discusses one of the ways to represent optimization models of the OMMM type, based on the use of the COMBI-2000 language (Complex for processing matrix information blocks, version 2000), which is a tool for describing pre- and post-optimization calculations, a means of communication with the optimization package and reflecting a database and recording mathematical models in a fairly convenient and simplified structure for users.
Detection of Specific IgG-Antibodies Against Toxoplasma gondii in the Serum and Milk of Domestic Donkeys During Lactation in China: A Potential Public Health Concern
Authors: Chen Long , Zhao Zi-Jian , Meng Qing-Feng
Published: October 2021

Toxoplasma gondii is a worldwide zoonotic protozoan. Donkeys are often susceptible to many pathological agents, acting as carriers of pathogens for other animal species and humans. However, data on the prevalence of T. gondii in donkeys during lactation and on the status of antibodies against T. gondii in donkey milk are lacking. A cross-sectional study evaluated the variation of the anti-T. gondii antibodies in the blood and milk of domestic donkeys during lactation. A total of 418 domestic donkeys were randomly selected from the Shandong province, eastern China from January 2019 to March 2020. The anti-T. gondii antibodies were found in 11.72% (49/418) serum and 9.81% (41/418) milk samples using a commercial ELISA kit, respectively. There was a very high consistency between the serum and milk (Spearman’s coefficient = 0.858, p-value < 0.0001 and Kendall’s tau = 0.688, p-value < 0.0001), particularly at the 45th to 60th day of lactation. The present results of the statistical analysis showed that the history of abortion (p = 0.026; adjusted OR = 2.20; 95% CI: 1.15–4.20) and cat in the house (p = 0.008; adjusted OR = 2.36; 95% CI: 1.26–4.44) were significantly associated with T. gondii infection in the domestic donkeys. This is the first report to detect antibodies against T. gondii in donkey milk in China. These results indicate a potential risk of humans contracting the infection through the consumption of raw milk from the naturally infected donkeys.
Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors vs. Dipeptidyl Peptidase-4 (DPP4) Inhibitors for New-Onset Dementia: A Propensity Score-Matched Population-Based Study With Competing Risk Analysis
Authors: Mui Jonathan V. , Zhou Jiandong , Lee Sharen , Leung Keith Sai Kit , Lee Teddy Tai Loy , Chou Oscar Hou In , Tsang Shek Long , Wai Abraham Ka Chung , Liu Tong , Wong Wing Tak , Chang Carlin , Tse Gary , Zhang Qingpeng
Published: October 2021

Introduction: The effects of sodium-glucose cotransporter 2 inhibitors (SGLT2I) and dipeptidyl peptidase-4 inhibitors (DPP4I) on new-onset cognitive dysfunction in type 2 diabetes mellitus remain unknown. This study aimed to evaluate the effects of the two novel antidiabetic agents on cognitive dysfunction by comparing the rates of dementia between SGLT2I and DPP4I users.

Methods: This was a population-based cohort study of type 2 diabetes mellitus patients treated with SGLT2I and DPP4I between January 1, 2015 and December 31, 2019 in Hong Kong. Exclusion criteria were <1-month exposure or exposure to both medication classes, or prior diagnosis of dementia or major neurological/psychiatric diseases. Primary outcomes were new-onset dementia, Alzheimer's, and Parkinson's. Secondary outcomes were all-cause, cardiovascular, and cerebrovascular mortality.

Results: A total of 13,276 SGLT2I and 36,544 DPP4I users (total n = 51,460; median age: 66.3 years old [interquartile range (IQR): 58–76], 55.65% men) were studied (follow-up: 472 [120–792] days). After 1:2 matching (SGLT2I: n = 13,283; DPP4I: n = 26,545), SGLT2I users had lower incidences of dementia (0.19 vs. 0.78%, p < 0.0001), Alzheimer's (0.01 vs. 0.1%, p = 0.0047), Parkinson's disease (0.02 vs. 0.14%, p = 0.0006), all-cause (5.48 vs. 12.69%, p < 0.0001), cerebrovascular (0.88 vs. 3.88%, p < 0.0001), and cardiovascular mortality (0.49 vs. 3.75%, p < 0.0001). Cox regression showed that SGLT2I use was associated with lower risks of dementia (hazard ratio [HR]: 0.41, 95% confidence interval [CI]: [0.27–0.61], P < 0.0001), Parkinson's (HR:0.28, 95% CI: [0.09–0.91], P = 0.0349), all-cause (HR:0.84, 95% CI: [0.77–0.91], P < 0.0001), cardiovascular (HR:0.64, 95% CI: [0.49–0.85], P = 0.0017), and cerebrovascular (HR:0.36, 95% CI: [0.3–0.43], P < 0.0001) mortality.

Conclusions: The use of SGLT2I is associated with lower risks of dementia, Parkinson's disease, and cerebrovascular mortality compared with DPP4I use after 1:2 ratio propensity score matching.
Interplay Between Gut Microbiota and Amino Acid Metabolism in Heart Failure
Authors: Tuerhongjiang Gulinigaer , Guo Manyun , Qiao Xiangrui , Lou Bowen , Wang Chen , Wu Haoyu , Wu Yue , Yuan Zuyi , She Jianqing
Published: October 2021

Heart failure (HF) is a complex clinical syndrome of which the incidence is on the rise worldwide. Cardiometabolic disorders are associated with the deterioration of cardiac function and progression of HF. Recently, there has been renewed interest in gut microbiota (GM) and its metabolites in the cardiovascular disease. HF-caused hypoperfusion could increase intestinal permeability, and a “leaky” bowel leads to bacterial translocation and make its metabolites more easily enter the circulation. Considerable evidence shows that the composition of microbiota and amino acids (AAs) has been altered in HF patients, and AAs could serve as a diagnostic and prognostic biomarker in HF. The findings indicate that the gut–amino acid–HF axis may play a key role in the progression of HF. In this paper, we focus on the interrelationship between the AA metabolism and GM alterations during the development of heart failure. We also discuss the potential prognostic and therapeutic value of the gut–amino acid–HF axis in the cortex of HF.
The Upregulation of Molecules Related to Tumor Immune Escape in Human Pituitary Adenomas
Authors: Xi Zhiyu , Jones Pamela S. , Mikamoto Masaaki , Jiang Xiaobin , Faje Alexander T. , Nie Chuansheng , Labelle Kathryn E. , Zhou Yunli , Miller Karen K. , Soberman Roy J. , Zhang Xun
Published: October 2021

Human pituitary adenomas are one of the most common intracranial neoplasms. Although most of these tumors are benign and can be treated medically or by transsphenoidal surgery, a subset of these tumors are fast-growing, aggressive, recur, and remain a therapeutic dilemma. Because antibodies against immune checkpoint receptors PD-1 and CLTA-4 are now routinely used for cancer treatment, we quantified the expression of mRNA coding for PD-1, CLTA-4, and their ligands, PD-L1, PD-L2, CD80, and CD86 in human pituitary adenomas and normal pituitary glands, with the ultimate goal of exploiting immune checkpoint therapy in aggressive pituitary adenomas. Aggressive pituitary adenomas demonstrated an increased expression of PD-L2, CD80, and CD86 in compared to that of normal human pituitary glands. Furthermore, aggressive pituitary tumors demonstrated significantly higher levels of CD80 and CD86 compared to non-aggressive tumors. Our results establish a rationale for studying a potential role for immune checkpoint inhibition therapy in the treatment of pituitary adenomas.
Computed Tomography-Based Radiomics Model to Predict Central Cervical Lymph Node Metastases in Papillary Thyroid Carcinoma: A Multicenter Study
Authors: Li Jingjing , Wu Xinxin , Mao Ning , Zheng Guibin , Zhang Haicheng , Mou Yakui , Jia Chuanliang , Mi Jia , Song Xicheng
Published: October 2021

Objectives

This study aimed to develop a computed tomography (CT)-based radiomics model to predict central lymph node metastases (CLNM) preoperatively in patients with papillary thyroid carcinoma (PTC).

Methods

In this retrospective study, 678 patients with PTC were enrolled from Yantai Yuhuangding Hot3spital (n=605) and the Affiliated Hospital of Binzhou Medical University (n=73) within August 2010 to December 2020. The patients were randomly divided into a training set (n=423), an internal test set (n=182), and an external test set (n=73). Radiomics features of each patient were extracted from preoperative plain scan and contrast-enhanced CT images (arterial and venous phases). One-way analysis of variance (ANOVA) and least absolute shrinkage and selection operator algorithm were used for feature selection. The K-nearest neighbor, logistics regression, decision tree, linear-support vector machine (linear-SVM), Gaussian-SVM, and polynomial-SVM algorithms were used to establish radiomics models for CLNM prediction. The clinical risk factors were selected by ANOVA and multivariate logistic regression. Incorporated with clinical risk factors, a combined radiomics model was established for the preoperative prediction of CLNM in patients with PTCs. The performance of the combined radiomics model was evaluated using the receiver operating characteristic (ROC) and calibration curves in the training and test sets. The clinical usefulness was evaluated through decision curve analysis (DCA).

Results

A total of 4227 radiomic features were extracted from the CT images of each patient, and 14 non-zero coefficient features associated with CLNM were selected. Four clinical variables (sex, age, tumor diameter, and CT-reported lymph node status) were significantly associated with CLNM. Linear-SVM led to the best prediction model, which incorporated radiomic features and clinical risk factors. Areas under the ROC curves of 0.747 (95% confidence interval [CI] 0.706–0.782), 0.710 (95% CI 0.634–0.786), and 0.764 (95% CI 0.654–0.875) were obtained in the training, internal, and external test sets, respectively. The linear-SVM algorithm also showed better sensitivity (0.702 [95% CI 0.600–0.790] vs. 0.477 [95% CI 0.409–0.545]) and accuracy (0.670 [95% CI 0.600–0.738] vs. 0.642 [95% CI 0.569–0.712]) than an experienced radiologist in the internal test set in the combined radiomics model. The calibration plot reflected a favorable agreement between the actual and estimated probabilities of CLNM. The DCA indicated the clinical usefulness of the combined radiomics model.

Conclusion

The combined radiomics model is a non-invasive preoperative tool that incorporates radiomic features and clinical risk factors to predict CLNM in patients with PTC.
Mangroves Fueling Livelihoods: A Socio-Economic Stakeholder Analysis of the Charcoal and Pole Production Systems in the World’s Longest Managed Mangrove Forest
Authors: Satyanarayana Behara , Quispe-Zuniga Melissa R. , Hugé Jean , Sulong Ibrahim , Mohd-Lokman Husain , Dahdouh-Guebas Farid
Published: October 2021

The declining mangrove cover worldwide highlights the necessity of understanding the linkages between ecological and socio-economic dimensions of mangrove management. This study analyses the socio-economic aspects of the pole and charcoal production systems at Matang Mangrove Forest Reserve (MMFR), known as the world’s longest managed mangrove forest, in Malaysia. We performed a socio-economic survey to identify the roles and relationships among stakeholders in the pole/charcoal production system and quantified the cash-flows in monetary value. Altogether, 160 interviews were conducted with contractors, forest officials, workers, middle-men, and consumers. The contractors are functioning as a “hub” from production to commercialization and receive major economic benefits. The commercialization of most charcoal (>80%) aims to its exportation to Japan while the commercialization of poles is local. Although the workers’ income was less than the minimum wage, they still prefer charcoal production jobs because of the availability and geographic proximity of these jobs. Our research suggests a standard salary and health insurance schemes for the workers to reduce social inequality/poverty and improve their well-being. Considering that mangroves occur in over 120 countries, our methodology can be used as a reference to unveil the socio-economic situation of mangrove-dependent communities as well as to map the economic cash-flow of the local activities that form the basis for long-term sustainable mangrove management plans.
Sex-Biased Mortality and Sex Reversal Shape Wild Frog Sex Ratios
Authors: Lambert Max R. , Ezaz Tariq , Skelly David K.
Published: October 2021

Population sex ratio is a key demographic factor that influences population dynamics and persistence. Sex ratios can vary across ontogeny from embryogenesis to death and yet the conditions that shape changes in sex ratio across ontogeny are poorly understood. Here, we address this issue in amphibians, a clade for which sex ratios are generally understudied in wild populations. Ontogenetic sex ratio variation in amphibians is additionally complicated by the ability of individual tadpoles to develop a phenotypic (gonadal) sex opposite their genotypic sex. Because of sex reversal, the genotypic and phenotypic sex ratios of entire cohorts and populations may also contrast. Understanding proximate mechanisms underlying phenotypic sex ratio variation in amphibians is important given the role they play in population biology research and as model species in eco-toxicological research addressing toxicant impacts on sex ratios. While researchers have presumed that departures from a 50:50 sex ratio are due to sex reversal, sex-biased mortality is an alternative explanation that deserves consideration. Here, we use a molecular sexing approach to track genotypic sex ratio changes from egg mass to metamorphosis in two independent green frog (Rana clamitans) populations by assessing the genotypic sex ratios of multiple developmental stages at each breeding pond. Our findings imply that genotypic sex-biased mortality during tadpole development affects phenotypic sex ratio variation at metamorphosis. We also identified sex reversal in metamorphosing cohorts. However, sex reversal plays a relatively minor and inconsistent role in shaping phenotypic sex ratios across the populations we studied. Although we found that sex-biased mortality influences sex ratios within a population, our study cannot say at this time whether sex-biased mortality is responsible for sex ratio variation across populations. Our results illustrate how multiple processes shape sex ratio variation in wild populations and the value of testing assumptions underlying how we understand sex in wild animal populations.
Repeated Sand Fly Bites of Infected BALB/c Mice Enhance the Development of Leishmania Lesions
Authors: Vojtkova Barbora , Frynta Daniel , Spitzova Tatiana , Lestinova Tereza , Votypka Jan , Volf Petr , Sadlova Jovana
Published: October 2021

Sand fly saliva has considerable immunomodulatory effects onLeishmaniainfections in mammalian hosts. Studies on severalLeishmania– sand fly - host combinations have demonstrated that co-inoculation withLeishmaniaparasites enhances pathogenicity, while pre-exposure of hosts to sand fly bites provides significant protection against infection. However, the third scenario, the effect of sand fly saliva on parasite development in hosts infected before exposure to sand flies, remains an understudied aspect ofLeishmania–host–vector interaction. Here we studied the effect of exposure ofL. major-infected BALB/c mice to repeated sand fly bites. Mice infected intradermally with sand fly-derivedLeishmaniawere repeatedly bitten byPhlebotomus duboscqifemales every two weeks. The lesion development was recorded weekly for ten weeks post-infection and parasite load and distribution in various organs were testedpost mortemusing qPCR. Repeated sand fly bites significantly enhanced the development of cutaneous lesions; they developed faster and reached larger size than in unexposed mice. Multiple sand fly bites also increased parasites load in inoculated ears. On the other hand, the distribution of parasites in mice body and their infectiousness to vectors did not differ significantly between groups. Our study provides the first evidence that multiple and repeated exposures of infected BALB/c mice to sand fly bites significantly enhance the progress of local skin infection caused byLeishmania majorand increase tissue parasite load, but do not affect the visceralization of parasites. This finding appeals to adequate protection of infected humans from sand fly bites, not only to prevent transmission but also to prevent enlarged lesions.
The Gut Microbiota of Newborn Calves and Influence of Potential Probiotics on Reducing Diarrheic Disease by Inhibition of Pathogen Colonization
Authors: Fan Peixin , Kim Miju , Liu Grace , Zhai Yuting , Liu Ting , Driver Joseph Danny , Jeong Kwangcheol C.
Published: October 2021

Calf diarrhea is one of the most concerning challenges facing both the dairy and beef cattle industry. Maintaining healthy gut microbiota is essential for preventing gastrointestinal disorders. Here, we observed significantly less bacterial richness in the abnormal feces with watery or hemorrhagic morphology compared to the normal solid feces. The normal solid feces showed high relative abundances of Osllospiraceae, Christensenellaceae, Barnesiella, and Lactobacillus, while the abnormal feces contained more bacterial taxa of Negativicutes, Tyzzerella, Parasutterella, Veillonella, Fusobacterium, and Campylobacter. Healthy calves had extensive bacterial-bacterial correlations, with negative correlation between Lactobacillus and potential diarrheagenic Escherichia coli-Shigella, but not in the abnormal feces. We isolated Lactobacillus species (L. reuteri, L. johnsonii, L. amylovorus, and L. animalis), with L. reuteri being the most abundant, from the healthy gut microbiota. Isolated Lactobacillus strains inhibited pathogenic strains including E. coli K88 and Salmonella Typhimurium. These findings indicate the importance of a diverse gut microbiota in newborn calf’s health and provide multiple potential probiotics that suppress pathogen colonization in the gastrointestinal tract to prevent calf diarrhea.
The Hebb Synapse Before Hebb: Theories of Synaptic Function in Learning and Memory Before Hebb (1949), With a Discussion of the Long-Lost Synaptic Theory of William McDougall
Authors: Brown Richard E. , Bligh Thaddeus W. B. , Garden Jessica F.
Published: October 2021

Since the work of Semon was rediscovered by Schacter in 1978, there has been a renewed interest is searching for the “engram” as the locus of memory in the brain and Hebb’s cell assembly has been equated with Semon’s engram. There have been many theories of memory involving some concept of synaptic change, culminating in the “Hebb Synapse” theory in 1949. However, Hebb said that the idea that any two cells or systems of cells that are repeatedly active at the same time will tend to become “associated,” was not his idea, but an old one. In this manuscript we give an overview of some of the theories of the neural basis of learning and memory before Hebb and describe the synaptic theory of William McDougall, which appears to have been an idea ahead of its time; so far ahead of its time that it was completely ignored by his contemporaries. We conclude by examining some critiques of McDougall’s theory of inhibition and with a short discussion on the fate of neuroscientists whose ideas were neglected when first presented but were accepted as important many decades later.
Endovascular Management of Cerebral Aneurysms of the Posterior Cerebral Artery
Authors: Li Xin-Yu , Li Cong-Hui , Wang Ji-Wei , Liu Jian-Feng , Li Hui , Gao Bu-Lang
Published: October 2021

Purpose: To investigate the safety and efficacy of endovascular embolization of cerebral aneurysms at the P1–P3 segments of the posterior cerebral artery (PCA).

Materials and Methods: Seventy-seven patients with 77 PCA aneurysms who were treated with endovascular embolization were enrolled, including 35 (45.5%) patients with ruptured aneurysms and 42 (54.5%) with unruptured ones. The pretreatment clinical data and aneurysm occlusion status after treatment and at follow-up were analyzed.

Results: All patients were successfully treated endovascularly, including coiling alone in 10 (13.0%) patients, stent-assisted coiling in 18 (23.4%), parent artery occlusion in 25 (32.5%), and pipeline embolization device (PED) in 24 (31.2%). Complete occlusion was achieved in 48 (62.3%) aneurysms, residual neck in 4 (5.2%), and residual aneurysm in the other 25 (32.5%) at the end of embolization. Periprocedural complications occurred in eight patients, including acute thrombosis in seven (9.1%) and intraprocedural subarachnoid hemorrhage in one (1.3%), with the total complication rate of 10.4%. Follow-up was performed in 60 patients (77.9%) for 42 ± 11 months; the mRS score was 0–2 in 55 (91.7%) patients, three in four patients (6.7%), and six in one patient (1.7%). Fifty-three (88.3%) patients (53 aneurysms) had stable or complete occlusion, and seven (11.7%) patients had aneurysm recurrence or residual aneurysm. Among 19 patients treated with PED at follow-up, 15 aneurysms (78.9%) proceeded to complete occlusion while four (21.1%) aneurysms showed residual aneurysm.

Conclusion: Endovascular embolization remains a good choice of treatment with high safety and efficacy for posterior cerebral artery aneurysms.
Peripheral Vestibular Dysfunction Is a Common Occurrence in Children With Non-syndromic and Syndromic Genetic Hearing Loss
Authors: Wang Alicia , Shearer A. Eliot , Zhou Guang Wei , Kenna Margaret , Poe Dennis , Licameli Greg R. , Brodsky Jacob R.
Published: October 2021

Hearing loss (HL) is the most common sensory deficit in humans and is frequently accompanied by peripheral vestibular loss (PVL). While often overlooked, PVL is an important sensory dysfunction that may impair development of motor milestones in children and can have a significant negative impact on quality of life. In addition, many animal and in vitro models of deafness use vestibular hair cells as a proxy to study cochlear hair cells. The extent of vestibular end organ dysfunction associated with genetic pediatric hearing loss is not well-understood. We studied children with a known genetic cause of hearing loss who underwent routine preoperative vestibular testing prior to cochlear implantation between June 2014 and July 2020. Vestibular testing included videonystagmography, rotary chair, video head impulse testing, and/or vestibular evoked myogenic potentials. Etiology of HL was determined through history, physical examination, imaging, laboratory testing, and/or genetic testing. Forty-four children (21 female/23 male) met inclusion criteria; 24 had genetic non-syndromic and 20 had genetic syndromic forms of HL. Mean age at the time of testing was 2.8 ± 3.8 years (range 7 months−17 years). The most common cause of non-syndromic HL was due to mutations in GJB2 (n = 13) followed by MYO15A (3), MYO6 (2), POU3F4 (2), TMPRSS3 (1), CDH23 (1), TMC1 (1), and ESRRB (1). The most common forms of syndromic HL were Usher syndrome (4) and Waardenburg (4), followed by SCID/reticular dysgenesis (3), CHARGE (2), CAPOS (1), Coffin-Siris (1), Jervell and Lange-Nielsen (1), Noonan (1), peroxisome biogenesis disorder (1), Perrault (1), and Trisomy 21 (1). Overall, 23 patients (52%) had PVL. A larger proportion of children with syndromic forms of HL had PVL (12/20, 60%) compared with children with genetic non-syndromic HL (11/24, 46%), though without statistical significant (p = 0.3). The occurrence of PVL varied by affected gene. In conclusion, PVL is a common finding in children with syndromic and non-syndromic genetic HL undergoing vestibular evaluation prior to cochlear implantation. Improved understanding of the molecular physiology of vestibular hair cell dysfunction is important for clinical care as well as research involving vestibular hair cells in model organisms and in vitro models.
Efficacy and Safety of Rotigotine Transdermal Patch on Neuropsychiatric Symptoms of Parkinson's Disease: An Updated Meta-Analysis and Systematic Review
Authors: Yan Junqiang , Ma Hongxia , Liu Anran , Huang Jiarui , Wu Jiannan , Yang Jianxue
Published: October 2021

Objective: The effects of rotigotine transdermal patch (RTG) on the neuropsychiatric symptoms of Parkinson's disease (PD) outcomes remain controversial. The aim of this review was to determine the efficacy and safety of RTG on the neuropsychiatric symptoms of PD.

Methods: In this systematic review and meta-analysis, PubMed, Cochrane Library, EMBASE, and Web of Science were searched for randomized controlled trials comparing RTG and placebo in PD up to May 10, 2021. We analyzed the data using Review Manager 5.2 software. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation Approach. In order to avoid false-positive results caused by random error, we use TSA software for trial sequential analysis (TSA).

Results: We included 10 studies (1,844 patients). The meta-analysis showed that, compared with placebo, RTG can significantly improve the scores for Apathy Scale (MD = −1.68, 95% confidence interval, CI: −2.74 to −0.62, P = 0.002; moderate certainty), Beck Depression Inventory-II (MD = −1.19, 95% CI: −2.26 to −0.11, P = 0.03; moderate certainty), the Non-Motor Symptoms Scale (MD = −3. 66, 95% CI: −4. 30 to −3.01, P < 0.00001; moderate certainty), the sleep/fatigue domains of the Parkinson's Disease Non-motor Symptom Assessment Scale (MD = −2.03, 95% CI: −3.08 to −0.98, P = 0.0001; moderate certainty), the mood/apathy domains of the Non-motor Symptom Scale (MD = −2.48, 95% CI: −4.07 to −0.89, P = 0.002; high certainty), the eight-item Parkinson's Disease Questionnaire (MD = −4. 93, 95% CI: −6.79 to −3.07, P < 0.00001; moderate certainty), and the 39-item Parkinson's Disease Questionnaire (MD = −3.52, 95% CI: −5.25 to −1.79, P < 0.0001; high certainty). However, there was no statistically significant difference on the Snaith–Hamilton Pleasure Scale (MD = −0.12, 95% CI: −0.58 to 0.34, P = 0.61). Our results showed that RTG exerts a positive effect on sleep. According to the TSA, the results implied that, except for the Beck Depression Inventory-II, conclusive evidence have been obtained in the RTG group. It has been proven in our meta-analysis that rotigotine has good safety and tolerability.

Conclusions: RTG can effectively improve the neuropsychiatric symptoms, sleep quality, and quality of life in patients with PD.
Involvement of ADGRV1 Gene in Familial Forms of Genetic Generalized Epilepsy
Authors: Dahawi Maha , Elmagzoub Mohamed S. , A. Ahmed Elhami , Baldassari Sara , Achaz Guillaume , Elmugadam Fatima A. , Abdelgadir Wasma A. , Baulac Stéphanie , Buratti Julien , Abdalla Omer , Gamil Sahar , Alzubeir Maha , Abubaker Rayan , Noé Eric , Elsayed Liena , Ahmed Ammar E. , Leguern Eric
Published: October 2021

Background: Genetic generalized epilepsies (GGE) including childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), and GGE with tonic–clonic seizures alone (GGE-TCS), are common types of epilepsy mostly determined by a polygenic mode of inheritance. Recent studies showed that susceptibility genes for GGE are numerous, and their variants rare, challenging their identification. In this study, we aimed to assess GGE genetic etiology in a Sudanese population.

Methods: We performed whole-exome sequencing (WES) on DNA of 40 patients from 20 Sudanese families with GGE searching for candidate susceptibility variants, which were prioritized by CADD software and functional features of the corresponding gene. We assessed their segregation in 138 individuals and performed genotype–phenotype correlations.

Results: In a family including three sibs with GGE-TCS, we identified a rare missense variant in ADGRV1 encoding an adhesion G protein-coupled receptor V1, which was already involved in the autosomal recessive Usher type C syndrome. In addition, five other ADGRV1 rare missense variants were identified in four additional families and absent from 119 Sudanese controls. In one of these families, an ADGRV1 variant was found at a homozygous state, in a female more severely affected than her heterozygous brother, suggesting a gene dosage effect. In the five families, GGE phenotype was statistically associated with ADGRV1 variants (0R = 0.9 103).

Conclusion: This study highly supports, for the first time, the involvement of ADGRV1 missense variants in familial GGE and that ADGRV1 is a susceptibility gene for CAE/JAE and GGE-TCS phenotypes.
Neuromuscular Age-Related Adjustment of Gait When Moving Upwards and Downwards
Authors: Dewolf Arthur H. , Sylos-Labini Francesca , Cappellini Germana , Zhvansky Dmitry , Willems Patrick A. , Ivanenko Yury , Lacquaniti Francesco
Published: October 2021

Locomotor movements are accommodated to various surface conditions by means of specific locomotor adjustments. This study examined underlying age-related differences in neuromuscular control during level walking and on a positive or negative slope, and during stepping upstairs and downstairs. Ten elderly and eight young adults walked on a treadmill at two different speeds and at three different inclinations (0°, +6°, and −6°). They were also asked to ascend and descend stairs at self-selected speeds. Full body kinematics and surface electromyography of 12 lower-limb muscles were recorded. We compared the intersegmental coordination, muscle activity, and corresponding modifications of spinal motoneuronal output in young and older adults. Despite great similarity between the neuromuscular control of young and older adults, our findings highlight subtle age-related differences in all conditions, potentially reflecting systematic age-related adjustments of the neuromuscular control of locomotion across various support surfaces. The main distinctive feature of walking in older adults is a significantly wider and earlier activation of muscles innervated by the sacral segments. These changes in neuromuscular control are reflected in a reduction or lack of propulsion observed at the end of stance in older adults at different slopes, with the result of a delay in the timing of redirection of the centre-of-mass velocity and of an unanticipated step-to-step transition strategy.
The Association Between Dairy Product Consumption and Asthenozoospermia Risk: A Hospital-Based Case-Control Study
Authors: Wang Xiao-Bin , Wu Qi-Jun , Liu Fang-Hua , Zhang Shuang , Wang Han-Yuan , Guo Ren-Hao , Leng Xu , Du Qiang , Zhao Yu-Hong , Pan Bo-Chen
Published: October 2021

Background: Evidence of an association between dairy product and main related dairy nutrient intake, and the asthenozoospermia risk have been limited and controversial.

Methods: A hospital-based case-control study including 549 men with asthenozoospermia and 581 normozoospermic controls was carried out in the infertility clinics of Shengjing Hospital of China Medical University between June, 2020 and December, 2020. Dietary intake was assessed with a validated food frequency questionnaire. According to the World Health Organization guidelines, semen parameters were collected through masturbation and were measured with WLJY9000 instrument and flow cytometry. The daily intake of dairy products and related nutrients was categorized into three groups according to control distribution, and the lowest tertile was used as the reference category. An unconditional multiple logistic regression was used to estimate the odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) for asthenozoospermia risk.

Results: After adjustment for potential confounders, we found no statistically significant associations between the intake of total dairy products and asthenozoospermia risk (ORT3vs.T1 = 1.19, 95%CI = 0.85–1.67). Additionally, we generated null findings regarding the main related nutrients from dairy, including protein (ORT3vs.T1 = 1.19, 95%CI = 0.85–1.68), fat (ORT3vs.T1 = 1.28, 95%CI = 0.91–1.80), calcium (ORT3vs.T1 = 1.20, 95%CI = 0.85–1.68), saturated fatty acids (ORT3vs.T1 = 1.30, 95%CI = 0.92–1.83), and phosphorous (ORT3vs.T1 = 1.18, 95%CI = 0.84–1.67), and the asthenozoospermia risk. Of note, after stratification by body mass index (BMI), and the saturated fatty acids consumption from dairy was significantly associated with a higher asthenozoospermia risk (ORT3vs.T1 = 1.76, 95%CI = 1.01–3.09) among participants with a BMI below 25 kg/m2.

Conclusion: This study provided limited evidence of an association between the intake of total dairy products and the main related dairy nutrients including protein, fat, calcium, saturated fatty acids, and phosphorus, and the asthenozoospermia risk. Further studies are warranted to confirm our findings in the future.
Assessment of Industrially Produced Trans Fatty Acids in Traditional Dishes, Arabic Sweets, and Market Food Products and Its Risks on Non-communicable Diseases in Lebanon
Authors: Hoteit Maha , Zoghbi Edwina , Rady Alissar , Shankiti Iman , Ibrahim Carla , Al-Jawaldeh Ayoub
Published: October 2021

Industrially produced trans fatty acids (IP-TFAs) are a major dietary contributor to non-communicable diseases worldwide. To address the industrially produced trans fatty acids food sources in Lebanon, a mapping exercise was enrolled between January 2019 and April 2021 to establish a national database. The 2019 survey was a pooled data from five separate sources and had relatively 30 types of traditional dishes. In contrast, the subsequent surveys in 2020 had a sample of 35 types of Arabic sweets and 80 types of market food products. The 2021 survey covered all types of butter and margarine available in the Lebanese markets. Our findings show that about 93% of the products tested in Lebanon, between 2019 and 2021, met the World Health Organization recommendations, while about 7% exceeded the limit. The mean level of the IP-TFAs elaidic and linolelaidic acids in most traditional dishes (0.9%), Arabic sweets (0.6%), butter, and margarine (1.6%), and market foods (0.52%) were relatively low compared with other countries. Although trans fatty acids have a small impact on heart disease mortality in Lebanon, they are unquestionably significant. The persistence of food products with high quantities of trans fatty acids poses a health risk to Lebanese citizens. Fortunately, proper laws in Lebanon can easily remedy this situation.
Predicting the Initial Treatment Response to Transarterial Chemoembolization in Intermediate-Stage Hepatocellular Carcinoma by the Integration of Radiomics and Deep Learning
Authors: Peng Jie , Huang Jinhua , Huang Guijia , Zhang Jing
Published: October 2021

Objectives

We aimed to develop radiology-based models for the preoperative prediction of the initial treatment response to transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) since the integration of radiomics and deep learning (DL) has not been reported for TACE.

Methods

Three hundred and ten intermediate-stage HCC patients who underwent TACE were recruited from three independent medical centers. Based on computed tomography (CT) images, recursive feature elimination (RFE) was used to select the most useful radiomics features. Five radiomics conventional machine learning (cML) models and a DL model were used for training and validation. Mutual correlations between each model were analyzed. The accuracies of integrating clinical variables, cML, and DL models were then evaluated.

Results

Good predictive accuracies were showed across the two cohorts in the five cML models, especially the random forest algorithm (AUC = 0.967 and 0.964, respectively). DL showed high accuracies in the training and validation cohorts (AUC = 0.981 and 0.972, respectively). Significant mutual correlations were revealed between tumor size and the five cML models and DL model (each P < 0.001). The highest accuracies were achieved by integrating DL and the random forest algorithm in the training and validation cohorts (AUC = 0.995 and 0.994, respectively).

Conclusion

The radiomics cML models and DL model showed notable accuracy for predicting the initial response to TACE treatment. Moreover, the integrated model could serve as a novel and accurate method for prediction in intermediate-stage HCC.