bluuebunny/crossref_metadata_2025 huggingface dataset:
In situ assessment of the liver microcirculation in mechanically ventilated rats using sidestream dark-field imaging
Authors: Černý V , Turek Z , Pařízková R
Published: February 2021

Assessment of hepatic microcirculation by on-line visualization
has been impossible for a long time. Sidestream dark-field (SDF)
imaging is a relatively new method allowing direct visualization of
both mucosal microcirculation and surface layers microcirculation
of solid organs using hand-held probe for direct contact with
target tissue. The aim of this study was to evaluate the feasibility
of studying the rat hepatic microcirculation in situ by SDF
imaging. The liver lobes were left in situ, and images were
obtained using SDF imaging on the surface of the liver via upper
midline laparotomy. Images were captured intermittently during
10-sec apnoea and recorded. The microvascular parameters were
compared with previous validation studies. Clear high contrast
SDF images were successfully obtained. Quantitative analysis
revealed a mean FSD (functional sinusoidal density) of 402±15
cm/cm2, a sinusoidal diameter of 10.2±0.5 μm and postsinusoidal
venular diameter of 33.9±13 μm. SDF imaging is a suitable
noninvasive method for accurate quantification of the basic
microcirculatory parameters of the liver in situ without a need to
exteriorize the liver lobes. This method seems to be applicable in
animal studies with possibility to use SDF imaging also
intraoperatively, providing unique opportunity to study liver
microcirculation during various experimental and clinical settings.
Analisis Quality of Service Routing MPLS OSPF Terhadap Gangguan Link Failure
Authors: Budiman Arief , Sucipto Adi , Dian Anas Rosyid
Published: February 2021

Penerapan metode routing dalam kegiatan yang menggunakan jaringan komputer dalam lingkup besar diperlukan oleh administrator jaringan, agar dapat melakukan pengoptimalan lauyanan jaringan. Pemilihan metode routing akan membantu dalam mewujudkan perkembangan jaringan yang baik, namun dibutuhkan metode routing yang memiliki kinerja bagus tidak hanya dalam kondisi jaringan yang baik tapi juga pada kondisi jaringan yang mengalami gangguan.Salah satu metode yang memiliki kemampuan yang baik dalam jaringan yang semakin besar adalah Multiprotocol Lable Switching (MPLS), dan dapat dikombinasikan dengan protokol Open Shortest Path First (OSPF). Tujuan penerapan metode MPLS OSPF adalah untuk melihat bagaimana metode tersebut melakukan pengiriman data dalam berbagai kondisi. Tentunya agar membuat jaringan menjadi lebih baik kinerjanya dalam mengirimkan paket data, dengan mencari rute atau jalur yang terbaik pada topologi jaringanPenelitian ini akan mengimplementasikan metode routing MPLS OSPF kedalam beberapa bentuk topologi jaringan berupa prototipe, dengan memberikan skenario pengujian berupa gangguan pemutusan link atau link failure. Pengujian dianalisa menggunakan tools Wireshark.Hasil yang didapat pada penelitian ini menunjukkan bahwa metode routting MPLS OSPF menunjukkan hasil yang baik dalam menangani gangguan, dengan nilai parameter QoS yang tergolong dalam kategori baik. Nilai throughput didapat mengalami penurunan besar nilai pada kondisi gangguan link failure.
Frostid: Aplikasi Pelaporan Jalan Banjir Berbasis Warga Pada Navigasi Berlalu Lintas
Authors: Mandyartha Eka Prakarsa , Faroqi Asif
Published: February 2021

Di Indonesia, banjir merupakan masalah utama yang dialami saat musim penghujan setiap tahunnya. Jalan banjir membawa dampak kerugian kepada pengendara kendaraan bermotor misalnya dapat menyebabkan kerusakan mesin, serta penyebab utama terjadinya karat pada kendaraan bermotor. Oleh karena itu, diperlukan upaya peringatan dini, berupa sistem pelaporan banjir, yang memberikan informasi kepada pengendara sehingga mereka dapat mengantisipasi jalan banjir. Pada penelitian ini diusulkan aplikasi pelaporan jalan banjir secara online yang berfokus pada peta navigasi berlalu-lintas untuk pengguna jalan. Aplikasi ini melibatkan partisipasi warga secara aktif (crowdsourcing) yaitu pengumpulan dan penyebaran informasi banjir dilakukan oleh kerumunan (crowd) warga dan dinamakan dengan Flooded Road Reporting System Indonesia (Frostid). Aplikasi mobile Frostid dikembangkan dalam lingkungan sistem operasi Android. Pendekatan pengembangan agile Mobile-D diterapkan. Penerimaan pengguna terhadap aplikasi dievaluasi menggunakan model TAM (Technology Acceptance Model). Metriks yang dievaluasi meliputi kegunaan yang dirasakan, kemudahan pengunaan yang dirasakan, sikap pengguna terhadap aplikasi, dan niat untuk menggunakan. Berdasarkan hasil analisis statistik deskriptif hasil pengujian penerimaan pengguna, dapat disimpulkan bahwa konsep crowdsourcing dalam aplikasi pelaporan jalan banjir diterima oleh pengguna. Kesediaan pengguna untuk merekomendasikan kepada orang lain, juga selaras dengan konsep crowdsourcing, dimana nilai dari aplikasi akan optimal jika banyak pengguna yang berkontribusi.
Analisis Loyalitas Agen Biasa dan Agenstok Menggunakan Model RFM (Recency,Frequency, Monetery) dan Algoritma K-Medoids pada BC 4 HPAI Pekanbaru
Authors: Monalisa Siti , Erza Imelda
Published: February 2021

PT.Herbal Penawar Alwahida Indonesia (HPAI) merupakan perusahaan bisnis halal network di Indonesia yang fokus pada produk-produk herbal. Salah satu BC (Bussines center) HPAI yang terdapat di pekanbaru yaitu,BC 4 HPAI beralamat dijalan Melati III No.4 Bina Widya,Panam. Berdasarkan obeservasi yang dilakukan, data transaksi pelanggan pada tahun 2019 di BC 4 mencapai 1000-2000 transaksi setiap bulannya, yang terdiri dari data agen biasa dan agenstok. Berdasarkan wawancara dengan owner BC 4 HPAI Pekanbaru, masalah yang terjadi yaitu pihak BC 4 HPAI belum bisa mendapatkan informasi dari setiap data agen biasa dan agen stok,mana pelanggan yang potensial dan loyal terhadap perusahaan. Sehingga menyebabkan pihak BC akan sulit untuk menentukan strategi pemasaran yang tepat dalam memanfaatkan kesempatan atau peluang yang ada dalam pemasaran. Mengatasi permasalahan tersebut, penelitian  ini menerapkan strategi customer Relationship Management (CRM) yaitu menggunakan Metode RFM untuk mengetahui karakteristik atau prilaku agen biasa dan agenstok kemudian Clustering menggunakan Agoritma K-Medoids untuk pengelompokan sesuai kemiripan karakteristik agenbiasa dan agenstok yang telah didapat sebelumnya. Dengan percobaan 2 cluster sampai dengan 7 cluster, menghasilkan 2 Cluster Terbaik agen biasa dan 3 Cluster Terbaik agenstok berdasarkan DBI (Davies Bouldin Index). Dengan masing-masing nilai DBI terbaik 0.228 agen biasa dan 0.234 agenstok. Hasil tertinggi 2 cluster agen biasa berada pada cluster 1 dengan tipe pelanggan Superstar yang memiliki 472 customer loyal. dan hasil tertinggi dari 3 cluster agenstok berada pada cluster 3 dengan tipe pelanggan Superstar yang memiliki 60 customer loyal.
Klasifikasi Citra Game Batu Kertas Gunting Menggunakan Convolutional Neural Network
Authors: Naufal Mohammad Farid , Huda Solichul , Budilaksono Aryo , Yustisia Wisnu Aria , Arius Astri Agustina , Miranti Fania Alya , Prayoga Farrel Arghya Tito
Published: February 2021

Permainan batu, gunting, dan kertas sangat populer di seluruh dunia. Permainan ini biasanya dimainkan saat sedang berkumpul untuk mengundi ataupun hanya bermain untuk mengetahui yang menang dan yang kalah. Namun, perkembangan zaman dan teknologi mengakibatkan orang dapat berkumpul secara virtual. Untuk bisa melakukan permainan ini secara virtual, penelitian ini membuat model klasifikasi citra untuk membedakan objek tangan yang menunjuk batu, kertas, dan gunting. Performa metode klasifikasi merupakan hal yang harus diperhatikan dalam kasus ini. Salah satu metode klasifikasi citra yang populer adalah Convolutional Neural Network (CNN). CNN adalah salah satu jenis neural network yang biasa digunakan pada data klasifikasi citra. CNN terinspirasi dari jaringan syaraf manusia. Algoritma ini memiliki 3 tahapan yang dipakai, yaitu convolutional layer, pooling layer, dan fully connected layer. Uji coba 5-Fold cross validation klasifikasi objek tangan yang menunjuk citra batu, kertas, dan gunting menggunakan CNN pada penelitian ini menghasilkan rata-rata akurasi sebesar 97.66%.
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Authors: Vivsyana Inna
Published: February 2021

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Authors: Ostrovyk Dmytro
Published: February 2021

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Social and Political Activity of Peasantry in 1905-1907
Authors: Pasichna Yulia , Berestovyi Andriy
Published: February 2021

By the beginning of 1905, a crisis was impending in all spheres of Russian society. Agrarian problems caused by objective and subjective factors prompted the peasantry to declare their principled positions on solving agrarian problems. The period of 1905-1907 is a vivid example of the struggle of the driving independent force of the revolution, the peasantry, for carrying out an agrarian revolution. Goal: To study the social and political activity of the Russian peasantry in 1905-1907. During 1905-1907, Russia was unsettled by a tide of the social and political activity of the peasantry. The protests, which began in Poltava and Kharkiv Provinces, spread throughout the state and in a short time became uncontrollable by the authorities. Scholars give different figures for the total number of peasant unrests, but despite these differences, it is not difficult to determine that during 1905-1907 peasant unrests covered up to 50% of all European Russia in different periods of peasants� revolutionary activity. Manifestations of the social and political activity of the peasantry can be observed in early 1905 in the spontaneous seizure of landowners� estates, later the peasants started to pillage, plunder, damage agricultural implements, go on strikes, and cut down forests without permission. The manifestations of early 1905 did not become a novelty for Russian society, but 1905 � 1907 were a test for the power structures of the state. After all, the peasantry, although they still �believed in the tsar�, reacted to the unsystematic actions of the power in solving agrarian problems by radical actions and the large-scale protests.
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Authors: Lasinska Marianna
Published: February 2021

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Authors: Kryvosheia Ihor
Published: February 2021

[���.]: Marek Melnyk (Red.). Polacy i Ukraincy: Komunikacja-dialog-pojednanie. Biblioteka Tradycji Nr. CLXIX. Rzym-Krakow: Wydawnictwo Collegium Columbium; UWM, 2020. 254 s.
Innate Immune Responses of Galleria mellonella to Mycobacterium bovis BCG Challenge Identified Using Proteomic and Molecular Approaches
Authors: Asai Masanori , Sheehan Gerard , Li Yanwen , Robertson Brian D. , Kavanagh Kevin , Langford Paul R. , Newton Sandra M.
Published: February 2021

The larvae of the insect Galleria mellonella, have recently been established as a non-mammalian infection model for the Mycobacterium tuberculosis complex (MTBC). To gain further insight into the potential of this model, we applied proteomic (label-free quantification) and transcriptomic (gene expression) approaches to characterise the innate immune response of G. mellonella to infection with Mycobacterium bovis BCG lux over a 168 h time course. Proteomic analysis of the haemolymph from infected larvae revealed distinct changes in the proteome at all time points (4, 48, 168 h). Reverse transcriptase quantitative PCR confirmed induction of five genes (gloverin, cecropin, IMPI, hemolin, and Hdd11), which encoded proteins found to be differentially abundant from the proteomic analysis. However, the trend between gene expression and protein abundance were largely inconsistent (20%). Overall, the data are in agreement with previous phenotypic observations such as haemocyte internalization of mycobacterial bacilli (hemolin/β-actin), formation of granuloma-like structures (Hdd11), and melanization (phenoloxidase activating enzyme 3 and serpins). Furthermore, similarities in immune expression in G. mellonella, mouse, zebrafish and in vitro cell-line models of tuberculosis infection were also identified for the mechanism of phagocytosis (β-actin). Cecropins (antimicrobial peptides), which share the same α-helical motif as a highly potent peptide expressed in humans (h-CAP-18), were induced in G. mellonella in response to infection, giving insight into a potential starting point for novel antimycobacterial agents. We believe that these novel insights into the innate immune response further contribute to the validation of this cost-effective and ethically acceptable insect model to study members of the MTBC.
Radiation Exposure Reduction and Patient Outcome by Using Very Low Frame Rate Fluoroscopy Protocol (3.8 + 7.5 fps) During Percutaneous Coronary Intervention
Authors: Gupta Ankush , Chhikara Sanya , Vijayvergiya Rajesh , Barwad Parag , Prasad Krishna , Datta Rajat , Mahesh Nalin K. , Maurya Preetika , Singh Navreet
Published: February 2021

Objectives: In this study, we intend to analyze the feasibility and efficacy of very low frame rate fluoroscopy (VLFF) protocol using a combination of 3.8 and 7.5 fps while performing Percutaneous Coronary Intervention (PCI).

Methods: A retrospective cohort including 193 patients undergoing PCI under the VLFF protocol (Post-VLFF group) was compared with a retrospective cohort of 133 patients, who underwent PCI prior to implementation of VLFF protocol (Pre-VLFF group). In the Pre-VLFF group, all PCIs were performed using fluoroscopy frame rate of 15 fps. In the Post-VLFF group, 3.8 fps was used to guide catheter engagement, coronary lesion wiring, pre-and post-dilation, and 7.5 fps was used for lesion assessment and stent placement. Increasing use of fluoroscopic storage in place of cineangiography was also encouraged. Cine acquisition in both groups was performed at 15 fps. Primary endpoint was radiation exposure measured by Air Kerma. Secondary endpoints were procedure related outcomes and patient related outcomes (Major Adverse Cardiac Events including all-cause mortality, Target Lesion Failure, Myocardial Infarction, and Stroke).

RESULTS: Post-VLFF group showed 74.7% reduction in Air Kerma as compared to Pre-VLFF group (433 ± 27 mGy vs. 1,714 ± 140 mGy; p < 0.0001), with no increase in the fluoroscopy time (15.38 ± 0.98 min Post-VLFF vs. 17.06 ± 1.29 min Pre-VLFF; p = 0.529) and contrast volume (116.5 ± 4.9 ml Post-VLFF vs. 116.7 ± 6 ml Pre-VLFF; p = 0.700). Both groups had comparable procedural success and complications rates as well as incidence of MACE.

Conclusions: The very low frame rate fluoroscopy protocol is a feasible, effective, and safe method to significantly reduce the radiation exposure during PCI without any compromise on procedural and patient outcomes.
Identification of Maturity-Onset Diabetes of the Young Caused by Mutation in FOXM1 via Whole-Exome Sequencing in Northern China
Authors: Zhong Liang , Zhao Zengyi , Hu Qingshan , Li Yang , Zhao Weili , Li Chuang , Xu Yunqiang , Rong Ruijuan , Zhang Jing , Zhang Zifeng , Li Nan , Liu Zanchao
Published: February 2021

Diabetes mellitus is a highly heterogeneous disorder encompassing different types with particular clinical manifestations, while maturity-onset diabetes of the young (MODY) is an early-onset monogenenic diabetes. Most genetic predisposition of MODY has been identified in European and American populations. A large number of Chinese individuals are misdiagnosed due to defects of unknown genes. In this study, we analyzed the genetic and clinical characteristics of the Northern China. A total of 200 diabetic patients, including 10 suspected MODY subjects, were enrolled, and the mutational analysis of monogenic genes was performed by whole-exome sequencing and confirmed by familial information and Sanger sequencing. We found that clinical features and genetic characteristics have varied widely between MODY and other diabetic subjects in Northern China. FOXM1, a key molecule in the proliferation of pancreatic β-cells, has a rare mutation rs535471991, which leads to instability within the phosphorylated domain that impairs its function. Our findings indicate that FOXM1 may play a critical role in MODY, which could reduce the misdiagnose rate and provide promising therapy for MODY patients.
Ethnicity/Race and Age-Specific Variations of Serum AMH in Women—A Review
Authors: Kotlyar Alexander M. , Seifer David B.
Published: February 2021

Purpose of Review

In this review, we summarize ethnic/race- and age-related variation in AMH and discuss the underpinnings behind these differences.

Recent findings

Anti-mullerian hormone (AMH) has become a widely used method of ovarian reserve testing over the last 15 years. Numerous studies have shown substantial ethnic/race and age-related differences. When compared to age-matched Caucasian women, AMH levels tend to be lower in black and Hispanic women. Chinese women tend to have significantly greater AMH levels prior to age 25 than Caucasian women. When considering subpopulations within ethnicities, at least one study noted lower AMH levels among Maya women compared to other Hispanic women. Age exhibits a positive trend with AMH up until at least 25 years of age with a consistent decline after 34 years of age extending to menopause.

AMH levels are highly variable among ethnicities and race with higher age-matched levels typically seen in Caucasian women. Age does not exhibit a consistent linear relationship with AMH, but a consistent decline is seen starting in the third decade of life and proceeding to menopause.
Tri-Spine Horseshoe Crab Aquaculture, Ranching and Stock Enhancement: Perspectives and Challenges
Authors: Xu Peng , Bai Haiwei , Xie Xiaoyong , Wang Chun-Chieh , Huang Xing , Wang Xueping , Zhang Mingming , Ye Zhenyu , Zhu Junhua , Zhen Wenquan , Cheung Siu Gin , Shin Paul K. S. , Kwan Kit Yue
Published: February 2021

As a well-known example of “living fossil,” horseshoe crabs are ecologically significant macroinvertebrates in coastal and estuarine ecosystems. The tri-spine horseshoe crab, Tachypleus tridentatus, has been widely utilized for Tachypleus amebocyte lysate production and food consumption since the 1980s, which led to considerable population declines along the west coast of the Pacific Ocean. The declining horseshoe crab population is expected to have ecological and social impacts. Stock enhancement through captive rearing of juveniles is cited as an important alternative to repopulate the native T. tridentatus, which in turn supports sustainable resource utilization and research activities. The hatchery production techniques for this species have gradually developed following the mass culture efforts in Japan since the late 1980s. However, the previous studies have primarily concerned the feed types and husbandry conditions to maximize the growth and survival of the juveniles. Little is known about the practicability and effectiveness of releasing large numbers of hatchery-bred individuals through releasing programs. In this review, we (1) summarize the available captive breeding and rearing techniques, (2) discuss the release strategies that could potentially improve the survival of released juveniles, and (3) identify the future opportunities and challenges in establishing technical frameworks to support responsible stock enhancement programs for T. tridentatus. The information should benefit future horseshoe crab fisheries management efforts in the attempt to restore the severely depleted populations.
Knee Cartilage Thickness Differs Alongside Ages: A 3-T Magnetic Resonance Research Upon 2,481 Subjects via Deep Learning
Authors: Si Liping , Xuan Kai , Zhong Jingyu , Huo Jiayu , Xing Yue , Geng Jia , Hu Yangfan , Zhang Huan , Wang Qian , Yao Weiwu
Published: February 2021

Background: It was difficult to distinguish the cartilage thinning of an entire knee joint and to track the evolution of cartilage morphology alongside ages in the general population, which was of great significance for studying osteoarthritis until big imaging data and artificial intelligence are fused. The purposes of our study are (1) to explore the cartilage thickness in anatomical regions of the knee joint among a large collection of healthy knees, and (2) to investigate the relationship between the thinning pattern of the cartilages and the increasing ages.

Methods: In this retrospective study, 2,481 healthy knees (subjects ranging from 15 to 64 years old, mean age: 35 ± 10 years) were recruited. With magnetic resonance images of knees acquired on a 3-T superconducting scanner, we automatically and precisely segmented the cartilage via deep learning and calculated the cartilage thickness in 14 anatomical regions. The thickness readings were compared using ANOVA by considering the factors of age, sex, and side. We further tracked the relationship between the thinning pattern of the cartilage thickness and the increasing ages by regression analysis.

Results: The cartilage thickness was always thicker in the femur than corresponding regions in the tibia (p < 0.05). Regression analysis suggested cartilage thinning alongside ages in all regions (p < 0.05) except for medial and lateral anterior tibia in both females and males (p > 0.05). The thinning speed of men was faster than women in medial anterior and lateral anterior femur, yet slower in the medial patella (p < 0.05).

Conclusion: We established the calculation method of cartilage thickness using big data and deep learning. We demonstrated that cartilage thickness differed across individual regions in the knee joint. Cartilage thinning alongside ages was identified, and the thinning pattern was consistent in the tibia while inconsistent in patellar and femoral between sexes. These findings provide a potential reference to detect cartilage anomaly.
Determinants of Frequent Attendance in Primary Care. A Systematic Review of Longitudinal Studies
Authors: Hajek André , Kretzler Benedikt , König Hans-Helmut
Published: February 2021

Introduction: There is a lack of a systematic review synthesizing longitudinal studies investigating the determinants of frequent attendance in primary care. The goal of our systematic review was to fill this gap in knowledge.

Methods: Three electronic databases (Medline, PsycINFO, and CINAHL) were searched. Longitudinal observational studies analyzing the predictors of frequent attendance in primary care were included. Data extraction covered methods, sample characteristics, and main findings. Selection of the studies, extracting the data and evaluation of study quality was performed by two reviewers. In the results section, the determinants of frequent attendance were presented based on the (extended) Andersen model.

Results: In total, 11 longitudinal studies have been included in our systematic review. The majority of studies showed that frequent attendance was positively associated with the predisposing characteristics lower age, and unemployment. Moreover, it was mainly not associated with enabling resources. Most of the studies showed that need factors, and in particular worse self-rated health, lower physical functioning and physical illnesses were associated with an increased likelihood of frequent attendance. While most studies were of good quality, several of the included studies did not perform sensitivity analysis or described how they dealt with missing data.

Discussion: Our systematic review showed that particularly lower age, unemployment and need factors are associated with the likelihood of becoming a frequent attender. Enabling resources are mainly not associated with the outcome measure. Future research should concentrate on the determinants of persistent frequent attendance due to the high economic burden associated with it.
Deficiency in the Screening Process of Fabry Disease: Analysis of Chronic Kidney Patients Not on Dialysis
Authors: Battaglia Yuri , Fiorini Fulvio , Azzini Cristiano , Esposito Pasquale , De vito Alessandro , Granata Antonio , Storari Alda , Mignani Renzo
Published: February 2021

Fabry Disease (FD), a rare and progressive, X-linked lysosomal storage disorder, is caused by mutations in the α-galactosidase A (GLA) gene which leads to enzymatic deficiency of GLA. Misdiagnosed and undiagnosed FD cases are common for the variable FD phenotype, ranging from asymptomatic and/or impairment of single organs, which is typically seen in females and in patients with late-onset mutation, to multiple organ disease, which is frequently found in males with classic GLA mutation. Consequently, for an early diagnosis and an efficient treatment of FD, three different strategies of screening, new-born screening, high-risk screening and familiar screening, have been conducted. However, most of FD screening in the CKD population has been carried out in hemodialysis patients and kidney transplant recipients, for whom the renal damage is already irreversible, so the effectiveness of enzymatic replacement therapy is limited and delayed therapeutic intervention results in worse long-term outcomes. This review investigates the actual strategies of screening initiatives for the identification of FD, examining in detail those performed in CKD patients not on dialysis.
Immune Profiling of Parkinson’s Disease Revealed Its Association With a Subset of Infiltrating Cells and Signature Genes
Authors: Zhang Xi , Shao Zhihua , Xu Sutong , Liu Qiulu , Liu Chenming , Luo Yuping , Jin Lingjing , Li Siguang
Published: February 2021

Parkinson’s disease (PD) is an age-related and second most common neurodegenerative disorder. In recent years, increasing evidence revealed that peripheral immune cells might be able to infiltrate into brain tissues, which could arouse neuroinflammation and aggravate neurodegeneration. This study aimed to illuminate the landscape of peripheral immune cells and signature genes associated with immune infiltration in PD. Several transcriptomic datasets of substantia nigra (SN) from the Gene Expression Omnibus (GEO) database were separately collected as training cohort, testing cohort, and external validation cohort. The immunoscore of each sample calculated by single-sample gene set enrichment analysis was used to reflect the peripheral immune cell infiltration and to identify the differential immune cell types between PD and healthy participants. According to receiver operating characteristic (ROC) curve analysis, the immunoscore achieved an overall accuracy of the area under the curve (AUC) = 0.883 in the testing cohort, respectively. The immunoscore displayed good performance in the external validation cohort with an AUC of 0.745. The correlation analysis and logistic regression analysis were used to analyze the correlation between immune cells and PD, and mast cell was identified most associated with the occurrence of PD. Additionally, increased mast cells were also observed in our in vivo PD model. Weighted gene co-expression network analysis (WGCNA) was used to selected module genes related to a mast cell. The least absolute shrinkage and selection operator (LASSO) analysis and random-forest analysis were used to analyze module genes, and two hub genes RBM3 and AGTR1 were identified as associated with mast cells in the training cohort. The expression levels of RBM3 and AGTR1 in these cohorts and PD models revealed that these hub genes were significantly downregulated in PD. Moreover, the expression trend of the aforementioned two genes differed in mast cells and dopaminergic (DA) neurons. In conclusion, this study not only exhibited a landscape of immune infiltrating patterns in PD but also identified mast cells and two hub genes associated with the occurrence of PD, which provided potential therapeutic targets for PD patients (PDs).
Mesenchymal Stem Cell-Based Therapy for Stroke: Current Understanding and Challenges
Authors: Li Weifeng , Shi Linli , Hu Bei , Hong Yimei , Zhang Hao , Li Xin , Zhang Yuelin
Published: February 2021

Stroke, the most prevalent cerebrovascular disease, causes serious loss of neurological function and is the leading cause of morbidity and mortality worldwide. Despite advances in pharmacological and surgical therapy, treatment for functional rehabilitation following stroke is limited with a consequent serious impact on quality of life. Over the past decades, mesenchymal stem cell (MSCs)-based therapy has emerged as a novel strategy for various diseases including stroke due to their unique properties that include easy isolation, multipotent differentiation potential and strong paracrine capacity. Although MSCs have shown promising results in the treatment of stroke, there remain many challenges to overcome prior to their therapeutic application. In this review, we focus on the following issues: the scientific data from preclinical studies and clinical trials of MSCs in the treatment of stroke; the potential mechanisms underlying MSC-based therapy for stroke; the challenges related to the timing and delivery of MSCs and MSC senescence.
Intracranial Bleeding After Reperfusion Therapy in Acute Ischemic Stroke
Authors: Charbonnier Guillaume , Bonnet Louise , Biondi Alessandra , Moulin Thierry
Published: February 2021

Intracranial hemorrhage is one of the most feared complications following brain infarct. Ischemic tissues have a natural tendency to bleed. Moreover, the first recanalization trials using intravenous thrombolysis have shown an increase in mild to severe intracranial hemorrhage. Symptomatic intracerebral hemorrhage is strongly associated with poor outcomes and is an important factor in recanalization decisions. Stroke physicians have to weigh the potential benefit of recanalization therapies, first, with different risks of intracranial hemorrhage described in randomized controlled trials, and second with numerous risk markers that have been found to be associated with intracranial hemorrhage in retrospective series. These decisions have become quite complex with different intravenous thrombolytics and mechanical thrombectomy. This review aims to outline some elements of the pathophysiological mechanisms and classifications, describe most of the risk factors identified for each reperfusion therapy, and finally suggest future research directions that could help physicians dealing with these complications.
Predisposing Factors for Sexual Dysfunction in Multiple Sclerosis
Authors: Altmann Patrick , Leutmezer Fritz , Leithner Katharina , Monschein Tobias , Ponleitner Markus , Stattmann Miranda , Rommer Paulus Stefan , Zrzavy Tobias , Zulehner Gudrun , Berek Klaus , Berger Thomas , Bsteh Gabriel
Published: February 2021

Sexual dysfunction (SD) in people with multiple sclerosis (pwMS) has a detrimental impact on individual health-related quality of life (HRQoL). It is not clear whether SD in multiple sclerosis (MS) is an independent symptom or merely a byproduct of other symptoms such as depression or anxiety. This cross-sectional study of 93 pwMS determines risk factors for SD in MS based on prevalence, HRQoL, and associated disease outcomes. Diagnosis of SD was determined based on the Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19) and correlated with physical disability (measured by Expanded Disability Status scale, EDSS), depression and anxiety [Hospital Anxiety and Depression Scale (HADS)], and HRQoL [Multiple Sclerosis Quality of Life-54 (MSQoL-54)]. Multivariate regression models were performed to determine independent risk factors for SD in pwMS. Almost half of the participants in this study (46%) reported SD. HRQoL was significantly poorer in patients with MS suffering from SD (median [IQR] MSQoL-54 scores: physical subscale 52 [41–68] vs. 81 [69–89], p < 0.001; mental subscale 50 [38–82] vs. 86 [70–89], p < 0.001). In the multivariate model, EDSS was the only independent risk factor for SD (OR 18.1 for EDSS ≥4 [95% CI 3.3–31.4, p < 0.001]), while depression and anxiety were not. We conclude that the risk for SD is growing with increasing EDSS and is independent of depression or anxiety. Screening for SD becomes particularly relevant in patients with growing disability.
Different Neural Mechanisms Underlie Non-habitual Honesty and Non-habitual Cheating
Authors: Speer Sebastian P. H. , Smidts Ale , Boksem Maarten A. S.
Published: February 2021

There is a long-standing debate regarding the cognitive nature of (dis)honesty: Is honesty an automatic response or does it require willpower in the form of cognitive control in order to override an automatic dishonest response. In a recent study (Speer et al., 2020), we proposed a reconciliation of these opposing views by showing that activity in areas associated with cognitive control, particularly the inferior frontal gyrus (IFG), helped dishonest participants to be honest, whereas it enabled cheating for honest participants. These findings suggest that cognitive control is not needed to be honest or dishonest per se but that it depends on an individual’s moral default. However, while our findings provided insights into the role of cognitive control in overriding a moral default, they did not reveal whether overriding honest default behavior (non-habitual dishonesty) is the same as overriding dishonest default behavior (non-habitual honesty) at the neural level. This speaks to the question as to whether cognitive control mechanisms are domain-general or may be context specific. To address this, we applied multivariate pattern analysis to compare neural patterns of non-habitual honesty to non-habitual dishonesty. We found that these choices are differently encoded in the IFG, suggesting that engaging cognitive control to follow the norm (that cheating is wrong) fundamentally differs from applying control to violate this norm.
Food Oral Processing—An Industry Perspective
Authors: Devezeaux De Lavergne Marine , Young Ashley K. , Engmann Jan , Hartmann Christoph
Published: February 2021

We illustrate how scientific understanding of Food Oral Processing enables food product development with specific benefits for several target populations. in vivo, in vitro, and in silico approaches are discussed in the context of their ability to quantify oral processing from the molecular to the macroscopic scale. Based on this understanding, food structures with enhanced performance in terms of hedonic and nutritional properties as well as appropriateness for age and certain medical conditions can be developed. We also discuss current gaps and highlight development opportunities from an industry perspective.
Case Report: Significant Response to Immune Checkpoint Inhibitor Camrelizumab in a Heavily Pretreated Advanced ER+/HER2− Breast Cancer Patient With High Tumor Mutational Burden
Authors: Wang Rong , Yang Yuchen , Ye Wei-Wu , Xiang Jianxing , Chen Songan , Zou Wei-Bin , Wang Xiao-Jia , Chen Tianhui , Cao Wen-Ming
Published: February 2021

Endocrine treatment plus CDK4/6 inhibitors have become standard of care for estrogen receptor positive (ER+) breast cancer. Although immune checkpoint inhibitors (ICIs) have shown promising antitumor activity in a variety of cancer types, only limited success has been achieved for metastatic breast cancer (mBC) patients, especially the ER+ subtype, which usually exhibit lower tumor mutation burden (TMB) compared with other subtypes and therefore perceived as immunologically quiescent. Here we present a case of an ER+/HER2- but TMB-high mBC patient who had significant response to combination therapy with anti-PD-1 antibody camrelizumab and vinorelbine and obtained partial response (PR) with a progression-free survival (PFS) of 5 months after failure of multiple lines of therapy. Our case indicates that TMB may serve as a potential biomarker in immunotherapy selection for normally immunologically “cold” tumors such as ER+ mBC, also molecular monitoring during the whole treatment course plays an important role in patient management.
Artificial Intelligence for Personalized Medicine in Thyroid Cancer: Current Status and Future Perspectives
Authors: Li Ling-Rui , Du Bo , Liu Han-Qing , Chen Chuang
Published: February 2021

Thyroid cancers (TC) have increasingly been detected following advances in diagnostic methods. Risk stratification guided by refined information becomes a crucial step toward the goal of personalized medicine. The diagnosis of TC mainly relies on imaging analysis, but visual examination may not reveal much information and not enable comprehensive analysis. Artificial intelligence (AI) is a technology used to extract and quantify key image information by simulating complex human functions. This latent, precise information contributes to stratify TC on the distinct risk and drives tailored management to transit from the surface (population-based) to a point (individual-based). In this review, we started with several challenges regarding personalized care in TC, for example, inconsistent rating ability of ultrasound physicians, uncertainty in cytopathological diagnosis, difficulty in discriminating follicular neoplasms, and inaccurate prognostication. We then analyzed and summarized the advances of AI to extract and analyze morphological, textural, and molecular features to reveal the ground truth of TC. Consequently, their combination with AI technology will make individual medical strategies possible.
Identification of an Immune Gene-Associated Prognostic Signature and Its Association With a Poor Prognosis in Gastric Cancer Patients
Authors: Guan Xiaoqing , Xu Zhi-Yuan , Chen Runzhe , Qin Jiang-Jiang , Cheng Xiang-Dong
Published: February 2021

The immune response plays a critical role in gastric cancer (GC) development, metastasis, and treatment. A better understanding of the tumor-immune system interactions in gastric cancer may provide promising diagnostic, prognostic, and therapeutic biomarkers for patients with this disease. In the present study, we aimed to identify a prognostic signature of GC through a comprehensive bioinformatics analysis on the tumor-immune interactions as well as the molecular characteristics. We firstly identified two immunophenotypes and immunological characteristics by employing multiple algorithms, such as the single sample Gene Sets Enrichment Analysis and Cell type Identification By Estimating Relative Subsets of RNA Transcripts. Next, we developed a six-immune-gene signature as a promising independent prognostic biomarker for GC using Lasso Cox regression and verified it via the external validation set and systematically correlated the immune signature with GC clinicopathologic features and genomic characteristics. Finally, a nomogram was successfully constructed based on the immune signature and clinical characteristics and showed a high potential for GC prognosis prediction. This study may shed light on the treatment strategies for GC patients from the perspective of immunology.
Caregiver Report of Executive Functioning in Adolescent Females With Anorexia Nervosa or Autism Spectrum Disorder
Authors: Timko C. Alix , Herrington John D. , Bhattacharya Anushua , Kuschner Emily S. , Yerys Benjamin E.
Published: February 2021

Current literature suggesting a shared endophenotype between individuals with anorexia nervosa (AN) and autism spectrum disorder (ASD) related to executive functioning (EF) has several limitations: performance-based instead of ecologically valid measures of set-shifting are used, lack of comparisons between same-sex groups, and reliance on adult samples only. This was the first study directly comparing female youth with ASD to female youth with AN using an ecologically valid measure of EF. A secondary data analysis combined caregiver-reported EF on the Behavior Rating Inventory of Executive Functioning (BRIEF) for 22 female adolescent youth with AN and 29 female adolescent youth with ASD. EF in each group was compared to population norms, and EF was compared between groups. Compared to population norms, adolescents with AN had elevated scores on shift, initiate, and emotional control scales, and adolescents with ASD had elevated scores on all scales of the BRIEF and were more likely to have scores in the clinical range. There were significant differences between groups on all but three scales. The cognitive profiles and clinical scores of AN females were not comparable to those of ASD females. The findings reveal a clear clinical impairment in females with ASD but not in females with AN. The results do not support the hypothesis of similar real-world EF profiles between these groups. The results encourage further exploration into the similarities and distinctions between these two disorders.
Predicting Uncertain Multi-Dimensional Adulthood Outcomes From Childhood and Adolescent Data in People Referred to Autism Services
Authors: Forbes Gordon , Lord Catherine , Elias Rebecca , Pickles Andrew
Published: February 2021

Introduction

Autism spectrum disorder is a highly heterogeneous diagnosis. When a child is referred to autism services or receives a diagnosis of autism spectrum disorder it is not known what their potential adult outcomes could be. We consider the challenge of making predictions of an individual child’s long-term multi-facetted adult outcome, focussing on which aspects are predictable and which are not.

Methods

We used data from 123 adults participating in the Autism Early Diagnosis Cohort. Participants were recruited from age 2 and followed up repeatedly through childhood and adolescence to adulthood. We predicted 14 adult outcome measures including cognitive, behavioral and well-being measures. Continuous outcomes were modeled using lasso regression and ordinal outcomes were modeled using proportional odds regression. Optimism corrected predictive performance was calculated using cross-validation or bootstrap. We also illustrated the prediction of an overall composite formed by weighting outcome measures by priorities elicited from parents.

Results

We found good predictive performance from age 9 for verbal and non-verbal IQ, and daily living skills. Predictions for symptom severity, hyperactivity and irritability improved with inclusion of behavioral data collected in adolescence but remained modest. For other outcomes covering well-being, depression, and positive and negative affect we found no ability to predict adult outcomes at any age. Predictions of composites based on parental priorities differed in magnitude and precision depending on which parts of the adult outcome were given more weight.

Conclusion

Verbal and non-verbal IQ, and daily living skills can be predicted well from assessments made in childhood. For other adult outcomes, it is challenging to make meaningful predictions from assessments made in childhood and adolescence using the measures employed in this study. Future work should replicate and validate the present findings in different samples, investigate whether the availability of different measures in childhood and adolescence can improve predictions, and consider systematic differences in priorities.
Pathways From Family Violence to Adolescent Violence: Examining the Mediating Mechanisms
Authors: Li Spencer D. , Xiong Ruoshan , Liang Min , Zhang Xiaohua , Tang Wei
Published: February 2021

Purpose

Past research has documented a significant relationship between family violence and adolescent violence. However, much is unknown about the processes through which this association occurs, especially in the non-Western cultural context. To address this gap, we propose an integrated model encompassing multiple pathways that connect family violence to adolescent violence. Specifically, this study investigates how family violence is related to adolescent violence through violent peer association, normative beliefs about violence, and negative emotions.

Method

We tested the model using the two-wave survey data collected from a probability sample of more than 1,100 adolescents residing in one of the largest metropolitan areas in China in 2015 to 2016.

Results and Conclusions

The results indicated that family violence predicted adolescent violence perpetration. Violent peer association, normative beliefs, and negative emotions, however, mediated much of the relationship between family violence and adolescent violence.
Centennials, FOMO, and Loneliness: An Investigation of the Impact of Social Networking and Messaging/VoIP Apps Usage During the Initial Stage of the Coronavirus Pandemic
Authors: Fumagalli Elena , Dolmatzian Marina Belen , Shrum L. J.
Published: February 2021

The current COVID-19 pandemic has had obvious, well-documented devastating effects on people's physical health. In this research, we investigate its potential effects on people's mental health. Many people have experienced social isolation, as countries attempt to stem the spread of the disease through confinement and other forms of social distancing. Intuitively, such social isolation may increase feelings of loneliness, and people may take logical steps to reduce their feelings of social isolation and loneliness. One route is through the use of social networking apps (e.g., Facebook, Instagram) and messaging and VoIP apps (e.g., WhatsApp, iMessage). In this research, we investigate the effects of pandemic-induced social isolation on social networking and messaging apps, and potential related effects on loneliness. We surveyed young adults (N = 334) who are part of the Centennial cohort (born after 1995) from three different countries (Italy, Argentina, UK) and obtained their screen time usage data over a 4-week period starting from mid-March 2020. This sampling procedure allowed us to obtain data from respondents who were experiencing different degrees of mandated social isolation (lockdowns), which enabled us to determine whether social network and messaging app usage increased as a function of social isolation, and to test potential effects on levels of loneliness. Results showed that only social network usage increased in the initial stage of confinement as a function of lockdown initiation. Additionally, social network app usage was associated with increased feelings of loneliness, and this relation was mediated by fear of missing out (FOMO). In contrast, messaging app usage was associated with decreased feelings of loneliness, and was unrelated to FOMO. These results suggest that technology may be useful for mitigating the impact of loneliness during social isolation but that it is necessary to promote usage of messaging and VoIP apps, rather than social networking apps, because they are directly associated with decreases in loneliness without increasing FOMO.