bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Scholarships on University Persistence: A Case Study
Authors: BERLANGA Vanesa , CORTI Franciele , PEREA Eva
Published: April 2022

As we enter the 21st century, the social dimension of Higher Education is one of the key elements in university policies. Among measures aimed at retaining students, scholarship and study grant policies help to ensure equality. In Spain, the establishment of the Study Aid Programme (PAE) for degree studies is an outstanding innovative initiative. This study is aimed at assessing the importance of the PAE as an economic factor in equity, access and academic performance in the first year at university. The data used is that available on all students who began degree studies at Abat Oliba CEU University from the 2009-10 academic years to the 2015-16 academic years. The results confirm that obtaining a scholarship becomes an incentive that influences key aspects for persistence, such as the degree of effort and educational commitment with positive results on students’ performance.
Societal Progress Indicators and Co-Responsibility for All a Possible Answer to Sustainable Social and Economic Development during the Global Pandemic
Authors: TOMOZII Elena Simona , HUANG Lei
Published: April 2022

The aim of this paper is to introduce a pertinent management model for municipalities and relevant groups to support the local communities in dealing with social and economic issues, or as in our case, with the effects of the global pandemic, while promoting sustainable development, through corporate social co-responsibility and efficient allocation and reallocation of resources. SPIRAL Methodology was used to implement exploratory research using the focus group as main research method and ESPOIR software for the statistical analysis. 2275 answers were collected from 198 citizens in Brasov Municipality. The citizens’ answers positively correlate with the social and economic situation, dominated by the effects of the Great Recession. Mostly, well-being through their eyes is related to the working place, purchasing power, education and mental and physical health. Secondly citizens focus on improving their lives and contributing to the society. Lastly, they pay attention to the personal equilibrium. SPIRAL represents a useful tool in supporting governments and local stake holders to identify the pain points, find solutions and locally available resources while, sharing responsibility and successfully overcoming the negative impact of the global pandemic over the economy and society. When comparing the effects SPRIAL methodology had in the communities where it was applied, with the current situation around the world and with the United Nations 2030 Agenda for Sustainable Development, we contribute to enriching the management knowledge by providing a comprehensive tool that promotes sustainable development, measures wellbeing and nurtures cooperation and social innovation.
REGISTRASI DRIVE THRU UNTUK PEMERIKSAAN LABORATORIUM PCR COVID-19 TERINTEGRASI SIM-RS
Authors: Riyandi Albert , Achmad Meizi Fachrizal
Published: April 2022

Menurut satgas penanganan covid-19 Indonesia, terjadi kenaikan kasus covid-19 sebesar 2,8% sejak tanggal 27 desember 2020 walaupun penerapan protokol kesehatan sudah sangat efektif. Sesuai dengan keputusan Menteri Kesehatan Indonesia sebagai langkah tracing setiap pemeriksaan penegakkan covid-19 berdasarkan rekomendasi World Health Organization (WHO) dilakukan dengan metode RT-PCR SARSCoV-2 (PCR) dan wajib mengisi formulir 6. Dalam langkah pencegahan di Rumah Sakit untuk mengurangi kontak antar pasien, pemeriksaan lab PCR dapat dilakukan dengan model pemeriksaan drive thru. Pemeriksaan PCR dengan model ini dilakukan didalam kendaraan pada area parkir rumah sakit. Terjadi permasalahan ketika layanan drive thru ini diterapkan yaitu kepadatan lalulintas dan penuhnya area parkir, karena pasien harus mengisi formulir 6 didalam kendaraan sebelum diambil sampel PCR. Waktu tertinggi yang dibutuhkan pada saat observasi untuk menyelesaikan pelayanan drive thru adalah 39,67 menit. Hal ini terjadi karena formulir yang diisi harus di input ulang kedalam Sistem Informasi Managemen Rumah Sakit (SIM-RS) sehingga membutuhkan waktu. Tentunya hal ini tidak sejalan dengan kebijakan Managemen Rumah Sakit untuk pelayanan Drive Thru maksimal 15 menit. Sistem Informasi Registrasi Drive Thru Pemeriksaan Laboratorium PCR Covid-19 yang Terintegrasi SIM-RS menjadi solusi efektif dan sangat membantu pelayanan rumah sakit. Hal ini dibuktikan dari perbedaan signifikan pelayanan yang diberikan dengan menggunakan sistem dan sebelum menggunakan sistem dengan rata-rata selisih waktu sebesar 26,2 menit. Dengan rata-rata waktu pelayanan sebesar 37,17 menit sebelum penggunaan sistem dan rata-rata 10,97 menit setelah penggunaan sistem. Model drive thru bukan hanya bisa digunakan untuk restoran tapi bisa diterapkan untuk pelayanan rumah sakit terlebih disandingkan oleh SIM-RS.
FAKTOR-FAKTOR YANG BERHUBUNGAN DENGAN STATUS GIZI KURANG PADA BALITA DI MASA PANDEMI
Authors: Afriani Dini , Sutisna Sutisna , Permana Rizki Aditya
Published: April 2022

Prevalensi status gizi kurang pada balita di Sumedang mencapai 3,28%. Faktor penyebabstatus gizi pada balita yakni asupan makanan, dan tingkat pendapatan keluarga. Masabalita merupakan masa kehidupan yang sangat penting yaitu proses tumbuh kembangsangat pesat pada pertumbuhan fisik dan perkembangan psikomotorik, mental, dan sosial.Penelitian bertujuan mengetahui hubungan asupan makanan, pendapatan keluarga denganstatus gizi kurang pada balita. Penelitian ini dilakukan di Desa Cipamekar KecamatanConggeang. Jenis penelitian Deskriptif korelasional dengan rancangan Cross-sectionalsampel penelitian adalah ibu yang mempunyai balita usia 0-60 bulan sebanyak 178responden menggunakan teknik total sampling. Teknik pengumpulan data menggunakaninstrumen penelitian berupa kuesioner. Analisis data yang digunakan berupa uji statistikchi-square. Hasil penelitian ini menunjukan bahwa balita yang mengalami gizi kurangsebanyak 2,2%. Untuk hasil bivariate asupan makanan menunjukkan nilai p-value =0,002 yang berarti adanya hubungan antara asupan makanan pada balita dengan statusgizi balita, sedangkan variable pendapatan keluarga nilai P-value = 0,015 adanyahubungan antara pendapatan keluarga dengan status gizi balita. Penelitian ini diharapkanbermanfaat bagi orang tua yang memiliki balita yaitu dengan cara sosialisasi edukasitentang asupan makanan, pemanfaatan pendapatan keluarga dengan resiko terjadinya gizikurang pada balita.
PENGALAMAN PETUGAS POS KESEHATAN PESANTREN DALAM MERAWAT SANTRI YANG TERKONFIRMASI COVID 19
Authors: Rahmat Rahmat
Published: April 2022

Data World Health Organization  melaporkan negara Indonesia menempati peringkat ke 18 di Asia dengan kasus covid 19. Angka kasus Covid-19 di Indonesia terkonfirmasi sejak 03 Januari 2020 sampai 05 Maret 2021 sebanyak 1.361.098 orang dengan angka kematian mencapai 36.897 orang. Pesatren Baiturrahman yang terletak di Kampung Bojong Rancakole kecamatan Ciparay Kabupaten bandung yang terdiri 650 santri mulai tanggal 31 Januari mulai untuk melakukan pembelajaran tatap muka dengan protokol kesehatan secara ketat. Dalam keberjalanan selama di pesantren kesehatan santri dipantau oleh pos Kesehatan pasantren yang di dampingi dari klinik pratama yang di jadwalkan 3 x dalam seminggu, namun dalam keseharian tim dari pos kesehatan pasantren terus memantau kesehatan semua santri melalui wali santri. Setelah 2 minggu di lakukan pemeriksaan ada 125 santri yang sakit dan koordinasi dengan klinik makan santri yang sakit maka dilakukan rapid test antigen dan didapatkan 4 yang rekatif. Dengan kondisi yang terjadi 4 orang yang reaktif maka koodinasi puskesmas dan diputuskan untuk dilakukan PCR dan di dapatkan hasil 3 orang positif COVID-19. Pada tanggal 1 Maret 2021 dilakukan pemeriksaan semua santri dengan menggunakan Rapid test Antigen untuk yang tidak bergejala dan PCR untuk yang bergejala dan di dapatkan 11 santri hasil PCR yang dinyatakan positif dan harus dilakukan isolasi mandiri di asrama selama 14 hari, dan yang dengan hasil negatif diijinkan untuk pulang kerumah masing-masing. Asrama Baiturrahman selama 14 hari melakukan perawatan dan pemantauan santri yang hasil PCR positif, petugas dari pos Kesehatan pesantren secara pengalaman belum pernah punya pengalaman merawat santri yang isolasi. Dan dari latar belakang pendidikan rata rata adalah bukan dari datar belakang kesehatan, dari 5 orang petugas hanya 2 orang yang latar belakang sudah teredukasi kesehatan terutama virus COVID-19. Selama dilakukan isolasi dan dilakukan perawatan dari mulai penyediaan makankan, olah raga dan aktifitas berjemur dan kajian keislaman maka semua santri yang diisolasi dinyatakan sembuh dan boleh pulang dari Puskesmas
ANALISA BULLWHIP EFFECT PENGADAAN STOCK FRANCHISE AYAM SABANA
Authors: SABILAH ADE IRPAN
Published: April 2022

The COVID-19 pandemic made some companies must pay attention to all their business needs appropriately and measurably.Strategic use in some companies there are maing the limited on the stock supply, it is expected to reduce the losses that will be experienced by business people. The Sabana franchise has problems in determining the optimal safety stock so that there is no bullwhip effect in the supply chain for these raw materials. The losses caused by the bullwhip effect are not only on product availability but also on storage costs in manufacturers or retailers. The purpose of this study is to determine the value, causes, and proposed solutions to reduce the occurrence of the Bullwhip Effect and can optimally forecast inventory requirements using the Single Exponential Smoothing method.
Controllable and Scale-Up Synthesis of Nickel-Cobalt Boride@Borate/RGO Nanoflakes via Reactive Impingement Mixing: A High-Performance Supercapacitor Electrode and Electrocatalyst
Authors: Qian Yudan , Wu Yechao , Gu Fan , Zhou Zhiming , Huang Zaimei , Tang Xinyue , Pan Shuang , Zhang Shangcong , Chen Shinan , Zhang Qingcheng , Chen Yihuang , Wang Shun
Published: April 2022

Large-scale synthesis of graphene-based nanomaterials in stirred tank reactor (STR) often results in serious agglomeration because of the poor control during micromixing process. In this work, reactive impingement mixing is conducted in a two-stage impinging jet microreactor (TS-IJMR) for the controllable and scale-up synthesis of nickel-cobalt boride@borate core-shell nanostructures on RGO flakes (NCBO/RGO). Benefiting from the good process control and improved micromixing efficiency of TS-IJMR, NCBO/RGO nanosheet provides a large BET surface area, abundant of suitable mesopores (2–5 nm), fast ion diffusion, and facile electron transfer within the whole electrode. Therefore, NCBO/RGO electrode exhibits a high specific capacitance of 2383 F g−1 at 1 A g−1, and still retains 1650 F g−1 when the current density is increased to 20 A g−1, much higher than those of nickel boride@borate/RGO (NBO/RGO) and cobalt boride@borate/RGO (CBO/RGO) synthesized in TS-IJMR, as well as NCBO/RGO-S synthesized in STR. In addition, an asymmetric supercapacitor (NCBO/RGO//AC) is constructed with NCBO/RGO and activated carbon (AC), which displays a high energy density of 53.3 W h kg−1 and long cyclic lifespan with 91.8% capacitance retention after 5000 charge-discharge cycles. Finally, NCBO/RGO is used as OER electrocatalyst to possess a low overpotential of 309 mV at a current density of 10 mA cm−2 and delivers a good long-term durability for 10 h. This study opens up the potential of controllable and scale-up synthesis of NCBO/RGO nanosheets for high-performance supercapacitor electrode materials and OER catalysts.
Application of Fe Based Composite Catalyst in Biomass Steam Gasification to Produce Hydrogen Rich Gas
Authors: Zhou Liang , Yang Zhiyong , Wei Deju , Zhang Heng , Lu Wei
Published: April 2022

A series of composite catalysts with different Fe-based load amounts were prepared and applied to the experiment of biomass gasification assisted by steam. The structure of the catalyst was analyzed by XRD, SEM, TEM, N2 adsorption-desorption, and H2-TPR. The effect of the change of Fe load amounts on the catalytic activity was studied, and the optimal conditions of the gasification reaction were selected. The relationship between catalyst structure and catalytic capacity was clarified. The results showed that under the optimal reaction conditions, the catalyst showed better catalytic activity when Fe load amounts were 10%. The proportion of hydrogen in the gasification gas is as high as 42.2% and the hydrogen production is 27.65 g/kg. The tar content reaches the lowest value of 34.07g/Nm3.
The Influence of Fracture Growth and Coalescence on the Energy Budget Leading to Failure
Authors: Fattaruso Laura , Cooke Michele , McBeck Jessica
Published: April 2022

Unraveling the details of fracture propagation leading to catastrophic rock failure is critical for understanding the precursors to earthquakes. Here we present numerical simulations of fracture growth using a work optimization criterion. These simulations apply work optimization to fracture propagation by finding the propagation orientation that minimizes the external work at each increment of fracture growth, repeating this process for each growing fracture tip in the model. We simulate published uniaxial compression experiments performed on a cylinder of marble with pre-cut fractures of varied lengths, orientations, and positions. This suite of experiments provides an ideal benchmark for the numerical simulations because of the relatively simple boundary conditions and the range of pre-cut fracture geometries that focus deformation. We compare the results of homogeneous, isotropic model material to results that incorporate hundreds of small randomly oriented and distributed microcracks representing internal weaknesses, such as grain boundaries. From these numerical models, we find that slip on and propagation of microcracks governs the non-linear stress-strain response observed before failure under axial compression. We use a suite of Monte Carlo realizations incorporating different initial seeding of microcracks to explore the range of fracture propagation paths that might result from inherent variation between rock samples. We find that while models that include microcracks begin to propagate fractures at smaller cumulative axial strains than an equivalent homogeneous isotropic model, ultimately, models including heterogeneity require more energy to reach failure than the homogeneous model. These results highlight the critical role of heterogeneity, such as microcracks, within the processes leading up to failure.
Research on Thermal-Hydraulic Parameter Prediction Method of the Small Lead–Bismuth Fast Reactor Core Based on Adaptive RBF Neural Network
Authors: Wu Hong , Li Ren , Zhao Pengcheng , Yu Tao , Zhao Yanan
Published: April 2022

In this study, a cladding surface temperature prediction method based on an adaptive RBF neural network was proposed. This method can significantly improve the accuracy and efficiency of the thermal safety evaluation of the lead–bismuth fast reactor. First, based on the sub-channel analysis program SUBCHANFLOW, the core sub-channel model of the small lead–bismuth fast reactor SPALLER-100 was established. Second, the calculated 2000 groups of core power distribution and coolant flow distribution data were used as training samples. The adaptive RBF neural network model was trained to predict the surface temperature of fuel elements in the lead–bismuth fast reactor. Finally, by comparison, the effectiveness and superiority of the adaptive RBF neural network method were proved. The results indicate that the relative error of the maximum temperature of the fuel cladding predicted using the adaptive RBF neural network method was less than 0.5%, which can be used for the rapid prediction of the thermal and hydraulic parameters of the lead–bismuth fast reactor.
Simplifying Small Area Estimation With rFIA: A Demonstration of Tools and Techniques
Authors: Stanke Hunter , Finley Andrew O. , Domke Grant M.
Published: April 2022

The United States (US) Department of Agriculture Forest Service Forest Inventory and Analysis (FIA) program operates the national forest inventory of the US. Traditionally, the FIA program has relied on sample-based approaches—permanent plot networks and associated design-based estimators—to estimate forest variables across large geographic areas and long periods of time. These approaches generally offer unbiased inference on large domains but fail to provide reliable estimates for small domains due to low sample sizes. Rising demand for small domain estimates will thus require the FIA program to adopt non-traditional estimation approaches that are capable of delivering defensible estimates of forest variables at increased spatial and temporal resolution, without the expense of collecting additional field data. In light of this challenge, the development of small area estimation (SAE) methods—estimation techniques that support inference on small domains—for FIA data has become an active and highly productive area of research. Yet, SAE methods remain difficult to apply to FIA data, due in part to the complex data structures and survey design used by the FIA program. Herein, we present the potential of rFIA, an open-source R package designed to increase the accessibility of FIA data, to simplify the application of a broad suite of SAE methods to FIA data. We demonstrate this potential via two case studies: (1) estimation of contemporary county-level forest carbon stocks across the conterminous US using a spatial Fay-Herriot model; and (2) temporally-explicit estimation of multi-decadal trends in merchantable wood volume in Washington County, Maine using a Bayesian multi-level model. In both cases, we show the application of SAE techniques offers considerable improvements in precision over FIA's traditional, post-stratified estimators. Finally, we offer a discussion of the potential role that rFIA and other open-source tools might play in accelerating the adoption of SAE techniques among users of FIA data.
Comprehensive Analysis of miRNA-Mediated Regulatory Network and Identification of Prognosis Biomarkers in Rectal Cancer
Authors: Tang Tingting , Yu Sisi , Song Zekai , Pan Xiaofu , Xu Fang , Wu Yanke , Zhang Liang
Published: April 2022

Rectal cancer is a malignant tumor with poor prognosis. Identification of prognostic biomarkers is needed to improve overall survival of rectal cancer patients. Here, we firstly identified miR-20a-5p significantly classifying high-risk group and low-risk group of rectal cancer patients. We also found that several known miRNAs miR-142-5p, miR-486-5p, miR-490-3p and miR-133a-3p played important roles in rectal cancer. Secondly, we constructed and analyzed a rectal cancer-related miRNA-mRNA network. A rectal cancer-related functional module was identified from the miRNA-mRNA network. Survival analysis demonstrated great prognosis capacity of the module to distinguish rectal cancer patients. Thirdly, a rectal cancer-related miRNA-lncRNA network was constructed, which followed power law distribution. Hub miRNAs and lncRNAs of the network were suggested to show significant prognosis ability and be enriched in cancer-related pathways. Fourthly, we constructed a rectal cancer-related ceRNA network and detected several typical lncRNA-miRNA-mRNA crosstalk, such as HAND2-AS1, HAND2 and miR-20a-5p crosstalk and MBNL1-AS1, miR-429 and LONRF2 crosstalk, which were validated to function in improving overall survival of rectal cancer patients. Finally, we identified the regulatory feedback that was constituted by transcriptional factors and lncRNAs, including MEIS1, MEIS2 and multiple lncRNAs. We also demonstrated that these lncRNAs were high related to immune cell infiltration. All these results can help us to uncover the molecular mechanism and provide new light on miRNA-mediated gene crosstalks in rectal cancer.
Identification of a Gene Signature to Aid Treatment Decisions by Integrated Analysis of Mutated Genes Between Primary and Metastatic Prostate Cancer
Authors: Li Qinyu , Xiao Xueyan , Chen Bingliang , Song Guoda , Zeng Kai , Miao Jianping
Published: April 2022

Prostate cancer is one of the most common malignancies in males. Despite the recent development of advanced diagnostic platforms and treatment, patients with metastatic disease still have a poor five-year survival rate. Cancer metastasis is correlated with the characteristics of the tumor microenvironment and is significantly associated with patient prognosis. In this study, we obtained mutated genes with significant differences between primary and metastatic prostate cancer from the COSMIC database. Unsupervised consensus clustering was used based on the 1,051 genes obtained, and two PCa clusters were identified, which exhibited different prognostic outcomes and immune characteristics. Next, we generated a scoring system and evaluated the prognostic value of riskscore and its potential to aid treatment decisions in clinical practice. The riskscore could be applied to predict patients’ response to immunotherapy and sensitivity to Docetaxel. In conclusion, this study performed an integrated analysis of mutated genes between primary and metastatic prostate cancer and provides a novel assessment scheme to precisely select treatment strategies.
Case Report: Omicron BA.2 Subvariant of SARS-CoV-2 Outcompetes BA.1 in Two Co-infection Cases
Authors: Gjorgjievska Marija , Mehandziska Sanja , Stajkovska Aleksandra , Pecioska-Dokuzovska Slavica , Dimovska Anica , Durmish Idriz , Ismail Sara , Pavlovska Teodora , Stojchevska Antonija , Amedi Haris , Andonova Jasna , Nikolovska Marija , Velickovikj Sara , Mitrev Zan , Kungulovski Ivan , Kungulovski Goran
Published: April 2022

Trends from around the world suggest that the omicron BA.2 subvariant is increasing in proportion to the original BA.1 subvariant. Here we report two cases of co-infection with omicron BA.1 and omicron BA.2 in co-exposed individuals. In both individuals, genome sequencing and/or S-gene specific PCR identified omicron BA.1 at early time-points, which was replaced by omicron BA.2 at later time-points of the infection. The timeline of our data supports the proposition that BA.2 outcompetes BA.1 in a real-life scenario, and in time becomes the dominant variant in the upper respiratory tract of the host.
Distribution of Forward-Looking Responsibility in the EU Process on AI Regulation
Authors: Hedlund Maria
Published: April 2022

Artificial Intelligence (AI) is beneficial in many respects, but also has harmful effects that constitute risks for individuals and society. Dealing with AI risks is a future-oriented endeavor that needs to be approached in a forward-looking way. Forward-looking responsibility is about who should do what to remedy or prevent harm. With the ongoing EU policy process on AI development as a point of departure, the purpose of this article is to discuss distribution of forward-looking responsibility for AI development with respect to what the obligations entail in terms of burdens or assets for the responsible agents and for the development of AI. The analysis builds on the documents produced in the course of the EU process, with a particular focus on the early role of the European Parliament, the work of the High-Level Expert Group on AI, and the Commission's proposal for a regulation of AI, and problematises effects of forward-looking responsibility for the agents who are attributed forward-looking responsibility and for the development of AI. Three issues were studied: ethics by design, Artificial General Intelligence (AGI), and competition. Overall, the analysis of the EU policy process on AI shows that competition is the primary value, and that the perspective is technical and focused on short-term concerns. As for ethics by design, the question of which values should be built into the technology and how this should be settled remained an issue after the distribution of responsibility to designers and other technical experts. AGI never really was an issue in this policy process, and it was gradually phased out. Competition within the EU process on AI is a norm that frames how responsibility is approached, and gives rise to potential value conflicts.
Sustained Drug Release From Liposomes for the Remodeling of Systemic Immune Homeostasis and the Tumor Microenvironment
Authors: Zheng Anjie , Xie Fang , Shi Sanyuan , Liu Shounan , Long Jinfeng , Xu Yuhong
Published: April 2022

Myeloid Derived Suppressor Cells (MDSCs) play important roles in constituting the immune suppressive environment promoting cancer development and progression. They are consisted of a heterogeneous population of immature myeloid cells including polymorphonuclear MDSC (PMN-MDSC) and monocytes MDSC (M-MDSC) that are found in both the systemic circulation and in the tumor microenvironment (TME). While previous studies had shown that all-trans retinoic acid (ATRA) could induce MDSC differentiation and maturation, the very poor solubility and fast metabolism of the drug limited its applications as an immune-modulator for cancer immunotherapy. We aimed in this study to develop a drug encapsulated liposome formulation L-ATRA with sustained release properties and examined the immuno-modulation effects. We showed that the actively loaded L-ATRA achieved stable encapsulation and enabled controlled drug release and accumulation in the tumor tissues. In vivo administration of L-ATRA promoted the remodeling of the systemic immune homeostasis as well as the tumor microenvironment. They were found to promote MDSCs maturation into DCs and facilitate immune responses against cancer cells. When used as a single agent treatment, L-ATRA deterred tumor growth, but only in immune-competent mice. In mice with impaired immune functions, L-ATRA at the same dose was not effective. When combined with checkpoint inhibitory agents, L-ATRA resulted in greater anti-cancer activities. Thus, L-ATRA may present a new IO strategy targeting the MDSCs that needs be further explored for improving the immunotherapy efficacy in cancer.
The Infection, Coinfection, and Abundance of Intestinal Protozoa Increase the Serum Levels of IFABP2 and TNF-α in Patients With Rheumatoid Arthritis
Authors: Guzmán-Guzmán Iris Paola , Nogueda-Torres Benjamín , Zaragoza-García Oscar , Navarro-Zarza José Eduardo , Briceño Olivia , Pérez-Rubio Gloria , Falfán-Valencia Ramcés , Gutiérrez-Pérez Ilse Adriana , Parra-Rojas Isela
Published: April 2022

Protozoa, nematodes, and platyhelminths are of clinical interest due to their role on the modulation of the immune responses. To determine the frequency of infection by intestinal parasites as well as the status of single or mixed infection (coinfection) and its relation with inflammation and intestinal permeability markers in patients with rheumatoid arthritis (RA), a cross-sectional study was conducted in 18 women diagnosed with RA. A fecal sample of each participant was analyzed for parasitic identification. The DAS28-erythrocyte sedimentation rate score, as well as the serum levels of TNF-α, IL-10, IL-17A, and the intestinal fatty-acid binding protein 2 (IFABP2), was determined through the ELISA technique. The T CD4+ and CD8+ lymphocytes' proportions were determined by flow cytometry. In this study, 50% (n = 9) of the total sample tested were positive to the presence of intestinal protozoa (27% by single infection and 22.2% by coinfection). Blastocystis sp. and Endolimax nana were the most frequently identified protozoa. The serum levels of IFABP2 were increased in patients with infection by protozoa, mainly in those individuals with coinfection and a larger abundance of Blastocystis sp. We found that coinfection by protozoa was related to higher levels of TNF-α and higher frequency of T CD4+ lymphocytes, mainly in patients under antirheumatic treatment. Infection by intestinal protozoa is associated with increased intestinal permeability in patients with RA; thus, infection, coinfection, and abundance of intestinal protozoa should be clinically screened because they could be an associated factor to the clinical variability of the disease.
Responsive Neurostimulation Targeting the Anterior, Centromedian and Pulvinar Thalamic Nuclei and the Detection of Electrographic Seizures in Pediatric and Young Adult Patients
Authors: Beaudreault Cameron P. , Muh Carrie R. , Naftchi Alexandria , Spirollari Eris , Das Ankita , Vazquez Sima , Sukul Vishad V. , Overby Philip J. , Tobias Michael E. , McGoldrick Patricia E. , Wolf Steven M.
Published: April 2022

Background

Responsive neurostimulation (RNS System) has been utilized as a treatment for intractable epilepsy. The RNS System delivers stimulation in response to detected abnormal activity, via leads covering the seizure foci, in response to detections of predefined epileptiform activity with the goal of decreasing seizure frequency and severity. While thalamic leads are often implanted in combination with cortical strip leads, implantation and stimulation with bilateral thalamic leads alone is less common, and the ability to detect electrographic seizures using RNS System thalamic leads is uncertain.

Objective

The present study retrospectively evaluated fourteen patients with RNS System depth leads implanted in the thalamus, with or without concomitant implantation of cortical strip leads, to determine the ability to detect electrographic seizures in the thalamus. Detailed patient presentations and lead trajectories were reviewed alongside electroencephalographic (ECoG) analyses.

Results

Anterior nucleus thalamic (ANT) leads, whether bilateral or unilateral and combined with a cortical strip lead, successfully detected and terminated epileptiform activity, as demonstrated by Cases 2 and 3. Similarly, bilateral centromedian thalamic (CMT) leads or a combination of one centromedian thalamic alongside a cortical strip lead also demonstrated the ability to detect electrographic seizures as seen in Cases 6 and 9. Bilateral pulvinar leads likewise produced reliable seizure detection in Patient 14. Detections of electrographic seizures in thalamic nuclei did not appear to be affected by whether the patient was pediatric or adult at the time of RNS System implantation. Sole thalamic leads paralleled the combination of thalamic and cortical strip leads in terms of preventing the propagation of electrographic seizures.

Conclusion

Thalamic nuclei present a promising target for detection and stimulation via the RNS System for seizures with multifocal or generalized onsets. These areas provide a modifiable, reversible therapeutic option for patients who are not candidates for surgical resection or ablation.
Mitochondrial Transplantation Attenuates Neural Damage and Improves Locomotor Function After Traumatic Spinal Cord Injury in Rats
Authors: Lin Ming-Wei , Fang Shih-Yuan , Hsu Jung-Yu C. , Huang Chih-Yuan , Lee Po-Hsuan , Huang Chi-Chen , Chen Hui-Fang , Lam Chen-Fuh , Lee Jung-Shun
Published: April 2022

Mitochondrial dysfunction is a hallmark of secondary neuroinflammatory responses and neuronal death in spinal cord injury (SCI). Even though mitochondria-based therapy is an attractive therapeutic option for SCI, the efficacy of transplantation of allogeneic mitochondria in the treatment of SCI remains unclear. Herein, we determined the therapeutic effects of mitochondrial transplantation in the traumatic SCI rats. Compressive SCI was induced by applying an aneurysm clip on the T10 spinal cord of rats. A 100-μg bolus of soleus-derived allogeneic mitochondria labeled with fluorescent tracker was transplanted into the injured spinal cords. The results showed that the transplanted mitochondria were detectable in the injured spinal cord up to 28 days after treatment. The rats which received mitochondrial transplantation exhibited better recovery of locomotor and sensory functions than those who did not. Both the expression of dynamin-related protein 1 and severity of demyelination in the injured cord were reduced in the mitochondrial transplanted groups. Mitochondrial transplantation also alleviated SCI-induced cellular apoptosis and inflammation responses. These findings suggest that transplantation of allogeneic mitochondria at the early stage of SCI reduces mitochondrial fragmentation, neuroapoptosis, neuroinflammation, and generation of oxidative stress, thus leading to improved functional recovery following traumatic SCI.
Distinct Cecal and Fecal Microbiome Responses to Stress Are Accompanied by Sex- and Diet-Dependent Changes in Behavior and Gut Serotonin
Authors: Lyte Joshua M. , Koester Lucas R. , Daniels Karrie M. , Lyte Mark
Published: April 2022

Although diet- and stress-induced perturbations in the microbiome (biotic and abiotic factors) associate with changes in host behavior via the microbiota-gut-brain axis, few mechanisms have been identified. The identification of causative pathways by which the microbiome influences host behavior therefore would benefit from the application of evidence-based conceptual frameworks. One such causal framework is microbial endocrinology which is the study of neuroendocrine axes as avenues of bi-directional neurochemical-based host-microbe crosstalk. As such, we investigated the relationship between diet- and stress-induced alterations in behavior, regional gut serotonergic response, and concomitant changes in the cecal and fecal bacterial populations of male and female mice. Our results demonstrate that sex is a dominant factor in determining compositional changes in the gut microbiome in response to stress and diet modifications. Intestinal serotonergic responses to stress were observed in both sexes but dietary modifications uniquely affected region-specific changes in males and females. Likewise, behavioral alterations diverged between male and female mice. Together, these results demonstrate distinct sex-dependent relationships between cecal and fecal bacterial taxa and behavioral- and serotonergic-responses to stress and diet. The present study demonstrates the importance of including both male and female sexes in the examination of the microbiota-gut-brain axis. As different microbial taxa were identified to associate with the behavioral and gut serotonergic responses of male and female mice, certain bacterial species may hold sex-dependent functional relevance for the host. Future investigations seeking to develop microbiome-based strategies to afford host stress resilience should include sex-based differences in the microbiome.
Lonicerae Japonicae Flos Extract Promotes Sleep in Sleep-Deprived and Lipopolysaccharide-Challenged Mice
Authors: Hua Ruifang , Ding Yan , Liu Xiaolong , Niu Bingxuan , Chen Xinfeng , Zhang Jingjing , Liu Kerui , Yang Pei , Zhu Xiaofei , Xue Jintao , Wang Hui
Published: April 2022

Lonicerae Japonicae Flos (LJF) is commonly used in Chinese herbal medicines and exhibits anti-viral, anti-oxidative, and anti-inflammatory properties. The reciprocal relationship between sleep, the immune system and the central nervous system is well-established in the animal models. In this study, we used the mouse model to analyze the beneficial effects of the LJF on the dysregulated sleep-wakefulness cycle in response to acute sleep deprivation and lipopolysaccharide (LPS)-induced inflammation and the potential underlying mechanisms. Polysomnography data showed that LJF increased the time spent in non-rapid eye movement (NREM) sleep during the day under basal conditions. Furthermore, latency to sleep was reduced and the time spent in rapid eye movement (REM) sleep was increased during recovery from acute sleep deprivation. Furthermore, LJF-treated mice showed increased REM sleep and altered electroencephalogram (EEG) power spectrum in response to intra-peritoneal injection of LPS. LJF significantly reduced the levels of proinflammatory cytokines such as IL-6, TNF-α, and IL-1β in the blood serum as well as hippocampus, and medial prefrontal cortex (mPFC) tissues in the LPS-challenged mice by inhibiting microglial activation. Moreover, LJF increased the time spent in REM sleep in the LPS-challenged mice compared to the control mice. These results suggested that LJF stimulated the sleep drive in response to acute sleep deprivation and LPS-induced inflammation, thereby increasing REM sleep for recovery and neuroprotection. In conclusion, our findings demonstrate that the clinical potential of LJF in treating sleep disorders related to sleep deprivation and neuro-inflammation.
Maternal Hypoxia Increases the Excitability of Neurons in the Entorhinal Cortex and Dorsal Hippocampus of Rat Offspring
Authors: Amakhin Dmitry V. , Soboleva Elena B. , Postnikova Tatiana Yu. , Tumanova Natalia L. , Dubrovskaya Nadezhda M. , Kalinina Daria S. , Vasilev Dmitrii S. , Zaitsev Aleksey V.
Published: April 2022

Prenatal hypoxia is a widespread condition that causes various disturbances in later life, including aberrant central nervous system development, abnormalities in EEG rhythms, and susceptibility to seizures. Hypoxia in rats on the 14th day of embryogenesis (E14) disrupts cortical neuroblast radial migration, mainly affecting the progenitors of cortical glutamatergic neurons but not GABAergic interneurons or hippocampal neurons. Thus, hypoxia at this time point might affect the development of the neocortex to a greater extent than the hippocampus. In the present study, we investigated the long-term effects of hypoxia on the properties of the pyramidal neurons in the hippocampus and entorhinal cortex (EC) in 3-week-old rats subjected to hypoxia on E14. We observed a reduction in the total number of NeuN-positive neurons in EC but not in the CA1 field of the hippocampus, indicating an increased cell loss in EC. However, the principal neuron electrophysiological characteristics were altered in the EC and hippocampus of animals exposed to hypoxia. The whole-cell patch-clamp recordings revealed a similar increase in input resistance in neurons from the hippocampus and EC. However, the resting membrane potential was increased in the EC neurons only. The recordings of field postsynaptic potentials (fPSPs) in the CA1 hippocampal area showed that both the threshold currents inducing fPSPs and population spikes were lower in hypoxic animals compared to age-matched controls. Using the dosed electroshock paradigm, we found that seizure thresholds were lower in the hypoxic group. Thus, the obtained results suggest that maternal hypoxia during the generation of the pyramidal cortical neurons leads to the increased excitability of neuronal circuitries in the brain of young rats. The increased excitability can be attributed to the changes in intrinsic neuronal properties.
Prolonged Continuous Theta Burst Stimulation Can Regulate Sensitivity on Aβ Fibers: An Functional Near-Infrared Spectroscopy Study
Authors: Li Chong , Zhang Nannan , Han Qiong , Zhang Lifang , Xu Shuo , Tu Shuting , Xie Yong , Wang Zhiyong
Published: April 2022

Objective

High-frequency repetitive transcranial magnetic stimulation (rTMS) induces analgesic effects in both experimental pain and clinical pain conditions. However, whether rTMS can modulate sensory and pain thresholds on sensory fibers is still unclear. Here, we compared the effects of three rTMS paradigms on sensory and pain thresholds conducted by different sensory fibers (Aβ, Aδ, and C fibers) with sham stimulation and investigate the potential brain activation using functional near-infrared spectroscopy (fNIRS).

Methods

Forty right-handed healthy subjects were randomly allocated into one of four groups. Each subject received one session rTMS [prolonged continuous theta-burst stimulation (pcTBS), intermittent theta-burst stimulation (iTBS), 10 Hz rTMS or sham]. Current perception threshold (CPT), pain tolerance threshold (PTT), and fNIRS were measured at baseline, immediately after stimulation, and 1 h after stimulation, respectively.

Results

Significant differences between treatments were observed for changes for CPT 2,000 Hz between baseline and 1 h after rTMS (F = 6.551, P < 0.001): pcTBS versus sham (P = 0.004) and pcTBS versus 10 Hz rTMS (P = 0.007). There were significant difference in average HbO μm in the right frontopolar cortex (FPC) [channel 23: P = 0.030 (pcTBS versus sham: P = 0.036)], left dorsolateral prefrontal cortex (DLPFC) [channel 7: P = 0.006 (pcTBS versus sham: P = 0.004)], left FPC [channel 17: P = 0.014 (pcTBS versus sham: P = 0.046), channel 22: P = 0.004 (pcTBS versus sham: P = 0.004)] comparing four group in 1 h after stimulation in PTT 2000 Hz (Aβ-fiber).

Conclusion

Prolonged continuous theta-burst stimulation can regulate sensitivity on Aβ fibers. In addition, single-session pcTBS placed on left M1 can increase the excitability of DLPFC and FPC, indicating the interaction between M1 and prefrontal cortex may be a potential mechanism of analgesic effect of rTMS. Studies in patients with central post-stroke pain are required to confirm the potential clinical applications of pcTBS.
Hyper-Adaptation in the Human Brain: Functional and Structural Changes in the Foot Section of the Primary Motor Cortex in a Top Wheelchair Racing Paralympian
Authors: Morita Tomoyo , Hirose Satoshi , Kimura Nodoka , Takemura Hiromasa , Asada Minoru , Naito Eiichi
Published: April 2022

The human brain has the capacity to drastically alter its somatotopic representations in response to congenital or acquired limb deficiencies and dysfunctions. The main purpose of the present study was to elucidate such extreme adaptability in the brain of an active top wheelchair racing Paralympian (participant P1) who has congenital paraplegia (dysfunction of bilateral lower limbs). Participant P1 has undergone long-term wheelchair racing training using bilateral upper limbs and has won a total of 19 medals in six consecutive summer Paralympic games as of 2021. We examined the functional and structural changes in the foot section of the primary motor cortex (M1) in participant P1 as compared to able-bodied control participants. We also examined the functional and structural changes in three other individuals (participants P2, P3, and P4) with acquired paraplegia, who also had long-term non-use period of the lower limbs and had undergone long-term training for wheelchair sports (but not top athletes at the level of participant P1). We measured brain activity in all the participants using functional magnetic resonance imaging (MRI) when bimanual wrist extension-flexion movement was performed, and the structural MRI images were collected. Compared to 37 control participants, participant P1 showed significantly greater activity in the M1 foot section during the bimanual task, and significant local GM expansion in this section. Significantly greater activity in the M1 foot section was also observed in participant P4, but not in P2 and P3, and the significant local GM expansion was observed in participant P2, but not in P3 and P4. Thus, functional or structural change was observed in an acquired paraplegic participant, but was not observed in all the paraplegic participants. The functional and structural changes typically observed in participant P1 may represent extreme adaptability of the human brain. We discuss the results in terms of a new idea of hyper-adaptation.
Amino Acid and Fatty Acid Metabolism Disorders Trigger Oxidative Stress and Inflammatory Response in Excessive Dietary Valine-Induced NAFLD of Laying Hens
Authors: Jian Huafeng , Xu Qianqian , Wang Xiaoming , Liu Yating , Miao Sasa , Li Yan , Mou Tianming , Dong Xinyang , Zou Xiaoting
Published: April 2022

Non-alcoholic fatty liver disease (NAFLD) is a chronic and metabolic liver disease and commonly occurs in humans with obesity and type 2 diabetes mellitus (T2DM); such a condition also exists in animals such as rodents and laying hens. Since the pathogenesis of fatty liver hemorrhagic syndrome (FLHS) of laying hens is similar to human NAFLD, hen's FLHS is commonly selected as a study model of NAFLD. Altered circulating amino acids, particularly elevated branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs), are consistently reported in patients with NAFLD and T2DM. How long-term dietary individual BCAA, such as valine, impacts amino acid and fatty acid metabolism remains unknown. In this study, we demonstrated that when laying hens are fed with dietary valine at different levels (59, 0.64, 0.69, 0.74, and 0.79%) in a feeding trial that lasted for 8 weeks, long-term exposure to excessive valine diets at 0.74 and 0.79% levels could induce amino acid imbalance, impair amino acid metabolism, increase fatty acid synthesis, and inhibit fatty acid utilization. Long-term intake of excessive dietary valine could result in impaired amino acid metabolism via inhibiting C/EBP-β/asparagine synthetase (Asns). This process is mediated by downregulating the general control nonderepressible-eukaryotic initiation factor 2α- activating transcription factor (GCN2-eIF2α-ATF4) pathway and elevating corresponding circulating BCAAs and AAAs levels, which could ultimately result in amino acid imbalance. High levels of dietary valine stimulated lipid deposition by suppressing the GCN2-eIF2α-ATF4-fibroblast growth factor-19 (FGF19)-target of rapamycin complex 1 (TORC1) signaling pathway to promote fatty acid synthesis, repress fatty acid utilization, and eventually accelerate the development of NAFLD. The Spearman correlation analysis revealed that circulating amino acid imbalance is significantly associated with fatty acid metabolism disorder and enhanced oxidative stress. The inhibition of the GCN2-TORC1 pathway induced autophagy suppression to trigger liver oxidative stress and inflammatory response. In conclusion, our results revealed the adverse metabolic response to excessive dietary valine mediated by amino acid and fatty acid metabolism disorders. This study also suggested reducing dietary valine as a novel approach to preventing and treating NAFLD in humans and FLHS in laying hens.
Airway Microbiota in Patients With Synchronous Multiple Primary Lung Cancer: The Bacterial Topography of the Respiratory Tract
Authors: Qian Kai , Deng Yi , Krimsky William S. , Feng Yong-Geng , Peng Jun , Tai Yong-Hang , Peng Hao , Jiang Li-Hong
Published: April 2022

Microbes and microbiota dysbiosis are correlated with the development of lung cancer; however, the airway taxa characteristics and bacterial topography in synchronous multiple primary lung cancer (sMPLC) are not fully understood. The present study aimed to investigate the microbiota taxa distribution and characteristics in the airways of patients with sMPLC and clarify specimen acquisition modalities in these patients. Using the precise positioning of electromagnetic navigation bronchoscopy (ENB), we analyzed the characteristics of the respiratory microbiome, which were collected from different sites and using different sampling methods. Microbiome predictor variables were bacterial DNA burden and bacterial community composition based on 16sRNA. Eight non-smoking patients with sMPLC in the same pulmonary lobe were included in this study. Compared with other sampling methods, bacterial burden and diversity were higher in surface areas sampled by bronchoalveolar lavage (BAL). Bacterial topography data revealed that the segment with sMPLC lesions provided evidence of specific colonizing bacteria in segments with lesions. After taxonomic annotation, we identified 4863 phylotypes belonging to 185 genera and 10 different phyla. The four most abundant specific bacterial community members detected in the airway containing sMPLC lesions were Clostridium, Actinobacteria, Fusobacterium, and Rothia, which all peaked at the segments with sMPLC lesions. This study begins to define the bacterial topography of the respiratory tract in patients with sMPLC and provides an approach to specimen acquisition for sMPLC, namely BAL fluid obtained from segments where lesions are located.