bluuebunny/crossref_metadata_2025 huggingface dataset:
Progress towards delivering high metabolisable energy ryegrass
Authors: Beechey-Gradwell Zac Beechey-Gradwell
Published: February 2022

A method developed at AgResearch to increase leaf fatty acids (FA) and plant growth called ‘High metabolizable energy’ (‘HME’) could elevate the nutritional quality and productivity of perennial ryegrass-based pastures. The industry strategy has been to perform HME ryegrass field trials offshore to test whether the herbage FA, gross energy (GE) and yield enhancing traits observed in containment translate into field swards. To complement the field testing programme, we have also characterised the growth and nutritional profile of HME miniswards under simulated grazing in containment. The results from one such trial are presented. The major changes measured in HME miniswards; increased FA (+0.8–1.4 %DW), increased GE (+0.3–0.5 MJ/kgDM), and generally similar herbage DW production, closely mirror data from field trials with hemizygous HME populations in the Midwest USA. Changes in other HME nutritional components were generally minor, although WSC was reduced late in the diurnal cycle. Secondary effects of HME on photosynthesis appear to be diminished in swards, suggesting that HME yield benefits may be limited to specific environment and management scenarios. The primary benefit of HME technology is thus expected to come from increasing the energy density of pasture, and animal feeding trials using homozygous HME material are now required.
Nitrogen effects on species’ contributions to grazed pasture mixtures under nitrogen loss and application restrictions
Authors: Soe Myint Thinzar , Black Alistair , Moot Derrick
Published: February 2022

New regulations to the use of N fertiliser will impact on seed mixture decisions for new pastures. To help inform these decisions, the effects of N on species and species interactions in pasture mixtures were examined. Ten mixtures of perennial ryegrass (PR), white clover (WC) and plantain (P) were sown on 31 March 2017 and grown ±N fertiliser (275 kg/ha in Year 1 reduced to 200 kg N/ha/year) under grazed and irrigated conditions at Lincoln University. After 4 years, an equi-proportional mixture of PR and WC (based on seed count) optimised average total yield (TY), weed yield (WY), metabolisable energy (ME) and crude protein (CP) regardless of N level. The optimal sowing rate was 12.2 kg PR and 7.0 kg WC/ha. Average TY of the optimal mixture was 20.5 t DM/ha/year with 4% WY, 11 MJ/kg DM ME and 21% CP. Pasture yield and quality responded to change in species proportions away from the optimal mixture, including the addition of P. The magnitude of the TY and WY responses was greater with than without N fertiliser because the identity effects of PR and P, and the way all three species interacted, depended on N level.
Agricultural Transformations – NZ pastoral farming systems past, present and future
Authors: King Warren
Published: February 2022

There are increasing calls for agriculture in NZ to be transformed. The signals from Wellington, especially, suggest that government investors in the primary sector (MPI, MBIE) do not consider that ‘business as usual’ will deliver the improvements in environmentalperformance demanded by the voting public. The Crown Research Institute whose primary focus is pastoral agriculture – AgResearch – has adopted a strapline: ‘Driving prosperity by transforming agriculture? But what does this transformation actually mean?
Encounters and the Differential Genesis of Thought inThe Logic of Sense
Authors: Bowden Sean
Published: February 2022

Several themes treated in chapter 3 of Difference and Repetition are addressed at greater length in The Logic of Sense, published one year later. In particular, Deleuze's critique of ‘the privilege of designation’ and ‘the modality of solutions’, along with his positive claims about the relation between sense and problems, arguably summarise a number of analyses found in The Logic of Sense. However, despite the convergence between Difference and Repetition and The Logic of Sense as regards the sense–problem relation, The Logic of Sense does not explicitly address the other aspects of thought that Difference and Repetition considers inseparable from the sense–problem relation. In particular, the notion of ‘transcendental empiricism’ – that is, the idea that the conditions of experience themselves emerge from experience – is not explicitly mentioned in The Logic of Sense. There is no explicit discussion in The Logic of Sense of ‘encounters’ or ‘shocks’ and their role in the genesis of thought. And there is no explicit discussion in The Logic of Sense of the discordant relations between the different faculties of thought as they provoke and constrain one another in the elaboration of differential problems. This essay intends to argue that, despite the lack of explicit discussion, The Logic of Sense does advance an account of the differential genesis of thought, and along the same general lines as chapter 3 of Difference and Repetition.
Unfolding Life with Death: In Memoriam
Authors: Lorraine Tamsin
Published: February 2022

This paper explores how affirming events rather than substances, and difference rather than identities, might affect how one responds to life's exigencies, in particular the act of choosing when to end the life of a dog that was a beloved companion. The paper addresses the concepts of the event and the time of Aion as they are presented in The Logic of Sense, and examines the resonances these concepts have with a notion of learning presented in Difference and Repetition and a notion of essence presented in Expressionism in Philosophy: Spinoza. The argument is made that Deleuze presents us with a notion of death that is a part of the creative unfolding of life, and that affirming events rather than substances and difference rather than identities can give us insight into practical questions about how to live one's life.
Use of Virtual Video Call Communications in Family Visits: A Literature Review
Authors: Fitri Nila , Waluyo Agung , Maria Riri
Published: February 2022

Background: Family visits and patient assistance by the family during treatment experience limitations. limitations occur because of the COVID-19 pandemic which eliminated all family visits to patients, patients being treated in isolation rooms, elderly people living in nursing homes, and family limitations in visiting their cared for families.
Objective: Online visitation with a video call between patient and family can reduce the harm of isolation.
Method: The writing method uses a literature review to summarize and conclude several studies using video calls for family visitations in patients both hospitalized and elderly in nursing homes. Journal searches are carried out through both national and international databases. Search for related journals using the EBSCO, Pubmed, Proquest, Elsevier and Google Scholar databases.
Result: From the literature search, it was found that the use of video calls for online visitations of patients in hospitals and the elderly in nursing homes showed a decrease in anxiety, increased morale, reduced feelings of loneliness and isolation.
Why You’re Doing This: Sustaining Joy and Inspiration in the Scholarly Vocation
Authors: Blajer de la Garza Yuna , Egan Patrick , Shugars Sarah
Published: February 2022

“Why am I doing this?” is a question almost every Ph.D. student asks themselves. While this question is frequently inspired by the true challenges of academia, the examination of why we do what we do is fundamentally constructive. It serves to remind each of us that academia is more than a job, but is truly a vocation: a worthy calling that requires great dedication but can also bring genuine joy. The answer to why you’re doing this is grounded in a vocational practice that embraces the creativity, independence, and unique public contributions that are possible as an academic political scientist, regardless of the extent to which you intend to focus your future career on teaching, research or service. We discuss how to cultivate these practices in ways that help you sustain joy and inspiration as you complete the Ph.D. and begin to chart your own path through the scholarly vocation.
Efektifitas Media Permainan Flashcard Dalam Meningkatkan Pengetahuan Kesehatan Reproduksi Anak Usia Prasekolah
Authors: Kelrey Fathimah , Kombong Rita , Hatala Tri N
Published: February 2022

Pelaksanaan media flashcard sebagai media pembelajaran kesehatan reproduksi bagi anak usia pra-sekolah masih sangat jarang diterapkan oleh perawat di lingkup komunitas untuk memberikan pendidikan kesehatan. Tujuan penelitian untuk meningkatkan pengetahuan anak usia pra-sekolah tentang kesehatan reproduksi melalui flashcard. Metode Desian penelitian ini adalah eksperimental analitik menggunakan pre eksperiment dengan pendekatan pretest-postest design tanpa adanya kelompok kontrol. Teknik  sampling yang digunakan adalah purposif sampling  dengan jumlah sampel 30 responden. Kemudian dilakukan uji statistic dependen sample t-test (paired t test dengan α (taraf  kesalahan) sebesar 5%. Hasil dalam penelitian ini setelah dilakukan Uji Paired T-Test menunjuka niali p-value 0.000 atau < 0.05 yang berarti ada perbedaan nilai pre dan post test tingkat pengetahuan setelah dilakukan perlakuan. Kesimpulan adanya peningkatan tingkat pengetahuan setelah dialakukan perlakuan pendidikan kesehatan kepada anak usia prasekolah dengan menggunakan media flashcard. Saran, media flashcard dapat digunakan sebagai media pembelajaran pada anak usia dini.
Determinan Penggunaan Kuesioner Pra Skrining Perkembangan Anak Pada Kader Posyandu
Authors: Yunus Endriyani Martina , Yanti Eka Safitri , Imami Retno
Published: February 2022

Periode perkembangan bayi dan anak merupakan masa pertumbuhan dan perkembangan yang cepat dan ini menentukan perkembangan selanjutnya. Roesli (2009) dalampenelitiannya didapatkan bahwa balita mengalami gangguan motorik kasar sebanyak 31,2%, motorik halus 14,3%, sedangkan yang mengalami gangguan bahasa 19,1% dan yang mengalami gangguan personal sosial 11,5%. Pada periode perkembangan ini sangat diperlukan pemantauan untuk mendeteksi dini penyimpangan perkembangan anak. Penelitian ini bertujuan untuk mengetahui Determinan Penggunaan  Kuisioner Pra Skrining Perkembangan Anak pada Kader Posyandu di Wilayah Kerja Puskesmas Benteng Bangka Tengah tahun 2021. Jenis penelitian ini cross sectional,jenis pengambilan data total sampling. Penggunaan Kuisioner Pra Skrining Perkembangan Anak pada Kader Posyandu di Wilayah Kerja Puskesmas Benteng Bangka Tengah sebanyak 21 (35%) kader. Determinan yang berhubungan dengan Penggunaan  Kuisioner Pra Skrining Perkembangan Anak pada Kader Posyandu di Wilayah Kerja Puskesmas Benteng Bangka Tengah adalah keikutsertaan kader dalam pelatihan KPSP, ketersediaan sarana dan prasaran dan dukungan tenaga kesehatan. Puskesmas Benteng agar dapat memfasilitasi pelatihan KPSP bagi kader yang belum terlatih agar kemampuan kader dapat meningkat sehingga penggunaan KPSP dapat lebih merata.
Edukasi Pencegahan Stunting Berbasis Aplikasi Android Dalam Meningkatkan Pengetahuan Dan Sikap Ibu
Authors: FITRIAMI ELFIZA , Galaresa Achmad Vindo
Published: February 2022

Salah satu permasalahan tumbuh kembang pada balita adalah stunting. Stunting atau rendahnya index TB/U disebabkan oleh  kondisi sosial ekonomi, gizi ibu saat hamil, penyakit penyerta pada bayi, kurangnya asupan gizi pada bayi dan pola asuh serta tingkat pendidikan orang tua balita. Indonesia merupakan negara berkembang yang berkontribusi dalam pertumbuhan angka stunting pada balita di dunia, dimana saat ini Indonesia merupakan peringkat ke lima kejadian stunting pada balita di dunia. Berdasarkan data UNICEF (2020) menyebutkan angka kejadian stunting meningkat secara global sebasar 15% dikarenakan covid-19 pada tahun 2020. Sedangkan data menurut Kementerian Kesehatan Indonesia menyebutkan angka kejadian stunting cukup tinggi yaitu, 27,67% pada tahun 2020. Tujuan penelitian adalah mengetahui pengaruh edukasi stunting berbasis aplikasi android untuk meningkatkan pengetahuan dan sikap ibu sehingga kejadian stunting pada baduta dapat dicegah. Teknik sampling yang digunakan adalah purposive sampling. Alat yang akan digunakan adalah aplikasi media berbasis android, software WHO anthro, timbangan berat badan, microtoise dan kuesioner. Analisis data dengan menggunakan uji non parametrik (wilcoxon). Penelitian dilakukan di Puskesmas Tenayan Raya Pekanbaru dengan jumlah sampel 54 orang responden. Terdapat pengaruh edukasi stunting menggunakan aplikasi android (p) 0,0001<0,05 terhadap peningkatan pengetahuan dan sikap ibu di Puskemas Tenayan Raya Pekanbaru. Edukasi stunting menggunakan aplikasi android terbukti efektif tapi untuk kedepannya disarankan menggunakan lebih dua media edukasi stunting.
Pengaruh Practice Based Simulation Model Terhadap Peningkatan Psikomotor dan Self Efficacy
Authors: Galaresa Achmad Vindo , Fitriami Elfiza
Published: February 2022

Patient Simulation yang dapat berperan secara nyata atau High Fidelity Simulation  (HFS) belum banyak diterapkan di Indonesia. Practice based simulation model (PBSM) merupakan alternatif dari HFS karena dapat mempengaruhi skill performance dan self efficacy. Tujuan penelitian ini untuk menganalisis pengaruh PBSM terhadap psikomotor dan self efficacy mahasiswa keperawatan di nursing skill laboratory. Penelitian menggunakan metode kuantitatif (Quasy Eksperimen), dengan pendekatan pretest-posttest without control group. Populasi penelitian ini adalah mahasiswa di STIKes PMC pekanbaru. Pengambilan sampel menggunakan tehnik nonprobability sampling dengan 32 orang responden serta analisis data menggunakan Wilcoxon. PBSM berpengaruh terhadap psikomotor dan self efficacy (p) 0,000 < 0,05, kemampuan berpikir secara sadar memiliki kapasitas yang relatif terbatas dalam otak sehingga perlu dilatih dengan berbagai pendekatan ilmiah dan PBSM terbukti efektif meningkatkan psikomotor dan self efficacy. PBSM mempunyai kelebihan untuk meningkatkan psikomotor dan self efficacy mahasiswa, tetapi perlu dilakukan pendalam lebih lanjut terkait metode PBSM dengan cara, durasi waktu dan teknik pengukuran yang lebih berbeda.
Analisis Persepsi Masyarakat Dengan Sikap Memilih Pengobatan Tradisional Lo’i Keta Daripada Ke Rumah Sakit Di Era Pandemi Covid-19
Authors: Din Junai , Yuliana Sri , Rahman Arif
Published: February 2022

Era Pandemik Covid-19 mengubah perilaku masyarakat mencari pengobatan alternatif untuk meningkatkan daya imunitas tubuh dalam pencegahan penularan covid-19. Loi Keta merupakan obat tradisional yang dipercayai masyaraktat sebagai pencegahan dan pengobatan berbagai macam penyakit serta dapat meningkatakan imunitas tubuh saat pandemi covid-19. Penelitian ini untuk menganalisis persepsi dan sikap masyarakat dalam memilih pengobatan tradisional Loi Keta saat pandemi covid-19. Penelitian ini adalah penelitian kualitatif menggunakan purposive sampling, sampel sebanyak 15 partisipan. Hasil: Kembalinya perilaku konsumsi obat tradisional Lo’i Keta saat pandemi covid-19, karena takut tertular covid di fasilitas kesehatan. Loi keta dipercaya dapat meningkatkan imunitas tubuh, aman digunakan dan mudah didapatkan oleh masyarakat. Pemanfaatan Loi Keta dipercayai masyarakat sebagai pencegahan dan pengobatan penyakit kulit, bisul (Furunkel), cacat air (varicella), Gastritis, Liver, Cancer dan demam serta meningkat imunitas antibodi. Cara penggunaan obat tradisional Loi Keta yaitu diminum, dikunyah dan dibaluri pada lokasi yang sakit. Optimalisasi penggunaan obat tradisional  Loi Keta perlu di uji laboratorium untuk mengetahui kandungan pada Loi Keta.
Faktor-Faktor Yang Berhubungan dengan Kejadian Dysmenorrhea Primer Pada Remaja Putri
Authors: Leni Marleni
Published: February 2022

Dysmenorrhea adalah penyakit menstruasi yang menyebabkan ketidaknyamanan fisik dan dapat mengganggu aktivitas sehari-hari. Dysmenorrhea sering menyerang remaja putri diusia produktif. Angka kejadian Dysmenorrhea di dunia lebih dari 50% perempuan mengalami Dysmenorrhea, sedangkan di Indonesia mencapai 55% remaja mengalami Dysmenorrhea. Hasil studi pendahuluan diketahui dari 20 siswi terdapat 11 orang (55%) yang mengalami dysmenorrhea dan 9 orang (45%) tidak mengalami dysmenorrhe. Tujuan penelitian ini adalah mengetahui faktor-faktor yang berhubungan dengan Dysmenorrhea. Metode : Penelitian ini merupakan penelitian deskriptif analitik dengan rancangan cross sectional. Populasi penelitian ini adalah seluruh remaja putri kelas X SMA Negeri 1 Banguntapan Bantul sebanyak 106 orang. Teknik sampling yang digunakan adalah proportionate stratified random sampling dengan jumlah sampel 84 orang. Analisis data menggunakan uji Chi-square. Hasil : Remaja putri yang mengalami dysmenorrhea Primer di SMA Negeri 1 Banguntapan Bantul sebesar 77,4%. Ada hubungan antara riwayat dysmenorrhea pada keluarga dengan kejadian dysmenorrhea (p value=0,000). Tidak ada hubungan antara Menarche di usia dini, Banyaknya darah menstruasi, Lama menstruasi, dan Status gizi dengan kejadian dysmenorrhea. esimpulan: Faktor yang mempengaruhi kejadian dysmenorrhea pada remaja putri kelas X di SMA Negeri 1 Banguntapan Bantul adalah riwayat nyeri menstruasi keluarga
Doing the Organization’s Work—Transcription for All Practical Governmental Purposes
Authors: Holder Alex , Elsey Christopher , Kolanoski Martina , Brooker Phillip , Mair Michael
Published: February 2022

By comparing two distinct governmental organizations (the US military and NASA) this paper unpacks two main issues. On the one hand, the paper examines the transcripts that are produced as part of work activities in these worksites and what the transcripts reveal about the organizations themselves. Additionally, the paper analyses what the transcripts disclose about the practices involved in their creation and use for practical purposes in these organizations. These organizations have been chosen as transcription forms a routine part of how they operate as worksites. Further, the everyday working environments in both organizations involve complex technological systems, as well as multi-party interactions in which speakers are frequently spatially and visually separated. In order to explicate these practices, the article draws on the transcription methods employed in ethnomethodology and conversation analysis research as a comparative resource. In these approaches audio-video data is transcribed in a fine-grained manner that captures temporal aspects of talk, as well as how speech is delivered. Using these approaches to transcription as an analytical device enables us to investigate when and why transcripts are produced by the US military and NASA in the specific ways that they are, as well as what exactly is being re-presented in the transcripts and thus what was treated as worth transcribing in the interactions they are intended to serve as documents of. By analysing these transcription practices it becomes clear that these organizations create huge amounts of audio-video “data” about their routine activities. One major difference between them is that the US military selectively transcribe this data (usually for the purposes of investigating incidents in which civilians might have been injured), whereas NASA’s “transcription machinery” aims to capture as much of their mission-related interactions as is organizationally possible (i.e., within the physical limits and capacities of their radio communications systems). As such the paper adds to our understanding of transcription practices and how this is related to the internal working, accounting and transparency practices within different kinds of organization. The article also examines how the original transcripts have been used by researchers (and others) outside of the organizations themselves for alternative purposes.
The Force of the Argument Source: The Partiality of the Source Influences the Evaluation of Political Arguments
Authors: Herne Kaisa , Sipinen Josefina , Kestilä-Kekkonen Elina , Mattinen Laura , Söderlund Peter
Published: February 2022

We study the influence of argument sources on argument quality evaluations. Argument source refers to the person who present the argument. We ask whether partial, impartial and reluctant sources generate different evaluations of argument quality. We explore the source effect via a survey experiment where participants are asked to evaluate the quality of political arguments. Previous research on source partiality mainly concerns persuasion. The results from these studies suggest that source characteristics such as expertise and trustworthiness affect the persuasiveness of communication. Both impartial and reluctant sources have been observed to promote persuasion, whereas partial sources tend to hinder it. However, the evidence on the difference between impartial and reluctant sources are inconclusive, and research on argument quality evaluations is scarce. In our study, respondents are randomly allocated into four conditions according to who presents a political argument: Control (no argument source); Partial Source, Reluctant Source and Impartial Source. Our results show that overall impartial sources give rise to higher evaluations of argument quality in comparison to reluctant sources, but not in comparison to partial sources. Furthermore, reluctant sources are also perceived low in credibility.
Automatic Thoughts and Facial Expressions in Cognitive Restructuring With Virtual Agents
Authors: Shidara Kazuhiro , Tanaka Hiroki , Adachi Hiroyoshi , Kanayama Daisuke , Sakagami Yukako , Kudo Takashi , Nakamura Satoshi
Published: February 2022

Cognitive restructuring is a well-established mental health technique for amending automatic thoughts, which are distorted and biased beliefs about a situation, into objective and balanced thoughts. Since virtual agents can be used anytime and anywhere, they are expected to perform cognitive restructuring without being influenced by medical infrastructure or patients' stigma toward mental illness. Unfortunately, since the quantitative analysis of human-agent interaction is still insufficient, the effect on the user's cognitive state remains unclear. We collected interaction data between virtual agents and users to observe the mood improvements associated with changes in automatic thoughts that occur in user cognition and addressed the following two points: (1) implementation of a virtual agent that helps a user identify and evaluate automatic thoughts; (2) identification of the relationship between a user's facial expressions and the extent of the mood improvement subjectively felt by users during the human-agent interaction. We focus on these points because cognitive restructuring by a human therapist starts by identifying automatic thoughts and seeking sufficient evidence to find balanced thoughts (evaluation of automatic thoughts). Therapists also use such non-verbal behaviors as facial expressions to detect changes in a user's mood, which is an important indicator for guidance. Based on the results of this analysis, we provide a technical guidance framework that fully automates the identification and evaluation of automatic thoughts to achieve a virtual agent that can interact with users by taking into account their verbal and non-verbal behaviors in face-to-face situations. This research supports the possibility of improving the effectiveness of mental health care in cognitive restructuring using virtual agents.
Case Report: Biatrial Myxoma With Pulmonary Embolism and Cerebral Embolism: Clinical Experience and Literature Review
Authors: Ran Haifeng , Chen Guiqin , Hu Jie , He Yulun , Liu Junwei , Li Fangling , Liu Heng , Zhang Tijiang
Published: February 2022

Cardiac myxoma is a common benign primary intracardiac tumor in the general population, and it is generally characterized as a benign tumor, and the morbidity of biatrial myxoma is low. Cases of biatrial myxoma in young patients are extremely rare. Furthermore, severe complications of cardiac myxoma, such as cerebral embolism, can have fatal consequences. Imaging can effectively assist in making a correct diagnosis and a safe and efficient surgical treatment plan. In this case report, we describe a unique case of a young woman who presented with biatrial myxoma accompanied by pulmonary embolism and cerebral embolism. Computed tomography pulmonary angiography (CTPA) detected multiple filling defects in the bilateral cardiac and bilateral inferior pulmonary artery basal branches. Transthoracic echocardiography (TTE) revealed irregular isoechoic masses in the bilateral atrium. Postoperative histopathology confirmed a biatrial myxoma. The patient was discharged on the ninth day after surgery.
Addressing Study Skills, Learning Theory and Critical Thinking Skills in Principles of Economics Courses
Authors: Howard Eric , Sarbaum Jeffrey
Published: February 2022

The Wall Street Journal recently noted that United States “employers say too many schools aren’t teaching students the skills they need—or even basic critical thinking”. This paper 1) motives the need for economics and other college educators to i) address study habits in the classroom, (ii) explain the importance of critical thinking skills, and (iii) define what critical thinking is to introductory students; and 2) provides an overview of how the authors accomplish this in their classrooms. The authors encourage readers to borrow this information to create a study skills and critical thinking module for their own students when teaching principles courses.
A Mini-Review of Pediatric Anthropometrics as Predictors of Future Insulin Resistance
Authors: DeLacey Sean , Josefson Jami L.
Published: February 2022

The impact of rising rates of childhood obesity is far reaching. Metabolic syndrome in children is increasing, yet for most children the consequences of excess adiposity will manifest in adulthood. Excess early fat accrual is a risk factor for future insulin resistance. However, certain types of fat and patterns of fat distribution are more relevant than others to metabolic risk. Therefore, adiposity measures are important. The link between childhood obesity and future insulin resistance was initially established with body mass index (BMI), but BMI is an in imperfect measure of adiposity. It is worthwhile to evaluate other anthropometrics as they may more accurately capture metabolic risk. While measures such as waist to height ratio are established as superior screening measures in adulthood - the findings are not as robust in pediatrics. Emerging evidence suggests that alternative anthropometrics may be slightly superior to BMI in identifying those youth most at risk of developing insulin resistance, but the clinical significance of that superiority appears limited. Increasing study is needed in longitudinal and varied cohorts to identify which pediatric anthropometric best predicts adult insulin resistance. We review alternative anthropometrics as predictors of future insulin resistance and identify current gaps in knowledge and potential future directions of inquiry.
Systematic Review of Safety and Efficacy of Second- and Third-Generation CD20-Targeting Biologics in Treating Immune-Mediated Disorders
Authors: Kaegi Celine , Wuest Benjamin , Crowley Catherine , Boyman Onur
Published: February 2022

Background

B cells can contribute to immune-mediated disorders. Targeting CD20 has proved to be efficacious in several B cell-mediated immunopathologies, as illustrated by the use of rituximab, the first anti-CD20 monoclonal antibody (mAb). Following rituximab, second- and third-generation anti-CD20 mAbs have been developed and tried in immune-mediated diseases, including obinutuzumab, ocrelizumab, ofatumumab, ublituximab, and veltuzumab. However, their safety and efficacy has not been systematically reviewed.

Objective

To evaluate safety and efficacy of obinutuzumab, ocrelizumab, ofatumumab, ublituximab, and veltuzumab for the treatment of immune-mediated disorders compared to placebo, conventional treatment or other biologics.

Methods

The PRISMA checklist guided the reporting of the data. We searched the PubMed database between 4 October 2016 and 22 July 2021 concentrating on immune-mediated disorders.

Results

The literature search identified 2220 articles. After screening titles and abstracts against the inclusion and exclusion criteria and assessing full texts, 27 articles were finally included in a narrative synthesis.

Conclusions

Obinutuzumab has shown promising results in a case series of patients with phospholipase A2 receptor-associated membranous nephropathy and mixed results in systemic lupus erythematosus. Ocrelizumab has been approved for the use in patients with relapsing-remitting multiple sclerosis and primary progressive multiple sclerosis. Ocrelizumab was also tested in patients with rheumatoid arthritis, demonstrating promising results, and in systemic lupus erythematosus, revealing mixed results; however, in these conditions, its use was associated with increased risk of serious infections. Ofatumumab received approval for treating patients with relapsing-remitting multiple sclerosis. Moreover, ofatumumab showed promising results in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis, rheumatoid arthritis, and systemic lupus erythematosus, as well as mixed results in phospholipase A2 receptor-associated membranous nephropathy. Ublituximab was assessed in relapsing-remitting multiple sclerosis and neuromyelitis optica spectrum disorder, with promising results, however, the included number of patients was too small to conclude. Veltuzumab was tested in patients with immune thrombocytopenia resulting in improved platelet counts.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier CRD4201913421.
Folate Receptor Beta for Macrophage Imaging in Rheumatoid Arthritis
Authors: Steinz Maarten M. , Ezdoglian Aiarpi , Khodadust Fatemeh , Molthoff Carla F. M. , Srinivasarao Madduri , Low Philip S. , Zwezerijnen Gerben J. C. , Yaqub Maqsood , Beaino Wissam , Windhorst Albert D. , Tas Sander W. , Jansen Gerrit , van der Laken Conny J.
Published: February 2022

Non-invasive imaging modalities constitute an increasingly important tool in diagnostic and therapy response monitoring of patients with autoimmune diseases, including rheumatoid arthritis (RA). In particular, macrophage imaging with positron emission tomography (PET) using novel radiotracers based on differential expression of plasma membrane proteins and functioning of cellular processes may be suited for this. Over the past decade, selective expression of folate receptor β (FRβ), a glycosylphosphatidylinositol-anchored plasma membrane protein, on myeloid cells has emerged as an attractive target for macrophage imaging by exploiting the high binding affinity of folate-based PET tracers. This work discusses molecular, biochemical and functional properties of FRβ, describes the preclinical development of a folate-PET tracer and the evaluation of this tracer in a translational model of arthritis for diagnostics and therapy-response monitoring, and finally the first clinical application of the folate-PET tracer in RA patients with active disease. Consequently, folate-based PET tracers hold great promise for macrophage imaging in a variety of (chronic) inflammatory (autoimmune) diseases beyond RA.
Explainable Artificial Intelligence for Mechanics: Physics-Explaining Neural Networks for Constitutive Models
Authors: Koeppe Arnd , Bamer Franz , Selzer Michael , Nestler Britta , Markert Bernd
Published: February 2022

(Artificial) neural networks have become increasingly popular in mechanics and materials sciences to accelerate computations with model order reduction techniques and as universal models for a wide variety of materials. However, the major disadvantage of neural networks remains: their numerous parameters are challenging to interpret and explain. Thus, neural networks are often labeled as black boxes, and their results often elude human interpretation. The new and active field of physics-informed neural networks attempts to mitigate this disadvantage by designing deep neural networks on the basis of mechanical knowledge. By using this a priori knowledge, deeper and more complex neural networks became feasible, since the mechanical assumptions can be explained. However, the internal reasoning and explanation of neural network parameters remain mysterious. Complementary to the physics-informed approach, we propose a first step towards a physics-explaining approach, which interprets neural networks trained on mechanical data a posteriori. This proof-of-concept explainable artificial intelligence approach aims at elucidating the black box of neural networks and their high-dimensional representations. Therein, the principal component analysis decorrelates the distributed representations in cell states of RNNs and allows the comparison to known and fundamental functions. The novel approach is supported by a systematic hyperparameter search strategy that identifies the best neural network architectures and training parameters. The findings of three case studies on fundamental constitutive models (hyperelasticity, elastoplasticity, and viscoelasticity) imply that the proposed strategy can help identify numerical and analytical closed-form solutions to characterize new materials.
COVID-19 Compulsory Vaccination: Legal and Bioethical Controversies
Authors: Gibelli Filippo , Ricci Giovanna , Sirignano Ascanio , De Leo Domenico
Published: February 2022

The imposition of compulsory health treatments has always been a subject of animated legal and bioethical debate. What is at stake are two opposing interests that are in their own way protected by international treaties and constitutional provisions: the right to individual self-determination and the duty to defend and preserve collective safety. The global health crisis related to the COVID-19 pandemic has placed the issue of the legitimacy of imposing compulsory vaccination at the center of the multifaceted debate on pandemic health policies. Indonesia, Tajikistan, Turkmenistan, and the Federated States of Micronesia are currently the only four countries in the world where the COVID-19 vaccine is mandatory for all citizens. Italy was the first country in the European Union to introduce this obligation, effective from 8 January 2022 by virtue of the decree-law approved on 5 January 2022, which imposed vaccination compulsory for everyone over the age of 50. Similar paths have been undertaken by Greece and Austria, where the obligation will start respectively on 16 January 2022 (for citizens aged over 60) and 1 February 2022 (for citizens of all ages). However, in many civilized countries, “selective” forms of compulsory vaccination, i.e., aimed at specific categories of individuals, especially healthcare professionals, are already provided for. The present work aims to offer a concise and as much as possible exhaustive overview of the main ethical and legal issues related to compulsory COVID-19 vaccination, with reference to both the Italian and the international context, mainly European.
Are Bacterial Persisters Dormant Cells Only?
Authors: Zou Jin , Peng Bo , Qu Jiuxin , Zheng Jun
Published: February 2022

Bacterial persisters are a sub-population of phenotypic variants that tolerate high concentrations of antibiotics within the genetically homogeneous cells. They resume division upon the removal of drugs. Bacterial persistence is one of major causes of antibiotic treatment failure and recurrent infection. Cell dormancy, triggered by toxin/antitoxin pair, (p)ppGpp, SOS response and ATP levels, is known to be the mechanistic basis for persistence. However, recent studies have demonstrated that bacteria with active metabolism can maintain persistence by lowering intracellular antibiotic concentration via an efflux pump. Additionally, others and our work have showed that cell wall deficient bacteria (CWDB), including both L-form and spheroplasts that produced by β-lactam antibiotics, are associated with antibiotic persistence. They are not dormant cells as their cell walls have been completely damaged. In this review, we discuss the various types of persisters and highlight the contribution of non-walled bacteria on bacterial persistence.
Soil Water Content Shapes Microbial Community Along Gradients of Wetland Degradation on the Tibetan Plateau
Authors: Li Meng , Zhang Kerou , Yan Zhongqing , Liu Liang , Kang Enze , Kang Xiaoming
Published: February 2022

Soil microbes are important components in element cycling and nutrient supply for the development of alpine ecosystems. However, the development of microbial community compositions and networks in the context of alpine wetland degradation is unclear. We applied high-throughput 16S rRNA gene amplicon sequencing to track changes in microbial communities along degradation gradients from typical alpine wetland (W), to wet meadow (WM), to typical meadow (M), to grassland (G), and to desert (D) in the Zoige alpine wetland region on the Tibetan Plateau. Soil water content (SWC) decreased as wetland degradation progressed (79.4 and 9.3% in W and D soils, respectively). Total organic carbon (TOC), total nitrogen (TN), and total phosphorus (TP) increased in the soils of WM, and then decreased with alpine wetlands degradation from WM to the soils of M, G, and D, respectively. Wetland degradation did not affect microbial community richness and diversity from W soils to WM, M, and G soils, but did affect richness and diversity in D soils. Microbial community structure was strongly affected by wetland degradation, mainly due to changes in SWC, TOC, TN, and TP. SWC was the primary soil physicochemical property influencing microbial community compositions and networks. In wetland degradation areas,Actinobacteriota,Acidobacteriota,Cholorflexi, andProteovacteriaclosely interacted in the microbial network. Compared to soils of W, WM, and M,Actinobacteriotaplayed an important role in the microbial co-occurrence network of the G and D soils. This research contributes to our understanding of how microbial community composition and networks change with varied soil properties during degradation of different alpine wetlands.
Electro-Acupuncture Improve the Early Pattern Separation in Alzheimer’s Disease Mice via Basal Forebrain-Hippocampus Cholinergic Neural Circuit
Authors: Li Long , Li Jianhong , Dai Yaling , Yang Minguang , Liang Shengxiang , Wang Zhifu , Liu Weilin , Chen Lidian , Tao Jing
Published: February 2022

Objectives

To explore the effect of electro-acupuncture (EA) treatment on pattern separation and investigate the neural circuit mechanism involved in five familial mutations (5 × FAD) mice.

Methods

Five familial mutations mice were treated with EA at Baihui (DU20) and Shenting (DU24) acupoints for 30 min each, lasting for 4 weeks. Cognitive-behavioral tests were performed to evaluate the effects of EA treatment on cognitive functions. 1H-MRS, Nissl staining, immunohistochemistry, and immunofluorescence were performed to examine the cholinergic system alteration. Thioflavin S staining and 6E10 immunofluorescence were performed to detect the amyloid-β (Aβ). Furthermore, hM4Di designer receptors exclusively activated by designer drugs (DREADDs) virus and long-term clozapine-N-oxide injection were used to inhibit the medial septal and vertical limb of the diagonal band and dentate gyrus (MS/VDB-DG) cholinergic neural circuit. Cognitive-behavioral tests and immunofluorescence were performed to investigate the cholinergic neural circuit mechanism of EA treatment improving cognition in 5 × FAD mice.

Results

Electro-acupuncture treatment significantly improved spatial recognition memory and pattern separation impairment, regulated cholinergic system via reduction neuron loss, upregulation of choline/creatine, choline acetyltransferase, vesicular acetylcholine transporter, and downregulation of enzyme acetylcholinesterase in 5 × FAD mice. Aβ deposition was reduced after EA treatment. Subsequently, the monosynaptic hM4Di DREADDs virus tracing and inhibiting strategy showed that EA treatment activates the MS/VDB-DG cholinergic neural circuit to improve the early pattern separation. In addition, EA treatment activates this circuit to upregulating M1 receptors positive cells and promoting hippocampal neurogenesis in the dentate gyrus (DG).

Conclusion

Electro-acupuncture could improve the early pattern separation impairment by activating the MS/VDB-DG cholinergic neural circuit in 5 × FAD mice, which was related to the regulation of the cholinergic system and the promotion of neurogenesis by EA treatment.
Association Between Anatomical Location and Hematoma Expansion in Deep Intracerebral Hemorrhage
Authors: Song Lei , Qiu Xiao-Ming , Guo Ting-Ting , Zhou Hang , Tang Dong-Fang , Wang Long-Sheng , Fu Yu-Fei , Chen Hui , Mao Hua-Qing , Wang Hai-Bao , Yu Yong-Qiang
Published: February 2022

Objective

To establish the relationship between hematoma sites of involvement and hematoma expansion (HE) in patients with deep intracerebral hemorrhage (ICH).

Methods

Eligible patients with deep ICH admitted to hospital within 6 hours of onset between 2018 and 2020 were included in this retrospective multi-center study. Individuals with secondary ICH were excluded. The volume of HE was evaluated based on admission and follow-up computed tomography scans. Associations between deep ICH sites of involvement and HE were examined using multivariable logistic regression analysis while adjusting for confounding covariates of HE.

Results

We enrolled 583 individuals from three stroke centers. Data from a final total of 460 patients were used in the analysis; of these patients, 159 (34.6%) had HE. In the crude model without adjustment, external capsule, anterior limb of the internal capsule, and posterior limb of the internal capsule (PLIC) involvement were correlated with HE. After fully adjusted models for sex, age, intraventricular hemorrhage, Glasgow Coma Scale admission score, baseline ICH volume, and time from onset to initial computed tomography, multivariable logistic regression revealed that the PLIC is a robust predictor of HE in patients with deep ICH (adjusted odds ratio = 2.73; 95% confidence interval = 1.75–4.26; p < 0.001).

Conclusion

Involvement of the posterior limb of the internal capsule in deep hemorrhage could be a promising predictor of HE.
Transcranial Direct Current Stimulation (tDCS) as a Useful Rehabilitation Strategy to Improve Cognition in Patients With Alzheimer's Disease and Parkinson's Disease: An Updated Systematic Review of Randomized Controlled Trials
Authors: Cammisuli Davide Maria , Cignoni Fabio , Ceravolo Roberto , Bonuccelli Ubaldo , Castelnuovo Gianluca
Published: February 2022

Alzheimer's disease (AD) and Parkinson's disease (PD) are neurodegenerative disorders characterized by cognitive impairment and functional decline increasing with disease progression. Within non-pharmacological interventions, transcranial direct current stimulation (tDCS) might represent a cost-effective rehabilitation strategy to implement cognitive abilities with positive implications for functional autonomy and quality-of-life of patients. Our systematic review aimed at evaluating the effects of tDCS upon cognition in people suffering from AD and PD. We searched for randomized controlled trials (RCTs) into PubMed, Web of Science, and Cochrane Library. Three review authors extracted data of interest, with neuropsychological tests or experimental cognitive tasks scores as outcome measures. A total of 17 RCTs (10 trials for AD and 7 trials for PD) were included. Compared with sham stimulation, tDCS may improve global cognition and recognition memory in patients with AD and also some executive functions (i.e., divided attention, verbal fluency, and reduction of sensitivity to interference) in patients with PD. Criticism remains about benefits for the other investigated cognitive domains. Despite preliminary emerging evidences, larger RCTs with common neuropsychological measures and long-term follow-ups establishing longevity of the observed effects are necessary for future research in applied psychology field, alongside improved clinical guidelines on the neurodegenerative disorders pertaining electrodes montage, sessions number, duration and intensity of the stimulation, and cognitive battery to be used.
Impaired Lower Limb Proprioception in Spinocerebellar Ataxia Type 3 and Its Affected Factors
Authors: Liu Xia-Hua , Wang Zhi-Yong , Li Ying , Xu Hao-Ling , Sikandar Arif , Ni Jun , Gan Shi-Rui
Published: February 2022

Background

Spinocerebellar ataxia type 3 (SCA3) is one of the most common hereditary neurodegenerative diseases. Postural control dysfunction is the main symptom of SCA3, and the proprioceptive system is a critical sensory component of postural control. Accordingly, proprioception quantification assessment is necessary in monitoring the progression of SCA3.

Objective

We aimed to quantitatively assess lower limb proprioception and investigate the relationship between proprioception and clinical characteristics in patients with SCA3.

Methods

A total of 80 patients with SCA3 and 62 health controls were recruited, and their lower limb proprioception was measured using the Pro-kin system. Clinical characteristics of the SCA3 patients were collected. Multivariable linear regression was used to investigate potential affected factors for lower limb proprioception.

Results

We found that the patients with SCA3 experience poorer lower limb proprioception characterized by significant impairment in the average trace error (ATE) and time to carry out the test time execution (TTE) compared to controls (P < 0.05). Moreover, there were significant differences in TTE between the right and left lower limbs (P < 0.05) of the patients. Regression analyses revealed that increasing age at onset (AAO) predicts poorer lower limb proprioception for both ATE (β = 2.006, P = 0.027) and TTE (β = 1.712, P = 0.043) and increasing disease duration predicts poorer lower limb proprioception for ATE (β = 0.874, P = 0.044). AAO (β = 0.328, P = 0.019) along with the expanded alleles (β = 0.565, P = 0.000) could affect the severity of ataxia. By contrast, ATE (β = 0.036, P = 0.800) and TTE (β = −0.025, P = 0.862) showed no significant predictors.

Conclusions

Lower limb proprioception in patients with SCA3 is significantly impaired when compared to healthy controls. Increasing AAO and disease duration are related to impaired lower limb proprioception.