bluuebunny/crossref_metadata_2025 huggingface dataset:
Up-regulation of MTHFD2 is associated with clinicopathological characteristics and poor survival in ovarian cancer, possibly by regulating MOB1A signaling
Authors: Cui Xiangrong , Su Huancheng , Yang Jiaolin , Wu Xueqing , Huo Kai , Jing Xuan , Zhang Sanyuan
Published: February 2022

Background

MTHFD2 is a folate-coupled metabolic enzyme, which has been proved to participant in the metabolic reprogramming and tumor cell-sustaining proliferative capacity. However, the function of MTHFD2 in the development of ovarian cancer and its potential molecular mechanisms is still unclear.

Materials and methods

The expression, various mutations, prognosis, and related network signaling pathways of MTHFD2 were analyzed using bioinformatics-related websites, including Oncomine, GEPIA, UCSC, cBioPortal, KM Plotter, TISIDB and TIMER. The prognostic value of MTHFD2 expression was validated by our own ovarian cancer samples using RT-qPCR. The migration ad invasion of ovarian cancer cells were further analyzed by CCK-8 and transwell assay. The Western-blot assay was performed to explore the protein levels of MTHFD2 and MOB1A.

Results

We obtained the following important results. (1) MTHFD2 expression was markedly up-regulated in ovarian cancer than normal samples. (2) Among patients with ovarian cancer, those with higher MTHFD2 expression was associated with lower survival rate. (3) The major mutation type of MTHFD2 in ovarian cancer samples was missense mutation. (4) MTHFD2 knockdown inhibited proliferation, migration, invasion, as well as the expression of MOB1A in vitro.

Conclusion

MTHFD2, as a NAD + -dependent enzyme, accelerated tumor progression by up-regulating MBO1A, suggesting that this protein may be an independent prognostic factor and a potential therapeutic target for future ovarian cancer treatments.
Pregnancy Management in Multiple Sclerosis and Other Demyelinating Diseases
Authors: Bove Riley M. , Houtchens Maria K.
Published: February 2022

PURPOSE OF REVIEW

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSDs) are chronic autoimmune demyelinating conditions of the central nervous system often diagnosed in women of childbearing age. Therefore, safe family planning, pregnancy, and postpartum management are important considerations for many patients with MS or NMOSD.

RECENT FINDINGS

Many patients with MS can safely become pregnant and remain well throughout pregnancy and the postpartum period with guidance from specialists on treatment planning. During pregnancy, women with NMOSD may face some increased risk of both neurologic and obstetric complications. Recent attention has focused on evaluating the safety of pharmacologic agents during pregnancy and breastfeeding. Unfortunately, care disparities remain common in both MS and NMOSD, and recovery of function is often not optimally managed in the postpartum period.

This article reviews the current state of knowledge on peripartum management in these neurologic conditions and offers practical considerations and case studies. When caring for women with MS and NMOSD of childbearing potential, treatment planning is important to optimize outcomes in both patient and newborn.
DFT Analysis of the Formation of a Titanium n-Butoxide Derivative [[Ti[O(CH2)3CH3]2Cl·OH]2]2 through OH Bridge Formation and Molecular Interactions between Butoxy Groups
Authors: Koike Katsuhiko
Published: February 2022

The structural changes of titanium n-butoxide derivatives in coatings prepared from a mixture of titanium butoxide in concentrated hydrochloric acid, which contains a five-coordinated titanium complex (Ti[O(CH2)3CH3]3Cl·H2O), are investigated using density functional theory calculations. Initially, the complex is stabilized owing to dimer formation through molecular interactions. Subsequently, stabilization occurs due to OH bridge formation upon butanol elimination. The two dimers then unite to form [[Ti[O(CH2)3CH3]2Cl·OH]2]2 owing to the molecular interactions between the butoxy groups.
Modernity and Contemporaneity
Authors: Protopapadakis Evangelos D. , Arabatzis Georgios , Đikanović Mina , Iliopoulos Georgios , Jevtić Nevena , Kaluđerović Željko , Kormas Panagiotis , Moutzouri Antonia , Popović Una , Prole Dragan , Psarros Nikos , Roussidi Konstantina , Rujević Goran
Published: February 2022

Modernity and Contemporaneity is the 3rd volume in the Hellenic-Serbian Philosophical Dialogue Series, a project that was initiated as an emphatic token of the will and commitment to establish permanent and fruitful collaboration between two strongly bonded Departments of Philosophy, this of the National and Kapodistrian University of Athens, and that of the University of Novi Sad respectively. This collaboration was founded from the very beginning upon friendship, mutual respect and strong engagement, as well us upon our firm resolution to establish a solid continuity in the editing project. The publication of this volume allows us to entertain feelings of contentment and confidence that this objective of the project has been accomplished.
Sztuka popularna jako źródło uczenia się dorosłych
Authors: Litawa Aleksandra
Published: February 2022

W artykule podjęto próbę uzasadnienia tezy, że sztuka popularna może stanowić dla dorosłych źródło uczenia się. Problem rozpatrywano w kontekście nurtu pedagogii publicznej oraz andragogicznych koncepcji uczenia się autorstwa Jacka Mezirowa oraz Knuda Illerisa. Dla zobrazowania problemu posłużono się wybranymi tekstami kultury popularnej z dziedziny filmu, street artu i serialu telewizyjnego. Przeprowadzone analizy pozwoliły sformułować trzy wnioski. Po pierwsze, sztuka popularna może być źródłem transformatywnego uczenia się. Po drugie, uczenie się w relacji ze sztuką popularną może przebiegać w trzech wymiarach: poznawczym, emocjonalnym oraz społecznym. Trzeci wniosek pozwala uznać sztukę popularną za formę publicznej pedagogii.
Doświadczanie transnarodowych sieci – auto/biograficzne konstruowanie znaczeń
Authors: Słowik Aneta
Published: February 2022

Autorka w swoim artykule, wykorzystując auto/biograficzny wywiad narracyjny, przedstawia konstruowane znaczenia doświadczania transnarodowych sieci (własnej – badaczki oraz narratorki-migrantki). Pomocny w tym procesie jest wybór teoretycznych podstaw, tj. transnarodowych sieci oraz wymiaru mikro w teoriach migracyjnych. Kolejno dokonuje identyfikacji transnarodowych sieci, które nazywa sieciami „przed”, „tam” i „po”, pokazując powiązania biografii badaczki z biografią narratorki.
Sprawozdanie z XXXIII Konferencji Naukowej Forum Pedagogów
Authors: Achremowicz Hanna , Pilawska-Gronostaj Roksana
Published: February 2022

W dniach 26–27 października 2021 roku odbyło się XXXIII Forum Pedagogów, cykliczna konferencja naukowa, która tym razem miała szczególny charakter. Oprócz części stricte naukowej konferencja wrocławska stała się okazją do uhonorowania profesora Jerzego Semkowa, który był jednym z pomysłodawców idei spotkań w ramach Forum Pedagogów. Tematyka tegorocznej konferencji og- niskowała się na problematyce andragogicznej, którą określał tytuł (Z)rozumieć teraźniejszość, myśleć o przyszłości – między wizją a praktyką w edukacji dorosłych. Została ona zorganizowana przez Zakład Edukacji Dorosłych i Studiów Kulturowych oraz Pracownię Metodologii Badań nad Edukacją Instytutu Pedagogiki Uniwersytetu Wrocławskiego. Konferencja została objęta patronatem honorowym Rektora Uniwersytetu Wrocławskiego prof. dr. hab. Przemysława Wiszewskiego. Patronat naukowy nad wydarzeniem objęło Akademickie Towarzystwo Andragogiczne. Organizację konferencji wspierali: doktorantki Szkoły Doktorskiej (Roksana Pilawska-Gronostaj i Hanna Achremowicz), studenci kierunku pedagogiki, specjalność: Edukacja Dorosłych i Marketing Społeczny oraz członkowie Inter- dyscyplinarnego Koła Naukowego Variograf.
Tabu językowe w arabskich przekładach Biblii
Authors: Król Iwona
Published: February 2022

Niniejszy artykuł przedstawiający wybrane rozwiązania translatorskie obecne we współczesnych przekładach tekstów biblijnych na język arabski stanowi poszerzenie badań Marka Pieli dotyczących przekładów Biblii hebrajskiej na język polski. Przeprowadzone przeze mnie analizy dotyczą głównie strategii przekładu wyrazów i wyrażeń należących do sfery tabu, przy czym skupiam się na takich aspektach, jak: dosłowność, dokładność, idiomatyczność, adekwatność stylistyczna czy ewentualne zniekształcenia sensu.
(DES)ENCUENTROS INTERESPECIES.TENSIONES EN TORNO A LA CAZA DEL JABALÍ EN URUGUAY.
Authors: Poliak Almeida Leticia
Published: February 2022

El presente artículo se centra en el estudio de la representación y los conflictos en torno a la caza del jabalí en Uruguay, entre cazadores, colectivos animalistas, conservacionistas y actores del Estado afines a la temática. En esta práctica, el perro de caza es fundamental para algunos cazadores en Uruguay, actividad en la cual muchas veces los perros resultan heridos o mueren. En este sentido, existen colectivos animalistas y conservacionistas que tienen diferentes posiciones frente a esta práctica, ya que argumentan que existe una amenaza al bienestar de los animales, o que la caza con perros genera impactos negativos en la conservación de especies nativas. En relación a esto, existen desconexiones y contradicciones desde el Estado en cuanto a políticas de protección animal que responden a diferentes conceptualizaciones y percepciones de los animales no humanos en nuestra sociedad. Muchas de estas categorías se contradicen con la definición de bienestar animal y las normativas existentes. Estas son criticadas tanto por activistas como por cazadores. Las diferentes categorizaciones generan precariedad al momento de elaborar políticas públicas, influyendo directamente en el imaginario del colectivo social y viceversa, lo cual dificulta la generación de propuestas dialogantes.
CAZA RECREATIVA, ¿POR QUÉ? UN ESTUDIO DE CASO ETNOGRÁFICO E HISTÓRICO DEL NORTE DE CHIPRE.
Authors: Betz-Heinemann Khalil Avi
Published: February 2022

In this paper I answer the question of why people, particularly men, hunt recreationally. I combine ethnography and archival research to explore the personal motivations of contemporary recreational hunters in Northern Cyprus. I then go on to examine histories of recreational hunting by different colonisers of Cyprus. In both past and present cases, my analysis reveals that recreational hunting is a personal practice in being free in the context of everyday life in a coercive civilisation. In addition, recreational hunting is recognised as being entangled with gains in political rights in the wake of the Enlightenment and its extension to newly free citizens, men in particular. Furthermore, the history of recreational hunting situates it as spatially juxtaposed against the fixed settlements of coercive civilization, echoing protected areas today. I conclude that male citizens hunt recreationally seeking a passing taste of elitist ways of being free, as it is a demonstration of the limited sovereignty over one’s life that being a legal citizen offers.
EN EL ENTRAMADO DEL BOSQUE: UNA EXPLORACIÓN SENSORIAL DE LOS PAISAJES DE CAZA EN ALEMANIA.
Authors: Gieser Thorsten
Published: February 2022

In this article I offer a sensory exploration of hunting landscapes in contemporary Germany. In a first step, I show how such landscapes are built on and materially structured as cultural landscapes through hunting practices. In the remainder of the article, I examine more specifically how hunters perceive this landscape while being engaged in hunting and looking for game animals. Drawing on Merleau-Ponty’s phenomenology of perception, I describe not only what “objects” hunters single out in this landscape as relevant for their practice. More importantly, I extend perception from a mere “object recognition” to the skilled sensing of perceptual Gestalt relations in the landscape, guided by embodied sensations. Hunters’ perception conceived this way thus becomes an atmospheric practice within the meshwork of a whole elemental weatherworld. I conclude by showing how a phenomenological understanding of hunters’ perception might help ethnographers to open up new horizons of more-than-human worlds.
Development of a new job satisfaction scale for healthcare staff in emergency departments
Authors: Naji Al Smadi Audai , Ariff Tengku Mohammad , Abugabah Ahed
Published: February 2022

Background/Aims

Assessing factors that affect job satisfaction among healthcare staff, and formulating comprehensive strategies to improve job satisfaction, is fundamental to healthcare organisations. This study aimed to develop and validate a tool to measure staff job satisfaction in emergency departments of hospitals in Jordan.

Methods

The job satisfaction scale was developed using a literature review, instrument validation and statistical testing using exploratory factor analysis and Cronbach's alpha. A self-administered questionnaire was sent to 200 healthcare staff working in emergency departments in hospitals in Jordan between 14 April and 5 May 2020.

Results

A total of 112 respondents returned a completed questionnaire. Exploratory factor analysis yielded 16 strong explanatory items that affect job satisfaction, which could be grouped into four domains: physical environment and workplace safety; supervisor support; promotion and compensation; and communication and relationships with coworkers. The tool was found to have good reliability and validity. Low to moderate levels of satisfaction were found in most domains.

Conclusions

The findings of this study provide evidence for the psychometric properties of a newly developed scale to measure the level of job satisfaction of healthcare staff working in emergency departments.
Accessing specialist healthcare: experiences of women diagnosed with advanced cervical cancer in Ghana
Authors: Hobenu Kafui Abra , Naab Florence
Published: February 2022

Background/Aims

Cervical cancer is a leading cause of death in women in Ghana, and is often only diagnosed at the advanced stage. This study explored the experiences of women diagnosed with advanced cervical cancer as they access specialist healthcare in Ghana.

Methods

The study was conducted at a radiotherapy centre in a teaching hospital in Ghana. Purposive sampling technique was used to select 15 women aged between 33 and 67 years with advanced cervical cancer. Face-to-face in-depth interviews were conducted to gather information from participants regarding their experiences of services. Interviews were audio recorded with participants' consent. Data were analysed using content analysis.

Results

Content analysis revealed three themes: diagnostic process, information concerns and healthcare staff's attitudes. The following subthemes were also identified: delays, misdiagnosis, information gaps, perceived lack of knowledge from healthcare staff, positive attitudes from healthcare staff and breaking bad news.

Conclusions

The findings highlight the need to educate healthcare professionals about the symptoms of cervical cancer to allow early and accurate diagnosis. Training is also needed to equip healthcare staff with the therapeutic communication skills and strategies required for communicating bad news to patients.
Considerations for speech and language therapy management of dysphagia in patients who are critically ill with COVID-19: a single centre case series
Authors: Clunie Gemma M , Bolton Lee , Lovell Lindsay , Bradley Elizabeth , Bond Cara , Bennington Sarah , Roe Justin
Published: February 2022

Background/Aims

Patients treated with intubation and tracheostomy for COVID-19 infection are at risk of increased incidence of laryngeal injury, dysphagia and dysphonia. Because of the novelty of the SARS-CoV-2 virus, little is known about the type of dysphagia patients experience as a result of infection and critical illness. The aim of this case series report was to progress understanding of COVID-19 and dysphagia following admission to an intensive care unit and to guide speech and language therapy clinical practice in the ongoing pandemic.

Methods

A retrospective case review was conducted of all patients at Imperial College Healthcare NHS Trust, London who underwent a tracheostomy because of COVID-19 and received an instrumental assessment of swallowing in the early stages of the pandemic.

Results

A total of 11 patients were identified, and descriptive statistics were used to present demographic data, with a narrative account of their dysphagia profile used to describe presentation. Causes and presentation of dysphagia were heterogenous, with each patient requiring individualised clinical management to maximise outcome. A positive trend was seen in terms of recovery trajectory and progressing to oral intake.

Conclusions

This study reports on early experience of the presentation of dysphagia in patients with COVID-19 and demonstrates the value of instrumental assessment. It indicates the need for further research to consolidate knowledge and guide clinical practice.
RESEARCH ROUNDUP
Authors: Winter George
Published: February 2022

George Winter provides an overview of recently published articles that are of interest to practice nurses. Should you wish to look at any of the papers in more detail, a full reference is provided.
Reducing the rate of negative ureteroscopy: predictive factors and the role of preoperative imaging
Authors: Brodie AC , Johnston TJ , Lloyd P , Hemsworth L , Barabas M , Keoghane SR
Published: February 2022

Introduction

The aim of this study was to investigate factors that may predict a negative ureteroscopy (URS) performed for ureteric calculi in prestented patients and to assess preoperative imaging in reducing the rate of negative URS.

Methods

Data were collected on emergency stent placement for a ureteric calculus from April 2011 to February 2016 (Group A) and October 2016 to October 2019 (Group B). Data included patient demographics, indication for a stent, stone characteristics, baseline bloods, urine culture, readmission, negative URS rate and the use of pre-URS imaging. Multivariate logistic regression was used for statistical analysis.

Results

Of 257 patients who underwent emergency stent insertion, 251 underwent deferred URS for a ureteric calculus and 6 avoided URS due to pre-URS imaging. Indications for stent were pain (42%), sepsis (39%) and acute kidney injury (19%). Mean stone size was 7.8mm, mean stone density was 699 Hounsfield units (HU) and the stone locations were upper (62%), mid (13%) and lower ureter (25%). The overall negative URS rate was 12%. The negative URS rate was lower in patients with pre-URS imaging compared with those with none, 6% and 14%, respectively (OR=2.33, 95% CI: 0.69–7.56, p=0.2214). Logistic regression analysis indicated stone size as the only significant predictor of a negative URS, where the greater the size of the stone the less likely URS would be negative (β=0.75, 95% CI: 0.60–0.94 p=0.011).

Conclusions

Utilising pre-URS imaging can lead to a reduction in negative URS rate. Stone size <5mm appears to be the subgroup most likely to benefit from imaging.
The learning curve and safety of continuous intraoperative vagus nerve monitoring in thyroid surgery
Authors: Patel A , Ally M , Venkatachalam V , Hearn M , Mochloulis G
Published: February 2022

Introduction

Continuous intraoperative nerve monitoring allows for continuous feedback on the integrity of the recurrent laryngeal nerve (RLN) and the quality of its induced myogenic potential. The aims of this study were to assess the time requirements and risks associated with vagus nerve electrode placement when learning the technique.

Methods

This is a prospective observational study carried out in a single otolaryngology department at the start of a trainee’s placement. A total of 40 vagus nerve dissections in 31 consecutive operations (22 hemithyroidectomies, 9 total thyroidectomies) using automatic periodic stimulation (APS, Medtronic) are included. Of the electrode placements, 10 were performed by the trainer and 30 by the trainee. The time required for each surgical step and complications relating to vagus nerve dissection were recorded.

Results

The average (median+IQR) total additional time attributable to vagus nerve dissection, electrode placement and baseline electromyogenic assessment was 3.1mins (2.5–3.3) for the trainer and 4.8mins (4.1–5.3) for the trainee (p<0.0001). There was a downward trend in time requirement for the trainee (not statistically significant, p=0.080). Total operative time was 38min (35–45) for hemithyroidectomy and 56min (53–62) for total thyroidectomy. There was a mix of benign (74%) and malignant (26%) histology, no intraoperative complications relating to autonomic dysfunction and one (2.5%) transient nerve palsy.

Conclusions

Operative time attributable to vagus nerve electrode placement is short and the procedure is easy to learn. Appropriate surgical technique and careful anaesthetic considerations allow monitoring to be performed safely, and may reduce the rate of RLN palsy.
Freeform shaping of fused silica substrates via viscous deformation induced by a laser patterned, stressed film
Authors: Beckmann Clemens M. , Richter Lukas Janos , Ihlemann Jürgen
Published: February 2022

Freeform optics enable improved optical solutions but their fabrication usually requires complicated precision machining processes. We report on an approach for freeform shaping of optical surfaces via a stress-induced viscous deformation of glass plates. We studied the deformation of fused silica substrates covered by specifically laser patterned films of substoichiometric silicon oxide during annealing at about 1100 °C in an oxidizing ambient. The obtained large deformation of the substrates can be understood by a mostly viscous deformation but can be described in analogy to a purely elastic deformation. Our results demonstrate the feasibility of a method for freeform shaping of individual optical substrates that only requires the preparation of a flat surface.
Optimization of pulse self-compression in hollow capillary fibers using decreasing pressure gradients
Authors: Galán Marina Fernández , Conejero Jarque Enrique , San Roman Julio
Published: February 2022

The improvement of techniques for the generation of near-infrared (NIR) few-cycle pulses is paving the way for new scenarios in time-resolved spectroscopy and the generation of ultrashort extreme-ultraviolet pulses through high-harmonic generation. In this work, we numerically study how to optimize the self-compression of NIR pulses using decreasing pressure gradients in hollow capillary fibers (HCFs). We identify a moderate nonlinear regime in which sub-cycle pulses are obtained with very good temporal quality from an input 30 fs pulse centered at a 800 nm wavelength and coupled as the fundamental mode of an argon-filled HCF fully evacuated at the output end. Surprisingly, we observe that there is a relatively broad region of parameters for which the optimum self-compression takes place, defined by a simple relation between the input pulse energy and the initial gas pressure.
Flexible frequency-selective rasorber based on metal-graphene hybrid metamaterial
Authors: Yang Yaojia , Wu Bian , Chen Biao , Zhao Yutong
Published: February 2022

In this work, we demonstrate a flexible frequency-selective rasorber (FSR) with great angular stability and conformal superiority using metal-graphene hybrid metamaterial. The metamaterial is fabricated by filling the designed metal patterns with graphene-based ink. It can replace the traditional resistors to introduce loss for the absorption purpose. Therefore, the FSR does not need any lumped components soldered onto its surface, enabling a high flexibility and conformal capability. The metal-graphene FSR is fabricated and measured on flexible substrates that have a 60° angular stability and a 128° conformal angle. The simulations and experiments confirmed that the proposed metal-graphene FSR exhibits excellent angular stability and considerable flexibility, making it ideal for stealth systems.
Visible and near-infrared programmable multi-level diffractive lenses with phase change material Sb2S3
Authors: Jia Wei , Menon Rajesh , Sensale-Rodriguez Berardi
Published: February 2022

In this paper, we discuss flat programmable multi-level diffractive lenses (PMDL) enabled by phase change materials working in the near-infrared and visible ranges. The high real part refractive index contrast (Δn ∼ 0.6) of Sb2S3 between amorphous and crystalline states, and extremely low losses in the near-infrared, enable the PMDL to effectively shift the lens focus when the phase of the material is altered between its crystalline and amorphous states. In the visible band, although losses can become significant as the wavelength is reduced, the lenses can still provide good performance as a result of their relatively small thickness (∼ 1.5λ to 3λ). The PMDL consists of Sb2S3 concentric rings with equal width and varying heights embedded in a glass substrate. The height of each concentric ring was optimized by a modified direct binary search algorithm. The proposed designs show the possibility of realizing programmable lenses at design wavelengths from the near-infrared (850 nm) up to the blue (450 nm) through engineering PMDLs with Sb2S3. Operation at these short wavelengths, to the best of our knowledge, has not been studied so far in reconfigurable lenses with phase-change materials. Therefore, our results open a wider range of applications for phase-change materials, and show the prospect of Sb2S3 for such applications. The proposed lenses are polarization insensitive and can have the potential to be applied in dual-functionality devices, optical imaging, and biomedical science.
Excitation and manipulation of both magnetic and electric surface plasmons
Authors: Peng Ruiguang , Zhao Qian , Meng Yonggang , Wen Shizhu
Published: February 2022

Surface plasmons (SPs) is the cornerstone in terahertz (THz) near-field photonics, which play crucial roles in the miniaturization and integration of functional devices. The excitation and manipulation of SPs, however, is currently restricted to electric SPs paradigm, while magnetic SPs receive less attention despite the importance of magnetic light-matter interactions. Here, a scheme is proposed to simultaneously convert the propagating waves in free space into magnetic and electric SPs using a single ultracompact device. First, a plasmonic structure composed of connected slit rings is designed and demonstrated to support both electric and magnetic SPs, which is ascribed to the two distinct eigenmodes of oscillating electrons and vortex currents, respectively. Second, with the assistance of an anisotropic and gradient metasurface, orthogonal linear polarized components of incident THz beams are coupled into different electric and magnetic SP channels with little crosstalk. Furthermore, by encoding two distinct polarization-dependent phase profile into the metasurface, it is shown that the resulting meta-device can individually tailor the wavefronts of magnetic and electric SPs, thus simultaneously engineering magnetic and electric near-field distributions. This work can pave the road to realize bi-channel and on-chip devices, and inspire more integrated functionalities especially related to near-field manipulations of magnetic SPs.
In silico prediction of HIV-1-host molecular interactions and their directionality
Authors: Chai Haiting , Gu Quan , Hughes Joseph , Robertson David L.
Published: February 2022

Human immunodeficiency virus type 1 (HIV-1) continues to be a major cause of disease and premature death. As with all viruses, HIV-1 exploits a host cell to replicate. Improving our understanding of the molecular interactions between virus and human host proteins is crucial for a mechanistic understanding of virus biology, infection and host antiviral activities. This knowledge will potentially permit the identification of host molecules for targeting by drugs with antiviral properties. Here, we propose a data-driven approach for the analysis and prediction of the HIV-1 interacting proteins (VIPs) with a focus on the directionality of the interaction: host-dependency versus antiviral factors. Using support vector machine learning models and features encompassing genetic, proteomic and network properties, our results reveal some significant differences between the VIPs and non-HIV-1 interacting human proteins (non-VIPs). As assessed by comparison with the HIV-1 infection pathway data in the Reactome database (sensitivity > 90%, threshold = 0.5), we demonstrate these models have good generalization properties. We find that the ‘direction’ of the HIV-1-host molecular interactions is also predictable due to different characteristics of ‘forward’/pro-viral versus ‘backward’/pro-host proteins. Additionally, we infer the previously unknown direction of the interactions between HIV-1 and 1351 human host proteins. A web server for performing predictions is available at http://hivpre.cvr.gla.ac.uk/.
Inference of trajectory presence by tree dimension and subset specificity by subtree cover
Authors: Tenha Lovemore , Song Mingzhou
Published: February 2022

The complexity of biological processes such as cell differentiation is reflected in dynamic transitions between cellular states. Trajectory inference arranges the states into a progression using methodologies propelled by single-cell biology. However, current methods, all returning a best trajectory, do not adequately assess statistical significance of noisy patterns, leading to uncertainty in inferred trajectories. We introduce a tree dimension test for trajectory presence in multivariate data by a dimension measure of Euclidean minimum spanning tree, a test statistic, and a null distribution. Computable in linear time to tree size, the tree dimension measure summarizes the extent of branching more effectively than globally insensitive number of leaves or tree diameter indifferent to secondary branches. The test statistic quantifies trajectory presence and its null distribution is estimated under the null hypothesis of no trajectory in data. On simulated and real single-cell datasets, the test outperformed the intuitive number of leaves and tree diameter statistics. Next, we developed a measure for the tissue specificity of the dynamics of a subset, based on the minimum subtree cover of the subset in a minimum spanning tree. We found that tissue specificity of pathway gene expression dynamics is conserved in human and mouse development: several signal transduction pathways including calcium and Wnt signaling are most tissue specific, while genetic information processing pathways such as ribosome and mismatch repair are least so. Neither the tree dimension test nor the subset specificity measure has any user parameter to tune. Our work opens a window to prioritize cellular dynamics and pathways in development and other multivariate dynamical systems.
The efficacy of an unrestricted cycling ketogenic diet in preclinical models of IDH wild-type and IDH mutant glioma
Authors: Javier Rodrigo , Wang Wenxia , Drumm Michael , McCortney Kathleen , Sarkaria Jann N. , Horbinski Craig
Published: February 2022

Infiltrative gliomas are the most common neoplasms arising in the brain, and remain largely incurable despite decades of research. A subset of these gliomas contains mutations inisocitrate dehydrogenase 1(IDH1mut) or, less commonly,IDH2(together called “IDHmut”). These mutations alter cellular biochemistry, and IDHmutgliomas are generally less aggressive than IDH wild-type (IDHwt) gliomas. Some preclinical studies and clinical trials have suggested that various forms of a ketogenic diet (KD), characterized by low-carbohydrate and high-fat content, may be beneficial in slowing glioma progression. However, adherence to a strict KD is difficult, and not all studies have shown promising results. Furthermore, no study has yet addressed whether IDHmutgliomas might be more sensitive to KD. The aim of the current study was to compare the effects of a unrestricted, cycling KD (weekly alternating between KD and standard diet) in preclinical models of IDHwtversus IDHmutgliomas.In vitro, simulating KD by treatment with the ketone body β-hydroxybutyrate had no effect on the proliferation of patient-derived IDHwtor IDHmutglioma cells, either in low or normal glucose conditions. Likewise, an unrestricted, cycling KD had no effect on thein vivogrowth of patient-derived IDHwtor IDHmutgliomas, even though the cycling KD did result in persistently elevated circulating ketones. Furthermore, this KD conferred no survival benefit in mice engrafted with Sleeping-Beauty transposase-engineered IDHmutor IDHwtglioma. These data suggest that neither IDHwtnor IDHmutgliomas are particularly responsive to an unrestricted, cycling form of KD.
Intergeneration transfer of diet patterns? Parental self-report of diet and their report of their young adult children with ASD
Authors: Kranz Sibylle , Lukacs Julia , Bishop Jason , Block Martin E.
Published: February 2022

Autism Spectrum Disorder (ASD) affects two percent of American children and often results in neophobia, hypersensitivity to foods, and firmly set food preferences, leading to higher proportions of individuals suffering from diet-related chronic diseases. Our objective was to conduct an explorative pilot study to examine parents’ perception of food intake for themselves and their young adult children with ASD. We employed comparative analysis to discover potential pathways to improve diet quality and lower the risk for chronic disease in individuals with ASD. Data from an online survey in n = 493 parent-child dyads on parentally reported intake patterns, food group, and food consumption was analyzed using kappa statistics to determine the level of agreement between reported parental and child intake patterns, body weight status and activity level. Average age was 48 years for parents and 22 years for their children, respectively. Parent-child agreement for obesity was high. We found very strong agreement between the reported diet variety (kappa = 0.82) and changing daily intake (kappa = 0.63) and strong agreement for some vegetable intake patterns (kappa = 0.61 for orange, white, and starchy vegetables) but not in meat intake (no agreement). Results of this study indicate evidence for perceived intergenerational transfer of dietary intake patterns, which may offer effective approaches to change parental diet, to subsequently improve diet quality in young adults with ASD and prevent diet-related chronic diseases in individuals with ASD.
“I got a bunch of weed to help me through the withdrawals”: Naturalistic cannabis use reported in online opioid and opioid recovery community discussion forums
Authors: Meacham Meredith C. , Nobles Alicia L. , Tompkins D. Andrew , Thrul Johannes
Published: February 2022

A growing body of research has reported on the potential opioid-sparing effects of cannabis and cannabinoids, but less is known about specific mechanisms. The present research examines cannabis-related posts in two large online communities on the Reddit platform (“subreddits”) to compare mentions of naturalistic cannabis use by persons self-identifying as actively using opioids versus persons in recovery. We extracted all posts mentioning cannabis-related keywords (e.g., “weed”, “cannabis”, “marijuana”) from December 2015 through August 2019 from an opioid use subreddit and an opioid recovery subreddit. To investigate how cannabis is discussed at-scale, we identified and compared the most frequent phrases in cannabis-related posts in each subreddit using term-frequency-inverse document frequency (TF-IDF) weighting. To contextualize these findings, we also conducted a qualitative content analysis of 200 random posts (100 from each subreddit). Cannabis-related posts were about twice as prevalent in the recovery subreddit (n = 908; 5.4% of 16,791 posts) than in the active opioid use subreddit (n = 4,224; 2.6% of 159,994 posts, p < .001). The most frequent phrases from the recovery subreddit referred to time without using opioids and the possibility of using cannabis as a “treatment.” The most frequent phrases from the opioid subreddit referred to concurrent use of cannabis and opioids. The most common motivations for using cannabis were to manage opioid withdrawal symptoms in the recovery subreddit, often in conjunction with anti-anxiety and GI-distress “comfort meds,” and to enhance the “high” when used in combination with opioids in the opioid subreddit. Despite limitations in generalizability from pseudonymous online posts, this examination of reports of naturalistic cannabis use in relation to opioid use identified withdrawal symptom management as a common motivation. Future research is warranted with more structured assessments that examines the role of cannabis and cannabinoids in addressing both somatic and affective symptoms of opioid withdrawal.
Physiological and transcriptional immune responses of a non-model arthropod to infection with different entomopathogenic groups
Authors: Black Joseph L. , Clark Mason K. , Sword Gregory A.
Published: February 2022

Insect immune responses to multiple pathogen groups including viruses, bacteria, fungi, and entomopathogenic nematodes have traditionally been documented in model insects such as Drosophila melanogaster, or medically important insects such as Aedes aegypti. Despite their potential importance in understanding the efficacy of pathogens as biological control agents, these responses are infrequently studied in agriculturally important pests. Additionally, studies that investigate responses of a host species to different pathogen groups are uncommon, and typically focus on only a single time point during infection. As such, a robust understanding of immune system responses over the time of infection is often lacking in many pest species. This study was conducted to understand how 3rd instar larvae of the major insect pest Helicoverpa zea responded through the course of an infection by four different pathogenic groups: viruses, bacteria, fungi, and entomopathogenic nematodes; by sampling at three different times post-inoculation. Physiological immune responses were assessed at 4-, 24-, and 48-hours post-infection by measuring hemolymph phenoloxidase concentrations, hemolymph prophenoloxidase concentrations, hemocyte counts, and encapsulation ability. Transcriptional immune responses were measured at 24-, 48-, and 72-hours post-infection by quantifying the expression of PPO2, Argonaute-2, JNK, Dorsal, and Relish. This gene set covers the major known immune pathways: phenoloxidase cascade, siRNA, JNK pathway, Toll pathway, and IMD pathway. Our results indicate H. zea has an extreme immune response to Bacillus thuringiensis bacteria, a mild response to Helicoverpa armigera nucleopolyhedrovirus, and little-to-no detectable response to either the fungus Beauveria bassiana or Steinernema carpocapsae nematodes.
Reducing calibration time in motor imagery-based BCIs by data alignment and empirical mode decomposition
Authors: Xiong Wei , Wei Qingguo
Published: February 2022

One of the major reasons that limit the practical applications of a brain-computer interface (BCI) is its long calibration time. In this paper, we propose a novel approach to reducing the calibration time of motor imagery (MI)-based BCIs without sacrificing classification accuracy. The approach aims to augment the training set size of a new subject by generating artificial electroencephalogram (EEG) data from a few training trials initially available. The artificial EEG data are obtained by first performing empirical mode decomposition (EMD) and then mixing resulting intrinsic mode functions (IMFs). The original training trials are aligned to common reference point with Euclidean alignment (EA) method prior to EMD and pooled together with artificial trials as the expended training set, which is input into a linear discriminant analysis (LDA) classifier or a logistic regression (LR) classifier. The performance of the proposed algorithm is evaluated on two motor imagery (MI) data sets and compared with that of the algorithm trained with only real EEG data (Baseline) and the algorithm trained with expanded EEG data by EMD without data alignment. The experimental results showed that the proposed algorithm can significantly reduce the amount of training data needed to achieve a given performance level and thus is expected to facilitate the real-world applications of MI-based BCIs.
External quality assessment of COVID-19 real time reverse transcription PCR laboratories in India
Authors: Kaur Harmanmeet , Mukhopadhyay Labanya , Gupta Nivedita , Aggarwal Neeraj , Sangal Lucky , Potdar Varsha , Inbanathan Francis Yesuraj , Narayan Jitendra , Gupta Swati , Rana Salaj , Vijay Neetu , Singh Harpreet , Kaur Jasmine , Kumar Vinit , Kaundal Nirmal , Abraham Priya , Ravi Vasanthapuram
Published: February 2022

Sudden emergence and rapid spread of COVID-19 created an inevitable need for expansion of the COVID-19 laboratory testing network across the world. The strategy to test-track-treat was advocated for quick detection and containment of the disease. Being the second most populous country in the world, India was challenged to make COVID-19 testing available and accessible in all parts of the country. The molecular laboratory testing network was augmented expeditiously, and number of laboratories was increased from one in January 2020 to 2951 till mid-September, 2021. This rapid expansion warranted the need to have inbuilt systems of quality control/ quality assurance. In addition to the ongoing inter-laboratory quality control (ILQC), India implemented an External Quality Assurance Program (EQAP) with assistance from World Health Organization (WHO) and Royal College of Pathologists, Australasia. Out of the 953 open system rRTPCR laboratories in both public and private sector who participated in the first round of EQAP, 891(93.4%) laboratories obtained a passing score of > = 80%. The satisfactory performance of Indian COVID-19 testing laboratories has boosted the confidence of the public and policy makers in the quality of testing. ILQC and EQAP need to continue to ensure adherence of the testing laboratories to the desired quality standards.
Pharmacological and genetic activation of cAMP synthesis disrupts cholesterol utilization in Mycobacterium tuberculosis
Authors: Wilburn Kaley M. , Montague Christine R. , Qin Bo , Woods Ashley K. , Love Melissa S. , McNamara Case W. , Schultz Peter G. , Southard Teresa L. , Huang Lu , Petrassi H. Michael , VanderVen Brian C.
Published: February 2022

There is a growing appreciation for the idea that bacterial utilization of host-derived lipids, including cholesterol, supports Mycobacterium tuberculosis (Mtb) pathogenesis. This has generated interest in identifying novel antibiotics that can disrupt cholesterol utilization by Mtb in vivo. Here we identify a novel small molecule agonist (V-59) of the Mtb adenylyl cyclase Rv1625c, which stimulates 3’, 5’-cyclic adenosine monophosphate (cAMP) synthesis and inhibits cholesterol utilization by Mtb. Similarly, using a complementary genetic approach that induces bacterial cAMP synthesis independent of Rv1625c, we demonstrate that inducing cAMP synthesis is sufficient to inhibit cholesterol utilization in Mtb. Although the physiological roles of individual adenylyl cyclase enzymes in Mtb are largely unknown, here we demonstrate that the transmembrane region of Rv1625c is required during cholesterol metabolism. Finally, the pharmacokinetic properties of Rv1625c agonists have been optimized, producing an orally-available Rv1625c agonist that impairs Mtb pathogenesis in infected mice. Collectively, this work demonstrates a role for Rv1625c and cAMP signaling in controlling cholesterol metabolism in Mtb and establishes that cAMP signaling can be pharmacologically manipulated for the development of new antibiotic strategies.
Validation method for determining enrofloxacin and tylosin levels in broiler liver, kidney, and muscle using high-performance liquid chromatography
Authors: Wijayanti Agustina Dwi , Ardiansyah Rahmad Dwi , Pratama Anggi Muhtar , Haryanto Aris , Fitriana Ida
Published: February 2022

Background and Aim: Enrofloxacin and tylosin can be combined into an antibiotic formulation which is expected to have a broader range of antibacterial activity against various infections in broilers. Validation method analysis of the levels of these two active compounds needs to be done for future use in pharmacokinetic or residual studies. The present study aims to determine a suitable validation method of isocratic high-performance liquid chromatography (HPLC) to measure the concentration of antibiotic combinations in the broiler liver, kidney, and muscles.

Materials and Methods: The combination of enrofloxacin and tylosin in the liver, kidney, and muscle was validated by HPLC method to find the procedures, processes, equipment, and systems used, consistently provides the appropriate results. The chromatography system consisted of an Octadecyl-silica column of 5 μm in diameter and 150 mm in length with a mobile phase of a mixture of 0.05 M monobasic sodium phosphate (pH 2.5) and acetonitrile (65:35 v/v). The solution was detected at a wavelength of 280 nm, 30°C, a flow rate of 1 mL/min, and an injection volume of 20 μL. The combination antibiotics powder was produced from PT Tekad Mandiri Citra, Bandung, Indonesia, and broiler tissues obtained from day-old chick broilers maintained for 30 days with free antibiotic feed.

Results: Validation of a combination solution of enrofloxacin and tylosin shows the linearity values of enrofloxacin and tylosin in the liver, kidney, and muscles as r2=0.9988, r2=0.9999, r2=0.9997, r2=0.9989, r2=0.9978, and r2=0.9962. The accuracy and precision values of enrofloxacin in the liver, kidney, and muscles were 5.53, 6.23, and 6.93, respectively. The values of accuracy and precision of tylosin in the liver, kidney, and muscles were 10.43, 4.63, and 7.16%, respectively. The retention times for enrofloxacin and tylosin were 1.945-2.000 min and 4.175-4.342 min. The limit of detection (LOD) and limit of quantity (LOQ) values for enrofloxacin were 3.03 and 10.1 μg/g, respectively. In contrast, the LOD and LOQ values for tylosin were 9.05 and 30.17 μg/g, respectively.

Conclusion: The value of linearity, accuracy, precision, specificity, and sensitivity of the combined solution of enrofloxacin and tylosin showed promising results.