Miracle-dz/UniFAR-FTUs huggingface dataset:
A first-in-human phase 0 clinical study of RNA interference–based spherical nucleic acids in patients with recurrent glioblastoma

RNA interference–based spherical nucleic acid nanoconjugates are a potentially safe and brain-penetrant approach for glioblastoma treatment. A golden opportunity to treat glioblastoma Glioblastoma (GBM) is a difficult cancer to treat, partly due to the blood-brain and blood-tumor barriers. Kumthekar et al. studied NU-0129, spherical nucleic acids consisting of gold nanoparticle cores conjugated with small interfering RNA oligonucleotides targeting Bcl2L12, for the treatment of GBM. After performing toxicology studies in cynomolgus monkeys, the authors conducted a first-in-human single-arm clinical trial of very low-dose NU-0129 in eight patients with recurrent GBM. By analyzing gold accumulation, the authors found that NU-0129 passed through the blood-brain barrier and accumulated in the tumor, where it reduced Bcl2L12 protein abundance. These results suggest that spherical nucleic acid nanoconjugates can potentially treat GBM. Glioblastoma (GBM) is one of the most difficult cancers to effectively treat, in part because of the lack of precision therapies and limited therapeutic access to intracranial tumor sites due to the presence of the blood-brain and blood-tumor barriers. We have developed a precision medicine approach for GBM treatment that involves the use of brain-penetrant RNA interference–based spherical nucleic acids (SNAs), which consist of gold nanoparticle cores covalently conjugated with radially oriented and densely packed small interfering RNA (siRNA) oligonucleotides. On the basis of previous preclinical evaluation, we conducted toxicology and toxicokinetic studies in nonhuman primates and a single-arm, open-label phase 0 first-in-human trial (NCT03020017) to determine safety, pharmacokinetics, intratumoral accumulation and gene-suppressive activity of systemically administered SNAs carrying siRNA specific for the GBM oncogene Bcl2Like12 (Bcl2L12). Patients with recurrent GBM were treated with intravenous administration of siBcl2L12-SNAs (drug moniker: NU-0129), at a dose corresponding to 1/50th of the no-observed-adverse-event level, followed by tumor resection. Safety assessment revealed no grade 4 or 5 treatment–related toxicities. Inductively coupled plasma mass spectrometry, x-ray fluorescence microscopy, and silver staining of resected GBM tissue demonstrated that intravenously administered SNAs reached patient tumors, with gold enrichment observed in the tumor-associated endothelium, macrophages, and tumor cells. NU-0129 uptake into glioma cells correlated with a reduction in tumor-associated Bcl2L12 protein expression, as indicated by comparison of matched primary tumor and NU-0129–treated recurrent tumor. Our results establish SNA nanoconjugates as a potential brain-penetrant precision medicine approach for the systemic treatment of GBM.
Academic careers and the COVID-19 pandemic: Reversing the tide

The pandemic has affected research operations and disproportionately affected underrepresented minority researchers, requiring concrete strategies to reverse these losses. The COVID-19 pandemic halted research operations at academic medical centers. This shutdown has adversely affected research infrastructure, the current research workforce, and the research pipeline. We discuss the impact of the pandemic on overall research operations, examine its disproportionate effect on underrepresented minority researchers, and provide concrete strategies to reverse these losses.
Does the Prefrontal Cortex Play an Essential Role in Consciousness? Insights from Intracranial Electrical Stimulation of the Human Brain

A central debate in philosophy and neuroscience pertains to whether PFC activity plays an essential role in the neural basis of consciousness. Neuroimaging and electrophysiology studies have revealed that the contents of conscious perceptual experience can be successfully decoded from PFC activity, but these findings might be confounded by postperceptual cognitive processes, such as thinking, reasoning, and decision-making, that are not necessary for consciousness. To clarify the involvement of the PFC in consciousness, we present a synthesis of research that has used intracranial electrical stimulation (iES) for the causal modulation of neural activity in the human PFC. This research provides compelling evidence that iES of only certain prefrontal regions (i.e., orbitofrontal cortex and anterior cingulate cortex) reliably perturbs conscious experience. Conversely, stimulation of anterolateral prefrontal sites, often considered crucial in higher-order and global workspace theories of consciousness, seldom elicits any reportable alterations in consciousness. Furthermore, the wide variety of iES-elicited effects in the PFC (e.g., emotions, thoughts, and olfactory and visual hallucinations) exhibits no clear relation to the immediate environment. Therefore, there is no evidence for the kinds of alterations in ongoing perceptual experience that would be predicted by higher-order or global workspace theories. Nevertheless, effects in the orbitofrontal and anterior cingulate cortices suggest a specific role for these PFC subregions in supporting emotional aspects of conscious experience. Overall, this evidence presents a challenge for higher-order and global workspace theories, which commonly point to the PFC as the basis for conscious perception based on correlative and possibly confounded information.
Assessing encapsulation of curcumin in cocoliposome: In vitro study

Abstract Curcumin has been known and used in the medical and industrial world. One way to improve its stability, bioavailability and its medical applications is using encapsulation method. In this research, we studied cocoliposome (coconut liposome) as the encapsulation material. The encapsulation efficiency (EE), loading capacity (LC), release rate (RR), as well as the free radical scavenging activity, measured by inhibition ratio (IR), of curcumin in encapsulation product were studied on varying cholesterol compositions and in simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.4) conditions. We found that curcumin encapsulation in cocoliposome (CCL) formulation was influenced by cholesterol composition and pH conditions. The EE, LC and free radical scavenging activity diminished under both the SIF and SGF conditions when the cholesterol concentration enhanced. However, the RR increased as the cholesterol intensified. The condition to acquire the most favorable encapsulation parameter values was at 10% cholesterol composition. Furthermore, the IR results at 10% cholesterol concentration of CCL was 67.70 and 82.13% in SGF and SIF milieu, respectively. The CCL formulation thrived better under SIF conditions for free radical scavenging activities.
Contesting Social Responsibilities of Business: Experiences in Context

The last decade has been marked by massive contestations related to the social responsibilities of business, in both the global South and global North (Ozkazanc-Pan, 2019). This Special Issue aims to explore the local and contextualized experiences of social responsibilities (Karam & Jamali, 2017; Matten & Moon, 2020) and how they are contested (Alamgir & Banerjee, 2019; McCarthy, Soundararajan & Taylor, 2020; Soundararajan, Spence & Rees, 2018). These include interpersonal, inter-organizational, institutional, ideological, and discursive contestations, among others (e.g. GutierrezHuerter et al., 2020; Hamann et al., 2020; Whelan et al., 2009), while emphasizing elements such as the micro-level dynamics of relational work (Girschik, Svystunova & Lysova 2020; Glavas, 2016; Gond & Moser, 2021; Noronha, D’Cruz & Banday, 2020;), conflict (Brand, Blok & Verweij, 2020), tensions (Mitra & Buzzanell, 2017; Nyberg & Wright, 2013), unintended consequences (Banerjee & Jackson, 2017) and power (Shamir, 2005). Our objectives are three-fold. First, we want to re-conceptualize the social responsibilities of business organizations by advancing research using a relational perspective. Second, we seek to explore and bring to the fore experiences of different forms of contestation of these social responsibilities. Third, we aim to highlight the role of context of the social responsibilities of business (Pisani et al., 2017), focusing especially on contestation in overlooked geographic settings and sites of marginalization.
Academically Eligible and Ineligible Pell Grant Community College Students: A Qualitative Investigation

Objective: The purpose of this research is twofold: first, to investigate financially eligible Pell Grant community college students’ perceptions of barriers and enablers to student success, and second, to critique the financial aid satisfactory academic progress (SAP) criteria through a cross-case comparison of students who are meeting and are not meeting the academic requirements. Method: To complete this investigation, I conducted semistructured interviews with financially eligible Pell Grant community college students (N = 62) who were meeting SAP (n = 31) and who were not meeting SAP (n = 31). To analyze the data, I drew on Brint and Karabel’s theory of democratization and diversion as well as Gutiérrez and Lewis’s conceptualization of empowerment theory, and I followed Braun and Clarke’s six-step iterative thematic approach. Results: Financially eligible Pell Grant community college students believe students need motivation, enough resources to meet their responsibilities, and cultural capital to succeed. Observable differences were identified between the two student groups in three areas: environmental responsibilities to resources ratios, cultural capital, and powerlessness. Contributions: Through this article, I created a platform for the voices of financially eligible Pell Grant community college students and their perceptions of barriers and enablers to student success. By conducting the cross-case analysis, the potentially arbitrary nature of the SAP criteria is apparent, despite the real consequences they create for students. This research contributes a long overdue qualitative critique of the SAP criteria, but additional research is warranted.
GPR clutter suppression by online stochastic tensor decomposition

ABSTRACT The clutter suppression is an active research area for ground-penetrating radar (GPR) and the current trends use low rank and sparse decomposition (LRSD) based methods which provide an overwhelming advantage over classical low-rank methods. However, there are not many studies about tensor decomposition methods which actually provide powerful tools such as tensor robust principal component analysis (TRPCA) method for decomposing a matrix into its low rank and sparse components, namely, clutter and target parts. In addition to the success of TRPCA and motivated by tensor decomposition results in video background subtraction compared to LRSD, we propose a new GPR clutter suppression method based on online stochastic tensor decomposition (OSTD) by adding a simple pre-transformation step. The proposed method is tested on both simulated and real datasets. Obtained results prove its superiority over the state-of-the-art clutter suppression methods.
Analysis of a Hospital Librarian Mediated Literature Search Service at a Regional Health Service in Australia

ABSTRACT This research evaluated the quality and impact of a health librarian-mediated literature search service at a regional hospital in Victoria, Australia. A survey was e-mailed to all users of the mediated literature search service. The service had a key impact on knowledge development and clinical practice; improved policies and procedures; and increased productivity. Specifically, it indicated that 83.02% of respondents obtained new knowledge, whilst 46.23% confirmed clinical practice. A further 31 responses indicated that choice of tests, medications and advice given to patients was influenced. This research indicated that librarian’s searching expertise can indirectly contribute to patient care activities.
Investigation of the Information-Seeking Behavior of Hospitalized Patients at the General Hospital of Corfu

ABSTRACT The purpose of this article is to investigate the information-seeking behavior of hospitalized patients in a peripheral hospital in Greece, based on Wilson’s theoretical model. After a thorough literature review, we report on the results of a cross-sectoral sur\vey that was conducted based on Wilson’s macro-model of information-seeking behavior. The survey exploits the feedback we obtained from 150 hospitalized patients in the General Hospital of Corfu island in Greece. For the feedback collection, we relied on a structured questionnaire that was distributed to patients and correlates information-seeking behavior of hospitalized patients’ clinical data and eHealth Literacy. According to our findings, the most commonly recorded factors that pertain to information needs of hospitalized patients relate to treatment information, procedural information as well as information about the patients’ rights and support. The main information sources to which patients turn for receiving information are digital scientific sources, health professionals, other patients, insurance funds, family members and friends and the media. Concerning the most frequent obstacles associated with the information-seeking process, these account primarily to individual, interpersonal and environmental factors. Finally, the research came to a conclusion with the adaptation of Wilson’s theoretical model to hospitalized patients by confirming the original-initial model. The findings of our survey reveal the necessity to equip hospital units with adequate staff and to develop programs that offer updated information services to the hospitalized population. Moreover, our survey suggests that the availability of advanced health-related information services can empower the general population toward establishing e-Health literacy skills as well as toward increasing their level of satisfaction from the quality of the health services offered. In this direction, a clinical librarian program would empower hospitals worldwide to make their patients literate about health-related information.
‘No one remains living in the past’: the dynamics of pottery technological styles in southwestern Ethiopia

ABSTRACT This article examines the pottery technological styles of the Oromo, the Yem and the Dawro ethnolinguistic groups in southwestern Ethiopia. It provides a comparative examination of the technological choices each group makes at different stages of pottery production, which, in turn, produce and reproduce their group identities. In southwestern Ethiopia, pottery-making lies within the domain of women, with social restrictions prohibiting male involvement. Potters are marginalised and transmit pottery-making knowledge and skills through learning networks, mainly between immediate family members. Each pottery-making community practises distinct technological traditions and styles, but all communities are now acquiring new technological skills in response to developing socio-economic dynamics. Examination of the incorporation of new elements into pottery-making due to both socio-economic changes at the local level and global phenomena may provide clues about the changing dynamics of the craft in the recent and more distant past.
The Carboneras Beach archaeological site on Bioko Island (Equatorial Guinea): old data and new stories about a unique culture

ABSTRACT Off the coast of Cameroon, Bioko Island was populated by the Bubi at an early stage of the Bantu expansion, although surprisingly they did not use iron until the arrival of the Europeans much later. Unfortunately, despite some research having been undertaken, mostly during the Spanish colonial period, the local archaeological sequence remains poorly known. On the basis of some short excavations carried out on Bioko, this paper evaluates the state of knowledge of the island’s archaeology. There is a pressing need for more research on the island, in contrast to the continent, where archaeological knowledge has made significant progress in recent decades. So far there are no clear archaeological connections between the two. However, some clues suggest that the Bubi’s ancestors may have inhabited the mainland in southwestern Cameroon before emigrating to the islands, perhaps 2000 years ago. In view of the rapid development of infrastructure on Bioko, as well as on the mainland of Equatorial Guinea, a major multidisciplinary research programme centred on archaeology should be launched without further delay.
If the equal weighted portfolio is so great, why isn’t it working in South Africa?

ABSTRACT This paper considers the recent underperformance of the equal weighted portfolio of South African Top 40 stocks relative to the market capitalisation weighted portfolio. It highlights the impact of the increased concentration of market capitalisation weights in the Top 40, which is currently at extreme levels. Furthermore, lower levels in the benefits of diversification, through higher average correlations, has reduced the positive impact of rebalancing. Finally, the turnover in index constituents has been higher than average in recent years and this has caused a further drag on performance. The combination of these effects has had a negative impact on the equal weighted portfolio’s relative performance. A rudimentary linear model, with these factors as inputs, that highlights the importance of monitoring these drivers to improve the equal weighted portfolio’s relative performance is presented.
First total syntheses of four natural bioactive glucosides

Abstract The efficient total syntheses of four biologically interesting natural glucosides Ethylconiferin, Butylconiferin, 2’-Butoxyethylconiferin and Balajaponin B, have been achieved for the first time starting from commercially available Vanilline via concise reaction sequence of 8–10 steps with the overall yield of 26–41%. This work definitely laid the foundation for the further pharmacological study of this kind of natural compounds. Meanwhile, currently developed approach could be used as a general synthetic strategy for the syntheses of other monolignol glucosides and their derivatives, and provides an opportunity for further study of the structure-activity relationship of this kind of glucosides. Graphical Abstract
Determination of yield and yield components and seed quality of peanuts (Arachis hypogaea L.) at different harvest times.

The objective of this work was to investigate the effects of early or late harvest times on the changing yield and yield component and the seed quality of peanuts. It was determined that harvest time had statistically significant effects on plant height, primary branch number, primary branch length, per plant pod number, per plant yield, 100 seed weight, shelling percentages, pod yield, fresh and dry weight, harvest index, oil content, protein content, carbohydrate and ash ratio andoleic/linoleic acid ratio. The highest pod yield was determined by the third harvest times in both years, because of having a high podper plant yield, per plant pod number, 100 seed weight, shelling percentage and harvest index. The protein and oil ratios were increased by delaying the harvest time, whereas the carbohydrate ratio decreased. In particular, it was revealed that the oleic/linoleic acid ratio increased because of increasing seed size and the amount of oleic acid throughout the delay in the harvest. As a result of this study although fourth and fifth harvest times were observed in terms of the highest 100 seed weight, there were problems due to the harvest lost and the formation of substances that threaten human health such as aflatoxin in the delayed harvest times. Therefore, there is no point waiting to take a very high pod yield at late harvest times. It was suggested that earlier cultivars or earlier planting and harvest times should instead be used for pod yield and healthy crops
Cooperative regulation of coupled oncoprotein translation and stability in triple-negative breast cancer by EGFR and CDK12

Evidence has long suggested that epidermal growth factor receptor (EGFR) may play a prominent role in triple-negative breast cancer (TNBC) pathogenesis, but clinical trials of EGFR inhibitors have yielded disappointing results. Using a candidate drug screen, we discovered that inhibition of CDK12 dramatically sensitizes diverse models of TNBC to EGFR blockade. Instead of functioning through CDK12’s well-established roles proximal to transcription, this combination therapy drives cell death through the 4E-BP1-dependent suppression of the translation and consequent stability of driver oncoproteins, including MYC. A genome-wide CRISPR/Cas9 screen identified the CCR4-NOT complex as a major determinant of sensitivity to the combination therapy whose loss renders 4E-BP1 unresponsive to drug-induced dephosphorylation, rescuing MYC translational suppression and stability. The central roles of CCR4-NOT and 4E-BP1 in response to the combination therapy were further underscored by the observation of CNOT1 loss and rescue of 4E-BP1 phosphorylation in TNBC cells that naturally evolved therapy resistance. Thus, pharmacological inhibition of CDK12 reveals a long proposed EGFR dependence in TNBC that functions through the cooperative regulation of translation-coupled oncoprotein stability.
Zoonotic spillover of SARS-CoV-2: mink-adapted virus in humans

The COVID-19 pandemic caused by SARS-CoV-2 started in fall 2019. A range of different mammalian species, including farmed mink, have been confirmed as susceptible to infection with this virus. We report here the spillover of mink-adapted SARS-CoV-2 from farmed mink to humans after extensive adaptation that lasted at least 3 months. We found the presence of four mutations in the S gene (that gave rise to variant: G75V, M177T, Y453F and C1247F) and others in an isolate obtained from SARS-CoV-2 positive patient.
Using soil knowledge for the evaluation of mid‐infrared diffuse reflectance spectroscopy for predicting soil physical and mechanical properties

Mid‐infrared diffuse reflectance spectroscopy can provide rapid, cheap and relatively accurate predictions for a number of soil properties. Most studies have found that it is possible to estimate chemical properties that are related to surface and solid material composition. This paper focuses on prediction of physical and mechanical properties, with emphasis on the elucidation of possible mechanisms of prediction. Soil physical properties that are based on pore‐space relationships such as bulk density, water retention and hydraulic conductivity cannot be predicted well using MIR spectroscopy. Hydraulic conductivity was measured using a tension‐disc permeameter, excluding the macropore effect, but MIR spectroscopy did not give a good prediction. Properties based on the soil solid composition and surfaces such as clay content and shrink‐swell potential can be predicted reasonably well. Macro‐aggregate stability in water can be predicted reasonably as it has a strong correlation with carbon content in the soil. We found that most of the physical and mechanical properties can be related back to the fundamental soil properties such as clay content, carbon content, cation exchange capacity and bulk density. These connections have been explored previously in pedotransfer functions studies. The concept of a spectral soil inference system is reiterated: linking the spectra to basic soil properties and connecting basic soil properties to other functional soil properties via pedotransfer functions.