bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simple and economical RNA extraction and storage packets for viral detection from serum or plasma
Authors: Hernandez Sarah , Cardozo Fátima , Myers David R. , Rojas Alejandra , Waggoner Jesse J. 
Published: January 2022

AbstractRNA extraction is an essential step for detection and surveillance of common viral pathogens. Currently, sample processing and RNA extraction are costly and rely on proprietary materials that are difficult to acquire, maintain, and safely discard in low-resource settings. We developed an economical RNA extraction and storage protocol that eliminates the use of instrumentation, expensive materials, and cold chain requirements. Through an iterative process, we optimized viral lysis and RNA binding to and elution from glass fiber membranes. Protocol changes were evaluated by testing eluates in virus-specific real-time RT-PCRs (rRT-PCRs). Efficient, non-toxic viral lysis was achieved with a sucrose buffer including KCl, proteinase K and carrier RNA. Glass fiber membranes demonstrated concentration-dependent RNA binding of three arthropod-borne RNA viruses (arboviruses): dengue, chikungunya and Oropouche. Membrane binding was significantly increased in an acidic arginine binding buffer. For the clinical evaluation, 36 dengue virus (DENV)-positive serum samples were extracted in duplicate in the optimized protocol and results were compared to a commercial method. DENV RNA was successfully extracted from 71/72 replicates (98.6%) in the extraction packets, and rRT-PCR Ct values correlated between the techniques. Five clinical samples were selected to evaluate ambient-temperature storage up to 7 days on dried glass fiber membranes. DENV RNA was stable at 1, 3 and 7 days post extraction, with a mean difference in eluate RNA concentration of 0.14 log10 copies/μL. At a cost of $0.08 /sample, RNA extraction and storage packets address key limitations to available protocols and may increase capacity for molecular detection of RNA viruses.
Cardiac Damage Risk in Radiotherapy of Esophageal Cancer: The Importance of Baseline Cardiac Risk Profile
Authors: Ghaznavi Hamid , Allaveisi Farzaneh , Taghizadeh-Hesary Farzad 
Published: January 2022

AbstractBackgroundThe radiotherapy techniques are evolving. Besides optimal tumor coverage, considering organs at risk (OAR) is pertinent to radiation oncologists. In esophageal cancer radiotherapy, heart is the main OAR. Studies on excess absolute risk (EAR) of cardiovascular disease (CVD) in esophageal cancer radiotherapy are limited in the main literature. Therefore, this study was conducted to estimate the EAR of CVD in patients with esophageal cancer treated with the IMRT technique.Materials and MethodsSeventeen patients with esophageal cancer were selected. The patients were planned for the IMRT technique, and the 10-year EAR of CVD was estimated using the linear model. The data of major CVD risk factors [including age, smoking, and family history of heart attack, systolic blood pressure, total and HDL cholesterol, and high sensitivity c-reactive protein (hsCRP)] were obtained and the baseline risk of CVD was categorized into low- and high-risk groups using the Reynolds risk score.ResultsFamily history of heart disease and smoking increased the EAR of CVD significantly compared to the cholesterol and hsCRP. The 10-year EAR of the high-risk group was more than four times of the low-risk group at all ages. In the low-risk group, EAR of CVD after radiotherapy of esophageal cancer can increase by up to 9.1%, while in the high-risk group, EAR increased by 34.89%.ConclusionsAdding the baseline CVD risk factors improved the estimation of EAR of heart disease after esophageal cancer radiotherapy with the IMRT technique.
Targeted degradation of PCNA outperforms stoichiometric inhibition to result in programed cell death
Authors: Chang Shih Chieh , Gopal Pooja , Lim Shuhui , Wei Xiaona , Chandramohan Arun , Mangadu Ruban , Smith Jeffrey , Ng Simon , Gindy Marian , Phan Uyen , Henry Brian , Partridge Anthony 
Published: January 2022

ABSTRACTTargeted protein degradation has emerged as a powerful technology – both as a biological tool and for broadening the therapeutic proteome. As tools to probe this approach on historically intractable targets, we have previously advanced ‘biodegraders’ — targeted degradation fusion constructs composed of mini-proteins/peptides linked to modified E3 ligase receptors. Herein, we gain deeper insights into the utility and potential of biodegraders, through a detailed study on Con1-SPOP, a biodegrader which rapidly degrades the potential cancer target, proliferating cell nuclear antigen (PCNA). In a variety of settings, the active biodegrader (Con1-SPOP) proved pharmacologically superior to its stoichiometric (non-degrading) inhibitor equivalent (Con1-SPOPmut). Specifically, in addition to more potent anti-proliferative effects in both 2D cell culture and 3D spheroids, PCNA degradation uniquely induced DNA damage, cell apoptosis and necrosis. Global proteomic profiling of a stable cell-line expressing Con1-SPOP under doxycycline (Dox) induction revealed that impaired mitotic division and mitochondria dysfunction is a direct consequence of PCNA degradation, effects not seen with the stoichiometric inhibitor protein. To evaluate the therapeutic potential of biodegraders, we showed that Dox-induced Con1-SPOP achieved complete tumor-growth inhibition in a xenograft model. To explore application of biodegraders as a novel therapeutic modality, modified mRNA encoding Con1-SPOP was synthesized and encapsulated into lipid nanoparticles (LNPs). The approach successfully delivered mRNA in vitro to deplete endogenous PCNA within hours of application and with nanomolar potency. Overall, our results demonstrate the utility of biodegraders as biological tools and highlight target-degradation as a more efficacious approach versus stoichiometric inhibition. Finally, once in vivo delivery and expression are optimized, biodegraders may be leveraged as an exciting therapeutic modality.
Rapidly evolving viral motifs target biophysically constrained binding pockets of host proteins
Authors: Shuler Gal , Hagai Tzachi 
Published: January 2022

SummaryEvolutionary changes in the host-virus interactome can alter the course of infection, but the biophysical and regulatory constraints that shape interface evolution remain largely unexplored. Here, we focus on viral mimicry of short host-like peptide motifs that allow binding to host domains and modulation of cellular pathways. We observe that motifs from unrelated viruses preferentially target conserved, widely expressed and highly connected host proteins, enriched with regulatory and essential functions. The interface residues within these host domains are more conserved and bind a larger number of cellular proteins than similar motif-binding domains that are not known to interact with viruses.In stark contrast, rapidly evolving viral-binding human proteins form few interactions with other cellular proteins, display high tissue specificity and their interface residues have few inter-residue contacts. Our results distinguish between highly conserved and rapidly evolving host-virus interfaces, and show how regulatory, functional and biophysical factors limit host capacity to evolve, allowing for efficient viral subversion of host machineries.
Establishment of physiologically relevant oxygen gradients in microfluidic organ chips
Authors: Grant Jennifer , Lee Elizabeth , Almeida Micaela , Kim Seongmin , LoGrande Nina , Goyal Girija , Sesay Adama Marie , Breault David T. , Prantil-Baun Rachelle , Ingber Donald E. 
Published: January 2022

AbstractIn vitro models of human organs must accurately reconstitute oxygen concentrations and gradients that are observed in vivo to mimic gene expression, metabolism, and host-microbiome interactions. Here we describe a simple strategy to achieve physiologically relevant oxygen tension in a two-channel human small intestine-on-a-chip (Intestine Chip) lined with primary human duodenal epithelium and intestinal microvascular endothelium in parallel channels separated by a porous membrane while both channels are perfused with oxygenated medium. This strategy was developed using computer simulations that predicted lowering the oxygen permeability of poly-dimethlysiloxane (PDMS) chips in specified locations using a gas impermeable film will allow the cells to naturally decrease the oxygen concentration through aerobic respiration and reach steady-state oxygen levels < 36 mm Hg (< 5%) within the epithelial lumen. The approach was experimentally confirmed using chips with embedded oxygen sensors that maintained this stable oxygen gradient. Furthermore, Intestine Chips cultured with this approach supported formation of a villus epithelium interfaced with a continuous endothelium and maintained intestinal barrier integrity for 72 h. This strategy recapitulates in vivo functionality in an efficient, inexpensive, and scalable format that improves the robustness and translatability of Organ Chip technology for studies on microbiome as well as oxygen sensitivity.
Chronic brain functional ultrasound imaging in freely moving rodents performing cognitive tasks
Authors: Hady Ahmed El , Takahashi Daniel , Sun Ruolan , Akinwale Oluwateniola , Boyd-Meredith Tyler , Zhang Yisi , Charles Adam S , Brody Carlos D 
Published: January 2022

AbstractFunctional ultrasound imaging (fUS) is an emerging imaging technique that indirectly measures neural activity via changes in blood volume. To date it has not been used to image chronically during cognitive tasks in freely moving animals. Performing those experiments faces a number of exceptional challenges: performing large durable craniotomies with chronic implants, designing behavioural experiments matching the hemodynamic timescale, stabilizing the ultrasound probe during freely moving behavior, accurately assessing motion artifacts and validating that the animal can perform cognitive tasks at high performance while tethered. In this study, we provide validated solutions for those technical challenges. In addition, we present standardized step-by-step repro-ducible protocols, procedures and data processing pipelines that open up the opportunity to perform fUS in freely moving rodents performing complex cognitive tasks. Moreover, we present proof-of-concept analysis of brain dynamics during a decision making task. We obtain stable recordings from which we can robustly decode task variables from fUS data over multiple months. Moreover, we find that brain wide imaging through hemodynamic response is nonlinearly related to cognitive variables, such as task difficulty, as compared to sensory responses previously explored.
A predicted developmental and evolutionary morphospace for grapevine leaves
Authors: Chitwood Daniel H. , Mullins Joey 
Published: January 2022

ABSTRACTUsing conventional statistical approaches there exist powerful methods to classify shapes. Embedded in morphospaces is information that allows us to visualize theoretical leaves. These unmeasured leaves are never considered nor how the negative morphospace can inform us about the forces responsible for shaping leaf morphology. Here, we model leaf shape using an allometric indicator of leaf size, the ratio of vein to blade areas. The borders of the observable morphospace are restricted by constraints and define an orthogonal grid of developmental and evolutionary effects which can predict the shapes of possible grapevine leaves. Leaves in the genusVitisare found to fully occupy morphospace available to them. From this morphospace we predict the developmental and evolutionary shapes of grapevine leaves that are not only possible, but exist, and argue that rather than explaining leaf shape in terms of discrete nodes or species, that a continuous model is more appropriate.
Efficacy of Pulmoary exercise administered in Supine, 45°, or 90° long sitting position on pulmonary parameters of patients with COPD: A Study Protocol
Authors: Awolola Eniola , Maharaj Sonill , Ojo Oluwafemi , Adeyeye Olufunke 
Published: January 2022

AbstractBackgroundPulmonary rehabilitation is a program commonly structured for the rehabilitation of chronic lung diseases like COPD, chronic bronchitis, and emphysema. It aims to increase the patients’ quality of life by decreasing the symptoms frequently experienced from respiratory diseases.MethodsForty-two (42) patients aged 40 and above with Chronic Obstructive Pulmonary Disorders will be assessed for eligibility for the study. The study design will be a double-blinded, randomized control trial with three intervention groups and three parallel placebo control groups.ACBT, Autogenic drainage, and Reciprocal pulley exercise will be administered as an intervention in various body positions for 5 minutes, respectively. Ten continuous outcome variables at a different point with a minimum repeated measurement of six per subject will be utilized as an outcome measure. Baseline Pulmonary Function Test (PFT) will be assessed on entry into the study and after every procedure. MRC breathlessness scale, six minutes’ walk (6MWT) test, and CAT assessment test will be assessed at every two (2) weeks of the study. Data will be analyzed using descriptive and inferential statistics of repeated ANOVA; P<0.05.DiscussionThe study outcome will determine pulmonary rehabilitation’s efficacy in various body positions on selected pulmonary parameters of COPD patients and identify the most productive approach among upper limb exercises, autogenic drainage, or ACBT in different fundamental body positionTrial Registrationwww.pactr.org: PACTR202005890624077
A Systematic Review of Datasets to Research the Effect of Policy and Place on Immigrants’ Health
Authors: Allen Chenoa D. 
Published: January 2022

AbstractState and local immigrant policies—which regulate immigrants’ rights and access to services and material resources—shape self-rated health and health care access for Hispanic/Latino immigrants. However, due to data limitations, we know little about their impacts on non-Hispanic immigrants or on objective measures of health. To help researchers address these gaps, this systematic review creates a comprehensive resource indexing nationally-representative US datasets that can be used to measure the effects of policy and place on immigrant health. Following PRISMA guidelines, I searched ICPSR and federal data repositories for nationally-representative, population-based, longitudinal or repeated cross-sectional datasets that included health/health care access, race/ethnicity, and state or county of residence. I extracted information about race, ethnicity, migration, language, and geocodes in each dataset for each year, 2005–2021. Data searches (final search December 2021) identified 54 datasets, many of which have never been used to study the effects of policies on immigrant health. These data sources have unexploited potential to advance this literature. For example, longitudinal data sources will allow researchers to examine the effects of policies on the same individuals over time, while datasets with detailed measures of race/ethnicity and migration can be used to distinguish which immigrants are most impacted.
An Acyclic Phosphonate Prodrug of HPMPC is Effective Against VZV in Skin Organ Culture and Mice
Authors: Lloyd M , Liu D , Lyu J , Fan J , Overhulse JM , Kashemirov BA , Prichard MN , McKenna CE , Moffat JF 
Published: January 2022

AbstractVaricella zoster virus (VZV) causes chicken pox and shingles and is prevalent worldwide. Acyclovir and penciclovir (and its prodrugs) are first-line treatments for VZV infections, but they are not highly potent against VZV and resistance may arise in immunocompromised people on long-term therapy. HPMPC (cidofovir) is active against VZV, but cidofovir is not approved for treating VZV diseases, is nephrotoxic, and is not orally bioavailable. Here, we present the synthesis and evaluation of USC-373, a phosphonate prodrug of HPMPC with activity against VZV and other DNA viruses. In cultured fibroblasts, it was potent against VZV Ellen laboratory strain and was not overtly toxic, with EC50 of 4 nM and CC50 of 0.20 μM, producing a selectivity index of 50. In ARPE-19 cells, USC-373 was effective against VZV-ORF57-Luc wild type strain and the acyclovir-resistant isogenic strain. In human skin organ culture, USC-373 formulated in cocoa butter and applied topically prevented VZV-ORF57-Luc spread without toxicity. In NuSkin mice with human skin xenografts, one daily dose of 3 mg/kg was effective by the subcutaneous route, and one daily dose of 10 mg/kg was effective by the oral route. Remarkably, a 10 mg/kg oral dose given every other day was also effective. USC-373 was well tolerated and mice did not lose weight or show signs of distress. The prodrug modifications of USC-373 increase the potency and oral bioavailability compared to its parent nucleoside analog, HPMPC.
Unobservable land value in rural China and its microeconomic implication on land lease behavior
Authors: He Xu , Sakurai Takeshi 
Published: January 2022

PurposeTotal farmland value exceeds its value in agriculture but is not directly perceptible to villagers in China. Thus, the exceeded part is often neglected when discussing farmer’s land transaction decision. This study aims to revisit the question about how land titling project affects farmer’s land renting-out and investigate how this unobservable land value would distort the intentional effects of land titling.Design/methodology/approachThis paper first modifies a two-period model by incorporating the unobservable part of land value into the farmers’ leasing decision problem. Following the implications from the theoretical analysis, this study then exploits the difference-in-differences and the triple-differences approach to confirm the distorting effects that are resulted from the unobservable land value.FindingsThe modified theoretical model of this study reveals that land titling would encourage farmers to rent out land when the unobservable land value is predicted to be low but discourage farmers’ willingness to rent-out when this value is predicted to be high. The core reason for this significant conclusion lands in the uncertainty of the unobservable land value. Empirical analysis then provided two evidences for this presumption. Furthermore, this study also gave a disproof of the argument that the uncovered discouraging effect is due to a stronger endowment effect.Originality/valueThis paper contributes to the literature by highlighting the unobservable land value in the farmers’ land-related decisions. This part of land value is always neglected in previous discussions about the land tenure system, but it would cause distorting effects especially in regions without private land ownership.
Critical analysis of risks factors in using public-private partnership in building critical infrastructure resilience: a systematic review
Authors: Ampratwum Godslove , Tam Vivian W.Y. , Osei-Kyei Robert 
Published: January 2022

Purpose
Public–private partnership (PPP) has been adopted in many areas especially within the architecture, engineering and construction research domain. However, the PPP in critical infrastructure resilience (CIR) has not received the needed attention even though it has been acclaimed to be the panacea for building infrastructure resilience. This paper aims to adopt a systematic review to proactively identify the risks factors that pertains to using PPP as a mechanism to build the resilience of critical infrastructure.

Design/methodology/approach
Using a systematic methodology, a total record of 51 academic publications and 5 institutional reports from reputable organizations were identified and analyzed.

Findings
The selected literature was subjected to content analysis to retrieve 46 risk factors in PPP in CIR. The outcome of the systematic revealed the topmost risks as corruption, natural and unavoidable catastrophes, wars, terrorism, sabotage, cost overrun issues, a lack of centralized mechanism for coordinating integrated actions, inconsistent government policies, inadequate supervision, high operational cost due to robust and redundant measure, lack of supporting infrastructure, lack of open and integrated communication, unstable government, political interference, lack of PPP experience and legislation change. A conceptual framework was developed by grouping the identified risks under 13 categories.

Research limitations/implications
The outcome of this study will be a guide for decision makers and stakeholders with the responsibility of building the resilience of critical infrastructure.

Originality/value
The study contributes to CIR research area by providing an in-depth knowledge on risks that are inherent in PPP in CIR.
Pakistan State Oil: multidimensional strategic issues of a market leader
Authors: Qureshi Jawaid Ahmed , Shamsi Aamir Firoz , Arif Farrah 
Published: January 2022

Learning outcomes
The learning outcomes are as follows: to analyze the multidimensional and complex crises, and market stature of a company that was a market and industry leader in a developing country; to evaluate and interpret the outcomes of decisions pertaining declining profits, outstanding receivables, branding, marketing and radical reforms to overcome the challenges of sustainable growth, customers and employees’ loyalty, market stature and leadership crises; and to design strategic solutions for sustaining its leadership position and combating severe challenges.

Case overview/synopsis
The purpose of this paper is to ponder upon various crises that Pakistan State Oil (PSO) was facing, so that learners can critically analyze, assess and design strategic solutions for it. PSO was the state-run market leader in the petroleum industry. The company had been struggling to combat multiple types of turmoil at a time. Its huge fund of receivables was blocked in circular debt that caused the company budget constraints and deficits. Due to a government policy shift, the demand for its furnace oil substantially reduced and profits plummeted. The countless internal and external crises posed severe menace to its competitive position vis-a-vis its rivals. This qualitative case study garners data from eight interviews from senior managers in the petroleum industry and adds content analysis technique to acquire pertinent data from renowned media sources and subsequent analysis. The drastic crises left PSO with dearth of funds and declining profitability. Consequently, due to limited marketing budget, creativity of its marketing team for devising effective marketing programs to raise market share was compromised. PSO underwent the issues of brand sustainability, sustainable growth, customers and employees’ loyalty, and market stature to financial and leadership crises. However, despite limitations, it still enjoyed a market leadership position among its rivals in the industry by occupying more than half of the chunk of market in the petroleum industry. This is a unique case study of a state-owned giant company facing multidimensional menaces. It offers tremendous learning opportunities for students who can devise creative strategic solutions and link theories and models with practice.

Complexity academic level
Graduate (MBA), MS, PhD (management and administrative sciences); Suitable for teaching in chapters: Anywhere but ideally near the middle or end of the above courses.

Supplementary materials
Teaching notes are available for educators only.

Subject code
CCS 11: Strategy.