bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tetraploidy accelerates adaption under drug-selection in a fungal pathogen
Authors: Avramovska Ognenka , Rego Emily , Hickman Meleah A 
Published: March 2021

AbstractBaseline ploidy significantly impacts evolutionary trajectories, and in particular, tetraploidy has been associated with higher rates of adaptation compared to haploidy and diploidy. While the majority of experimental evolution studies investigating ploidy useSaccharomyces cerivisiae, the fungal pathogenCandida albicansis a powerful system to investigate ploidy dynamics, particularly in the context of antifungal drug resistance.C. albicanslaboratory and clinical strains are predominantly diploid, but have also been isolated as haploid and polyploid. Here, we evolved diploid and tetraploidC. albicansfor ∼60 days in the antifungal drug caspofungin. Tetraploid-evolved lines adapted faster than diploid-evolved lines and reached higher levels of caspofungin resistance. While diploid-evolved lines generally maintained their initial genome size, tetraploid-evolved lines rapidly underwent genome-size reductions and did so prior to caspofungin adaption. Furthermore, fitness costs in the absence of drug selection were significantly less in tetraploid-evolved lines compared to the diploid-evolved lines. Taken together, this work supports a model of adaptation in which the tetraploid state is transient but its ability to rapidly transition ploidy states improves adaptative outcomes and may drive drug resistance in fungal pathogens.
Coro2a, An Expression Quantitative Trait Gene UnderlyingEstq1, Controls Uterine Responsiveness to Estradiol
Authors: Findley Joseph , McGee Elizabeth , Lin Chin-Yo , Krementsov Dimitry , Teuscher Cory 
Published: March 2021

AbstractThe response of the uterus to 17β-estradiol (E2) is genetically controlled, with marked variation observed depending on the mouse strain studied. Previous studies from our laboratory using high (C57BL6/J; B6) and low uterine responders (C3H/HeJ; C3H) to E2led to the identification ofEstq1-Estq5, five quantitative trait loci (QTL) controlling phenotypic variation in uterine growth and eosinophilic leukocyte infiltration. Transcriptional profiling subsequently identified coronin actin binding protein 2A (Coro2a) as a candidate for an expression quantitative trait gene (eQTG) underlyingEstq1. Here we show that like mRNA expression, allele specific expression of CORO2A in both the uterine epithelium and stroma similarly co-segregates with uterine responsiveness. Utilizing B6.C3H congenic mice carrying theCoro2aC3Hallele, we confirm the genetic linkage betweenCoro2aandEstq1. Lastly, we show that B6-Coro2a-/-and B6-Coro2aB6/-mice phenocopy uterine responsiveness of mice carrying theCoro2aC3H/C3HandCoro2aB6/C3Halleles respectively, consistent with a haploinsufficiency model of genetic control. Together, these results identifyCoro2aas the eQTG underlyingEstq1, and establish a critical role forCoro2ain E2-regulated responses.
Molecular Basis for Reduced Cleavage Activity and Drug Resistance in D30N HIV-1 protease
Authors: Bihani Subhash C , Hosur Madhusoodan V 
Published: March 2021

AbstractNelfinavir is one of the FDA approved HIV-1 protease inhibitors and is a part of HAART therapy for the treatment of HIV-AIDS. Nelfinavir was the first HIV-1 protease inhibitor to be approved as a Paediatric formulation. The application of HAART had resulted into significant improvement in the life of AIDS patients. However, emergence of drug resistance in HIV-1 protease limited the use of many of these drugs including nelfinavir. A unique mutation observed frequently in patients treated with nelfinavir is D30N as it is selected exclusively by nelfinavir. It imparts very high resistance to nelfinavir but unlike other primary mutations does not give cross resistance to the majority of other drugs. D30N mutation also significantly reduces cleavage activity of HIV-1 protease and affects the viral fitness. Here, we have determined structures of D30N HIV-1 protease in unliganded form and in complex with the drug nelfinavir. These structures provide rationale for reduced cleavage activity and molecular basis of resistance induced by D30N mutation. The loss of coulombic interaction part of a crucial hydrogen bond between the drug and the enzyme, is a likely explanation for reduced affinity and drug resistance towards nelfinavir. The decreased catalytic activity of D30N HIV protease, due to altered interaction with substrates and reduced stability of folding core may be the reasons for reduced replicative capacity of the HIV harboring D30N HIV-1 protease.
Transfer learning framework for cell segmentation with incorporation of geometric features
Authors: Jin Yinuo , Toberoff Alexandre , Azizi Elham 
Published: March 2021

AbstractWith recent advances in multiplexed imaging and spatial transcriptomic and proteomic technologies, cell segmentation is becoming a crucial step in biomedical image analysis. In recent years, Fully Convolutional Networks (FCN) have achieved great success in nuclei segmentation inin vitroimaging. Nevertheless, it remains challenging to perform similar tasks onin situtissue images with more cluttered cells of diverse shapes. To address this issue, we propose a novel transfer learning, cell segmentation framework incorporating shape-aware features in a deep learning model, with multi-level watershed and morphological post-processing steps. Our results show that incorporation of geometric features improves generalizability to segmenting cells inin situtissue images, using solelyin vitroimages as training data.
Ultrapotent miniproteins targeting the receptor-binding domain protect against SARS-CoV-2 infection and disease in mice
Authors: Case James Brett , Chen Rita E. , Cao Longxing , Ying Baoling , Winkler Emma S. , Goreshnik Inna , Shrihari Swathi , Kafai Natasha M. , Bailey Adam L. , Xie Xuping , Shi Pei-Yong , Ravichandran Rashmi , Carter Lauren , Stewart Lance , Baker David , Diamond Michael S. 
Published: March 2021

SUMMARYDespite the introduction of public health measures and spike protein-based vaccines to mitigate the COVID-19 pandemic, SARS-CoV-2 infections and deaths continue to rise. Previously, we used a structural design approach to develop picomolar range miniproteins targeting the SARS-CoV-2 receptor binding domain. Here, we investigated the capacity of modified versions of one lead binder, LCB1, to protect against SARS-CoV-2-mediated lung disease in human ACE2-expressing transgenic mice. Systemic administration of LCB1-Fc reduced viral burden, diminished immune cell infiltration and inflammation, and completely prevented lung disease and pathology. A single intranasal dose of LCB1v1.3 reduced SARS-CoV-2 infection in the lung even when given as many as five days before or two days after virus inoculation. Importantly, LCB1v1.3 protectedin vivoagainst a historical strain (WA1/2020), an emerging B.1.1.7 strain, and a strain encoding key E484K and N501Y spike protein substitutions. These data support development of LCB1v1.3 for prevention or treatment of SARS-CoV-2 infection.
Minute Zero
Authors: Mucharraz y Cano Yvette 
Published: March 2021

Learning outcomes
The expected learning outcomes are: to clarify the meaning of resilience and its attributes. To explore the influence of the leader on the development of organizational resilience. To identify critical decisions for the recovery of a business after an external event such as the earthquake that took place on September 19th in Mexico City. To point out the stages for the development of organizational resilience, in the short, and long term: anticipation, coping and adaptation. To clarify the actions that could be taken to prepare an organization for an extreme event or respond to a large-scale crisis.

Case overview/synopsis
The case is framed within the context of the September 19, 2017 earthquake in Mexico City. ProActive Strategies’ offices collapsed, causing some people to lose their lives and others to be injured. The protagonist needed to decide if the organization could survive and recover or needed to be closed after the earthquake. After ProActive Strategies survived and recovered, it was possible to identify the main stages to develop organizational resilience in this organization: anticipation, coping and adaptation. Also, the paper provides empirical evidence about how organizational resilience is anchored in the attributes at individual and community levels that include human, economic, social and political capitals, enhanced by technological capital. Furthermore, the enablers of resilience add external entities and the ecosystem at a macro-level, considering political, social and economic aspects of the context.

Complexity academic level
The study level and expertise required to address this case is medium. The richness of the discussion from the perspective of the students is related to the possibility to empathize with the protagonist and the different actors involved and to build on previous experience with crisis management to observe the potential risks and courses of action. Moreover, the professor also requires taking a neutral position to balance the requirements from a humanitarian perspective, with the business needs.

Subject code

Supplementary materials
Teaching notes are available for educators only.

Subject code
CSS 6: Human resource management.
Decision-making system for higher education university selection: comparison of priorities pre- and post-COVID-19
Authors: Nanath Krishnadas , Sajjad Ali , Kaitheri Supriya 
Published: March 2021

PurposeUniversity selection in higher education is a complex task for aspirants from a decision-making perspective. This study first aims to understand the essential parameters that affect potential students' choice of higher education institutions. It then aims to explore how these parameters or priorities have changed given the impact of the COVID-19 pandemic. Learning about the differences in priorities for university selection pre- and post-COVID-19 pandemic might help higher education institutions focus on relevant parameters in the post-pandemic era.Design/methodology/approachThis study uses a mixed-method approach, with primary and secondary data (university parameters from the website and LinkedIn Insights). We developed a university selector system by scraping LinkedIn education data of various universities and their alumni records. The final decision-making tool was hosted on the web to collect potential students' responses (primary data). Response data were analyzed via a multicriteria decision-making (MCDM) model. Portal-based data collection was conducted twice to understand the differences in university selection priorities pre- and post-COVID-19 pandemic. A one-way MANOVA was performed to find the differences in priorities related to the university decision-making process pre- and post-COVID-19.FindingsThis study considered eight parameters of the university selection process. MANOVA demonstrated a significant change in decision-making priorities of potential students between the pre- and post-COVID-19 phases. Four out of eight parameters showed significant differences in ranking and priority. Respondents made significant changes in their selection criteria on four parameters: cost (went high), ranking (went low), presence of e-learning mode (went high) and student life (went low).Originality/valueThe current COVID-19 pandemic poses many uncertainties for educational institutions in terms of mode of delivery, student experience, campus life and others. The study sheds light on the differences in priorities resulting from the pandemic. It attempts to show how social priorities change over time and influence the choices students make.
The maternal foam plug constitutes a reservoir for the desert locust's bacterial symbionts
Authors: Lavy Omer , Gophna Uri , Ayali Amir , Gihaz Shalev , Fishman Ayelet , Gefen Eran 
Published: March 2021

SummaryA hallmark of the desert locust's ancient and deserved reputation as a devastating agricultural pest is that of the long‐distance, multi‐generational migration of locust swarms to new habitats. The bacterial symbionts that reside within the locust gut comprise a key aspect of its biology, augmenting its immunity and having also been reported to be involved in the swarming phenomenon through the emission of attractant volatiles. However, it is still unclear whether and how these beneficial symbionts are transmitted vertically from parent to offspring. Using comparative 16S rRNA amplicon sequencing and direct experiments with engineered bacteria, we provide evidence for vertical transmission of locust gut bacteria. The females may perform this activity by way of inoculation of the egg‐pod's foam plug, through which the larvae pass upon hatching. Furthermore, analysis of the composition of the foam revealed chitin to be its major component, along with immunity‐related proteins such as lysozyme, which could be responsible for the inhibition of some bacteria in the foam while allowing other, more beneficial, strains to proliferate. Our findings reveal a potential vector for the transgenerational transmission of symbionts in locusts, which contributes to the locust swarm's ability to invade and survive in new territories.
Longitudinal participation in delivery and payment reform programs among US Primary Care Organizations
Authors: Adler‐Milstein Julia , Linden Ariel , Bernstein Steven , Hollingsworth John , Ryan Andrew 
Published: March 2021

AbstractObjectiveTo assess longitudinal primary care organization participation patterns in large‐scale reform programs and identify organizational characteristics associated with multiprogram participation.Data SourcesSecondary data analysis of national program participation data over an eight‐year period (2009‐2016).Study DesignWe conducted a retrospective, observational study by creating a unique set of data linkages (including Medicare and Medicaid Meaningful Use and Medicare Shared Savings Program Accountable Care Organization (MSSP ACO) participation from CMS, Patient‐Centered Medical Home (PCMH) participation from the National Committee for Quality Assurance, and organizational characteristics) to measure longitudinal participation and identify what types of organizations participate in one or more of these reform programs. We used multivariate models to identify organizational characteristics that differentiate those that participate in none, one, or two‐to‐three programs.Data Extraction MethodsWe used Medicare claims to identify organizations that delivered primary care services (n = 56 ,287) and then linked organizations to program participation data and characteristics.Principal FindingsNo program achieved more than 50% participation across the 56,287 organizations in a given year, and participation levels flattened or decreased in later years. 36% of organizations did not participate in any program over the eight‐year study period; 50% participated in one; 13% in two; and 1% in all three. 14.31% of organizations participated in five or more years of Meaningful Use while 3.84% of organizations participated in five years of the MSSP ACO Program and 0.64% participated in at least five years of PCMH. Larger organizations, those with younger providers, those with more primary care providers, and those with larger Medicare patient panels were more likely to participate in more programs.Conclusions and RelevancePrimary care transformation via use of voluntary programs, each with their own participation requirements and approach to incentives, has failed to broadly engage primary care organizations. Those that have chosen to participate in multiple programs are likely those already providing high‐quality care.
Relationship between the skin barrier function of 2‐week‐old infants after bathing and facial skin problems during the first 6 weeks of life: A prospective observational cohort study
Authors: Shimizu Satsuki , Yonezawa Kaori , Haruna Megumi , Sasagawa Emi , Hikita Naoko , Sanada Hiromi , Minematsu Takeo 
Published: March 2021

AbstractAimThis study aimed to identify the relationship between the skin barrier function after bathing at 2 weeks of age and subsequent facial skin problems during the first 6 weeks of life.MethodsA prospective observational study was conducted from July 2017 to February 2018 on healthy newborns aged 2 weeks. Skin barrier function was evaluated before bathing and at 30 and 90 min after bathing by measuring transepidermal water loss (TEWL), stratum corneum hydration (SCH), sebum secretion, and skin pH. Infantile facial skin problems were assessed using skin condition diaries maintained by a parent for 4 weeks.ResultsAnalysis of the data from 56 infants showed that 29 infants (51.8%) experienced facial skin problems from 2 to 6 weeks of age. A lesser change in the sebum secretion on the forehead before bathing to 90 min after bathing and a higher SCH of the forehead before bathing were less likely to result in facial skin problems (adjusted odds ratio [AOR] = 0.98, 95% confidence interval [CI]: 0.97–0.99; AOR = 0.96, 95% CI: 0.92–0.99).ConclusionsA greater change in the sebum secretion on the forehead before bathing to 90 min after bathing and a lower SCH of the forehead before bathing were associated with subsequent infantile facial skin problems, indicating that a better ability to recover after bathing is important to prevent facial skin problems. Future studies should identify factors that enhance the recuperative functions of infantile skin.
Effect of feeding a pellet diet containing high sulphur with fresh cassava root supplementation on feed use efficiency, ruminal characteristics and blood metabolites in Thai native beef cattle
Authors: Prachumchai Rittikeard , Cherdthong Anusorn , Wanapat Metha , Supapong Chanadol , Khonkhaeng Benjamad , Suntara Chanon , Foiklang Suban 
Published: March 2021

AbstractThe objective of this experiment was to study the effect of feeding pellet containing high sulphur (PELFUR) diet and fresh cassava root (FCR) to Thai native beef cattle on feed use efficiency, ruminal characteristics and blood metabolites. Four male purebred Thai native beef cattle (1.5–2.0 years old) with initial body weight (BW) of 150 ± 15.0 kg were allocated with a 2 × 2 factorial arrangement in a 4 × 4 Latin square design. Factor A was FCR supplementation at 15 and 20 g/kg of BW. Factor B was the sulphur level in the PELFUR ration at 15 and 30 g/kg of dry matter (DM). No interaction effect was found among FCR supplementation and PELFUR in terms of feed intake and nutrient intake (p > 0.05). Cyanide intake was significantly increased based on FCR supplementation (p < 0.05), whereas sulphur intake was increased by level addition of PELFUR levels (p < 0.05). There were interaction effects among FCR supplementation and PELFUR on digestibility coefficients of DM and organic matter (OM) (p < 0.05). FCR supplementation at 20 g/kg BW with PELFUR 30 g/kg demonstrated the highest digestibility of DM and OM. Moreover, interactions were observed between FCR and PELFUR for bacterial populations (p < 0.01). The populations of bacteria were highest in FCR supplementation at 20 g/kg BW with PELFUR 30 g/kg at various feeding times. An interaction effect from among feeding FCR with PELFUR was found on blood thiocyanate concentrations at various feeding times (p < 0.01). The highest mean values of blood thiocyanate were observed when feeding FCR at 20 g/kg BW with PELFUR at 30 g/kg. No interaction effect was found between FCR and PELFUR on total volatile fatty acids (VFA) and their profiles (p > 0.05). However, the proportions of the total VFA at 0 and 4 h post‐feeding were increased when FCR at 20 g/kg BW was supplemented (p < 0.01). FCR at 20 g/kg BW could enhance propionate (C3) at 4 h post‐feeding when compared with FCR at 15 g/kg BW (p < 0.01). Moreover, supplementation of PELFUR at 30 g/kg increased the total VFA at 0 and 4 h post‐feeding, whereas the concentration of C3 at 4 h post‐feeding was enhanced (p < 0.05). However, no significant changes were found for any parameters among treatments and between the main effect of FCR and PELFUR supplementation (p > 0.05). In conclusion, feeding of two combinations (FCR 20 g/kg BW with PELFUR 30 g/kg) could promote the nutrient digestibility, the bacterial populations and the rate of disappearance of cyanide without having any adverse effect on rumen fermentation.
What factors shape surgical access in West Africa? A qualitative study exploring patient and provider experiences of managing injuries in Sierra Leone
Authors: Virk Amrit , Bella Jalloh Mohamed , Koedoyoma Songor , Smalle Isaac O , Bolton William , Scott J A , Brown Julia , Jayne David , Ensor Tim , King Rebecca 
Published: March 2021

IntroductionSurgical access is central to universalising health coverage, yet 5 billion people lack timely access to safe surgical services. Surgical need is particularly acute in post conflict settings like Sierra Leone. There is limited understanding of the barriers and opportunities at the service delivery and community levels. Focusing on fractures and wound care which constitute an enormous disease burden in Sierra Leone as a proxy for general surgical need, we examine provider and patient perceived factors impeding or facilitating surgical care in the post-Ebola context of a weakened health system.MethodsAcross Western Area Urban (Freetown), Bo and Tonkolili districts, 60 participants were involved in 38 semistructured interviews and 22 participants in 5 focus group discussions. Respondents included surgical providers, district-level policy-makers, traditional healers and patients. Data were thematically analysed, combining deductive and inductive techniques to generate codes.ResultsInteracting demand-side and supply-side issues affected user access to surgical services. On the demand side, high cost of care at medical facilities combined with the affordability and convenient mode of payment to the traditional health practitioners hindered access to the medical facilities. On the supply side, capacity shortages and staff motivation were challenges at facilities. Problems were compounded by patients’ delaying care mainly spurred by sociocultural beliefs in traditional practice and economic factors, thereby impeding early intervention for patients with surgical need. In the absence of formal support services, the onus of first aid and frontline trauma care is borne by lay citizens.ConclusionWithin a resource-constrained context, supply-side strengthening need accompanying by demand-side measures involving community and traditional actors. On the supply side, non-specialists could be effectively utilised in surgical delivery. Existing human resource capacity can be enhanced through better incentives for non-physicians. Traditional provider networks can be deployed for community outreach. Developing a lay responder system for first-aid and front-line support could be a useful mechanism for prompt clinical intervention.