bluuebunny/crossref_metadata_2025 huggingface dataset:
Proposing predictive maintenance strategy to increase OEE through system upgrade scenarios and AHP
Authors: Prasetyawan Y , Rachmayanti I
Published: March 2021

Maximizing the value of OEE is a crucial thing to do for a company in order to increase their productivity. OEE is one of the most common technique to measure equipment’s effectiveness. To enhance the number of OEE, it is very important to do a maintenance task to keep the equipment in a good condition. Predictive maintenance task is one of the maintenance strategies to see any potential failure in an equipment and do a preventive way to prevent it from a total stop/break down. As a result, understanding the needs to do a maintenance upgrades for better performance and proposing a good predictive maintenance strategy will enhance the value of OEE and result in cost savings. The objective of this paper is to propose the necessary predictive maintenance task using analytical hierarchy process (AHP) using three respondents to decide the AHP process and consistency ratio to get the most suitable maintenance task for fertilizer company as small medium enterprise.
Workload analysis using Modified Full Time Equivalent (M-FTE) and NASA-TLX methods to optimize engineer headcount in the engineering services department
Authors: Rachmuddin Y , Dewi D S , Dewi R S
Published: March 2021

With the increasing number of project initiatives, requests for engineering technical assistance are also increased. This raises a problem in the Engineering Services department which is uneven project workloads assigned among engineers, while there are no standard tools yet used to calculate accurate workload. To achieve maximum engineering productivity and performance, this study conducted to calculate engineer’s physical and mental workload. To calculate physical workload, the modified Full Time Equivalent (M-FTE) method is used, where engineer’s performance rating and allowance factors are also used to combine with the basic FTE calculation method. Estimate hours divided according to project’s level of complexity are converted into an index of FTE categories, i.e. underload, normal, and overloaded. The NASA-TLX method is used to get mental workload subjectively based on the average weight rating of six indicators. FTE index result shows adequate number of electrical engineers where half of them can still be assign to new project, while most of the instrument engineers already overloaded. Engineer’s mental workload from NASA-TLX result shows an average WWL (Weighted Workload) up to 81.72, which categorized as ‘Very High’ and corresponds to the nature of projects that always expected to be on schedule with high quality result.
Economic evaluation of mobile screening station waterless system operation of nickel laterite ore
Authors: Yustian A , Widodo E , Singgih M L
Published: March 2021

The study investigates the economic level of operating the Mobile Screening Station Waterless System (MSSWS) for the first-time application in the nickel laterite mining industry. Three investment alternatives are compared in this study to determine the most economical option, i.e.: maintaining existing Fixed Screening Station/FSS (alternative one), purchasing MSSWS (alternative two), and purchasing new FSS (alternative three). Evaluation is made by performing cost savings analysis, increment cash flow projections, NPV, and IRR calculation. Furthermore, sensitivity analysis of the most economic option will be done as well. The results show that MSSWS gives the highest NPV and IRR. The decreasing of ore hauling distance and water content that are contributed by MSSWS yields significant cost savings in terms of reducing hauled trucks’ investment and its operating cost. In accordance with this analysis, the economics of MSSWS is very sensitive to the changed of ore hauling distance. Therefore, this study has been successfully confirmed that purchasing of MSSWS is the most economical option. In addition to this result, a sensitivity analysis will be undertaken based on the situation that the moving of MSSWS over a certain period once the minimum change in the average ore hauling distance occurs.
Conceptual modeling of resilience measurement during natural disasters for SMEs
Authors: Utami I D , Santosa I , Rifa’i E
Published: March 2021

This study focuses on how to generate resilience information services to natural disasters for SMEs. The information in this study was using software or application developed based on a conceptual model formed as a framework for SMEs’ managers in dealing with natural disasters. The conceptual model was shaped based on actual data from SMEs’ owners and leaders, as well as stakeholders in four regencies in the Madura Island, Indonesia, namely Bangkalan, Sampang, Pamekasan and Sumenep, by identifying the variables or dimensions of SMEs’ resilience to natural disasters. The conceptual model was produced using sequence and use case diagrams to identify the relationship between risk and resilience dimensions to measure the level of resilience of SMEs. The level SMEs’ resilience to natural disasters was the basis of information received by SMEs’ owners and leaders. This study is expected to help SMEs to determine the level of SMEs’ resilience to the risk of natural disasters to minimize the existing risks.
Supplementary quality control features for the production department in Odoo ERP
Authors: Ahmadiyah A S , Ratna Y Y , Yotifa N N , Dinillah I
Published: March 2021

Odoo is one of the top Enterprise Resource Planning (ERP) applications. In particular, it is supported by a quality control module with the ability to control, trigger an alert, and check its purpose. This research strives to supplement the existing Odoo quality control module with parameters from past inspection data obtained before quality control migrates to Odoo. To support the study, we used a machine learning method to discover the intrinsic pattern from the dataset of quality control in the production process of baby biscuit products. The experiment shows that the additional quality control feature can provide the product measurement and tolerance threshold fed into Odoo quality control module. The additional feature is helpful for decision making and error minimization in setting quality control parameters and tolerance threshold. Furthermore, a high accuracy rate of 95.71% is obtained from the employed Decision Tree algorithm.
Analysing the barriers of reverse logistics implementation: A case study
Authors: Pramono S N W , Ulkhaq M M , Aulia Z
Published: March 2021

An increase in both consumers’ environmental awareness and government regulation related to the environment encourages industries to be more responsible for their products after consumption. As a result, a relatively new concept in logistics called reverse logistics (RL) is introduced. While the forward (or traditional) logistics refers to the process of distributing products from companies (or producers) to consumers, RL refers to the process of moving products from consumers to producers. This practice has attracted not only scholars but also practitioners in the field of supply chain and sustainability. A company could gain benefits from the implementation of RL since it can lead to higher profit. However, some barriers regard its implementation despite the benefits that make the company reluctant to implement it. Therefore, this study aims to investigate the barriers to implementing RL in a bottled drinking water company. Moreover, this study also analyses the interaction among the barriers to looking for the possible “root barrier”. The interpretative structural modelling and MICMAC analysis were used to accomplish the objective of the study. It is expected that the study could help the management to better formulate policies about the implementation of RL.
Work system analysis on puncher bar repair process in the production division of Akademi Teknik Soroako (Soroako Technical Academy)
Authors: Burhanuddin  , Dewi R S
Published: March 2021

One of the regular services in the Production Division of Akademi Teknik Soroako (Soroako Technical Academy) is repairing puncher bars of PT Vale Indonesia, One of the stages of his work is to straighten each punch bar. For straightening up each puncher bar, the worker needs to hammer each puncher bar with a 5 kg iron hammer manually. This operation requires enormous physical energy and high cognitive effort for controlling body movement, causing fatigue and cumulative musculoskeletal trauma. The research focuses on assessing the risk of musculoskeletal disorders on the straightening employing Ovako Work Posture Analysis System (OWAS) and Rapid Upper limb Assessment (RULA). The result of the study shows that the work postures while straightening the puncher bar has OWAS score = 2 which means it needs corrective action in the near term, and RULA score = 7 which means the work posture improvement should be made right now. Based on the OWAS and RULA score, several improvement programs and techniques are suggested in this study.
A Theoretical Study of Second Lyapunov Method on Stability of Zero Solution for a Delay Differential System
Authors: Hijab Anas A. , Khalil Muayyad M.
Published: March 2021

This study examined the asymptotic stability of delay differential systems using Lyapunov’s second method. It showed that the zero solutions are asymptotically stable when satisfying some necessary and sufficient conditions. The solution origin of the given system is asymptotically stable for small perturbations, which has no effect on equilibrium system if some conditions are held and it is asymptotically stable for large perturbations that moving system of its equilibrium then its comeback to it if other conditions are held. The proof of theorems in this article results by using and applying Gronwell-Bellman inequality which leads us to main result.
Synthesis of Iron-nickel Particles by Co-precipitation Technique and Used as a Contrast Medium in an MRI Machine
Authors: Mubarak T H , Mahmood O A , Shatti W A
Published: March 2021

In this study, Nickel Zinc Ferrite was prepared using the co-precipitation method according to the chemical formula Ni1-xZnxFe2O4, where the values of (x = 0,0.1,0.3,0.5,0.7,0.9) respectively, the structural and magnetic properties were studied through X-ray diffraction spectroscopy. FESEM showed the porosity and distribution of the homogeneous nanoparticles roughly, also its particle size. The vibration sample Magnetometer (VSM)was used to study magnetic properties, and the Fourier transform infrared (FTIR) spectra were measured in the range of 400-4000 cm−1. Magnetic nanoparticles effect on contrast factors in magnetic resonance imaging (MRI) images was studied, it showed Good and robust imaging technique for diagnosis and post-treatment evaluation for a wide range of diseases. MRI contrast can be enhanced by using negative or positive contrast agents, resulting in clearer (T1-weighted) or darker (T2-weighted) images, respectively, with super-magnetic nanoparticles yielding T2 contrast agents widely used in molecular imaging applications and cellular. As most of the work in this field focuses on the acquisition of biological species using nanoparticles, which in turn will improve the magnetic properties that lead to higher imaging.
Comprehensive health assessment and blood analyte reference intervals of gopher tortoises (Gopherus polyphemus) in southeastern FL, USA
Authors: Page-Karjian Annie , Rafferty Kathleen , Xavier Clerson , Stacy Nicole I , Moore Jon A , Hirsch Sarah E , Clark Samantha , Manire Charles A , Perrault Justin R
Published: March 2021

The gopher tortoise (Gopherus polyphemus), a keystone species, is declining throughout its geographic range. Lack of knowledge with respect to the potential infectious diseases present within wild populations creates a dilemma for wildlife biologists, conservationists and public policy makers. The objective of this study was to conduct a health assessment of two previously unstudied gopher tortoise aggregations located at two sites in southeastern FL. Samples were collected from 91 tortoises (48 adults, 35 juveniles, 8 hatchlings) captured at Florida Atlantic University’s Harbor Branch Oceanographic Institute, in Fort Pierce, FL, USA in 2019, and Loggerhead Park in Juno Beach, FL, USA, during 2018–2019. Samples of blood, nasal swabs and oral/cloacal swabs were analyzed for hematology, plasma protein electrophoretic profiles and infectious disease testing including Mycoplasma spp. serology and polymerase chain reaction (PCR) assays for Ranavirus, Herpesvirus and Anaplasma spp. Hematological and plasma protein electrophoresis reference intervals are presented for adult and juvenile tortoises from both sites combined. Clinical signs consistent with upper respiratory tract disease (URTD) were observed in 18/91 (20%) tortoises, and antibodies to Mycoplasma agassizii were detected in 33/77 (42.9%) tortoises. Adult tortoises were significantly more likely than juveniles to have URTD clinical signs, and statistically significant, positive relationships were observed between the presence of antibodies to Mycoplasma spp. and carapace length, packed cell volume and plasma globulin concentrations. Anaplasma spp. inclusions were observed in 8/82 (10%) tortoises, but PCR detected Anaplasma sp. in 21/83 (25%) tortoises. Herpesvirus and Ranavirus were not detected in any blood or swab samples. This work contributes important baseline information on the health of gopher tortoises toward the southern end of the species’ range.
Management of post-operative subcutaneous emphysema with the application of wound VAC therapy
Authors: Minarich Michael J , Henry Leonard R , Hardy Ashley , von Holzen Urs
Published: March 2021

Extensive subcutaneous emphysema (SE) complicates between 1 and 6% of elective thoracic procedures. The management of SE is varied, and may include increasing the suction of chest tubes, placement of additional chest tubes, placement of subcutaneous drains and creation of releasing incisions. We present five patients with post-operative SE treated successfully with a subcutaneous infraclavicular incision and wound VAC therapy. A 5-cm incision was made 2 cm below the clavicle down and through the pectoralis major fascia. A VAC dressing was fitted to the wound and suction was applied to −125 mm Hg. Data were retrospectively collected and analyzed. VAC dressing was placed a median of 6 days after initial operation. All patients had improvement in symptoms and resolution of SE by VAC dressing therapy. Subcutaneous infraclavicular incision and VAC dressing placement is a viable treatment for patients with post-operative SE who fail conservative therapy.
Model-based analysis of implanted hypoglossal nerve stimulation for the treatment of obstructive sleep apnea
Authors: Johnson Matthew D , Dweiri Yazan M , Cornelius Jason , Strohl Kingman P , Steffen Armin , Suurna Maria , Soose Ryan J , Coleman Michael , Rondoni John , Durand Dominique M , Ni Quan
Published: March 2021

Study Objectives

Individuals with obstructive sleep apnea (OSA), characterized by frequent sleep disruptions from tongue muscle relaxation and airway blockage, are known to benefit from on-demand electrical stimulation of the hypoglossal nerve. Hypoglossal nerve stimulation (HNS) therapy, which activates the protrusor muscles of the tongue during inspiration, has been established in multiple clinical studies as safe and effective, but the mechanistic understanding for why some stimulation parameters work better than others has not been thoroughly investigated.

Methods

In this study, we developed a detailed biophysical model that can predict the spatial recruitment of hypoglossal nerve fascicles and axons within these fascicles during stimulation through nerve cuff electrodes. Using this model, three HNS programming scenarios were investigated including grouped cathode (---), single cathode (o-o), and guarded cathode bipolar (+-+) electrode configurations.

Results

Regardless of electrode configuration, nearly all hypoglossal nerve axons circumscribed by the nerve cuff were recruited for stimulation amplitudes <3 V. Within this range, monopolar configurations required lower stimulation amplitudes than the guarded bipolar configuration to elicit action potentials within hypoglossal nerve axons. Further, the spatial distribution of the activated axons was more uniform for monopolar versus guarded bipolar configurations.

Conclusions

The computational models predicted that monopolar HNS provided the lowest threshold and the least sensitivity to rotational angle of the nerve cuff around the hypoglossal nerve; however, this setting also increased the likelihood for current leakage outside the nerve cuff, which could potentially activate axons in unintended branches of the hypoglossal nerve.

Clinical Trial Registration

NCT01161420.
Estimating design hydrologic extremes in a warming climate: alternatives, uncertainties and the way forward
Authors: Sharma Ashish , Hettiarachchi Suresh , Wasko Conrad
Published: March 2021

It is now well established that our warming planet is experiencing changes in extreme storms and floods, resulting in a need to better specify hydrologic design guidelines that can be projected into the future. This paper attempts to summarize the nature of changes occurring and the impact they are having on the design flood magnitude, with a focus on the urban catchments that we will increasingly reside in as time goes on. Two lines of reasoning are used to assess and model changes in design hydrology. The first of these involves using observed storms and soil moisture conditions and projecting how these may change into the future. The second involves using climate model simulations of the future and using them as inputs into hydrologic models to assess the changed design estimates. We discuss here the limitations in both and suggest that the two are, in fact, linked, as climate model projections for the future are needed in the first approach to form meaningful projections for the future. Based on the author's experience with both lines of reasoning, this invited commentary presents a theoretical narrative linking these two and identifying factors and assumptions that need to be validated before implementation in practice.

This article is part of a discussion meeting issue ‘Intensification of short-duration rainfall extremes and implications for flash flood risks’.
Using high-resolution climate change information in water management: a decision-makers' perspective
Authors: Orr H. G. , Ekström M. , Charlton M. B. , Peat K. L. , Fowler H. J.
Published: March 2021

The UK Climate Change Act requires the Environment Agency to report the risks it faces from climate change and actions taken to address these. Derived information from projections is critical to understanding likely impacts in water management. In 2019, the UK published an ensemble of high-resolution model simulations. The UKCP Local (2.2 km) projections can resolve smaller scale physical processes that determine rainfall and other variables at subdaily time-scales with the potential to provide new insights into extreme events, storm runoff and drainage management. However, simulations also need to inform adaptation. The challenge ahead is to identify and provide derived products without the need for further analysis by decision-makers. These include a wider evaluation of uncertainty, narratives about rainfall change across the projections and bias-corrected datasets. Future flood maps, peak rainfall estimates, uplift factors and future design storm profiles also need detailed guidance to support their use. Central government support is justified in the provision of up-to-date impacts information to inform flood risk management, given the large risks and exposure of all sectors. The further development of projections would benefit from greater focus and earlier scoping with industry representatives, operational tool developers and end users.

This article is part of a discussion meeting issue ‘Intensification of short-duration rainfall extremes and implications for flash flood risks’.
Risk factors for illness severity among pregnant women with confirmed SARS-CoV-2 infection – Surveillance for Emerging Threats to Mothers and Babies Network, 20 state, local, and territorial health departments, March 29, 2020 -January 8, 2021
Authors: Galang Romeo R. , Newton Suzanne M. , Woodworth Kate R. , Griffin Isabel , Oduyebo Titilope , Sancken Christina L. , Olsen Emily O’Malley , Aveni Kathy , Wingate Heather , Shephard Hanna , Fussman Chris , Alaali Zahra S. , Siebman Samantha , Halai Umme-Aiman , Lopez Camille Delgado , Barton Jerusha , Lush Mamie , Patrick Paul H. , Schlosser Levi , Sokale Ayomide , Chaudhary Ifrah , Reynolds Bethany , Sowunmi Similoluwa , Gaarenstroom Nicole , Read Jennifer S. , Chicchelly Sarah , de Wilde Leah , Azziz-Baumgartner Eduardo , Hall Aron J. , Tong Van T. , Ellington Sascha , Gilboa Suzanne M. ,   CDC COVID-19 Response Pregnancy and Infant Linked Outcomes Team
Published: March 2021

Background

Pregnant women with coronavirus disease 2019 (COVID-19) are at increased risk for severe illness compared with nonpregnant women. Data to assess risk factors for illness severity among pregnant women with COVID-19 are limited. This study aimed to determine risk factors associated with COVID-19 illness severity among pregnant women with SARS-CoV-2 infection.

Methods

Pregnant women with SARS-CoV-2 infection confirmed by molecular testing were reported during March 29, 2020–January 8, 2021 through the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET). Criteria for illness severity (asymptomatic, mild, moderate-to-severe, or critical) were adapted from National Institutes of Health and World Health Organization criteria. Crude and adjusted risk ratios for moderate-to-severe or critical COVID-19 illness were calculated for selected demographic and clinical characteristics.

Results

Among 5,963 pregnant women with SARS-CoV-2 infection, moderate-to-severe or critical COVID-19 illness was associated with age 30–39 years, Black/Non-Hispanic race/ethnicity, healthcare occupation, pre-pregnancy obesity, chronic lung disease, chronic hypertension, cardiovascular disease, and pregestational diabetes mellitus. Risk of moderate-to-severe or critical illness increased with the number of underlying medical or pregnancy-related conditions.

Conclusions

Pregnant women with moderate-to-severe or critical COVID-19 illness were more likely to be older and have underlying medical conditions compared to pregnant women with asymptomatic infection or mild COVID-19 illness. This information might help pregnant women understand their risk for moderate-to-severe or critical COVID-19 illness and inform targeted public health messaging.

Among pregnant women with COVID-19, older age and underlying medical conditions were risk factors for increased illness severity. These findings can be used to inform pregnant women about their risk for severe COVID-19 illness and public health messaging.
MAPK Pathway Inhibition as A Rational Therapeutic Strategy for MiR-138-5p/PAQR3 Dysregulation-mediated Epirubicin Resistance in Triple-negative Breast Cancer
Authors: Huang Jianbo , Zeng Shiyan , Xiao Yun , Wang Xiaoyi , Li Hongyuan , Xiang Tingxiu , Kong Lingquan , Ren Guosheng
Published: March 2021

Anthracyclines, such as epirubicin, activate the mitogen-activated protein kinase (MAPK) pathway in breast cancer (BC). Better predictors of tumor response are needed to guide de-intensification of anthracyclines when used in BC treatment. Here, we aimed to see if MAPK activation was responsible and targetable for epirubicin resistance, and to explore mechanisms and predictive markers for resistance. MAPK pathway inhibitors were used to ameliorate epirubicin resistance. Negative regulators of MAPK were screened to identify the essential gene cascades required for activation of the pathway. In vitro and in vivo approaches were applied to investigate epirubicin resistance. The regulatory miRNA was identified through bioinformatics-based screening and luciferase reporter assay. 114 estrogen receptor negative patients who received epirubicin monotherapy were included to evaluate predictive markers for tumor response. The MAPK pathway was activated in cells resistant to epirubicin; MAPK inhibition ameliorated epirubicin resistance. In triple-negative breast cancer (TNBC), progestin and adipoQ receptor 3 (PAQR3) were the most significantly decreased negative MAPK regulators. PAQR3 increased epirubicin sensitivity and suppressed MAPK activation in resistant cells. MiR-138-5p was increased in epirubicin resistant cells, and was shown to downregulate PAQR3, causing resistance in epirubicin resistant cells. PAQR3 was an independent factor in predicting response to epirubicin (OR=4.86, 95%CI=1.13-20.87, P=0.034), and possessed a high negative predictive value (NPV) (0.93; 95%CI=0.83-0.97). In addition, PAQR3 exhibited a better predictive value in patients older than 50 years (12.92 (95% CI, 1.43-116.78, P = 0.023). The combinative use of PAQR3 and topoisomerase II-α (TOP2A) led to an increased specificity (0.70; 95%CI=0.61-0.79), when compared with either PAQR3 or TOP2A alone. MAPK inhibition ameliorated epirubicin resistance. MiR-138-5p-induced PAQR3 reduction causes epirubicin resistance in TNBC via activation of MAPK cascades. PAQR3 is an independent and favorable predictor response to epirubicin in BC.
Tetraploidy accelerates adaption under drug-selection in a fungal pathogen
Authors: Avramovska Ognenka , Rego Emily , Hickman Meleah A
Published: March 2021

Baseline 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

Abstract

The 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

Nelfinavir 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

With 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

Despite 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.
Embedding Cultured Cells in Matrigel for Staining
Authors: Rodig Scott J.
Published: March 2021

Adherent cells normally are prepared for cell staining by growing on a suitable support. Suspension cells can be fixed directly or can be attached to a solid support by centrifugation, chemical cross-linking, or simple dehydration. An alternative approach for cells grown in culture is to prepare a fixed cell pellet that is embedded in a scaffold, such as Matrigel, and then processed, embedded in paraffin, and stained in a manner identical to formalin-fixed tissue specimens.
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

Purpose

University 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/approach

This 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.

Findings

This 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/value

The 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

A 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

Objective

To assess longitudinal primary care organization participation patterns in large‐scale reform programs and identify organizational characteristics associated with multiprogram participation.

Data Sources

Secondary data analysis of national program participation data over an eight‐year period (2009‐2016).

Study Design

We 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 Methods

We 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 Findings

No 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 Relevance

Primary 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.
Autopsies in pandemics – a perspective on barriers and benefits. Is it time for a revival?
Authors: Khatam‐Lashgari Apameh , Henningsen Mikkel Jon , Olsen Kristine Boisen , Jacobsen Christina , Hasselby Jane Preuss , Colville‐Ebeling Bonnie , Banner Jytte
Published: March 2021

Influenza virus and coronavirus pandemics regularly sweep the globe, at great cost of health and economy. Our aim was to conduct a PubMed search for autopsy studies on influenza and coronavirus to investigate the contribution of autopsies during pandemics, focussing on autopsy methods and procedures and the role of autopsy findings in pandemics. The retrieved autopsy studies generally relied on microscopy, polymerase chain reaction (PCR), immunostaining and electron microscopy. Most were small and reported on lung effects, including diffuse alveolar damage (DAD), pneumonia and tracheobronchitis. Antibiotic therapy has diminished a role for bacterial pneumonia, whereas obesity is an emerging risk factor. Autopsy studies have provided new insights into coronavirus disease 2019 (COVID‐19) treatments like anti‐coagulative therapy. Unfortunately, autopsies during pandemics are hampered by lack of guidelines, facilities and expertise for handling potentially infectious corpses and by widely varying recommendations for personal protective equipment and procedures. The Department of Forensic Pathology, at the Forensic Institute, at the University of Copenhagen in Denmark has, in collaboration with the Department of Pathology, Rigshospitalet, Copenhagen, initiated a prospective observational study on COVID‐19‐related deaths encompassing postmortem imaging, standardized autopsy procedures/reporting and extensive tissue sampling for histological, chemical, microbiological and genetic analysis. The study involves a diverse array of research groups at the University of Copenhagen, and the clinical field.
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

Aim

This 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.

Methods

A 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.

Results

Analysis 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).

Conclusions

A 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

The 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.