bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemoenzymatic semisynthesis of caffeic acid β-phenethyl ester, an antioxidative component in propolis, from raw coffee bean extract
Authors: Hashimoto Riichi , Iai Hiyori , Fujita Rie , Hanaya Kengo , Higashibayashi Shuhei , Inoue Hiroyoshi , Sugai Takeshi
Published: February 2021

Caffeic acid β-phenethyl ester (CAPE), an antioxidative bioactive catechol isolated from propolis, was semisynthesized from chlorogenic acid and related compounds in an extract of raw (unroasted) Robusta coffee (Coffea canephora) beans in 5 steps and a total yield of 31%. Oxidative degradation of the intermediates and target molecule was prevented by alkaline hydrolysis of the chlorogenic acids in the presence of sodium dithionite (Na2S2O4) and deprotection of the catecholic diacetate precursor by Candida antarctica lipase B-mediated transesterification as the final step.
The evaluation of lymph node cell proliferation response by liposomes loaded with major histocompatibility complex class II binding aquaporin 4 antigen peptide
Authors: Muraki Yo , Nishimoto Yutaka , Yamasaki Midori , Miyakawa Shuuichi , Sato Shuji
Published: February 2021

Autoimmune responses to aquaporin 4 (AQP4) cause neuromyelitis optica (NMO); thus, specific immunotolerance to this self-antigen could represent a new NMO treatment. We generated the liposome-encapsulated AQP4 peptide 201-220 (p201-220) to induce immunotolerance. Liposomes were generated using phosphatidylserine and the polyglycidol species PG8MG. The in vivo tissue distribution of the liposomes was tested using an ex vivo imaging system. To confirm the antigen presentation capacity of PG8MG liposomes, dendritic cells were treated with PG8MG liposome-encapsulated AQP4 p201-220 (AQP4-PG8MG liposomes). Immunotolerance induction by AQP4-PG8MG liposomes was evaluated using the ex vivo cell proliferation of lymph node cells isolated from AQP4 p201-220-immunized AQP4-deficient mice. Fluorescent dye-labeled PG8MG liposomes were distributed to the lymph nodes. AQP4 p201-220 was presented on dendritic cells. AQP4-PG8MG liposomes were tended to suppress immune responses to AQP4 p201-220. Thus, the encapsulation of AQP4 peptides in PG8MG liposomes represents a new strategy for suppressing autoimmune responses to AQP4.
Gene-set integrative analysis of multi-omics data using tensor-based association test
Authors: Chang Sheng-Mao , Yang Meng , Lu Wenbin , Huang Yu-Jyun , Huang Yueyang , Hung Hung , Miecznikowski Jeffrey C , Lu Tzu-Pin , Tzeng Jung-Ying
Published: February 2021

Motivation

Facilitated by technological advances and the decrease in costs, it is feasible to gather subject data from several omics platforms. Each platform assesses different molecular events, and the challenge lies in efficiently analyzing these data to discover novel disease genes or mechanisms. A common strategy is to regress the outcomes on all omics variables in a gene set. However, this approach suffers from problems associated with high-dimensional inference.

Results

We introduce a tensor-based framework for variable-wise inference in multi-omics analysis. By accounting for the matrix structure of an individual’s multi-omics data, the proposed tensor methods incorporate the relationship among omics effects, reduce the number of parameters, and boost the modeling efficiency. We derive the variable-specific tensor test and enhance computational efficiency of tensor modeling. Using simulations and data applications on the Cancer Cell Line Encyclopedia (CCLE), we demonstrate our method performs favorably over baseline methods and will be useful for gaining biological insights in multi-omics analysis.

Availability and implementation

R function and instruction are available from the authors’ website: https://www4.stat.ncsu.edu/~jytzeng/Software/TR.omics/TRinstruction.pdf.

Supplementary information

Supplementary data are available at Bioinformatics online.
Carryover effect of atrazine and its metabolite—from treated bovine spermatozoa to the embryo’s transcriptome†
Authors: Komsky-Elbaz A , Kalo D , Roth Z
Published: February 2021

Atrazine (ATZ) is an extensively used herbicide and ubiquitous environmental contaminant. ATZ and its metabolite, diaminochlorotriazine (DACT), cause several cellular and functional alterations in spermatozoa. We aimed to examine the effect of ATZ/DACT on spermatozoon DNA integrity, fertilization competence, embryonic development, and transcriptome profile of in vitro-produced embryos derived from fertilization with pre-exposed sperm.

Bovine spermatozoa exposed to ATZ (0.1 or 1 μM) or DACT (1 or 10 μM) during in vitro capacitation were used for in vitro fertilization of untreated oocytes. Cleavage and blastocyst-formation rates were evaluated 42 h and 7 days postfertilization, respectively. The association between DNA fragmentation and apoptosis (annexin V kit) was determined. Fertilization competence of annexin-positive (AV+) and annexin-negative (AV−) spermatozoa was examined. Microarray analysis was performed for 7-day blastocysts.

Intracytoplasmic sperm injection was performed with control (AV+, AV−) and DACT (AV+, AV−) spermatozoa. Cleavage rates did not differ between groups and blastocyst formation tended to be higher for AV− vs. AV+ in both control and DACT groups, suggesting that acrosome reaction, rather than DNA fragmentation, underlies the reduced cleavage. Transcriptomic analysis revealed 139 and 230 differentially expressed genes in blastocysts derived from ATZ- and DACT-exposed spermatozoa, respectively, relative to controls.

Proteomic analysis shown differential expression of proteins in ATZ- or DACT-treated spermatozoa, in particular proteins related to cellular processes and biological pathways. Therefore, we assume that factors delivered by the spermatozoa, regardless of DNA fragmentation, are also involved. Overall, the current study reveals a deleterious carryover effect of ATZ/DACT from the spermatozoa to the developing embryo.
A discrete bouncy particle sampler
Authors: Sherlock C , Thiery A H
Published: February 2021

Most Markov chain Monte Carlo methods operate in discrete time and are reversible with respect to the target probability. Nevertheless, it is now understood that the use of nonreversible Markov chains can be beneficial in many contexts. In particular, the recently proposed bouncy particle sampler leverages a continuous-time and nonreversible Markov process, and empirically shows state-of-the-art performance when used to explore certain probability densities; however, its implementation typically requires the computation of local upper bounds on the gradient of the log target density. We present the discrete bouncy particle sampler, a general algorithm based on a guided random walk, a partial refreshment of direction and a delayed-rejection step. We show that the bouncy particle sampler can be understood as a scaling limit of a special case of our algorithm. In contrast to the bouncy particle sampler, implementing the discrete bouncy particle sampler only requires pointwise evaluation of the target density and its gradient. We propose extensions of the basic algorithm for situations when the exact gradient of the target density is not available. In a Gaussian setting, we establish a scaling limit for the radial process as the dimension increases to infinity. We leverage this result to obtain the theoretical efficiency of the discrete bouncy particle sampler as a function of the partial-refreshment parameter, which leads to a simple and robust tuning criterion. A further analysis in a more general setting suggests that this tuning criterion applies more generally. Theoretical and empirical efficiency curves are then compared for different targets and algorithm variations.
Systematic review of classification systems for locally recurrent rectal cancer
Authors: Rokan Z , Simillis C , Kontovounisios C , Moran B J , Tekkis P , Brown G
Published: February 2021

Background

Classification of pelvic local recurrence (LR) after surgery for primary rectal cancer is not currently standardized and optimal imaging is required to categorize anatomical site and plan treatment in patients with LR. The aim of this review was to evaluate the systems used to classify locally recurrent rectal cancer (LRRC) and the relevant published outcomes.

Methods

A systematic review of the literature prior to April 2020 was performed through electronic searches of the Science Citation Index Expanded, EMBASE, MEDLINE and CENTRAL databases. The primary outcome was to review the classifications currently in use; the secondary outcome was the extraction of relevant information provided by these classification systems including prognosis, anatomy and prediction of R0 after surgery.

Results

A total of 21 out of 58 eligible studies, classifying LR in 2086 patients, were reviewed. Studies used at least one of the following eight classification systems proposed by institutions or institutional groups (Mayo Clinic, Memorial Sloan-Kettering – original and modified, Royal Marsden and Leeds) or authors (Yamada, Hruby and Kusters). Negative survival outcomes were associated with increased pelvic fixity, associated symptoms of LR, lateral compared with central LR and involvement of three or more pelvic compartments. A total of seven studies used MRI with specifically defined anatomical compartments to classify LR.

Conclusion

This review highlights the various imaging systems in use to classify LRRC and some of the prognostic indicators for survival and oncological clearance based on these systems. Implementation of an agreed classification system to document pelvic LR consistently should provide more detailed information on anatomical site of recurrence, burden of disease and standards for comparative outcome assessment.
Development of Individual Variability in Brain Functional Connectivity and Capability across the Adult Lifespan
Authors: Ma Liying , Tian Lixia , Hu Tianyu , Jiang Tianzi , Zuo Nianming
Published: February 2021

Individual variability exists in both brain function and behavioral performance. However, changes in individual variability in brain functional connectivity and capability across adult development and aging have not yet been clearly examined. Based on resting-state functional magnetic resonance imaging data from a large cohort of participants (543 adults, aged 18–88 years), brain functional connectivity was analyzed to characterize the spatial distribution and differences in individual variability across the adult lifespan. Results showed high individual variability in the association cortex over the adult lifespan, whereas individual variability in the primary cortex was comparably lower in the initial stage but increased with age. Individual variability was also negatively correlated with the strength/number of short-, medium-, and long-range functional connections in the brain, with long-range connections playing a more critical role in increasing global individual variability in the aging brain. More importantly, in regard to specific brain regions, individual variability in the motor cortex was significantly correlated with differences in motor capability. Overall, we identified specific patterns of individual variability in brain functional structure during the adult lifespan and demonstrated that functional variability in the brain can reflect behavioral performance. These findings advance our understanding of the underlying principles of the aging brain across the adult lifespan and suggest how to characterize degenerating behavioral capability using imaging biomarkers.
Effect of polymer type on the colonization of plastic pellets by marine bacteria
Authors: Hansen Josefine , Melchiorsen Jette , Ciacotich Nicole , Gram Lone , Sonnenschein Eva C
Published: February 2021

Plastic is omnipresent in the oceans and serves as a surface for biofilm-forming microorganisms. Plastic debris comprises different polymers, which may influence microbial colonization; here, we evaluated whether polymer type affects bacterial biofilm formation. Quantifying the biofilm on polyethylene (PE), polypropylene (PP) or polystyrene (PS) pellets by six marine bacterial strains (Vibrio,Pseudoalteromonas,Phaeobacter) demonstrated that each strain had a unique colonization behavior with either a preference for PS or PP over the other polymer types or no preference for a specific plastic type. PE, PP and PS pellets were exposed to natural seawater microbiota using free-living or total communities as inoculum. Microbial assembly as determined by 16S rRNA (V4) amplicon sequencing was affected by the composition of the initial inoculum and also by the plastic type. Known polymer and hydrocarbon degraders such as Paraglaciecola, Oleibacter and Hydrogenophaga were found in the plastic biofilms. Thus, on a community level, bacterial colonization on plastic is influenced by the microorganisms as well as the polymer type, and also individual strains can demonstrate polymer-specific colonization.
K+-specific importers Trk1 and Trk2 play different roles in Ca2+ homeostasis and signalling in Saccharomyces cerevisiae cells
Authors: Zimmermannova Olga , Felcmanova Kristina , Sacka Lenka , Colinet Anne-Sophie , Morsomme Pierre , Sychrova Hana
Published: February 2021

The maintenance of K+ and Ca2+ homeostasis is crucial for many cellular functions. Potassium is accumulated in cells at high concentrations, while the cytosolic level of calcium, to ensure its signalling function, is kept at low levels and transiently increases in response to stresses. We examined Ca2+ homeostasis and Ca2+ signalling in Saccharomyces cerevisiae strains lacking plasma-membrane K+ influx (Trk1 and Trk2) or efflux (Tok1, Nha1 and Ena1-5) systems. The lack of K+ exporters slightly increased the cytosolic Ca2+, but did not alter the Ca2+ tolerance or Ca2+-stress response. In contrast, the K+-importers Trk1 and Trk2 play important and distinct roles in the maintenance of Ca2+ homeostasis. The presence of Trk1 was vital mainly for the growth of cells in the presence of high extracellular Ca2+, whilst the lack of Trk2 doubled steady-state intracellular Ca2+ levels. The absence of both K+ importers highly increased the Ca2+ response to osmotic or CaCl2 stresses and altered the balance between Ca2+ flux from external media and intracellular compartments. In addition, we found Trk2 to be important for the tolerance to high KCl and hygromycin B in cells growing on minimal media. All the data describe new interconnections between potassium and calcium homeostasis in S. cerevisiae.
Clade-specific chromosomal rearrangements and loss of subtelomeric adhesins in Candida auris
Authors: Muñoz José F , Welsh Rory M , Shea Terrance , Batra Dhwani , Gade Lalitha , Howard Dakota , Rowe Lori A , Meis Jacques F , Litvintseva Anastasia P , Cuomo Christina A
Published: February 2021

Candida auris is an emerging fungal pathogen of rising concern due to global spread, the ability to cause healthcare-associated outbreaks, and antifungal resistance. Genomic analyses revealed that early contemporaneously detected cases of C. auris were geographically stratified into four major clades. While Clades I, III, and IV are responsible for ongoing outbreaks of invasive and multidrug-resistant infections, Clade II, also termed the East Asian clade, consists primarily of cases of ear infection, is often susceptible to all antifungal drugs, and has not been associated with outbreaks. Here, we generate chromosome-level assemblies of twelve isolates representing the phylogenetic breadth of these four clades and the only isolate described to date from Clade V. This Clade V genome is highly syntenic with those of Clades I, III, and IV, although the sequence is highly divergent from the other clades. Clade II genomes appear highly rearranged, with translocations occurring near GC-poor regions, and large subtelomeric deletions in most chromosomes, resulting in a substantially different karyotype. Rearrangements and deletion lengths vary across Clade II isolates, including two from a single patient, supporting ongoing genome instability. Deleted subtelomeric regions are enriched in Hyr/Iff-like cell-surface proteins, novel candidate cell wall proteins, and an ALS-like adhesin. Cell wall proteins from these families and other drug-related genes show clade-specific signatures of selection in Clades I, III, and IV. Subtelomeric dynamics and the conservation of cell surface proteins in the clades responsible for global outbreaks causing invasive infections suggest an explanation for the different phenotypes observed between clades.
Social and Physical Context Moderates Older Adults’ Affective Responses to Sedentary Behavior: An Ecological Momentary Assessment Study
Authors: Hevel Derek J , Drollette Eric S , Dunton Genevieve F , Maher Jaclyn P
Published: February 2021

Objectives

Older adults engage in excessive sedentary behaviors which hold significant health implications. Examining affect responses during sedentary behavior is not well understood despite the wealth of evidence linking affect and motivation. Contextual influences (i.e., social and physical) likely influence affective responses during sedentary behavior and therefore warrant further investigation.

Method

Older adults (n = 103, Mage = 72, range: 60–98) participated in a 10-day study where they received 6 randomly timed, smartphone-based Ecological Momentary Assessment (EMA) prompts/day. Participants reported their affect, current behavior, and context at each EMA prompt. Participants also wore an activPAL accelerometer to measure their sedentary behavior duration. Separate multilevel models examined the extent to which the context influences affective responses during self-report sedentary (vs nonsedentary) behaviors.

Results

The social context moderated the association between sedentary behavior and negative affect. The physical context moderated the association between sedentary behavior and positive affect.

Discussion

Interventions should consider the context of behaviors when designing interventions to reduce sedentary behavior as some contextual factors may attenuate, while other contexts may exacerbate, associations between activity-related behaviors and indicators of well-being.
Evidence of increased occurrence of Atlantic bluefin tuna in territorial waters of the United Kingdom and Ireland
Authors: Horton Thomas W , Block Barbara A , Davies Rachel , Hawkes Lucy A , Jones Duncan , Jones Hannah , Leeves Keith , Maoiléidigh Niall Ó , Righton David , van der Kooij Jeroen , Wall Dave , Witt Matthew J
Published: February 2021

Atlantic bluefin tuna (ABT, Thunnus thynnus; Linneaus, 1758) is an ecologically important apex-predator with high commercial value. They were once common off the coast of the United Kingdom (UK), before disappearing in the 1960s. In regions lacking commercial fisheries for ABT, such as the UK and Ireland, spatial data can be scarce. In these cases, sightings and bycatch databases can offset information shortfalls. Here, we document the reappearance of ABT into territorial waters of the UK from 2014 onwards, and increased occurrence off Ireland. We analyse a novel, multi-source dataset comprising occurrence data (2008–2019; 989 sightings and 114 tonnes of bycatch) compiled from a range of sources (scientific surveys, ecotours and fisheries). We show an increasing trend in effort-corrected ABT occurrence in (i) the pelagic ecosystem survey in the western English Channel and Celtic Sea (PELTIC), (ii) an ecotour operator, and (iii) the Irish albacore fishery in on-shelf and off-shelf waters. Sightings of ABT by the PELTIC correlated with modelled abundance estimates of ABT and the Atlantic multidecadal oscillation. These data demonstrate that sightings of ABT have increased off the UK and Ireland since 2014, following the same increasing trend (2010 onwards) as the eastern ABT population.
Exploring the role of temperature in observed inter-population differences of Atlantic cod(Gadus morhua)growth with a 4-dimensional modelling approach
Authors: Sokolova Nadezhda , Butzin Martin , Dahlke Flemming , Werner Karl Michael , Balting Daniel , Lohmann Gerrit , Pörtner Hans-Otto
Published: February 2021

Atlantic cod (Gadus morhua) is one of the most commercially important fish species in the North Atlantic. Environmental factors, such as water temperatures, influence growth of individuals over time, thus forming population-specific growth patterns across climatic regions. Here we develop an integrative approach to investigate the role of temperature in shaping geographic differences of cod growth in the Celtic Sea, North Sea, Iceland, and Barents Sea. We combine a physiology-based growth model and 50-years observational temperature data of 0.5 × 0.5° spatial resolution to simulate continuous growth of cod. The model generated weight-at-age data for the period 1959–2007 which we compared to observational data from fishery-independent scientific surveys. In the Celtic and the northern North Sea, simulated growth matches well observational data. We also show that relatively warm temperatures in the Celtic Sea facilitate maximum growth rates; future warming is likely to have a negative impact on growth of these cod stocks. Growth simulations in Icelandic waters and the Barents Sea are less consistent with local observational data. More complex growth patterns in these regions are probably shaped by ontogenetic shifts in temperature regimes, feeding conditions and physiological adaptations. These findings should stimulate further research on critical processes to be considered in population-specific projections of growth of cod and productivity.
ACE: the Advanced Cohort Engine for searching longitudinal patient records
Authors: Callahan Alison , Polony Vladimir , Posada José D , Banda Juan M , Gombar Saurabh , Shah Nigam H
Published: February 2021

Objective

To propose a paradigm for a scalable time-aware clinical data search, and to describe the design, implementation and use of a search engine realizing this paradigm.

Materials and Methods

The Advanced Cohort Engine (ACE) uses a temporal query language and in-memory datastore of patient objects to provide a fast, scalable, and expressive time-aware search. ACE accepts data in the Observational Medicine Outcomes Partnership Common Data Model, and is configurable to balance performance with compute cost. ACE’s temporal query language supports automatic query expansion using clinical knowledge graphs. The ACE API can be used with R, Python, Java, HTTP, and a Web UI.

Results

ACE offers an expressive query language for complex temporal search across many clinical data types with multiple output options. ACE enables electronic phenotyping and cohort-building with subsecond response times in searching the data of millions of patients for a variety of use cases.

Discussion

ACE enables fast, time-aware search using a patient object-centric datastore, thereby overcoming many technical and design shortcomings of relational algebra-based querying. Integrating electronic phenotype development with cohort-building enables a variety of high-value uses for a learning health system. Tradeoffs include the need to learn a new query language and the technical setup burden.

Conclusion

ACE is a tool that combines a unique query language for time-aware search of longitudinal patient records with a patient object datastore for rapid electronic phenotyping, cohort extraction, and exploratory data analyses.
Diagnostic Value of Neutrophil CD64 in Burn Patients With Infection in Chinese Population: A Systematic Review and Meta-analysis
Authors: Chen Zhao , Nurlan Turxun , Ning Fangyan , Zha Tianjian , Liu Xiaolong
Published: February 2021

Infection is one of the leading causes of death in burn patients. Many researchers regard neutrophil CD64 (nCD64) as a biomarker in the early diagnosis of burn patients with infection. Nevertheless, the conclusions are controversial. A comprehensive analysis of the diagnostic value of nCD64 for burn infection was performed in China using a meta-analysis method. Pubmed, Cochrane Library, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and China Wanfang databases were searched for studies on nCD64 as a diagnostic biomarker of burn patients with infection from the establishment of the databases to September 29, 2020. The data were analyzed by Stata 15.0 software. Six studies were identified. The results showed that the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.92 (95% confidence interval [CI]: 0.88~0.95), 0.82 (95% CI: 0.76~0.87), 5.10 (95% CI: 3.90~6.80), 0.10 (95% CI: 0.06~0.15), and 52 (95% CI: 29~94), respectively. The area under the curve was 0.94 (95% CI: 0.92~0.94). According to the analysis of the sepsis subgroup, it showed that nCD64 had good diagnostic value in the patients with burn sepsis in Chinese population. Neutrophil CD64 is highly efficient to diagnose burn infection in Chinese population. Therefore, nCD64 could be regarded as a valuable biomarker for the early diagnosis of burn infection in China, especially in patients with burn sepsis. Combined with other diagnostic indexes, nCD64 can be clinically used in the early diagnosis of burn infection to improve the sensitivity and specificity.
Governing secondary research use of health data and specimens: the inequitable distribution of regulatory burden between federally funded and industry research
Authors: Spector-Bagdady Kayte
Published: February 2021

Some of the most promising recent advances in health research offer opportunities to improve diagnosis and therapy for millions of patients. They also require access to massive collections of health data and specimens. This need has generated an aggressive and lucrative push toward amassing troves of human data and biospecimens within academia and private industry. But the differences between the strict regulations that govern federally funded researchers in academic medical centers (AMCs) versus those that apply to the collection of health data and specimens by industry can entrench disparities. This article will discuss the value of secondary research with data and specimens and analyze why AMCs have been put at a disadvantage as compared to industry in amassing the large datasets that enable this work. It will explore the limitations of this current governance structure and propose that, moving forward, AMCs should set their own standards for commercialization of the data and specimens they generate in-house, the ability of their researchers to use industry data for their own work, and baseline informed consent standards for their own patients in order to ensure future data accessibility.
Experimental and theoretical investigations on sensing and dynamic characteristics of PVDF thin film
Authors: Lin Yu-Chih , Huang Yu-Hsi , Ma Chien-Ching , Chang Chun-Kai
Published: February 2021

This research investigates both the steady-state and transient dynamic characteristics of polyvinylidene fluoride (PVDF), which is one of the most commonly used piezoelectric polymers. In steady-state vibration, the visible resonant mode fringe patterns are obtained using the amplitude-fluctuation electronic speckle pattern interferometry experiment, and the point-wise displacement data are measured by laser Doppler vibrometer–dynamic signal analysis. Finite element analysis is also performed, and the numerical results are compared with the experimental ones for the steady-state vibration. In a transient dynamic experiment, the history of dynamic impact generated by a steel ball is measured by the PVDF, and the experimental results are compared with the theoretical results obtained by the Hertz contact law. The comprehensive information about steady-state and transient dynamic properties of PVDF membranes obtained in this study is expected to contribute to the further development of the PVDF piezoelectric element.
Regression rate response in spin-stabilized solid fuel ramjets
Authors: Tahsini Amir Mahdi
Published: February 2021

The regression rate of the solid fuel in the spinning solid fuel ramjet is investigated here using numerical simulations. The finite volume solver of the reacting turbulent flow is developed to study the flow field in the back-step combustion chamber where the burning rate of the solid fuel is computed using the conjugate heat transfer. The dependence of the burning rate on the circumferential velocity of the ramjet is studied, and it is shown that the spin augments the burning rate due to the enhancement of the convective heat flux along the fuel grain. So, the spin can be used to improve the performance of the solid fuel ramjets. In addition, the effect of rapid change in spin velocity on the regression rate of the fuel is investigated, which shows the transient-burning behavior. The results show that although the spin may increase the burning rate by ∼10% in steady-state operation of the ramjet, the spin acceleration may cause the overshoot in burning rate with the peak value >30% in the unsteady operation.
The influences of corrosion on the tightening and anti-loosening properties of a flank-locking precision locknut
Authors: Chang Huey-Ling , Chen Chih-Ming , Lee Chun-Ying
Published: February 2021

Locknut is a critical component used in the precision machinery and its stable service performance over a long period of time in a variety of different environments presents a crucial challenge. In this study, a flank-locking precision locknut was pretreated in an immersion corrosion of 5 wt% NaCl solution to simulate the possible corrosion effects. The tightening and loosening of the locknut after 0-, 1-, 2- and 4-h corrosion treatments, respectively, was tested according to the ISO 2320 Standard. An in-house test setup with horizontal configuration was employed in measuring the torque–axial force characteristics under loading–unloading cycles. It was found that the corrosion of the locknut accelerated after 1-h immersion. The corroded specimens after 2- and 4-h treatment demonstrated more variance in measured tightening and loosening torques than their less corroded counterparts. However, after five loading–unloading cycles, the variance in measured torque decreased and the associated torque constants became more stable. Moreover, the torque constants were ∼10% higher for the 2- and 4-h corrosion-treated locknuts than their pristine counterpart. The surface morphology after corrosion and friction wear was closely related to the measured testing results.
Assessing the willingness of community pharmacists to test–treat–immunize during the COVID-19 pandemic in Puerto Rico
Authors: Silva-Suárez Georgina , Alvarado Reyes Yarelis , Colón-Pratts Frances M , Sanchez Jesus , Ortiz Blanca I , Rabionet Silvia E
Published: February 2021

Objective

The objective of this study was to assess community pharmacists’ willingness to test, treat and immunize for COVID-19 in Puerto Rico.

Methods

In this cross-sectional study, a 37-item survey was distributed via email and social media in May 2020 through REDCap online software. All licensed community pharmacists in Puerto Rico (N = 1200) were invited to complete the survey. Retired community pharmacists were excluded. Analysis of frequencies and chi-square tests were performed to evaluate the willingness to test, treat and immunize for COVID-19 and their associations with sociodemographic variables.

Key findings

The survey response rate was 26% (314/1200). Subjects’ mean age was 42 (±13), 86.1% were female, and most practiced in independent community or specialty pharmacy (62%). Among respondents, 44% reported willingness to test. Top concerns for testing were family (73.4%) and self (66.8%) exposure and ability to manage the workflow (53.3%). Most participants indicated their willingness to treat (88.4%) and to administer the COVID-19 vaccine (76.1%). Study participants who worked in retail pharmacies were more willing to test for COVID-19 (50.9%, P = 0.34) and to immunize (91.2%, P < 0.001). Pharmacists ≤39 years (90.3%), those who graduate in 2000 or later (88.3%), and those with a Pharm.D. degree or higher (88.6%), were more willing to immunize (P < 0.001).

Conclusions

Most community pharmacists were more willing to treat and immunize, than to perform COVID-19 testing. This underscores the need for training and workflow changes to facilitate the acquisition of this new role. Local pharmacists’ associations should advocate for a safe and manageable work environment. These efforts are vital to empower pharmacists to adopt new roles during a public health emergency.
Providing pharmaceutical care during the COVID-19 pandemic: attitudes and experiences of home-treated patients in Jordan
Authors: Mukattash Tareq L , Jarab Anan S , Al-Qerem Walid , Abu Farha Rana K , Itani Rania , Karout Samar , Mukattash Ibrahim L , Basheti Iman
Published: February 2021

Objectives

This study aims to explore home-treated COVID-19 patients’ experiences and perceptions of pharmaceutical care services offered during their sickness.

Methods

This is a cross-sectional online questionnaire study, where a 30-item questionnaire was texted via a link to COVID-19 patients who were tested positive previously. A list of anonymised numbers was obtained from different COVID-19 testing centres. The study received ethical approval from the Institutional Review Board at the King Abdulla University Hospital/Jordan University of Science and Technology.

Key findings

A total of 268 patients who were previously diagnosed with COVID-19 agreed to participate in this study. Only 22.9% of patients reported taking medications regularly. Almost one-third of respondents (28.7%) indicated that pharmacists were involved in prescribing medicine to patients. Almost half the respondents (49.6%) stated that they or their caregivers obtained information and advice about their medicine from the pharmacists. Only 54.9% of the respondents agreed/strongly agreed that pharmacists have enough scientific information to provide the necessary medical assistance to COVID-19 patients. Patients who work in the medical field, and who always get their medication from the same pharmacy, showed better perception towards pharmaceutical care services that might be provided to COVID-19 patients (P < 0.01).

Conclusions

Pharmacists had an unsatisfactory contribution to the management of the disease in outpatient settings. Moreover, there was a poor perception of the pharmacists’ role including their knowledge, communication skills and counselling skills. Thus, it is essential to improve pharmacists’ knowledge and practices about infectious diseases.
Roxadustat for the treatment of anemia in chronic kidney disease patients not on dialysis: a Phase 3, randomized, double-blind, placebo-controlled study (ALPS)
Authors: Shutov Evgeny , Sułowicz Władysław , Esposito Ciro , Tataradze Avtandil , Andric Branislav , Reusch Michael , Valluri Udaya , Dimkovic Nada
Published: February 2021

Background

Roxadustat is an orally active hypoxia-inducible factor prolyl hydroxylase inhibitor for the treatment of chronic kidney disease (CKD) anemia.

Methods

This Phase 3, multicenter, randomized, double-blind, placebo-controlled study examined patients with Stages 3–5 CKD, not on dialysis (NCT01887600). Patients were randomized (2:1) to oral roxadustat or placebo three times weekly for 52–104 weeks. This study examined two primary efficacy endpoints: European Union (European Medicines Agency)—hemoglobin (Hb) response, defined as Hb ≥11.0 g/dL that increased from baseline (BL) by ≥1.0 g/dL in patients with Hb >8.0 g/dL or ≥2.0 g/dL in patients with BL Hb ≤8.0 g/dL, without rescue therapy, during the first 24 weeks of treatment; US Food and Drug Administration—change in Hb from BL to the average Hb level during Weeks 28–52, regardless of rescue therapy. Secondary efficacy endpoints and safety were examined.

Results

A total of 594 patients were analyzed (roxadustat: 391; placebo: 203). Superiority of roxadustat versus placebo was demonstrated for both primary efficacy endpoints: Hb response [odds ratio = 34.74, 95% confidence interval (CI) 20.48–58.93] and change in Hb from BL [roxadustat – placebo: +1.692 (95% CI 1.52–1.86); both P < 0.001]. Superiority of roxadustat was demonstrated for low-density lipoprotein cholesterol change from BL, and time to first use of rescue medication (both P < 0.001). The incidences of treatment-emergent adverse events were comparable between groups (roxadustat: 87.7%, placebo: 86.7%).

Conclusions

Roxadustat demonstrated superior efficacy versus placebo in terms of both Hb response rate and change in Hb from BL. The safety profiles of roxadustat and placebo were comparable.
Predicting Spinal Surgery Candidacy From Imaging Data Using Machine Learning
Authors: Wilson Bayard , Gaonkar Bilwaj , Yoo Bryan , Salehi Banafsheh , Attiah Mark , Villaroman Diane , Ahn Christine , Edwards Matthew , Laiwalla Azim , Ratnaparkhi Anshul , Li Ien , Cook Kirstin , Beckett Joel , Macyszyn Luke
Published: February 2021

BACKGROUND

The referral process for consultation with a spine surgeon remains inefficient, given a substantial proportion of referrals to spine surgeons are nonoperative.

OBJECTIVE

To develop a machine-learning-based algorithm which accurately identifies patients as candidates for consultation with a spine surgeon, using only magnetic resonance imaging (MRI).

METHODS

We trained a deep U-Net machine learning model to delineate spinal canals on axial slices of 100 normal lumbar MRI scans which were previously delineated by expert radiologists and neurosurgeons. We then tested the model against lumbar MRI scans for 140 patients who had undergone lumbar spine MRI at our institution (60 of whom ultimately underwent surgery, and 80 of whom did not). The model generated automated segmentations of the lumbar spinal canals and calculated a maximum degree of spinal stenosis for each patient, which served as our biomarker for surgical pathology warranting expert consultation.

RESULTS

The machine learning model correctly predicted surgical candidacy (ie, whether patients ultimately underwent lumbar spinal decompression) with high accuracy (area under the curve = 0.88), using only imaging data from lumbar MRI scans.

CONCLUSION

Automated interpretation of lumbar MRI scans was sufficient to correctly determine surgical candidacy in nearly 90% of cases. Given that a significant proportion of referrals placed for spine surgery evaluation fail to meet criteria for surgical intervention, our model could serve as a valuable tool for patient triage and thereby address some of the inefficiencies within the outpatient surgical referral process.
Risk Factors Associated With Chronic Liver Enzyme Elevation in Persons With HIV Without Hepatitis B or C Coinfection in the Combination Antiretroviral Therapy Era
Authors: Wood Shannon , Won Seung Hyun , Hsieh Hsing-Chuan , Lalani Tahaniyat , Kronmann Karl , Maves Ryan C , Utz Gregory , Schofield Christina , Colombo Rhonda E , Okulicz Jason F , Blaylock Jason , Agan Brian K , Ganesan Anuradha
Published: February 2021

Background

As morbidity due to viral coinfections declines among HIV-infected persons, changes in liver-related morbidity are anticipated. We examined data from the US Military HIV Natural History Study (NHS), a cohort of military beneficiaries, to evaluate incidence and risk factors associated with chronic liver enzyme elevation (cLEE) in HIV-monoinfected patients in the combination antiretroviral therapy (cART) era.

Methods

Participants who were hepatitis B virus and hepatitis C virus seronegative with follow-up after 1996 were included. We defined chronic liver enzyme elevation (cLEE) as alanine aminotransferase elevations ≥1.25 times the upper limit of normal on at least 2 visits, for a duration of ≥6 months within 2 years. We used multivariate Cox proportional hazards models to examine risk factors for cLEE.

Results

Of 2779 participants, 309 (11%) met criteria for cLEE for an incidence of 1.28/100 PYFU (1.28–1.29/100 PYFU). In an adjusted model, cLEE was associated with Hispanic/other ethnicity (reference Caucasian: hazard ratio [HR], 1.744; 95% CI, 1.270–2.395), non–nucleoside reverse transcriptase inhibitor–based cART (reference boosted protease inhibitors: HR, 2.232; 95% CI, 1.378–3.616), being cART naïve (HR, 6.046; 95% CI, 3.686–9.915), or having cART interruptions (HR, 8.671; 95% CI, 4.651–16.164). African American race (HR, 0.669; 95% CI, 0.510–0.877) and integrase strand transfer inhibitor (INSTI)–based cART (HR, 0.222; 95% CI, 0.104–0.474) were protective.

Conclusions

Our findings demonstrate that initiation and continued use of cART are protective against cLEE and support the hypothesis that HIV infection directly impacts the liver. INSTI-based regimens were protective and could be considered in persons with cLEE.
Gene Targeting Facilitated by Engineered Sequence-Specific Nucleases: Potential Applications for Crop Improvement
Authors: Miki Daisuke , Wang Rui , Li Jing , Kong Dali , Zhang Lei , Zhu Jian-Kang
Published: February 2021

Humans are currently facing the problem of how to ensure that there is enough food to feed all of the world’s population. Ensuring that the food supply is sufficient will likely require the modification of crop genomes to improve their agronomic traits. The development of engineered sequence-specific nucleases (SSNs) paved the way for targeted gene editing in organisms, including plants. SSNs generate a double-strand break (DSB) at the target DNA site in a sequence-specific manner. These DSBs are predominantly repaired via error-prone non-homologous end joining and are only rarely repaired via error-free homology-directed repair if an appropriate donor template is provided. Gene targeting (GT), i.e. the integration or replacement of a particular sequence, can be achieved with combinations of SSNs and repair donor templates. Although its efficiency is extremely low, GT has been achieved in some higher plants. Here, we provide an overview of SSN-facilitated GT in higher plants and discuss the potential of GT as a powerful tool for generating crop plants with desirable features.
AtLURE1/PRK6-mediated signaling promotes conspecific micropylar pollen tube guidance
Authors: Liu Meiling , Wang Zhijuan , Hou Saiying , Wang Lele , Huang Qingpei , Gu Hongya , Dresselhaus Thomas , Zhong Sheng , Qu Li-Jia
Published: February 2021

Reproductive isolation is a prerequisite to form and maintain a new species. Multiple prezygotic and postzygotic reproductive isolation barriers have been reported in plants. In the model plant, Arabidopsis thaliana conspecific pollen tube precedence controlled by AtLURE1/PRK6-mediated signaling has been recently reported as a major prezygotic reproductive isolation barrier. By accelerating emergence of own pollen tubes from the transmitting tract, A. thaliana ovules promote self-fertilization and thus prevent fertilization by a different species. Taking advantage of a septuple atlure1null mutant, we now report on the role of AtLURE1/PRK6-mediated signaling for micropylar pollen tube guidance. Compared with wild-type (WT) ovules, atlure1null ovules displayed remarkably reduced micropylar pollen tube attraction efficiencies in modified semi-in vivo A. thaliana ovule targeting assays. However, when prk6 mutant pollen tubes were applied, atlure1null ovules showed micropylar attraction efficiencies comparable to that of WT ovules. These findings indicate that AtLURE1/PRK6-mediated signaling regulates micropylar pollen tube attraction in addition to promoting emergence of own pollen tubes from the transmitting tract. Moreover, semi-in vivo ovule targeting competition assays with the same amount of pollen grains from both A. thaliana and Arabidopsis lyrata showed that A. thaliana WT and xiuqiu mutant ovules are mainly targeted by own pollen tubes and that atlure1null mutant ovules are also entered to a large extent by A. lyrata pollen tubes. Taken together, we report that AtLURE1/PRK6-mediated signaling promotes conspecific micropylar pollen tube attraction representing an additional prezygotic isolation barrier.
First measurement using a nuclear emulsion detector of theνμcharged-current cross section on iron around the 1 GeV energy region
Authors: Oshima H , Matsuo T , Ali A , Aoki S , Berns L , Fukuda T , Hanaoka Y , Hayato Y , Hiramoto A , Ichikawa A K , Kawahara H , Kikawa T , Komatani R , Komatsu M , Kuretsubo K , Marushima T , Matsumoto H , Mikado S , Minamino A , Mizuno K , Morimoto Y , Morishima K , Naganawa N , Naiki M , Nakamura M , Nakamura Y , Nakano N , Nakano T , Nakaya T , Nishio A , Odagawa T , Ogawa S , Rokujo H , Sato O , Shibuya H , Sugimura K , Suzui L , Suzuki Y , Takagi H , Takahashi S , Takao T , Tanihara Y , Watanabe R , Yamada K , Yasutome K , Yokoyama M
Published: February 2021

We have carried out $\nu_{\mu}$ charged-current interaction measurement on iron using an emulsion detector exposed to the T2K neutrino beam in the J-PARC neutrino facility. The data samples correspond to $4.0 \times 10^{19}$ protons on target, and the neutrino mean energy is 1.49 GeV. The emulsion detector is suitable for precision measurements of charged particles produced in neutrino–iron interactions with a low momentum threshold thanks to a thin-layered structure and sub-$\mu$m spatial resolution. The charged particles are successfully detected, and their multiplicities are measured using the emulsion detector. The cross section was measured to be $\sigma^{\mathrm{Fe}}_{\mathrm{CC}} = (1.28 \pm 0.11({\mathrm{stat.}})^{+0.12}_{-0.11}({\mathrm{syst.}})) \times 10^{-38} \, {\mathrm{cm}}^{2}/{\mathrm{nucleon}}$. The cross section in a limited kinematic phase space of induced muons, $\theta_{\mu} < 45^{\circ}$ and $p_{\mu} > 400 \, {\rm MeV}/c$, on iron was $\sigma^{\mathrm{Fe}}_{\mathrm{CC \hspace{1mm} phase \hspace{0.5mm} space}} = (0.84 \pm 0.07({\mathrm{stat.}})^{+0.07}_{-0.06}({\mathrm{syst.}})) \times 10^{-38} \, {\mathrm{cm}}^{2}/{\mathrm{nucleon}}$. The cross-section results are consistent with previous values obtained via different techniques using the same beamline, and they are reproduced well by current neutrino interaction models. These results demonstrate the capability of the detector in the detailed measurement of neutrino–nucleus interactions around the 1 GeV energy region.
Leptin receptor expression in the dorsomedial hypothalamus stimulates breathing during NREM sleep indb/dbmice
Authors: Pho Huy , Berger Slava , Freire Carla , Kim Lenise J , Shin Mi-Kyung , Streeter Stone R , Hosamane Nishitha , Cabassa Meaghan E , Anokye-Danso Frederick , Dergacheva Olga , Amorim Mateus R , Fleury-Curado Thomaz , Jun Jonathan C , Schwartz Alan R , Ahima Rexford S , Mendelowitz David , Polotsky Vsevolod Y
Published: February 2021

Study Objectives

Obesity leads to obstructive sleep apnea (OSA), which is recurrent upper airway obstruction during sleep, and obesity hypoventilation syndrome (OHS), hypoventilation during sleep resulting in daytime hypercapnia. Impaired leptin signaling in the brain was implicated in both conditions, but mechanisms are unknown. We have previously shown that leptin stimulates breathing and treats OSA and OHS in leptin-deficient ob/ob mice and leptin-resistant diet-induced obese mice and that leptin’s respiratory effects may occur in the dorsomedial hypothalamus (DMH). We hypothesized that leptin receptor LepRb-deficient db/db mice have obesity hypoventilation and that restoration of leptin signaling in the DMH will increase ventilation during sleep in these animals.

Methods

We measured arterial blood gas in unanesthetized awake db/db mice. We subsequently infected these animals with Ad-LepRb or control Ad-mCherry virus into the DMH and measured ventilation during sleep as well as CO2 production after intracerebroventricular (ICV) infusions of phosphate-buffered saline or leptin.

Results

Awake db/db mice had elevated CO2 levels in the arterial blood. Ad-LepRb infection resulted in LepRb expression in the DMH neurons in a similar fashion to wildtype mice. In LepRb-DMH db/db mice, ICV leptin shortened REM sleep and increased inspiratory flow, tidal volume, and minute ventilation during NREM sleep without any effect on the quality of NREM sleep or CO2 production. Leptin had no effect on upper airway obstruction in these animals.

Conclusion

Leptin stimulates breathing and treats obesity hypoventilation acting on LepRb-positive neurons in the DMH.