bluuebunny/crossref_metadata_2025 huggingface dataset:
Refining reproduction number estimates to account for unobserved generations of infection in emerging epidemics
Authors: Brizzi Andrea , O’Driscoll Megan , Dorigatti Ilaria
Published: November 2021

Background

Estimating the transmissibility of infectious diseases is key to inform situational awareness and for response planning. Several methods tend to overestimate the basic (R0) and effective (Rt) reproduction numbers during the initial phases of an epidemic. The reasons driving the observed bias are unknown. In this work we explore the impact of incomplete observations and underreporting of the first generations of infections during the initial epidemic phase.

Methods

We propose a debiasing procedure which utilises a linear exponential growth model to infer unobserved initial generations of infections and apply it to EpiEstim. We assess the performance of our adjustment using simulated data, considering different levels of transmissibility and reporting rates. We also apply the proposed correction to SARS-CoV-2 incidence data reported in Italy, Sweden, the United Kingdom and the United States of America.

Results

In all simulation scenarios, our adjustment outperforms the original EpiEstim method. The proposed correction reduces the systematic bias and the quantification of uncertainty is more precise, as better coverage of the true R0 values is achieved with tighter credible intervals. When applied to real world data, the proposed adjustment produces basic reproduction number estimates which closely match the estimates obtained in other studies while making use of a minimal amount of data.

Conclusions

The proposed adjustment refines the reproduction number estimates obtained with the current EpiEstim implementation by producing improved, more precise estimates earlier than with the original method. This has relevant public health implications.

We propose a back-imputation procedure tackling the issue of unobserved initial generations of infections to reduce the bias observed in the early R0 and Rt estimates and apply it to EpiEstim using simulated and reported COVID-19 data to evaluate it.
Regional and temporal variations affect the accuracy of variant-specific SARS-CoV-2 PCR assays
Authors: Oh Chamteut , Sashittal Palash , Zhou Aijia , Wang Leyi , El-Kebir Mohammed , Nguyen Thanh H.
Published: November 2021

Monitoring the prevalence of SARS-CoV-2 variants is necessary to make informed public health decisions during the COVID-19 pandemic. PCR assays have received global attention, facilitating rapid understanding of variant dynamics because they are more accessible and scalable than genome sequencing. However, as PCR assays target only a few mutations, their accuracy could be compromised when these mutations are not exclusive to target variants. Here we show how to design variant-specific PCR assays with high sensitivity and specificity across different geographical regions by incorporating sequences deposited in the GISAID database. Furthermore, we demonstrate that several previously developed PCR assays have decreased accuracy outside their study areas. We introduce PRIMES, an algorithm that enables the design of reliable PCR assays, as demonstrated in our experiments to track dominant SARS-CoV-2 variants in local sewage samples. Our findings will contribute to improving PCR assays for SARS-CoV-2 variant surveillance.

Importance

Monitoring the introduction and prevalence of variants of concern (VOCs) and variants of interest (VOIs) in a community can help the local authorities make informed public health decisions. PCR assays can be designed to keep track of SARS-CoV-2 variants by measuring unique mutation markers that are exclusive to the target variants. However, the mutation markers can not be exclusive to the target variants depending on regional and temporal differences in variant dynamics. We introduce PRIMES, an algorithm that enables the design of reliable PCR assays for variant detection. Because PCR is more accessible, scalable, and robust to sewage samples over sequencing technology, our findings will contribute to improving global SARS-CoV-2 variant surveillance.
The anterior cruciate ligament in murine post-traumatic osteoarthritis: markers and mechanics
Authors: Ramos-Mucci Lorenzo , Elsheikh Ahmed , Keenan Craig , Eliasy Ashkan , D’Aout Kris , Bou-Gharios George , Comerford Eithne , Poulet Blandine
Published: November 2021

1

Osteoarthritis (OA) is a whole joint disease that affects all knee joint tissues. Ligaments, a matrix-rich connective tissue, play an important mechanical function that stabilises the knee joint and yet their role in OA is not well studied. Recent studies have shown that ligament extracellular matrix (ECM) structure is compromised in the early stages of OA, but it remains unclear how this affects ligament function and biomechanics. In this study, the aim was to investigate the structural, cellular and viscoelastic changes in the anterior cruciate ligament (ACL) in a murine non-invasive post-traumatic OA (PTOA) model. Non-invasive mechanical loading of the knee joint of C57BL/6J mice (10-week-old) was used as a PTOA model. Knee joints were analysed for joint space mineralisation and the ACLs were assessed with histology and mechanical testing. PTOA knee joints had a 33-46% increase in joint space mineralisation and PTOA knee joint ACLs exhibited ECM modifications, including collagen birefringence and COL2 and proteoglycan deposition. ECM changes were associated with cells expressing chondrogenic markers (SOX9 and RUNX2) expanding from the tibial enthesis to the ACL midbody. Viscoelastic and mechanical changes in the ACLs from PTOA knee joints included a 20-21% decrease in tangent modulus at 2MPa of stress, and a decrease strain rate sensitivity at higher strain rates and a significant increase in relaxation during stress-relaxation, but no changes to hysteresis and ultimate load to failure. These results demonstrate that ACL pathology and viscoelastic function is compromised in murine PTOA knee joints and provides further evidence of the important role of ligaments in the knee joint organ in health and disease.
Lack of Fe(II) transporters in basal Cyanobacteria complicates iron uptake in ferruginous Archean oceans
Authors: Enzingmüller-Bleyl Tristan C. , Boden Joanne S. , Herrmann Achim J. , Ebel Katharina W. , Sánchez-Baracaldo Patricia , Frankenberg-Dinkel Nicole , Gehringer Michelle M.
Published: November 2021

Introductory paragraph

Cyanobacteria oxygenated Earth’s atmosphere during the Great Oxygenation Event (GOE) through oxygenic photosynthesis. Their high iron requirement was presumed met by high levels of Fe(II) in the anoxic Archean ocean. Here we show that most basal Cyanobacteria cannot synthesize the primary Fe(II) transporter, FeoB. Relaxed molecular clock analyses estimate the arrival of FeoB, as well as the Fe(III) transporters, cFTR1 and FutB, in the Cyanobacteria after the GOE. Furthermore Pseudanabaena sp. PCC7367, a basal marine, benthic strain grown under simulated Archean conditions, constitutively expressed cftr1, even after the addition of Fe(II). By utilizing gene expression studies under a simulated Archean atmosphere, as well as comparative genomics, phylogenetics and molecular clock analyses, this study identified a need to reappraise iron uptake in ancestral Cyanobacteria, as genetic profiling suggests that scavenging of siderophore bound Fe(III), rather than Fe(II), appears to have been the means of iron acquisition prior to the GOE.
Lipid nanoparticles incorporating a GalNAc ligand enable in vivo liver ANGPTL3 editing in wild-type and somatic LDLR knockout non-human primates
Authors: Kasiewicz Lisa N. , Biswas Souvik , Beach Aaron , Ren Huilan , Dutta Chaitali , Mazzola Anne Marie , Rohde Ellen , Chadwick Alexandra , Cheng Christopher , Musunuru Kiran , Kathiresan Sekar , Malyala Padma , Rajeev Kallanthottathil G. , Bellinger Andrew M.
Published: November 2021

Standard lipid nanoparticles (LNPs) deliver gene editing cargoes to hepatocytes through receptor-mediated uptake via the low-density lipoprotein receptor (LDLR). Homozygous familial hypercholesterolemia (HoFH) is a morbid genetic disease characterized by complete or near-complete LDLR deficiency, markedly elevated blood low-density lipoprotein cholesterol (LDL-C) levels, and premature atherosclerotic cardiovascular disease. In order to enable in vivo liver gene editing in HoFH patients, we developed a novel LNP delivery technology that incorporates a targeting ligand—N-acetylgalactosamine (GalNAc)—which binds to the asialoglycoprotein receptor (ASGPR). In a cynomolgus monkey (Macaca fascicularis) non-human primate (NHP) model of HoFH created by somatic knockout of the LDLR gene via CRISPR-Cas9, treatment with GalNAc-LNPs formulated with an adenine base editor mRNA and a guide RNA (gRNA) targeting the ANGPTL3 gene yielded ~60% whole-liver editing and ~94% reduction of blood ANGPTL3 protein levels, whereas standard LNPs yielded minimal editing. Moreover, in wild-type NHPs, the editing achieved by GalNAc-LNPs compared favorably to that achieved by standard LNPs, suggesting that GalNAc-LNP delivery technology may prove useful across a range of in vivo therapeutic applications targeting the liver.
The bacterial actin-like cell division protein FtsA forms curved antiparallel double filaments upon binding of FtsN
Authors: Nierhaus Tim , McLaughlin Stephen H , Bürmann Frank , Kureisaite-Ciziene Danguole , Maslen Sarah , Skehel Mark J , Yu Conny WH , Freund Stefan MV , Funke Louise FH , Chin Jason W , Löwe Jan
Published: November 2021

Cell growth and division of walled bacteria depend on the synthesis and remodelling of peptidoglycan (PG). These activities are carried out by two multiprotein complexes, the elongasome and the divisome during cell elongation and division, respectively. Filaments of tubulin-like FtsZ form the cytoplasmic scaffold for divisome assembly, the Z-ring. In E. coli, the actin homologue FtsA anchors the Z-ring to the membrane and recruits downstream divisome components, including bitopic FtsN. FtsN is recruited late and activates the periplasmic PG synthase FtsWI. To start unravelling the activation mechanism involving FtsA and FtsN, we showed that E. coli FtsA forms antiparallel double filaments on lipid monolayers when also binding FtsN’s cytoplasmic tail, and that Vibrio maritimus FtsA crystallised as an equivalent double filament. We structurally located the FtsA-FtsN interaction site in FtsA’s IA-IC interdomain cleft and confirmed FtsA double filament formation in vivo using site-specific cysteine cross-linking. FtsA-FtsN double filaments reconstituted on and in liposomes preferred negative Gaussian curvature, as was previously shown for the elongasome’s actin, MreB. MreB filaments serve as curvature-sensing “rudders”, orienting insertion of PG around the cell’s circumference. We propose that curved antiparallel FtsA double filaments function similarly in the divisome: FtsA filaments, together with dynamic FtsZ filaments orient and concentrate cell-constricting septal PG synthesis in the division plane.
Loss of function of bHLH transcription factor Nrd1 in tomato induces an arabinogalactan protein-encoding gene and enhances resistance toPseudomonas syringaepv.tomato
Authors: Zhang Ning , Hecht Chloe , Sun Xuepeng , Fei Zhangjun , Martin Gregory B.
Published: November 2021

Basic helix-loop-helix (bHLH) transcription factors constitute a superfamily in eukaryotes but their roles in plant immunity remain largely uncharacterized. We found that the transcript abundance in tomato leaves of one bHLH transcription factor-encoding gene,Nrd1(negativeregulator of resistance toDC30001), was significantly increased after treatment with the immunity-inducing flgII-28 peptide. Plants carrying a loss-of-function mutation inNrd1(Λnrd1) showed enhanced resistance toPseudomonas syringaepv.tomato(Pst) DC3000 although early pattern-triggered immunity responses such as generation of reactive oxygen species and activation of mitogen-activated protein kinases after treatment with flagellin-derived flg22 and flgII-28 peptides were unaltered compared to wild-type plants. An RNA-Seq analysis identified a gene,Agp1, whose expression is strongly suppressed in anNrd1-dependent manner.Agp1encodes an arabinogalactan protein and overexpression of theAgp1gene inNicotiana benthamianaled to ∼10-fold lessPstgrowth compared to the control. These results suggest that the Nrd1 protein promotes tomato susceptibility toPstby suppressing the defense geneAgp1. RNA-Seq also revealed that loss of Nrd1 function has no effect on the transcript abundance of immunity-associated genes includingBti9, Core, Fls2, Fls3andWak1uponPstinoculation, suggesting that the enhanced immunity observed in the Δnrd1 mutants is due to the activation of key PRR signaling components as well as loss of Nrd1-regulated suppression ofAgp1.
INDUCED MUTATIONS INTaASN-A2REDUCE FREE ASPARAGINE CONCENTRATION IN THE WHEAT GRAIN
Authors: Alarcón-Reverte Rocío , Xie Yucong , Stromberger John , Cotter Jennifer D. , Mason Richard Esten , Pearce Stephen
Published: November 2021

Acrylamide is a neurotoxin and probable carcinogen formed as a processing contaminant during baking and production of different foodstuffs, including bread products. The amino acid asparagine is the limiting substrate in the Maillard reaction that produces acrylamide, so developing wheat varieties with low free asparagine concentrations in the grain is a promising approach to reduce dietary acrylamide exposure. A candidate gene approach was used to identify chemically-induced genetic variation inASPARAGINE SYNTHETASE 2(ASN2)genes that exhibit a grain-specific expression profile. In field trials, durum and common wheat lines carryingasn-a2null alleles exhibited reductions in free asparagine concentration in their grains of between 9 and 34% compared to wild-type sister lines. These plants showed no significant differences in spikelet number, grain size and weight, germination or baking quality traits. These non-transgenic variants can be deployed without restriction in elite wheat germplasm to reduce acrylamide-forming potential with no negative impacts on quality or agronomic performance.

Core ideas

Three wheatASPARAGINE SYNTHETASE 2knockout alleles were characterized in field experiments.

Mutant alleles conferred significant reductions in grain free asparagine concentration.

The alleles did not affect quality or agronomic traits.

These non-transgenic alleles can be deployed without restriction in wheat breeding programs.
Inversely proportional myelin growth due to alteredPmp22gene dosage identifies PI3K/Akt/mTOR signaling as a novel therapeutic target in HNPP
Authors: Krauter Doris , Ewers David , Hartmann Timon J , Volkmann Stefan , Kungl Theresa , Fledrich Robert , Goebbels Sandra , Nave Klaus-Armin , Sereda Michael W
Published: November 2021

Duplication of the gene encoding the myelin protein PMP22 causes the hereditary neuropathy Charcot-Marie-Tooth disease 1A (CMT1A), characterized by hypomyelination of medium to large caliber peripheral axons. Conversely, haplo-insufficiency ofPMP22leads to focal myelin overgrowth in hereditary neuropathy with liability to pressure palsies (HNPP). However, the molecular mechanisms of myelin growth regulation by PMP22 remain obscure. Here, we found that the major inhibitor of the myelin growth signaling pathway PI3K/Akt/mTOR, phosphatase and tensin homolog (PTEN) is increased in abundance in CMT1A and decreased in HNPP rodent models. Indeed, treatment of DRG co-cultures from HNPP mice with PI3K/Akt/mTOR pathway inhibitors reduced focal hypermyelination and, importantly, treatment of HNPP mice with the mTOR inhibitor Rapamycin improved motor behavior, increased compound muscle amplitudes (CMAP) and reduced tomacula formation in the peripheral nerve. InPmp22tgCMT1A mice, we uncovered that the differentiation defect of Schwann cells is independent from PI3K/Akt/mTOR activity, rendering the pathway insufficient as a therapy target on its own. Thus, while CMT1A pathogenesis is governed by dys-differentiation uncoupled from PI3K/Akt/mTOR signaling, targeting the pathway provides novel proof-of-principle for a therapeutic approach to HNPP.
Prostate tumor-induced stromal reprogramming generates Tenascin C that promotes prostate cancer metastasis through YAP/TAZ inhibition
Authors: Lee Yu-Chen , Lin Song-Chang , Yu Guoyu , Zhu Ming , Song Jian H , Rivera Keith , Pappin Darryl , Logothetis Christopher J. , Panaretakis Theocharis , Wang Guocan , Yu-Lee Li-Yuan , Lin Sue-Hwa
Published: November 2021

Metastatic prostate cancer (PCa) in bone induces bone-forming lesions that enhance PCa progression. How tumor-induced bone formation enhances PCa progression is not known. We have previously shown that PCa-induced bone originates from endothelial cells (EC) that have undergone endothelial-to-osteoblast (EC-to-OSB) transition by tumor-secreted BMP4. Here, we show that EC-to-OSB transition leads to changes in the tumor microenvironment that increases the metastatic potential of PCa cells. We found that conditioned medium (CM) from EC-OSB hybrid cells increases the migration, invasion and survival of PC3-mm2 and C4-2B4 PCa cells. Quantitative mass spectrometry (iTRAQ) identified Tenascin C (TNC) as one of the major proteins secreted from EC-OSB hybrid cells. TNC expression in tumor-induced osteoblasts was confirmed by immunohistochemistry of MDA-PCa118b xenograft and human bone metastasis specimens. Mechanistically, BMP4 increases TNC expression in EC-OSB cells through the Smad1-Notch/Hey1 pathway. How TNC promotes PCa metastasis was next interrogated by in vitro and in vivo studies. In vitro studies showed that a TNC neutralizing antibody inhibits EC-OSB-CM-mediated PCa cell migration and survival. TNC knockdown decreased, while addition of recombinant TNC or TNC overexpression increased migration and anchorage-independent growth of PC3 or C4-2b cells. When injected orthotopically, PC3-mm2-shTNC clones decreased metastasis to bone, while C4-2b-TNC overexpressing cells increased metastasis to lymph nodes. TNC enhances PCa cell migration through α5β1 integrin-mediated YAP/TAZ inhibition. These studies elucidate that tumor-induced stromal reprogramming generates TNC that enhances PCa metastasis and suggest that TNC may be a target for PCa therapy.
Fast and sensitive GCaMP calcium indicators for imaging neural populations
Authors: Zhang Yan , Rózsa Márton , Liang Yajie , Bushey Daniel , Wei Ziqiang , Zheng Jihong , Reep Daniel , Broussard Gerard Joey , Tsang Arthur , Tsegaye Getahun , Narayan Sujatha , Obara Christopher J. , Lim Jing-Xuan , Patel Ronak , Zhang Rongwei , Ahrens Misha B. , Turner Glenn C. , Wang Samuel S.-H. , Korff Wyatt L. , Schreiter Eric R. , Svoboda Karel , Hasseman Jeremy P. , Kolb Ilya , Looger Loren L.
Published: November 2021

Calcium imaging with protein-based indicators is widely used to follow neural activity in intact nervous systems. The popular GCaMP indicators are based on the calcium-binding protein calmodulin and the RS20 peptide. These sensors report neural activity at timescales much slower than electrical signaling, limited by their biophysical properties and trade-offs between sensitivity and speed. We used large-scale screening and structure-guided mutagenesis to develop and optimize several fast and sensitive GCaMP-type indicators. The resulting ‘jGCaMP8’ sensors, based on calmodulin and a fragment of endothelial nitric oxide synthase, have ultra-fast kinetics (rise times, 2 ms) and still feature the highest sensitivity for neural activity reported for any protein-based sensor. jGCaMP8 sensors will allow tracking of larger populations of neurons on timescales relevant to neural computation.
Microbial signals and lymphotoxin drive TNF-independent death of A20 and ABIN-1 deficient epithelium
Authors: Rusu Iulia , Mennillo Elvira , Li Zhongmei , Bain Jared L. , Sun Xiaofei , Ly Kimberly , Rosli Yenny Y. , Naser Mohammad , Wang Zunqiu , Advincula Rommel , Achacoso Philip , Shao Ling , Razani Bahram , Klein Ophir D. , Marson Alexander , Turnbaugh Jessie A. , Turnbaugh Peter J. , Malynn Barbara A. , Ma Averil , Kattah Michael G.
Published: November 2021

Anti-TNF antibodies are effective for treating patients with inflammatory bowel disease (IBD), but many patients fail to respond to anti-TNF therapy, highlighting the importance of TNF-independent disease. We previously demonstrated that acute deletion of two IBD susceptibility genes, A20 (Tnfaip3) and Abin-1 (Tnip1), in intestinal epithelial cells (IECs) sensitizes mice to both TNF-dependent and TNF-independent death. Here we show that TNF-independent IEC death after A20 and Abin-1 deletion is rescued by germ-free derivation or deletion of MyD88, while deletion of Trif provides only partial protection. Combined deletion of Ripk3 and Casp8, which inhibits both apoptotic and necroptotic death, completely protects against death after acute deletion of A20 and Abin-1 in IECs. A20 and Abin-1-deficient IECs are sensitized to TNF-independent, TNFR-1-mediated death in response to lymphotoxin alpha (LTα) homotrimers. Blockade of LTα in vivo reduces weight loss and improves survival when combined with partial deletion of MyD88. These data show that microbial signals, MyD88, and LTα all contribute to TNF-independent intestinal injury.

Here we show that germ-free derivation, MyD88 deletion, combined Ripk3 and Casp8 deletion, or anti-LTα, all reduce TNF-independent intestinal injury after A20 and Abin-1 deletion.
Lesions of the dorsal hippocampal formation interfere with background but not foreground contextual fear conditioning.
Authors: Phillips R G , LeDoux J E
Published: November 2021

The effects of hippocampal lesions on the conditioning of fear responses (freezing responses) to contextual stimuli (static, continuously present stimuli) were examined in three conditioning paradigms: forward pairing of a phasic tone conditioned stimulus (CS) with a footshock unconditioned stimulus (US), unpaired presentations of the CS and US, or presentations of the US alone. All three procedures resulted in the acquisition of conditioned freezing to contextual stimuli. Lesions of the dorsal hippocampus prevented the acquisition of contextual conditioning in the Paired procedure, as reported previously, but not in the Unpaired or US Alone procedures. In the Paired procedure, static contextual cues occur in the background, with the phasic tone CS being the primary stimulus that enters into the association with the US. However, in the other two procedures, where there is no phasic CS, the primary associations with the US involve static contextual stimuli, which are therefore in the foreground. We refer to these types of contextual conditioning as background and foreground contextual conditioning, respectively, and argue that the hippocampus is only involved in background contextual conditioning. These results have implications for understanding both fear conditioning and hippocampal function.
Persistent activation of protein kinase C during the development of long-term facilitation in Aplysia.
Authors: Sossin W S , Sacktor T C , Schwartz J H
Published: November 2021

We investigated activation of the two major neuronal protein kinase C (PKC) isoforms in Aplysia, Ca(2+)-activated Apl I and Ca(2+)-independent Apl II, during the induction and maintenance of behavioral sensitization of Aplysia defensive reflexes. Activation of PKC occurred during the training stimulus and persisted for at least 2 hr thereafter but was not maintained for 24 hr. The persistent activation required protein synthesis and was blocked by cyproheptidine, an agent that also blocked the initial activation of PKC. Persistent activation involved both an increase in membrane-associated Apl I and an increase in an autonomous kinase activity that may be related to a post-translational modification of Apl II. These results are consistent with the hypothesis that in addition to its role in producing the presynaptic facilitation of mechanosensory-motor neuron synapses that underlie short-term facilitation, PKC is needed for maintaining synaptic changes in an intermediate period that precedes the modifications accompanying consolidation of memory.
Who’s talking to whom in agribusiness? And should anyone listen? The network of intellectual influence in agribusiness research
Authors: Van Fleet David D. , McWilliams Abagail , Freeman Michael
Published: November 2021

Purpose

To develop an understanding of communication among agribusiness journals and to examine patterns of citations that allow the measurement and description of the structure of communication flows among those journals in a network.

Design/methodology/approach

The data for this study were gathered from the Journal Citation Reports (JCR) published by Thomson Scientific (Philadelphia). The authors conducted a bibliometric analysis, based on an international trade analogy to explain the network of agribusiness journals and how these journals communicate with business and economics journals.

Findings

Business and economics journals and, particularly the traditionally major ones, surprisingly were scarcely every used. However, the British Food Journal stood out with 50 citations to marketing and strategic management journals.

Research limitations/implications

There are predominantly four such limitations: only 33 journals were studied, only one 5-year time period was involved, that time period is a few years old and the journal characteristics were derived using data from the “Scopes” and “Information for Authors” text on the website of each journal.

Practical implications

Exchanges of agribusiness knowledge and information among diverse stakeholders (consumers, suppliers and public agencies) in a complex environment require a better understanding of the network of agribusiness journals and their relation to traditional business and economics journals.

Social implications

Networks of journals facilitate cooperation and interactions to improve developments in the field.

Originality/value

Examining citations from and to the field of agribusiness is interesting and important because knowledge is transferred through networks comprise those who contribute to journals, read them and learn from them, i.e. by “talking” to each other as well as by practitioners who also read and learn from those journals.
Understanding the relationship between organizational culture and inbound open innovation
Authors: Barjak Franz , Heimsch Fabian
Published: November 2021

Purpose

The relationship between corporate culture and inbound open innovation (OI) has been limited to two sub-constructs: a culture for openness and an innovation culture, but until now a richer conceptualization of corporate culture is missing.

Design/methodology/approach

The authors apply Quinn and Rohrbaugh's (1983) competing values framework and regress these together with company internal and external control variables on five measures of inbound OI, reflecting product innovation, process innovation and the sourcing of innovation activities. The authors use data from a survey of more than 250 Swiss companies, primarily SMEs.

Findings

The importance of the firms' market environments suggests that the results are affected by the specific situation in which the firms found themselves at the time of the survey: after a strong currency shock, inbound OI activities seem to be a reaction to external pressure that favored planning and rule-oriented (formal) cultures to implement cost-cutting process innovations.

Practical implications

Companies should develop a vision and a strategy, ensure open and transparent communication, have suitable reward and support mechanisms in place, adjust structures and processes, and institutionalize and formalize any change whenever they are confronted with a situation that requires a quick reaction and an adjustment to their degree of openness.

Originality/value

The paper clarifies the relationship between cultural traits and inbound OI, using a well-established understanding of corporate culture and differentiating between innovation types. It points to the importance of the external environment in order to understand the role of culture.
Genetic variation at the p53 locus of two ecologically divergent Microtus pine voles: identification of molecular markers for species assignment
Authors: QUINA Ana Sofia , TAVANEZ João Paulo , MATHIAS Maria da Luz
Published: November 2021

The Lusitanian (Microtus lusitanicus) and the Mediterranean (Microtus duodecimcostatus) pine voles are recently diverged sister species endemic of the Iberian Peninsula that can be identified with ecological and morphological characters, but in areas where the 2 species co‐occur, species designation may be difficult. Genetic discrimination between M. lusitanicus and M. duodecimcostatus has not been achieved yet possibly because of their estimated recent split and an evolutionary history that includes inter‐species gene flow. Following our previous observations on exons 5–7 of the p53 gene, here we analyze the potential use of the p53 genomic region as a discrimination marker of these species by extending our analyses to several kb upstream and downstream of the p53 gene and characterizing the degree of genetic differentiation in 7 markers within this region. Additionally, we fully sequenced the P53 protein of both species. We observed: (i) generally high differentiation in this region; (ii) M. duodecimcostatus showed in general higher values of nucleotide and haplotype diversities; (iii) the concatenated phylogenetic tree separates the 2 species; (iv) the 2 P53 proteins only differ in 1 amino acid; (v) 4 of the markers, 2 in p53, one in Atp1b2, and another in Wrap53, contain species‐specific genetic variation thus allowing a reliable discrimination between specimens from both species, irrespective of sampling location or introgression status. We provide additional data on the putative role of p53 in the evolution of these species and present researchers with a fast and cost‐effective resource for M. lusitanicus and M. duodecimcostatus identification.
Comparison of apical debris extrusion during root canal preparation in primary molars using different file systems: an in vitro study
Authors: Mohammadi Davood , Mehran Majid , Frankenberger Roland , BabeveyNejad Newsha , Banakar Morteza , Haghgoo Roza
Published: November 2021

This study aimed to compare the amount of debris extrusion of four endodontic systems made of Nickle‐Titanium alloy. This in vitro study was done on 80 extracted primary molars. They were selected by cone‐beam computed tomography and randomly divided into four groups (n = 20) to be prepared to the apical size of 25 by one of the systems: Reciproc, Protaper Universal, Neolix, or Hyflex CM. Debris was collected into Eppendorf microtubes and placed in an incubator to evaporate the washing solution. Debris was weighed by a digital scale of 0.01 g precision. Data were statistically analysed using SPSS software. Tukey’s comparison was used to determine the difference between the four file systems (α = 0.05). Debris extrusion after Reciproc preparation (0.00320) was significantly higher than the other (P < 0.05), with no significant difference having been observed among the other systems (P > 0.05). It can be concluded that all systems under investigation exhibited debris extrusion.
Leaps ahead in law but not in practice: Why we need to train in second trimester abortion care
Authors: Hudspith Anna , Paterson Helen , Caldwell Coleen , Whiting Rosie
Published: November 2021

Background

Abortion care has always been controversial, with health professionals worldwide continually working to offer well‐rounded safe services. Key improvements in New Zealand since abortion law reform include the ability to self‐refer, no formal certification under 20 weeks gestation, and change to the indications for abortion after 20 weeks. Nationally, we know that the second trimester abortion incidence is stable, and will therefore require an ongoing workforce to sustain the service.

Aims

To document the current second trimester workforce for medical and surgical abortion in New Zealand, and examine their training and practice.

Materials and Methods

Anonymous non‐discriminatory snowball survey covering the domains of demographics, barriers to abortion care, abortion training, abortion provision and procedure specifics using Qualtrics software.

Results

Eleven practitioners currently perform dilation and evacuation, and 33 wish to. Current providers have between zero and three other colleagues to assist them in service provision. Most learned by an informal apprenticeship model and operate relatively infrequently. There is variance in the cervical preparation and evacuation procedure as well as skillset and/or willingness for later gestations. Fifty‐nine practitioners' units currently provide medical abortion, and 62 wish to. There is more coherence in the regime of medical abortion, although the availability of this is affected by gestation and location.

Conclusion

For most women requesting second trimester abortions, additional time, cost and stress is still very much the status quo. District Health Boards need to prioritise training and workforce planning to ensure the availability of this essential service.
Chambered warm moist air eyelid warming devices – a review
Authors: Magno Morten Schjerven , Olafsson Jonatan , Beining Marie , Moschowits Emily , Lagali Neil , Wolffsohn James S. , Craig Jennifer P. , Dartt Darlene A. , Vehof Jelle , Utheim Tor P.
Published: November 2021

Background

Eyelid warming is an important treatment for meibomian gland dysfunction (MGD). Specialized chambered devices, using warm moist air have been developed.

Purpose

To critically evaluate the literature on the safety and efficacy of chambered warm moist air devices in MGD treatment and pinpoint areas of future research.

Methods

PubMed and Embase were searched on 06 June 2021. The search term was ‘(warm OR heat OR steam OR goggle OR spectacle OR moist air) AND (meibomian OR MGD OR blepharitis OR eyelid OR dry eye OR DED)’. All relevant articles with available English full text were included.

Results

Eighteen articles assessing the application of chambered warm moist air eyelid warming devices were identified. In single‐application studies, steam‐based eyelid warming increased the eyelid temperature and improved symptoms, lipid layer thickness, and tear film breakup time (TBUT). In treatment studies, the steam‐based devices improved TBUT and symptom scores. However, in the only randomized controlled trial (RCT) comparing chambered steam‐based heat to hot towel treatment, there was no difference between groups for the primary outcome measure; the proportion of subjects noting symptom improvement after 4 weeks.

Conclusion

Currently available chambered warm moist air eyelid warming devices are safe and effective at raising eyelid temperature to therapeutic levels and improving signs and symptoms of dry eye. However, it is not clear if they provide a greater benefit than other eyelid warming therapies. Further well‐conducted RCTs comparing moist and dry heat devices should be conducted on patients across the range of DED severities and subtype spectrum.
Looking deeper into ocular surface health: an introduction to clinical tear proteomics analysis
Authors: Nättinen Janika , Aapola Ulla , Nukareddy Praveena , Uusitalo Hannu
Published: November 2021

Ocular surface diseases are becoming more prevalent worldwide. Reasons for this include the ongoing population ageing and increasing use of digital displays, although ophthalmologists have a wide selection of tools, which can be implemented in the evaluation of the ocular surface health, methods, which enable the in‐depth study of biological functions are gaining more interest. These new approaches are needed, since the individual responses to ocular surface diseases and treatments can vary from person to person, and the correlations between clinical signs and symptoms are often low. Modern mass spectrometry (MS) methods can produce information on hundreds of tear proteins, which in turn can provide valuable information on the biological effects occurring on the ocular surface. In this review article, we will provide an overview of the different aspects, which are part of a successful tear proteomics study design and equip readers with a better understanding of the methods most suited for their MS‐based tear proteomics study in the field of ophthalmology and ocular surface.
Long‐term outcome of patients receiving haematopoietic allogeneic stem cell transplantation as first transplant for high‐risk Hodgkin lymphoma: a retrospective analysis from the Lymphoma Working Party‐EBMT
Authors: Gutiérrez‐García G. , Martínez C. , Boumendil A. , Finel H. , Malladi R. , Afanasyev B. , Tsoulkani A. , Wilson K. M. O. , Bloor A. , Nikoloudis M. , Richardson D. , López‐Corral L. , Castagna L. , Cornelissen J. , Giltat A. , Collin M. , Fanin R. , Bonifazi F. , Robinson S. , Montoto S. , Peggs K. S. , Sureda A.
Published: November 2021

We analysed long‐term outcome of patients receiving haematopoietic allogeneic stem cell transplantation (allo‐HSCT) as a first transplant for high‐risk Hodgkin lymphoma (HL). One hundred and ninety patients were included in this study, 63% of them had previously received brentuximab vedotin and/or checkpoint inhibitors. Seventy patients (37%) received an unrelated donor allo‐HSCT, 99 (51%) had myeloablative conditioning (MAC) and 60% had in vivo T‐cell/depleted grafts (TCD). The 100‐day cumulative incidence (CI) of grade II‐IV acute graft‐versus‐host disease (GVHD) was 25% and the 3‐year CI of chronic GVHD was 38%. The 3‐year CI of non‐relapse mortality (NRM) and relapse rate were 21% and 38% respectively. After a median follow‐up of 58 months, 3‐year overall survival (OS) and progression‐free survival (PFS) were 58% and 41% respectively. Multivariate analysis showed that, in comparison to reduced‐intensity conditioning regimens with or without TCD, MAC using TCD had similar NRM and a lower risk of relapse leading to significantly better OS and PFS. MAC without TCD was associated with higher NRM and worse survival outcomes. These results suggest that in patients with high‐risk HL and candidates of allo‐HSCT, a MAC strategy with TCD might be the best option.
An exploration of the Personal Relationship Advisory Group in a community learning disability service: A service development project
Authors: Coleman Sophie Elizabeth , Sharrock Emma
Published: November 2021

Accessible summary

The project aimed to explore discussions from the Personal Relationship Advisory Group (PRAG) meetings in a community adult learning disability team to influence the development of new relationship resources.

All meeting minutes within a 12‐month period were analysed to find themes.

The themes suggest the importance of the service looking at the whole person, such as their physical, emotional and social well‐being, when there are relationship concerns.

New resources that focus on personal sexuality, different types of relationships and Internet safety may be of benefit to the service.

Resources for carers may also be useful, such as helping carers to support people with learning disabilities to safely access relationships online.

Background

Adults with learning disabilities often face barriers when accessing relationships and can require additional support. The Personal Relationship Advisory Group (PRAG) is a provision in a community learning disability service in North England, which offers multidisciplinary advice regarding relationship concerns. The current project aimed to identify common themes within PRAG to influence the development of new resources in the service.

Materials and Methods

All meeting minutes within a 12‐month period were analysed using thematic analysis. There were a total of 16 minutes, which discussed 11 people with learning disabilities. This included six females and five males with a mean age of 30 (SD = 14.97).

Results

Individuals often had limited opportunity to develop relationships. There was a lack of understanding of sex and of how to behave appropriately in different types of relationships, with a need for individualised, accessible education. The Internet was commonly used to seek relationships, with many concerns regarding safety from carers or family. There were some unhelpful responses from others, such as the implementing of restrictions. Factors that may have an impact on the person's overall well‐being, such as their health, social issues and trauma, were often discussed.

Conclusions

The identified themes suggest the need for the service to take a holistic, biopsychosocial and individualised approach when supporting individuals with any relationship concerns. A multidisciplinary approach and collaboration with the individual and family/carers is key. It may be useful for the service to develop resources on topics such as personal sexuality, different types of relationships and Internet safety. Carer‐specific resources would also be beneficial, such as advice on how to safely support individuals to seek relationships on the Internet.
Walking a Fine Line: The Struggle for Parent Advocacy in the NYC Child Welfare System☆
Authors: Castellano Viola
Published: November 2021

This article investigates parent advocacy in the child welfare system amongst families living in low‐income and racialized urban areas, those most impacted by this system. Drawing from my fieldwork experience at the community‐based organization Child Welfare Organizing Project (CWOP) in East Harlem, New York, I interrogate the political trajectory of the organization, its practices, and its purpose. I analyze how the decision parents make to advocate is tied to the injustice, stigma, and surveillance they—and especially mothers—experience in the child welfare system. While exploring how parenting and its political dimension are reshaped for disfranchised mothers through advocacy, I describe the “fine line” between compliance and resistance that CWOP has walked throughout its history to preserve its existence. This article illustrates how this form of activism takes place within a fragmented and increasingly privatized welfare regime, in which community‐based organizations struggle for their right to remain political actors and not be overtaken by the logic of service provision. Through my analysis, I aim to contribute to anthropological understandings of the forms of political agency taken up by stigmatized subjects in their interactions with the state, and the limits the state demonstrates in “hearing” their claims and requests for change.
Phosphorus speciation and distribution in a variable‐charge Oxisol under no‐till amended with lime and/or phosphogypsum for 18 years
Authors: Firmano Ruan F. , Colzato Marina , Alleoni Luís R. F.
Published: November 2021

Long‐term management with lime and/or phosphogypsum (PG) can change phosphorus (P) forms across the soil profile. In this study, we used synchrotron‐based spectroscopy and sequential chemical fractionation to investigate P chemical species after long‐term (18 years) application of amendments in a subtropical Oxisol. The availability of nutrients increased with the combined use of lime and PG and a stratification of attributes was identified due to long‐term broadcast applications. X‐ray absorption near edge structure (XANES) spectra profiles revealed the predominance of P bounded to haematite (Hm) (48% on average) and also P bound to kaolinite (32% on average) species. Low proportions (16%) of calcium‐phosphates in the uppermost soil layer (0–5 cm) were found in the treatment that received high calcium (Ca) inputs by lime and PG broadcast. Few correlations were identified between the proportions of P species obtained by XANES and P fractions operationally defined by sequential chemical fractionation (SF). Our results suggest that P‐species bound to kaolinite can store stable P forms, which correlated (p < 0.05) with the residual P fractions obtained by SF, highlighting the importance of kaolinite as a legacy P store in Oxisols.

Highlights

Lime and phosphogypsum broadcast under no‐till improve soil fertility and P availability.

Labile and moderately labile P fractions were the only ones influenced by lime and/or phosphogypsum.

Proportions among P bounded to Fe‐ and Al‐(hydr)oxides with different structural may be affected by long‐term Al‐suppressors.

P‐species bounded to kaolinite may store stable P forms in Oxisols.
Metabolic dysfunction‐associated fatty liver disease and liver fibrosis: Prevalence and associated factors in the middle‐aged and older US population
Authors: Yang Sheng , Cheng Jiawen , Zhang Rui , Sun Huiwen , Zhang Hui , Lyu Sali , Duan Weiwei
Published: November 2021

Aim

The global burden of chronic liver disease is substantial. Limited studies have reported the prevalence of metabolic dysfunction‐associated fatty liver disease (MAFLD) and liver fibrosis among middle‐aged and older people. Therefore, we aimed to determine the nationwide prevalence of and associated factors for MAFLD and fibrosis in adults aged 45–79 years from the United States.

Methods

This cross‐sectional study utilized data from the 2017–2018 cycle of the National Health and Nutrition Examination Survey conducted with a nationally representative sample of the civilian, noninstitutionalized US population. Hepatic steatosis and fibrosis were assessed by transient elastography with controlled attenuation parameter and liver stiffness measurement, respectively.

Results

A total of 1186 eligible participants aged 45–79 years were finally included in the analyses. The estimated prevalence of MAFLD, significant fibrosis (F ≥ F2), and advanced fibrosis (F ≥ F3) was 48.6% (95% confidence interval [CI], 43.1%–54.0%), 9.5% (95% CI, 6.8%–12.7%), and 6.7% (95% CI, 4.1%–10.1%), respectively. Multivariable logistic regression revealed an increased MAFLD predisposition in subjects with metabolic disorders including overweight/obesity, abdominal obesity, hypertension, and diabetes mellitus. Moreover, the presence of depression was an independent and strong predictor of MAFLD risk (odds ratio = 3.23; 95% CI, 1.37–7.11). Elevated liver enzymes, hypertension, diabetes mellitus, hepatitis virus infection, and steatosis were associated with a high risk of significant fibrosis.

Conclusions

Newly defined MAFLD is highly prevalent in the US middle‐aged and older population. Approximately 1 in 10 people has significant liver fibrosis. In addition to metabolic disorders, the presence of depression potentially increases the risk of MAFLD.
Concept analysis of shame in nursing
Authors: Jaeb Michael A.
Published: November 2021

Nurses can facilitate opportunities for patients who feel shame to experience healing in their mental health. Disciplines such as psychology have extensive shame research, yet nursing may provide a unique perspective to bolster research on shame. The objective of this analysis is to examine the use of shame as a concept in nursing literature. This review was guided by Beth Rodgers’ Evolutionary approach to concept analysis. Rodgers' approach entails investigating attributes, related terms, surrogate terms, antecedents, and consequences of shame; and examining the use of the concept shame over time to determine if its use changed. Sampled literature came from Cumulative Index to Nursing and Allied Health Literature Plus with Full Text, PubMed, Web of Science, and Health Source: Nursing/Academic Edition. The final sample used for analysis included 334 sources published between 1993 and 2020. The use of shame did not change during these years. Attributes were negative sense of self, feeling worthless, and feeling vulnerable. There were no surrogate terms and three related terms: guilt, humiliation, and embarrassment. Antecedents were trauma, stigma, and perception of moral wrongdoing. Consequences included healthcare avoidance, social withdrawal or isolation, negative coping mechanisms, resilience, lifestyle changes, and healthy coping. There is a discrepancy between the conceptualization and use of shame in nursing and other disciplines. Other disciplines, such as psychology, provide more direction about how interpersonal interactions can elicit or alleviate feelings of shame. Nurses can apply this conceptualization in their clinical practice to support patients experiencing shame.