bluuebunny/crossref_metadata_2025 huggingface dataset:
Introduction of a condensed, reverse tricarboxylic acid cycle for additional CO2 fixation in plants
Authors: Wilson Nathan J. , Smith-Moore Caroline M. , Xu Yuan , Edwards Brianne , Hovary Christophe La , Barampuram Swathi , Li Kai , Aslett Denise , Ji Mikyoung , Lin Xuli , Vintila Simina , Kleiner Manuel , Xie Deyu , Shachar-Hill Yair , Grunden Amy , Sederoff Heike
Published: March 2022

Plants employ the Calvin-Benson cycle (CBC) to fix atmospheric CO2 for the production of biomass. The flux of carbon through the CBC is limited by the activity and selectivity of ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO). Alternative pathways that do not use RuBisCO to fix CO2 exist but occur only in anaerobic microorganisms. Rather than modifying existing routes of carbon metabolism in plants, we have developed a synthetic carbon fixation cycle that does not exist in nature, but is inspired by metabolisms of bacterial autotrophs. This synthetic cycle uses endogenous plant metabolites to fix CO2 and yield glyoxylate as a product. In this work, we build and characterize a condensed, reverse tricarboxylic acid (crTCA) cycle in vitro and in planta. We demonstrate that a simple, synthetic cycle can be used to fix carbon in vitro under aerobic and mesophilic conditions and that these enzymes retain activity when expressed transiently in planta. We then evaluate stable transgenic lines of Camelina sativa that have both phenotypic and physiologic changes. Transgenic C. sativa are shorter than controls with increased rates of photosynthetic CO2 assimilation and changes in photorespiratory metabolism. This first iteration of a build-test-learn phase of the crTCA cycle provides promising evidence that this pathway can be used to increase photosynthetic capacity in plants.
Seed Germination, Post-fire Plant Growth and Conservation of the Rare Endemic and Endangered Chamaecrista glandulosa var. mirabilis (Fabaceae)
Authors: Vilá Terrada Fernando J. , López Colón Jonathan A.
Published: March 2022

Conservation has been challenged by biodiversity loss drivers. Also, fire disturbance can temporarily change ecosystems. Fire effects in soil nutrients and pH, plant abundance, reproduction, seed weight, seed germination, and plant growth were assessed. Four seed starting systems were used for germination and growth under laboratory conditions. We found significant differences in the means of iron, manganese, nickel, soil pH, and plant height, and a significant positive linear relationship between seed weight and plant height. Results indicate that fires increase soil pH and cause changes in micronutrients that can increase plant growth. Large size plants are produced from high weight seeds. Finally, ex situ conservation and species reintroduction were feasible conservation strategies that should be integrated with in situ conservation.
Nuclear translocation triggered at the onset of hearing in cochlear inner hair cells of rats
Authors: Iyer Megana R. , Kalluri Radha
Published: March 2022

Nuclear position is precisely orchestrated during cell division, migration, and maturation of cells and tissues. Here we report a previously unrecognized, programmed movement of the nucleus in rat cochlear inner hair cells. This cell-type specific nuclear movement among hair cells of the inner ear offers a new glimpse into the cellular mechanisms involved in the functional maturation of inner hair cells. In early post-natal days, the nucleus sits at the very basal pole of the hair cell, far from the apically located mechano-transducing stereocilia, but close to where synapses with primary afferent and efferent neurons are forming. By maturity, the nucleus moves to occupy a new position half-way along the length of the cell. Remarkably, nuclear translocation happens quickly over the course of 1-2 post-natal days, coinciding with the onset of hearing. The movement of the nucleus likely signals the closing of a critical period correlated with the forming and refining of synapses at the onset of hearing.

Significance Statement

The misplacement of a cell’s nucleus has been implicated in hearing, vision, and muscular pathologies. In this study, we report a remarkably abrupt change in nuclear position in cochlear inner hair cells that coincides with the onset of hearing in rats, when hair cells switch from producing sensory-independent action potentials to sensory-dependent graded potentials. This work suggests that post-mitotic nuclear migration may be critical to the final phase of post-natal development in mammalian hearing.
Design of the mammalian cone photoreceptor to Off bipolar cell synapse
Authors: Grabner Chad P. , Futagi Daiki , Shi Jun , Bindokas Vytas , Kitano Katsunori , Schwartz Eric , DeVries Steven H.
Published: March 2022

Graded synapses in sensory systems reliably transmit small signals in the presence of continuous quantal noise. To understand how signaling is optimized during graded transmission, we counted the number of vesicles released by a mammalian cone terminal and compared it to the simultaneous responses in each Off bipolar cell type. Off bipolar cells contacting the terminal base comprised two groups depending on how they sampled transmitter release. In both groups, responses initially grew non-linearly with the number of released vesicles implicating a role for cooperativity during sparse release. One group sampled release from most of a cone’s ∼20 ribbons and can exploit averaging to improve signal reliability. The other, less-sensitive group made 1-3 contacts at the terminal center and responded to pooled transmitter, a consequence of membrane depolarization, using an insensitive kainate receptor. Off bipolar cells use different strategies to minimize transmission noise and encode cone output over different ranges.
Medial prefrontal cortex Notch1 signalling mediates methamphetamine-induced psychosis via Hes1-dependent suppression of GABAB1 receptor expression
Authors: Ni Tong , Zhu Li , Wang Shuai , Zhu Weili , Xue Yanxue , Zhu Yingjie , Ma Dongliang , Wang Hongyan , Guan Fanglin , Chen Teng
Published: March 2022

Methamphetamine (METH), a widely abused stimulant drug, induces psychosis in approximately half of abusers; this effect is becoming a major concern for society. Although the Notch1 signalling pathway has been shown to play a part in the pathogenesis of some psychiatric disorders, its role in METH-induced psychosis (MIP) is still unknown. Here, we showed that Notch1 signalling was downregulated in the medial prefrontal cortex (mPFC) in a MIP mouse model. Direct genetic and pharmacological manipulations of Notch1 signalling bidirectionally altered MIP-related behaviours and governed neuronal activity in the mPFC. Moreover, Notch1 signalling negatively regulated GABAB1 receptor expression in the mPFC of MIP mice through Hes1, a transcriptional repressor in Notch1 signalling. Further, we show that Hes1 can directly bind to the GABAB1 receptor promoter. Notably, pharmacological regulation of the GABAB receptor in the mPFC reversed the changes in MIP-related behaviours caused by the dysfunction of Notch1 signalling. Together, our findings uncover a previously unrecognised Notch1-Hes1-GABAB1 receptor-dependent mechanism involved in regulating mPFC neuronal activity and behavioural phenotypes in MIP. Our work provides mechanistic insight into the aetiology and pathophysiology of MIP.
Genomic and Transcriptomic Profiling of Phoenix Colonies
Authors: Sindeldecker Devin , Dunn Matthew , Zimmer Aubree , Anderson Matthew , Alfonzo Juan , Stoodley Paul
Published: March 2022

Pseudomonas aeruginosa is a Gram-negative bacterium responsible for numerous human infections. Previously, novel antibiotic tolerant variants known as phoenix colonies as well as variants similar to viable but non-culturable (VBNC) colonies were identified in response to high concentrations of aminoglycosides. In this study, the mechanisms behind phoenix colony and VBNC-like colony emergence were further explored using both whole genome sequencing and RNA sequencing. Phoenix colonies were found to have a single nucleotide polymorphism (SNP) in the PA4673 gene, which is predicted to encode a GTP-binding protein. No SNPs were identified within VBNC-like colonies compared to the founder population. RNA sequencing did not detect change in expression of PA4673 but revealed multiple differentially expressed genes that may play a role in phoenix colony emergence. One of these differentially expressed genes, PA3626, encodes for a tRNA pseudouridine synthase which when knocked out led to a complete lack of phoenix colonies. Although not immediately clear whether the identified genes in this study may have interactions which have not yet been recognized, they may contribute to the understanding of how phoenix colonies are able to emerge and survive in the presence of antibiotic exposure.
Moving Yeasts: Resolving the Mystery
Authors: Puri Gulab , Chaudhari Sulbha , Inamdar Areeb , Kohli Manish , Sangawe Vishal , Jadhav Chandrakant , Teja Lakshman , Adhapure Nitin
Published: March 2022

We have recently discovered a novel dimorphic yeastAureobasidium tremulumsp.nov. The species name tremulum indicates its trembling movement. With keen microscopic observations and various experimentation, we concluded that the movement is of two types, trembling movement, and actual displacement. The movement is because of two reasons; 1. Due to the dynamic movement of intracellular lipid granules, and; 2. Due to the movement of an intracellular bacterial population which is present as an endosymbiont. The mechanism of displacement has been hypothesized. The presence of both lipid granules and bacteria has been confirmed using microscopic analysis (Bright field, Phase contrast, confocal, Cryo-SEM, and HR-TEM). The bacterial presence was confirmed using whole-genome metagenomic analysis. Endosymbiotic bacteria have also been isolated and identified by 16s rRNA gene sequencing. Interestingly, some of them possibly are novel species. Also, the whole genome ofA.tremulumhas been announced. We also report on, restriction of the mode of bacterial mycophagy in presence of an antibiotic.
Predicting the pathogenicity of missense variants using features derived from AlphaFold2
Authors: Schmidt Axel , Röner Sebastian , Mai Karola , Klinkhammer Hannah , Kircher Martin , Ludwig Kerstin U.
Published: March 2022

Each individual genome harbors multiple missense variants, which can be systematically identified via genome or exome sequencing. This class of genetic variation can alter the functional properties of the respective protein, and thereby lead to clinically relevant phenotypes, such as cancer or Mendelian diseases. Despite advances in computational prediction scores, the classification of missense variants as clinically significant or benign remains a major challenge. Recently, the structure of the human proteome was derived with unprecedented accuracy using the artificial intelligence system AlphaFold2. However, the question of whether AlphaFold2 structures can improve the accuracy of computational pathogenicity prediction for missense variants remains unclear. To address this, we first engineered a set of features for each amino acid from these structures. We then trained a random forest to distinguish between proxy-benign and proxy-pathogenic missense variants derived from gnomAD. This yielded a novel AlphaFold2-based pathogenicity prediction score, termed AlphScore. Important feature classes used by AlphScore are solvent accessibility, amino acid network related features, features describing the physicochemical environment, and AlphaFold2’s quality parameter (pLDDT). AlphScore alone showed lower performance than existing scores, such as CADD or REVEL. However, when AlphScore was added to those scores, the performance always increased, as measured by the approximation of deep mutational scan data, as well as the prediction of expert-curated missense variants from the ClinVar database. Overall, our data indicate that the integration of AlphaFold2 predicted structures can improve pathogenicity prediction of missense variants.
Phenethylamine-producing gut bacteria induces diarrhea-predominant irritable bowel syndrome by increasing serotonin biosynthesis
Authors: Zhai Lixiang , Huang Chunhua , Ning Ziwan , Zhang Yijing , Zhuang Min , Yang Wei , Wang Xiaolei , Wang Jingjing , Zhang Eric Lu , Xiao Haitao , Zhao Ling , Lam Yan Y. , Chow Chi Fung Willis , Huang Jiandong , Yuan Shuofeng , Chan Kui Ming , Wong Hoi Leong Xavier , Bian Zhao-xiang
Published: March 2022

Despite the strong association between gut microbial dysbiosis, serotonin (5-HT) dysregulation and diarrhea-predominant irritable bowel syndrome (IBS-D), the mechanism by which changes in the gut microbiota contribute to the pathogenesis of IBS-D, particularly the role of dysregulated 5-HT production, remains unclear. The present study identifiedRuminococcus gnavusin the human gut microbiota as a key risk factor of IBS-D.R. gnavuswas significantly enriched in IBS-D patients and exhibited positive correlation with serum 5- HT level and severity of diarrhea symptoms. We showed thatR. gnavusinduced diarrhea-like symptoms in mice by promoting microbial shunting of essential aromatic amino acids to aromatic trace amines including phenethylamine and tryptamine, thereby stimulating the biosynthesis of peripheral 5-HT, a potent stimulator for gastrointestinal transit. This study identify gut-microbial metabolism of dietary amino acids as a cause of IBS-D and lays a foundation for developing novel therapeutic target for the treatment of IBS-D.

Graphical abstract
Gut microbiota-derived tryptamine impairs insulin sensitivity
Authors: Zhai Lixiang , Xiao Haitao , Lin Chengyuan , Lam Yan Y. , Wong Hoi Leong Xavier , Gong Mengxue , Wu Guojun , Deng Yusheng , Ning Ziwan , Huang Chunhua , Zhang Yijing , Zhuang Min , Yang Chao , Zhang Eric Lu , Zhao Ling , Zhang Chenhong , Fang Xiaodong , Jia Wei , Zhao Liping , Bian Zhao-xiang
Published: March 2022

Gut-microbiota plays a pivotal role in development of type 2 diabetes (T2D), yet the molecular mechanism remains elusive. Here, we show that tryptamine, a microbial metabolite of tryptophan, impairs glucose tolerance and insulin sensitivity. Tryptamine presents a higher level in monkeys with spontaneous diabetes and human with T2D and positively correlated with the glucose tolerance. In parallel, tryptamine level was suppressed by dietary fibers intervention in T2D subjects and negatively correlated with improvement of glucose tolerance. The inhibitory effect of tryptamine on insulin signaling as shown was dependent on a trace amine-associated receptor 1 (TAAR1)-extracellular signal-regulated kinase (ERK) signaling axis. Monoassociation of T2D-associated tryptamine-producing bacteriaRuminococcus gnavusimpairs insulin sensitivity in pseudo germ-free mice. Our findings indicate gut microbiota-derived tryptamine contributes to the development of insulin resistance in T2D and may serve as a new target for intervention.

Graphical Abstract
The Trypanosoma brucei RNA-binding protein DRBD18 ensures correct mRNA trans splicing and polyadenylation patterns
Authors: Bishola Tshitenge Tania , Clayton Christine
Published: March 2022

The parasite Trypanosoma brucei grows as bloodstream forms in mammals, and as procyclic forms in tsetse flies. Transcription is polycistronic, all mRNAs are trans spliced, and polyadenylation sites are defined by downstream splicing signals. Expression regulation therefore depends heavily on post-transcriptional mechanisms. The RNA-binding protein DRBD18 was previously implicated in the export of some mRNAs from the nucleus in procyclic forms. It copurifies the outer ring of the nuclear pore, mRNA export factors and exon-junction-complex proteins. We show that for >200 mRNAs, DRBD18 depletion caused preferential accumulation of versions with shortened 3’-untranslated regions, arising from use of polyadenylation sites that were either undetectable or rarely seen in non-depleted cells. The shortened mRNAs were often, but not always, more abundant in depleted cells than the corresponding longer versions in normal cells. Their appearance was linked to the appearance of trans spliced, polyadenylated RNAs containing only downstream 3’-untranslated-region-derived sequences. Experiments with one mRNA suggested that nuclear retention alone, through depletion of MEX67, did not affect mRNA length, suggesting a specific effect of DRBD18 on processing. Since DRBD18-bound mRNAs were enriched in polypyrimidine tract motifs, and it is found in both the nucleus and the cytoplasm, we suggest that DRBD18 acts in the nucleus by binding to polypyrimidine tracts in 3’-UTRs. DRBD18 binding might both prevent polypyrimidine tract recognition by splicing factors, and promote export of the bound RNAs to the cytosol.
Protein Optimization Evolving Tool (POET) based on Genetic Programming
Authors: Bricco Alexander R. , Miralavy Iliya , Bo Shaowei , Perlman Or , Farrar Christian T. , McMahon Michael T. , Banzhaf Wolfgang , Gilad Assaf A.
Published: March 2022

Proteins are used by scientists to serve a variety of purposes in clinical practice and laboratory research. To optimize proteins for greater function, a variety of techniques have been developed. For the development of reporter genes used in Magnetic Resonance Imaging (MRI) based on Chemical Exchange Saturation Transfer (CEST), these techniques have encountered a variety of challenges. Here we develop a mechanism of protein optimization using a computational approach known as “genetic programming”. We developed an algorithm called Protein Optimization Evolving Tool (POET). Starting from a small library of literature values, use of this tool allowed us to develop proteins which produce four times more MRI contrast than what was previously state-of-the-art. Next, we used POET to evolve peptides that produced CEST-MRI contrast at large chemical shifts where no other known peptides have previously demonstrated contrast. This demonstrated the ability of POET to evolve new functions in proteins. Interestingly, many of the peptides produced using POET were dramatically different with respect to their sequence and chemical environment than existing CEST producing peptides, and challenge prior understandings of how those peptides function. This suggests that unlike existing algorithms for protein engineering that rely on divergent evolution, POET relies on convergent evolution.
Differential effects of group III metabotropic glutamate receptors on spontaneous inhibitory synaptic currents in spine-innervating double bouquet and parvalbumin-expressing dendrite-targeting GABAergic interneurons in human neocortex
Authors: Lukacs Istvan P. , Francavilla Ruggiero , Field Martin , Hunter Emily , Howarth Michael , Horie Sawa , Plaha Puneet , Stacey Richard , Livermore Laurent , Ansorge Olaf , Tamas Gabor , Somogyi Peter
Published: March 2022

Diverse neocortical GABAergic neurons specialise in synaptic targeting and their effects are modulated by presynaptic metabotropic glutamate receptors (mGluRs) suppressing neurotransmitter release in rodents, but their effects in human neocortex are unknown. We tested whether activation of group III mGluRs by L-AP4 changes GABAA receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) in two distinct dendritic spine-innervating GABAergic interneurons recorded in vitro in human neocortex. Calbindin-positive double bouquet cells (DBC) had columnar “horsetail” axons descending through layers II-V innervating dendritic spines (48%) and shafts, but not somata of pyramidal and non-pyramidal neurons. Parvalbumin-expressing dendrite-targeting cell (PV-DTC) axons extended in all directions innervating dendritic spines (22%), shafts (65%) and somata (13%). As measured, 20% of GABAergic neuropil synapses innervate spines, hence DBCs, but not PV-DTCs, preferentially select spine targets. Group III mGluR activation paradoxically increased the frequency of sIPSCs in DBCs (to median 137% of baseline), but suppressed it in PV-DTCs (median 92%), leaving the amplitude unchanged. The facilitation of sIPSCs in DBCs may result from their unique GABAergic input being disinhibited via network effect. We conclude that dendritic spines receive specialised, diverse GABAergic inputs, and group III mGluRs differentially regulate GABAergic synaptic transmission to distinct GABAergic cell types in human cortex.
TrmB family transcription factor as a thiol-based regulator of oxidative stress response
Authors: Mondragon Paula , Hwang Sungmin , Kasirajan Lakshmi , Oyetoro Rebecca , Nasthas Angelina , Winters Emily , Couto-Rodriguez Ricardo L. , Schmid Amy , Maupin-Furlow Julie A.
Published: March 2022

Oxidative stress causes cellular damage including DNA mutations, protein dysfunction and loss of membrane integrity. Here we discovered TrmB (transcription regulator of mal operon) family proteins (Pfam PF01978) composed of a single winged-helix DNA binding domain (InterPro IPR002831) can function as thiol-based transcriptional regulators of oxidative stress responses. Using the archaeon Haloferax volcanii as a model system, we demonstrate that the TrmB-like OxsR is important for recovery of cells from hypochlorite stress. OxsR is shown to bind specific regions of genomic DNA, particularly during hypochlorite stress. OxsR-bound intergenic regions were found proximal to oxidative stress operons including genes associated with thiol relay and low molecular weight thiol biosynthesis. Further analysis of a subset of these sites, revealed OxsR to function during hypochlorite stress as a transcriptional activator and repressor. OxsR was shown to require a conserved cysteine (C24) for function and to use a CG-rich motif upstream of conserved BRE/TATA box promoter elements for transcriptional activation. Protein modeling suggested the C24 is located at a homodimer interface formed by antiparallel α helices, and that oxidation of this cysteine would result in the formation of an intersubunit disulfide bond. This covalent linkage may promote stabilization of an OxsR homodimer with the enhanced DNA binding properties observed in the presence of hypochlorite stress. The phylogenetic distribution TrmB family proteins, like OxsR, that have a single winged-helix DNA binding domain and conserved cysteine residue suggests this type of redox signaling mechanism is widespread in Archaea.

Importance

TrmB-like proteins, while not yet correlated with redox stress, are found in bacteria and widespread in archaea. Here we expand annotation of a large group of TrmB-like single winged-helix DNA binding domain proteins from diverse archaea to function as thiol-based transcriptional regulators of oxidative stress response. Using Haloferax volcanii as a model, we reveal the TrmB-like OxsR functions during hypochlorite stress as a transcriptional activator and repressor of an extensive gene co-expression network associated with thiol relay and other related activities. A conserved cysteine residue of OxxR serves as the thiol-based sensor for this function and likely forms an intersubunit disulfide bond during hypochlorite stress that stabilizes a homodimeric configuration with enhanced DNA binding properties. A CG-rich DNA motif in the promoter region of a subset of sites identified to be OxsR-bound is required for regulation; however, not all sites have this motif suggesting added complexity to the regulatory network.
EGFR-MAPK adaptor proteins mediate the epithelial response to Candida albicans via the cytolytic peptide toxin, candidalysin
Authors: Ponde Nicole O. , Lortal Léa , Tsavou Antzela , Hepworth Olivia W. , Wickramansinghe Don N. , Ho Jemima , Richardson Jonathan P. , Moyes David L. , Gaffen Sarah L. , Naglik Julian R.
Published: March 2022

Candida albicans (C. albicans) is a dimorphic human fungal pathogen that can cause severe oropharyngeal candidiasis (OPC, oral thrush) in susceptible hosts. During invasive infection, C. albicans hyphae invade oral epithelial cells (OECs) and secrete candidalysin, a pore-forming cytolytic peptide that is required for fungal pathogenesis at mucosal surfaces. Candidalysin induces cell damage and activates multiple MAPK-based innate signaling events that collectively drive the production of downstream inflammatory mediators. The activities of candidalysin are also dependent on the epidermal growth factor receptor (EGFR), but how these signals are integrated is undefined. Here, we identified five essential adaptor proteins as key mediators of the epithelial response to C. albicans infection on cultured OECs, including growth factor receptor bound protein 2 (Grb2), Grb2-associated-binding protein 1 (Gab1), Src homology and collagen (Shc), SH2 containing protein tyrosine phosphatase-2 (Shp2) and casitas B-lineage lymphoma (c-Cbl). All these signaling effectors were inducibly phosphorylated in response to C. albicans, in a candidalysin-dependent mechanism but additionally required EGFR phosphorylation, matrix metalloproteinases (MMPs) and cellular calcium flux. Of these, Gab1, Grb2 and Shp2 were the dominant drivers of ERK1/2 signaling and production of downstream cytokines. Together, these results identify the key adaptor proteins that drive EGFR signaling mechanisms, which determine oral epithelial responses to C. albicans.
Maternal and paternal sugar consumption interact to modify offspring life history and physiology
Authors: Camilleri Tara‐Lyn , Piper Matthew D. W. , Robker Rebecca L. , Dowling Damian K.
Published: March 2022

Intergenerational effects on offspring phenotypes occur in response to variation in both maternal and paternal nutrition. Because the combined maternal and paternal effects are rarely considered together, however, their relative contributions, and the capacity for interactions between parental diets to shape offspring life history and physiology are not understood.

To address this, we altered the sucrose levels of adult fruit flies (Drosophila melanogaster) prior to mating, across two generations, producing parent–parent and parent–offspring combinations that were either matched or mismatched in dietary sucrose. We then measured life span, fecundity, body mass and triglyceride levels in parents and offspring.

We reveal complex, non‐cumulative interactions, which involve diets of each parent and offspring, shape offspring phenotypes, but the effects were generally not consistent with an adaptive response to parental diet.

Notably, we find that interacting parental flies (sires and dams) lived longer when their sucrose treatments were matched, but they produced shorter lived offspring.

These results are suggestive of intergenerational conflict over optimal diets, and call for further research into the capacity, and mechanisms, for mismatches in parental environments to enhance offspring phenotype generally.

Our study also indicates that studies of maternal and paternal effects will need embrace experimental designs with power to test for interactions between maternal and paternal environments if they are to fully understand the ecological and evolutionary significance of parental effects on offspring fitness.

Read the free Plain Language Summary for this article on the Journal blog.
Using Activity Theory to explore the management of General Certificate of Education (GCSE) access arrangements
Authors: Hipkiss Amanda , Woods Kevin A.
Published: March 2022

Access arrangements are the way in which awarding bodies for public examinations in England, such as the General Certificate of Secondary Education, make reasonable adjustments for students with special educational needs and disabilities. SENCos have expressed concerns about the onerous nature of managing requirements for access arrangements, both administratively and practically, but there has been little explanation of why an apparently straightforward process proves so challenging. In this study, the development of a whole‐school system to improve the administrative and practical management of access arrangements is used to seek to understand how the requirements set (and re‐set) annually interact with school systems and processes to render the administration of access arrangements potentially complex, time‐consuming and unpredictable. Scotland's flexible, school‐led framework of requirements for the management of public examination assessment arrangements is highlighted as potentially more fit‐for‐purpose for the organisation of statutory reasonable adjustments for educational assessment.
Social risk adjustment in the hospital readmission reduction program: Pitfalls of peer grouping, measurement challenges, and potential solutions
Authors: Aswani Monica S. , Roberts Eric T.
Published: March 2022

Objective

To examine the limitations of peer grouping and associated challenges measuring social risk in Medicare's Hospital Readmission Reduction Program (HRRP). Under peer grouping, hospitals are divided into quintiles based on the proportion of a hospital's Medicare inpatients with Medicaid (“dual share”). This approach was implemented to address concerns that the HRRP unfairly penalized hospitals that disproportionately serve disadvantaged patients.

Data

Public data on hospitals in the HRRP.

Design

We examined the relationship between hospital dual share and readmission rates within peer groups; changes in hospitals' peer group assignments, readmission rates, and penalties; and the relationship between state Medicaid eligibility rules and peer groups.

Data Collection

Public data on hospital characteristics and readmission rates for 3119 hospitals from 2019 to 2020.

Principal Findings

The proportion of dual inpatients among hospitals of the same peer group varied by as much as 69 percentage points (ppt). Within peer groups, a one ppt increase in dual share was associated with a 0.01 ppt increase in the difference from the median readmission rate (p < 0.001). From 2019 to 2020, 8.8% of hospitals switched peer groups. Compared to hospitals that did not switch, those moving to a lower peer group had a higher mean penalty in 2020 (0.096 ppt; p = 0.006); those moving to a higher group had a lower mean penalty (−0.06 ppt; p = 0.079). However, changes in penalties did not correspond to changes in readmission rates. Hospitals in states with higher Medicaid income eligibility limits were more likely to be in higher peer groups.

Conclusions

Peer grouping is limited in the extent to which it accounts for differences in hospitals' patient populations, and it may not fully insulate hospitals from penalties linked to changes in patient mix. These problems arise from the construction of peer groups and the measure of social risk used to define them.
Risk factors for surgical site infections after paediatric appendectomies in tertiary care hospitals: A case‐control study
Authors: Lee‐Castellanos Catalina , Preciado‐Rodríguez María Camila , Palacios‐Ariza María Alejandra , Beltrán‐Higuera Sandra Jaqueline
Published: March 2022

Aim

To identify risk factors associated with surgical site infections in paediatric patients subjected to appendectomy.

Methods and Materials

We carried out an age‐matched case‐control study (1:3) using data from 2014–2019. Subjects were aged 1–17 and had been subjected to appendectomy. Cases were defined as patients who presented signs of infection in the surgical site within 30 days after the procedure.

Results

We obtained a sample of 352 subjects, 88 with surgical site infections. There were no significant differences between cases and controls in sociodemographic and clinical baseline variables. A conditional logistic regression model identified the following risk factors: use of iodopovidone (OR 77.08; 95%CI 4.21–1411.06), use of laparotomy (OR 3.04; 95%CI 1.29–7.19), and the number of days from initial consult to procedure (OR 2.18; 95%CI 1.21–3.92).

Conclusions

Risk factors for surgical site infections in this sample were all variables associated with the procedure or the immediate postoperative period, all of which are modifiable. This finding can serve as the basis for clinical recommendations that aim to improve the quality of care in the paediatric population.
Wilms' tumor 1 peptide‐loaded dendritic cell vaccination in patients with relapsed or refractory acute leukemia
Authors: Ogasawara Masahiro , Miyashita Mamiko , Yamagishi Yuka , Ota Shuichi
Published: March 2022

Introduction

The prognosis of patients with relapsed or refractory acute leukemia is poor. In the present pilot study, we treated relapsed or refractory acute leukemia patients with Wilms' tumor 1 (WT1) peptide‐loaded dendritic cells (DCs) and examined safety, clinical and immunological responses.

Methods

Eleven eligible patients were enrolled. DCs were administered every 2–3 weeks with OK‐432 adjuvant.

Results

The treatment was well tolerated. The reduction of leukemia cells or the expression of WT1 mRNA was observed in four patients which was maintained for a significant period of time. All the responding patients manifested immune responses against WT1 which might be related to clinical outcome. Decreases in the absolute number of regulatory T cells were observed following vaccination, indicating that DC vaccinations may contribute to the reversal of immunosuppression.

Conclusion

These results indicate that DC‐based immunotherapy is safe and feasible for patients with acute leukemia.
Zona pellucida glycoproteins: Relevance in fertility and development of contraceptive vaccines
Authors: Gupta Satish K.
Published: March 2022

Mammalian zona pellucida (ZP) is composed of three to four glycoproteins, which plays an important role during fertilization. Mutations in the genes encoding zona proteins are reported in women with empty follicle syndrome, degenerated oocytes and those with an abnormal or no ZP further emphasizing their relevance during fertility. Immunization with either native or recombinant ZP glycoproteins/proteins leads to curtailment of fertility in various animal species. Observed infertility is frequently associated with ovarian pathology characterized by follicular atresia and degenerative changes in ZP, which may be due to oophoritogenic T cell epitope(s) within ZP glycoproteins. To avoid ovarian dystrophy, B cell epitopes of ZP glycoproteins have been mapped by using bio‐effective monoclonal antibodies. Immunization with the immunogens encompassing the mapped B cell epitopes by and large led to amelioration of follicular atresia. However, their use for human application will require more rigorous research to establish their safety and reversibility of the contraceptive effect. Nonetheless, to minimize human‐animal conflicts, ZP‐based contraceptive vaccines have been used successfully in the population management of free‐ranging animal species such as feral horses, white‐tailed deer and elephants. To control zoonotic diseases, attempts are also underway to control the population of other animal species including stray dogs, which acts as one of the major vectors for the rabies virus.
Contraceptive efficacy of recombinant porcine zona proteins and fusion protein encompassing canine ZP3 fragment and GnRH in female beagle dogs
Authors: Gupta Satish K. , Toor Sagarika , Minhas Vidisha , Chaudhary Piyush , Raman Muthusamy , Anoop S. , Panda Amulya K.
Published: March 2022

Problem

To manage population of dogs (Canis familiaris), the efficacy of recombinant proteins‐based contraceptive vaccines to inhibit fertility has been evaluated in female beagle dogs.

Method of study

Female beagle dogs (n = 4) were immunized with physical mixture of Escherichia coli‐expressed recombinant porcine ZP3 with promiscuous T cell epitope of tetanus toxoid (TT‐KK‐pZP3) and porcine ZP4 with promiscuous T cell epitope of bovine RNase (bRNase‐KK‐pZP4), or with a fusion protein encompassing dog ZP3 fragment and two copies of GnRH with appropriate promiscuous T cell epitopes (dZP3‐GnRH2); control animals received only alum, the adjuvant. The immunized animals were followed‐up for antibody titres by ELISA as well as for fertility status subsequent to mating with male dogs.

Results

Active immunization of female dogs following a three injections schedule at 4‐week intervals with a physical mixture of TT‐KK‐pZP3 + bRNase‐KK‐pZP4 as well as dZP3‐GnRH2, led to generation of significant antibody titres against respective recombinant proteins. Active immunization with dZP3‐GnRH2 also led to generation of antibodies reactive with both dZP3 and GnRH. A booster dose on day 383 led to an increase in antibody titres and circulating antibodies against respective recombinant proteins could be observed on day 528. Antibodies in immune serum samples from dogs immunized with TT‐KK‐pZP3 + bRNase‐KK‐pZP4 or dZP3‐GnRH2 reacted with native canine ZP as assessed by an indirect immunofluorescence assay. Mating studies revealed a reduced number of pregnancies as well as a significant reduction in the number of pups born in the female dogs immunized with dZP3‐GnRH2 as compared to the adjuvanted control. Curtailment of pregnancy in dZP3‐GnRH2 immunized group was associated with antibody titres against dZP3‐GnRH2. However, immunization with recombinant TT‐KK‐pZP3 + bRNase‐KK‐pZP4 did not significantly decrease the number of pups born as compared to the adjuvanted control.

Conclusion

These studies revealed the potential of recombinant dZP3‐GnRH2‐based contraceptive vaccine to curtail fertility in female dogs. Large scale studies to establish the efficacy and safety of this recombinant protein for the management of community dog population are thus warranted.
Scales and otoliths as identity cards of the Indian oil sardine Sardinella longiceps (Teleostei: Clupeiformes) populations: Ultrastructure and ornamentation characteristics using light and scanning electron microscopy
Authors: Al Jufaili Saud M. , Echreshavi Sorour , Esmaeili Hamid Reza , Al Alawi Majid K.
Published: March 2022

Scale and otolith morphology and morphometry of Indian oil sardine Sardinella longiceps (Clupeidae) were investigated and described using light and scanning electron microscopy from eight different body regions for scales and the right and left otoliths. Scales of the Indian oil sardine show general characteristics of the other studied clupeids sand that are easily distinguishable from other fish groups, by having striae in the posterior field. The studied cycloid scales of S. longiceps were classified into three types based on the overall shape including circular (e.g. true circular and cordate), pentagonal and quadrilateral in the different body regions. The circular shape was the most common shape (87.5%), while the quadrilateral and pentagonal forms constituted 6.25% each. The results also showed that the relative scale size (J‐index) plays a desirable contribution in separating the examined populations. The results showed that the mean (or relative) scale size for all the eight regions in the Oman Sea population is larger than the Arabian Sea population. Also, another scale variable, the scale shape index (Si index), demonstrated variation (a mean of 0.86 to 1.1) in different regions of both populations from the Oman and Arabian Seas. Interestingly, here, we found that scale characters of S. longiceps not only differ from its other congeneric species, but also differ in the populations from both sides of the Oman Sea (Iran and Oman) and the Arabian Sea. It shows a positive signal for the presence of different taxonomic and management unit in the Oman and Arabian Seas. The idea should be approved by using integrated molecular and morphological traits. The otolith morphology of S. longiceps from the Oman and Arabian Seas was more conservative than the scales, which can be due to its function actin primarily as a balance organ and also enhancing hearing. The overall shape of S. longiceps otolith was lanceolate, with an elongated morphology and a well‐developed rostrum, an ostial sulcus acusticus that opens to the anterior/ dorsal margin. These morphological characters are also found in the Iranian population of S. longiceps. However, otolith displayed variation in biometric parameters among two populations and left and right otoliths and the RRL parameter were important characters to discriminate the Oman and Arabian Sea populations. Thus, the structural/biometrical variability of the otoliths may be used for population distinctness, especially in water bodies with various environmental factors, and the otolith has turned out to be a useful tool to track the life history of teleostean fishes in environments with physicochemical gradients.
Dental hygienists' scope of practice regulations and preventable non‐traumatic dental emergency department visits: A cross‐sectional study of 10 U.S. states
Authors: Akinlotan Marvellous A. , Ferdinand Alva O. , Maxey Hannah L. , Bolin Jane N. , Morrisey Michael A.
Published: March 2022

Objectives

As emergency department (ED) visits for non‐traumatic dental complaints continue to rise in the United States (U.S.), some states are implementing initiatives to expand access to the oral health workforce. This study examines the associations between the 2014 Dental Hygiene Professional Practice Index (DHPPI) and preventable dental ED visits.

Methods

In 2020, we used ED data from 10 U.S. states and ordinary least squares models to examine the relationship between the states’ DHPPI scores and preventable dental ED use. We stratified regressions by age to examine this relationship across different age cohorts and introduced interaction terms to assess the same relationship among rural and urban residents.

Results

On average, 23.8% of all non‐traumatic dental ED visits were identified as preventable. Controlling for other factors, a one‐point increase in DHPPI scores was associated with a decrease of 0.01 (95% CI −0.03, −0.02) preventable dental ED visits per 1000 county population in each year‐quarter. In the age‐stratified models, the strength of the association between DHPPI scores and preventable dental ED visits was higher in the 20 to 34 (−0.03, 95% CI −0.04, −0.02), and the 35 to 50 age cohorts (−0.17, 95% CI −0.00, −0.00). U.S. states with DHPPI scores below 60 saw significantly higher preventable dental ED visits among rural residents.

Conclusions

This study demonstrates that stringent state policies regarding the dental hygienist workforce are associated with higher preventable dental ED visits in the U.S. Policy makers and stake holders must address the scope of practice policies to alleviate the burden of access to oral healthcare.
Intraoperative transfusion management, antifibrinolytic therapy, coagulation monitoring and the impact on short‐term outcomes after liver transplantation—A systematic review of the literature and expert panel recommendations
Authors: Yoon Uzung , Bartoszko Justyna , Bezinover Dmitri , Biancofiore Gianni , Forkin Katherine T. , Rahman Suehana , Spiro Michael , Raptis Dimitri Aristotle , Kang Yoogoo ,   the ERAS4OLT.org Working Group
Published: March 2022

Background

Liver transplantation (LT) is frequently complicated by coagulopathy associated with end‐stage liver disease (ESLD), that is, often multifactorial.

Objectives

The objective of this systematic review was to identify evidence based intraoperative transfusion and coagulation management strategies that improve immediate and short‐term outcomes after LT.

Methods

PRISMA‐guidelines and GRADE‐approach were followed. Three subquestions were formulated. (Q); Q1: transfusion management; Q2: antifibrinolytic therapy; and Q3: coagulation monitoring.

Results

Sixteen studies were included for Q1, six for Q2, and 10 for Q3. Q1: PRBC and platelet transfusions were associated with higher mortality. The use of prothrombin complex concentrate (PCC) and fibrinogen concentrate (FC) were not associated with reductions in intraoperative transfusion or increased thrombotic events. The use of cell salvage was not associated with hepatocellular carcinoma (HCC) recurrence or mortality. Cell salvage and transfusion education significantly decreased blood product transfusions. Q2: Epsilon‐aminocaproic acid (EACA) and tranexamic acid (TXA) were not associated with decreased blood product transfusion, improvements in patient or graft survival, or increases in thrombotic events. Q3: Viscoelastic testing (VET) was associated with decreased allogeneic blood product transfusion compared to conventional coagulation tests (CCT) and is likely to be cost‐effective. Coagulation management guided by VET may be associated with increases in FC and PCC use.

Conclusion

Q1: A specific blood product transfusion practice is not recommended (QOE; low | Recommendation; weak). Cell salvage and educational interventions are recommended (QOE: low | Grade of Recommendation: moderate). Q2: The routine use of antifibrinolytics is not recommended (QOE; low | Recommendation; weak). Q3: The use of VET is recommended (QOE; low‐moderate | Recommendation; strong).
Fish assemblage response to removal of a low‐head dam in the lower reach of a tropical island river
Authors: Cancel Villamil Johann J. , Locke Sean A.
Published: March 2022

Dams are often removed from rivers to restore habitat connectivity for biota such as fish. Removal of inland dams is well studied in temperate mainland rivers but this approach has been little studied in fish assemblages in islands, tropic systems, or for dams near the mouth of the river. In Puerto Rico, one of the most intensively dammed territories in the world, all native river fishes migrate between fresh water and the sea, and previous work shows that these movements are impeded or blocked by dams.

Fish assemblages were compared before and after removal of the Cambalache dam, a porous, low‐head structure near the mouth of the Río Grande de Arecibo, as well as in two other rivers in western Puerto Rico, one with a similarly sized and positioned dam, and one reference river without artificial barriers. Fish were sampled using backpack electrofishing on 39 occasions during 2017–2019, including seven samples collected after removal of the Cambalache dam, at four to six sites per river.

Fish assemblages upstream from dams were poorer in species, and species richness showed a marginal tendency (p = 0.0515) to increase upstream of the Cambalache dam 3 months after its removal. The two small lowland dams studied herein limited the upstream extent of marine species, which recolonised upstream sites of the Río Grande de Arecibo after removal of the Cambalache dam. An estimate of relative density (catch per unit effort) of common native freshwater species was higher above these two dams, and decreased at upstream sites after removal of the Cambalache dam. The estimated relative density of a native freshwater species that is of conservation concern, the American eel (Anguilla rostrata), was reduced above dams, and increased upstream of the former Cambalache dam after its removal.

In extensive surveys conducted previously in Puerto Rico, sampling was concentrated higher in the catchment, and native fishes were more common and abundant below than above dams. The present work was conducted near the river mouth, and opposite results were observed. These contrasting results suggest that the effects of dams (or dam removal) on fish assemblages vary along the river gradient, although data from other systems are needed to confirm this.

The present results suggest low‐head dam removal to be a viable method of restoring connectivity in fish assemblages in lower reaches of rivers in Puerto Rico and, potentially, other tropical islands. Removal of dams near the mouth of the river appears to be of particular benefit to marine fish species that use lower river reaches.