bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractOxidative 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.ImportanceTrmB-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

AbstractCandida 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

Abstract

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.
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

AbstractObjectiveTo 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.DataPublic data on hospitals in the HRRP.DesignWe 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 CollectionPublic data on hospital characteristics and readmission rates for 3119 hospitals from 2019 to 2020.Principal FindingsThe 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.ConclusionsPeer 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

AbstractAimTo identify risk factors associated with surgical site infections in paediatric patients subjected to appendectomy.Methods and MaterialsWe 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.ResultsWe 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).ConclusionsRisk 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

AbstractIntroductionThe 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.MethodsEleven eligible patients were enrolled. DCs were administered every 2–3 weeks with OK‐432 adjuvant.ResultsThe 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.ConclusionThese 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

AbstractMammalian 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

AbstractProblemTo 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 studyFemale 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.ResultsActive 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.ConclusionThese 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

AbstractScale 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

AbstractObjectivesAs 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.MethodsIn 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.ResultsOn 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.ConclusionsThis 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

AbstractBackgroundLiver transplantation (LT) is frequently complicated by coagulopathy associated with end‐stage liver disease (ESLD), that is, often multifactorial.ObjectivesThe 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.MethodsPRISMA‐guidelines and GRADE‐approach were followed. Three subquestions were formulated. (Q); Q1: transfusion management; Q2: antifibrinolytic therapy; and Q3: coagulation monitoring.ResultsSixteen 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.ConclusionQ1: 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).