bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the rate and reversibility of large‐herbivore effects on community composition in a semi‐arid grassland ecosystem
Authors: Wilmer Hailey , Augustine David J. , Derner Justin D. , Milchunas Daniel G.
Published: August 2020

Questions

What are the rate, reversibility, and degree of symmetry in plant species compositional change in response to the addition and removal of cattle grazing in the shortgrass steppe? Specifically, how does the imposition and removal of grazing affect the abundance of perennial C4 shortgrasses and C3 midgrasses that are of primary importance for livestock production in the region?

Location

Shortgrass steppe, northeastern Colorado, USA, in the North American Great Plains.

Methods

We evaluate rates and magnitude of basal cover change in newly ungrazed and newly grazed sites (established in 1991), relative to change in long‐term (grazed and ungrazed) comparison treatments (established in 1939) over 25 years. We also compare shifts in species basal cover in newly implemented treatments relative to baseline community composition measured at the start of the study.

Results

Unlike the limited change observed in long‐term treatments between 1939 and 1991, we documented more rapid, reversible and largely symmetric effects of both the imposition and removal of grazing between 1992 and 2017. This was primarily due to differences in the rate of increase in basal cover of C3 midgrasses, litter, and bare ground. However, the rate and direction of change differed when assessed relative to continuously evaluated and (early‐treatment) baseline cover data.

Conclusions

Studies of plant community change in response to large‐herbivore grazing under varying ecological conditions and management regimes are needed to effectively guide the development and revision of state‐and‐transition models (STMs) for grassland managers, and to better detect and plan for dynamic ecological conditions. Effective adaptive management and STM development under a changing climate will recognize that effects of grazing and removal of grazing on shortgrass steppe can be reversible in a relatively symmetrical pattern, occurring within 6–16 years.
‘I'm unworthy of being in this space’: The origins of shame in medical students
Authors: Bynum William E. , Varpio Lara , Lagoo Janaka , Teunissen Pim W.
Published: August 2020

Objectives

Shame results from a negative global self‐evaluation and can have devastating effects. Shame research has focused primarily on graduate medical education, yet medical students are also susceptible to its occurrence and negative effects. This study explores the development of shame in medical students by asking: how does shame originate in medical students? and what events trigger and factors influence the development of shame in medical students?

Methods

The study was conducted using hermeneutic phenomenology, which seeks to describe a phenomenon, convey its meaning and examine the contextual factors that influence it. Data were collected via a written reflection, semi‐structured interview and debriefing session. It was analysed in accordance with Ajjawi and Higgs' six steps of hermeneutic analysis: immersion, understanding, abstraction, synthesis, illumination and integration.

Results

Data analysis yielded structural elements of students' shame experiences that were conceptualised through the metaphor of fire. Shame triggers were the specific events that sparked shame reactions, including interpersonal interactions (eg, receiving mistreatment) and learning (eg, low test scores). Shame promoters were the factors and characteristics that fuelled shame reactions, including those related to the individual (eg, underrepresentation), environment (eg, institutional expectations) and person‐environment interaction (eg, comparisons to others). The authors present three illustrative narratives to depict how these elements can interact to lead to shame in medical students.

Conclusions

This qualitative examination of shame in medical students reveals complex, deep‐seated aspects of medical students' emotional reactions as they navigate the learning environment. The authors posit that medical training environments may be combustible, or possessing inherent risk, for shame. Educators, leaders and institutions can mitigate this risk and contain damaging shame reactions by (a) instilling a true sense of belonging and inclusivity in medical learning environments, (b) facilitating growth mindsets in medical trainees and (c) eliminating intentional shaming in medical education.
Pharyngeal and upper esophageal sphincter motor dynamics during swallow in children
Authors: Damrongmanee Alisara , El‐Chammas Khalil , Fei Lin , Zang Huaiyu , Santucci Neha , Kaul Ajay
Published: August 2020

Background

Motor abnormalities of pharyngeal contraction or upper esophageal sphincter (UES) relaxation can lead to swallowing problems.

Methods

We reviewed high‐resolution esophageal manometry of children ≤18 years and classified into two groups based on the results of videofluoroscopic study of swallow (VFSS), as normal or abnormal. The UES metrics (integrated relaxation pressure [IRP], resting pressure [URP], and nadir pressure [UNP]), as well as peak pharyngeal pressure (velopharyngeal and meso‐hypopharyngeal), were analyzed.

Results

UES metrics: There were 142 and 19 subjects in the normal and abnormal groups, respectively. In the normal group, the median UES‐IRP at 0.2, 0.4, 0.6, 0.8 seconds, URP, and UNP were 1.0, 4.0, 11.0, 18.0, 53.5, and −1.0 mm Hg while in the abnormal group were 10.0, 13.0, 21.0, 25.5, 47.0, and 8.0 mm Hg. The UES‐IRP at 0.2, 0.4, 0.6 seconds, and UNP was significantly higher in the abnormal group.

Pharyngeal metrics: We included 58 subjects in normal and 10 subjects in the abnormal group. The median of peak velopharyngeal and meso‐hypopharyngeal pressures were lower in the abnormal group; 188.50 vs 210.50, P = .185 and 110.00 vs 144.75 mm Hg, P = .065.

Conclusions and Inferences

The UES‐IRP was lower than adults, URP was higher than preterm but less than adults, and UNP was lower than neonates but similar to adults. The pharyngeal pressures were higher than those reported for neonates and adults. Our data indicate that motor dynamics of swallowing may change from neonates to adulthood and reflect a maturational process. The subjects with abnormal VFSS had significantly higher UES‐IRP and UNP compared to normal VFSS.
Decreased smooth muscle function, peristaltic activity, and gastrointestinal transit in dystrophic (mdx) mice
Authors: Singh Kulpreet , Randhwa Gurpreet , Salloum Fadi N. , Grider John R. , Murthy Karnam S.
Published: August 2020

Background

Duchenne muscular dystrophy (DMD) is characterized by the lack of dystrophin in skeletal, cardiac, and smooth muscle. Slow colonic transit and constipation are common in DMD patients and animal models of DMD. However, the cause of this hypocontractility and the expression of contractile proteins in smooth muscle are unknown. The aim of the study was to investigate the expression of contractile proteins in the colonic smooth muscle and the function of the colon in control and mdx mice.

Methods

Muscle contraction was measured in muscle strips and isolated muscle cells. Peristaltic activity was measured in ex vivo preparations by spatiotemporal mapping, and gastrointestinal (GI) transit in vivo was measured by the distribution of fluorescent marker along the intestine and colon. mRNA expression of contractile proteins smoothelin, caldesmon, calponin, and tropomyosin was measured by qRT‐PCR.

Results

Expression of mRNA for contractile proteins was decreased in colonic smooth muscle of mdx mice compared with control. Contraction in response to acetylcholine and KCl was decreased in colonic muscle strips and in isolated muscle cells of mdx mice. Distension of ex vivo colons with Krebs buffer induced peristalsis in both control and mdx mice; however, significantly fewer full peristaltic waves were recorded in the colons of mdx mice. GI transit was also inhibited in mdx mice.

Conclusion and Inferences

The data indicate that the lack of dystrophin causes decrease in colonic smooth muscle contractility, peristalsis, and GI transit and provides the basis for analysis of mechanisms involved in smooth muscle dysfunction in DMD.
Turgor – a limiting factor for radial growth in mature conifers along an elevational gradient
Authors: Peters Richard L. , Steppe Kathy , Cuny Henri E. , De Pauw Dirk J.W. , Frank David C. , Schaub Marcus , Rathgeber Cyrille B.K. , Cabon Antoine , Fonti Patrick
Published: August 2020

A valid representation of intra‐annual wood formation processes in global vegetation models is vital for assessing climate change impacts on the forest carbon stock. Yet, wood formation is generally modelled with photosynthesis, despite mounting evidence that cambial activity is rather directly constrained by limiting environmental factors.

Here, we apply a state‐of‐the‐art turgor‐driven growth model to simulate 4 yr of hourly stem radial increment from Picea abies (L.) Karst. and Larix decidua Mill. growing along an elevational gradient. For the first time, wood formation observations were used to validate weekly to annual stem radial increment simulations, while environmental measurements were used to assess the climatic constraints on turgor‐driven growth.

Model simulations matched the observed timing and dynamics of wood formation. Using the detailed model outputs, we identified a strict environmental regulation on stem growth (air temperature > 2°C and soil water potential > −0.6 MPa). Warmer and drier summers reduced the growth rate as a result of turgor limitation despite warmer temperatures being favourable for cambial activity.

These findings suggest that turgor is a central driver of the forest carbon sink and should be considered in next‐generation vegetation models, particularly in the context of global warming and increasing frequency of droughts.
Vortioxetine versus other antidepressants in the treatment of burning mouth syndrome: An open‐label randomized trial
Authors: Adamo Daniela , Pecoraro Giuseppe , Coppola Noemi , Calabria Elena , Aria Massimo , Mignogna Michele
Published: August 2020

Objectives

This randomized open‐label trial compared the efficacy and tolerability of vortioxetine (15 mg/daily) with different antidepressants in the treatment of patients with burning mouth syndrome (BMS).

Methods

One and hundred fifty BMS patients were randomized into five groups and treated with either vortioxetine, paroxetine (20 mg/daily), sertraline (50 mg/daily), escitalopram (10 mg/daily) or duloxetine (60 mg/daily). The Visual Analogue Scale (VAS), Total Pain Rating Index (T‐PRI), Hamilton Rating Scales for Depression (HAM‐D) and Anxiety (HAM‐A), and Clinical Global Impression Improvement (CGI‐I) and Efficacy scales (CGI‐E) were performed at baseline and after 2, 4, 6, and 12 months of treatment. Any adverse events (AEs) were tabulated for each group. Descriptive statistics, including the Kruskal–Wallis non‐parametric test and the Friedman non‐parametric test for median comparisons between different times, were used.

Results

All the antidepressants (AD) were associated with a significant decrease in the VAS, T‐PRI, HAM‐A, HAM‐D, CGI‐I, and CGI‐E scores in the long‐term (p < .001). However, the response rate of the vortioxetine group showed a significant reduction after six months. The medians, after 6 months, were as follows: VAS 0.0; T‐PRI 2.0; HAM‐A 7.0; HAM‐D 7.0; CGI‐I 1.0; and CGI‐E 1.0 with a lower incidence of AEs (p < .019).

Conclusion

Vortioxetine was efficacious with a shorter latency of action and fewer AEs compared with other ADs.
Direct‐acting oral anti‐coagulants in dental practice: A Retrospective Observational Study (Part 1)
Authors: Kim Tony , Finkelman Matthew , Desai Bhavik , Farag Arwa
Published: August 2020

Objectives

The objective of this retrospective observational study was to determine the incidence of direct‐acting oral anti‐coagulant (DOA) use in patients receiving invasive dental procedures. The secondary objective was to investigate the precautionary measures implemented and the post/intraoperative complications associated with DOA use.

Methods

Electronic record database, Axium, was retrospectively reviewed, and patients using NGOA and treated between 2010 and 2017 were identified. Charts of patients who underwent invasive dental procedures were further reviewed to investigate the preoperative/intraoperative precautionary measures taken and identify any intraoperative/postoperative complications.

Results

A total of 130 patients were identified, with their annual number steadily rising from 12 in 2011 to 52 in 2016. Among those, 64 patients (49.23%) underwent invasive dental procedures. Pretreatment medical consults were obtained in all patients undergoing invasive procedures; however, only 7 (10.94%) were instructed to discontinue their DOA. Preoperative laboratory testing was obtained for two patients. Intraoperatively, 34 (53.13%) cases of excessive bleeding were reported, all were locally controlled with hemostatic agents. Only 4 instances of postoperative complications were documented.

Conclusions

Despite the rise in the use of DOA, there is no consistent pattern for preoperative laboratory testing and DOA discontinuations. Expert consensus may be of great importance to develop practice guidelines.
Non‐impacted tooth extractions and antibiotic treatment: A RCT study
Authors: Cinquini Chiara , Marchionni Saverio , Derchi Giacomo , Miccoli Mario , Gabriele Mario , Barone Antonio
Published: August 2020

Objectives

A controlled, single‐blind, randomized clinical trial was performed to evaluate usefulness of antibiotics in preventing pain and complications after tooth extractions and benefits of probiotics in reducing gastro‐intestinal symptoms associated with antibiotic therapy.

Materials and methods

A total of 159 patients were enrolled in this trial. After tooth extractions, patients were allocated to one of the groups: group 1 received postoperatively amoxicillin + clavulanic acid; group 2 received the same antibiotic therapy with an adjunctive probiotic treatment; and group 3 received neither antibiotics nor probiotics. Follow‐up visits were planned at 7, 14, and 21 days after tooth extractions (T1, T2, and T3), and parameters assessed were pain, presence of abscess, edema, fever, alveolitis, trismus, pain, difficulty in daily routine activities, and gastro‐intestinal symptoms.

Results

The number of patients reporting pain at T1 was significantly higher in the control group when compared to group 2 (p = .016), while no difference for pain intensity was observed between groups. No surgical site infection was observed in any of the groups. Intestinal symptoms seemed to be tackled by probiotic administration.

Conclusions

Pain was the most important symptom in the control group. Antibiotics were not necessary after non‐impacted tooth extractions, and probiotics can reduce gastro‐intestinal symptoms associated with antibiotics.
Metastasis to the oral and maxillofacial region: A systematic review
Authors: Kirschnick Laura Borges , Schuch Lauren Frenzel , Cademartori Mariana Gonzalez , Vasconcelos Ana Carolina Uchoa
Published: August 2020

Objectives

The purpose of this systematic review was to incorporate the information published on metastatic lesions in the in the oral and maxillofacial region into a comprehensive analysis of their demographic, clinical, and imaginological features and survival rate.

Materials and methods

An electronic search was undertaken in the subsequent databases: PubMed, Web of Science, Scopus, EMBASE, and LILACS. All papers included were case reports or case series. Absolute and relative frequencies were obtained by descriptive analysis. Overall survival was defined by the Kaplan–Meier method.

Results

This systematic review identified 217 studies from 33 countries, comprising 348 cases. Male individuals were more affected (n = 199/57.68%) in the 5th to 7th decades of life. The most usual primary site was the lung in men (n = 49/14.08%) and the breast in women (n = 40/11.49%). Jawbones were affected in 183 cases (53.19%), with the posterior mandible (n = 96/66.66%) representing the preferred site. In soft tissues, the gingiva (n = 80/23.25%) was more affected. Clinical presentation was a nodular mass with or without ulceration (n = 280/85.89%). Imaginological examinations revealed radiolucent/hypodense lesions (n = 115/59.28%). The mean survival time was eight months.

Conclusion

Despite the rare occurrence of metastatic lesions in the oral and maxillofacial region, the current systematic review offers substantial data that could assist clinicians and surgeons.
Nurses’ perceptions of their role in functional focused care in hospitalised older people: An integrated review
Authors: Swoboda Nicholas Leo , Dahlke Sherry , Hunter Kathleen F.
Published: August 2020

Aim

The aim of this integrative review was to identify nurses’ perspectives of their role in influencing the functional status of hospitalised older people.

Methods

An integrative review using Whittemore and Knafls’ method was conducted using EBSCOhost CINAHL, Ovid MEDLINE(R), EBSCOhost, Social Gerontology, Cochrane Database of Systematic Reviews and ProQuest Dissertations & Theses data bases. Only studies with nurses’ perspectives, or beliefs about their role in function‐focused care were included. Content analysis was used to develop the themes nurses’ role in function‐focused care and barriers to functional care.

Results

The review found 12 relevant articles. Nurses believed that they were responsible for function‐focused care, yet functional care tasks were often missed. Organisational contexts created many barriers to providing function‐focused care for patients. Nurses felt powerless to address these overarching problems in their organisations.

Conclusion

Nurses understand the importance of functional care yet often fail to carry out functional care interventions. Lack of organisational support creates a workplace that is short on staff, time and equipment and does not prioritise functional care needs. Nurse leaders and healthcare organisations need to reprioritise function‐focused care for the good of patients, families and healthcare budgets.
The use of non‐surgical interventions in patients with peri‐implantitis; a systematic review and meta‐analysis
Authors: Almershed Nizar , Adams Robert , Mort Joelle , Farnell Damian , Thomas David W , Claydon Nicholas
Published: August 2020

Objectives

To systematically assess the efficacy of different non‐surgical treatment methods to manage peri‐implantitis reported to date in the literature, together with its correlation with time following therapy.

Materials and Methods

A systematic literature review was undertaken to identify randomised control trials of the non‐surgical management of peri‐implantitis published up to November 2019. The search was limited to English language human studies containing follow‐up periods of ≥3 months and for sample size of 10 or more patients. A meta‐analysis was implemented for the following clinical parameters: Peri‐implant pocket depth (PPD), bleeding on probing (BOP), clinical attachment level (CAL), radiographic bone loss (RBL) and mucosal recession (MR).

Results

Twelve articles met the inclusion criteria. Two principal treatment modalities were identified; mechanical debridement and laser therapy, with two adjunctive therapies antimicrobial and antiseptic agents. Non‐surgical interventions (ultrasonic scalers, Er:YAG laser and powdered air‐abrasive devices) showed significant clinical improvement in the short term (<3 months). Clinical benefit was demonstrated with the adjunctive use of antimicrobial agents in the short term but diminished with time. Antiseptic agents alone have no significant effect. Non‐surgical therapies applied in these studies failed to arrest mucosal recession, peri‐implant bone loss or reduce the counts of viable pathogens in the long term.

Conclusion

The evidence demonstrate that the clinical parameters of peri‐implantitis, i.e. BOP, PPD and CAL may all be improved by simple mechanical debridement, using either ultrasonic instrumentation or Er:YAG laser therapy; adjunctive antimicrobial and antiseptic therapy. Further randomised control trials in this area are, however, required.
Time‐ and frequency‐domain analysis of repolarization phase during recovery from exercise in healthy subjects
Authors: Piccirillo Gianfranco , Moscucci Federica , Iorio Claudia Di , Fabietti Marcella , Mastropietri Fabiola , Crapanzano Davide , Bertani Gaetano , Sabatino Teresa , Zaccagnini Giulia , Lospinuso Ilaria , Magrì Damiano
Published: August 2020

Background/aim

Recently, data from temporal dispersion of myocardial repolarization analysis have gained a capital role in the sudden cardiac death risk stratification. Aim of this study was to evaluate the influence of heart rate, autonomic nervous system, and controlled breathing on different myocardial repolarization markers in healthy subjects.

Method

Myocardial repolarization dispersion markers from short‐period (5 minutes) electrocardiogram (ECG) analysis (time and frequency domain) have been obtained in 21 healthy volunteers during the following conditions: free breathing (rest); controlled breathing (resp); the first 5 minutes of postexercise recovery phases (exercisePeak), maximum sympathetic activation; and during the second 5 minutes of postexercise recovery phases (exerciseRecovery), intermediate sympathetic activation. Finally, we analyzed the whole repolarization (QTe), the QT peak (QTp), and T peak ‐ T end intervals (Te).

Results

During the exercisePeak, major part of repolarization variables changed in comparison to the rest and resp conditions. Particularly, QTe, QTp, and Te standard deviations (QTeSD, QTpSD, and TeSD); variability indexes (QTeVI and QTpVI), normalized variances (QTeVN, QTpVN, and TeVN); and the ratio between short‐term QTe, QTp, and Te variability RR (STVQTe/RR, STVQTp/RR, and STVTe/RR) increased. During exerciseRecovery, QTpSD (P < .05), QTpVI (P < .05), QTeVN (P < .05), QTpVN (P < .001), TeVN (P < .05), STVQTe/RR (P < .05), STVQTp/RR (P < .001), and STVTe/RR (P < .001) were significantly higher in comparison to the rest. The slope between QTe (0.24 ± 0.06) or QTp (0.17 ± 0.06) and RR were significantly higher than Te (0.07 ± 0.06, P < .001).

Conclusion

Heart rate and sympathetic activity, obtained during exercise, seem able to influence the time domain markers of myocardial repolarization dispersion in healthy subjects, whereas they do not alter any spectral components.
Rate‐dependent aberrancy and cardiac resynchronization therapy
Authors: Haseeb Sohaib , Gul Enes Elvin
Published: August 2020

Left bundle branch block (LBBB) can result in significant dyssynchrony in left ventricular (LV) contraction, ultimately leading to cardiac remodeling. LBBB can be rate dependent and may appear with LV systolic dysfunction. Cardiac resynchronization therapy (CRT) has been demonstrated to improve hemodynamics as well as clinical symptoms in patients with LBBB. We describe the case of a 57‐year‐old man who underwent CRT implantation due to exertional dyspnea, rate‐dependent LBBB, and impaired left LV systolic function.
Behind the scene: Paracetamol hypersensitivity in children
Authors: Sipahi Cimen Sevgi , Yucel Esra , Ozceker Deniz , Suleyman Ayse , Hizli Demirkale Zeynep , Sayili Ugurcan , Guler Nermin , Ozdemir Cevdet , Tamay Zeynep Ulker
Published: August 2020

Background

Paracetamol, a non‐steroidal anti‐inflammatory drug, is commonly being used for fever and pain relief worldwide. The aim of this study was to evaluate children with a suspected history of paracetamol hypersensitivity.

Methods

Sixty patients who were referred to our clinic in between January 2015 and December 2018 with a suspected history of paracetamol hypersensitivity were included. Reactions were classified according to the European Network for Drug Allergy (ENDA)/Global Allergy and Asthma European Network classification and European Academy of Allergy and Clinical Immunology (EAACI)/ENDA Position Paper. Diagnoses were confirmed by skin tests and oral challenge tests (OCTs). In those with verified paracetamol hypersensitivity, an OCT with a strong COX‐1 inhibitor was performed to classify the type of the reaction to refer as either selective or cross‐intolerance hypersensitivity. A subsequent OCT with a selective COX‐2 inhibitor was performed in those cross‐intolerant patients to find out a safe alternative drug.

Results

Sixty OCTs with paracetamol were performed to patients with a median age of 8.5 years, and hypersensitivity to paracetamol was verified in 8 patients. Four children were classified as selective responders, and 3 were classified as cross‐intolerant after OCT with a COX‐1 inhibitor. Overall, skin test positivity for paracetamol was detected in only one patient, in whom OCT with paracetamol was negative. In all 3 cross‐intolerant patients, a safe alternative non‐steroidal anti‐inflammatory drug was identified after an OCT with a selective COX‐2 inhibitor.

Conclusion

OCT stands as the gold‐standard procedure in verifying the diagnosis of patients with paracetamol‐induced drug hypersensitivity, as well as, in defining the type of reactions and finding out safe alternative drugs.
Liver failure and x‐linked immunodeficiency type 47
Authors: Gumm Alexis J. , Basel Donald G. , Thakrar Pooja , Suchi Mariko , Telega Grzegorz
Published: August 2020

Patients with defects in the ATP6AP1 gene have rarely been described. ATP6AP1‐related disorders are a subtype of CDG, which result in enzyme deficiencies affecting multiple organ systems ranging from mild to life‐threatening. Of the 13 patients described, all had hepatopathy, but this is the first case to be successfully transplanted. We describe two brothers who developed hyperbilirubinemia shortly after birth and progressed to liver failure, case 1 by 12 months of age, with successful transplant 2 years later, and case 2 by 4 months of age, who passed away while awaiting liver transplant. Both boys were found to have a new variant in the ATP6AP1 gene: c.932/p.Leu311Gln. Although the identified ATP6AP1 gene variant was classified as unknown significance at the time, both children's phenotypes fit with what has been described for ATP6AP1‐related disorders. Therefore, this result appears to have been diagnostic for both boys. This rare type of CDG, X‐linked immunodeficiency type 47 (OMIM #300972), particularly in patients who progress to liver failure requiring transplant, should be included on the differential of liver failure in infants and toddlers, and its gene should be added to the diagnostic workup for such cases.
Calcineurin inhibitor (CNI)‐associated skin cancers: New insights on exploring mechanisms by which CNIs downregulate DNA repair machinery
Authors: Ume Adaku C. , Pugh Jennifer M. , Kemp Michael G. , Williams Clintoria R.
Published: August 2020

The use of the calcineurin inhibitors (CNI) cyclosporine (CsA) and tacrolimus remains a cornerstone in post‐transplantation immunosuppression. Although these immunosuppressive agents have revolutionized the field of transplantation medicine, its increased skin cancer risk poses a major concern. A key contributor to this phenomenon is a reduced capacity to repair DNA damage caused by exposure to ultraviolet (UV) wavelengths of sunlight. CNIs decrease DNA repair by mechanisms that remain to be fully explored. Though CsA is known to decrease the abundance of key DNA repair enzymes, less is known about how tacrolimus yields this effect. CNIs hold the capacity to inhibit both of the main catalytic calcineurin isoforms (CnAα and CnAβ). However, it is unknown which isoform regulates UV‐induced DNA repair, which is the focus of this review. It is with hope that this insight spurs investigative efforts that conclusively addresses these gaps in knowledge. Additionally, this research also raises the possibility that newer CNIs can be developed that effectively blunt the immune response while mitigating the incidence of skin cancers with immunosuppression.
ApoE deficiency promotes hepatic pathology by aggravating Th17/Treg imbalance in murine schistosomiasis japonica
Authors: Guan Fei , Zhang Chongyang , Jiang Chunjie , Jacques Muziazia Lupemba , Bai Yang , Lu Shengjun , Liu Wenqi , Lei Jiahui
Published: August 2020

Aims

The Schistosoma japonicum (S japonicum)‐infected ApoE gene deficiency (ApoE−/−) mice were used to determine effect of ApoE on hepatic immunopathology.

Methods

Murine activities and appetite, body weight, and ratio of liver weight to its body weight (Hepatic mass index, HMI) were observed. Worm load and liver egg burden were evaluated as the infection intensity. Number and size of liver egg granulomas and serum levels of alanine aminotransferase (ALT) were investigated. We analysed hepatic fibrosis by markers of fibrosis in tissue, detected hepatic Th17 and Treg frequency by flow cytometry, and measured hepatic expressions of RORγt, Foxp3, IL‐17A and TGF‐β1 via qPCR. Lipid metabolism was determined by serum levels of cholesterol (TC) and triglyceride (TG) as well as hepatic Oil red O staining.

Results

In the infected ApoE−/− mice, the increased infection intensity aggravated the hepatic immunopathology (evidenced by increased HMI, elevated egg granulomas and increased ALT levels) and fibrosis (increased hepatic collagen deposition). ApoE deficiency resulted in significantly elevated ratio of hepatic Th17/Treg and higher serum levels of TC and TG, along with higher level of hepatic Oil red O staining.

Conclusions

ApoE deficiency promotes hepatic pathology and fibrosis by exacerbating Th17/Treg imbalance and altering lipid metabolism in murine schistosomiasis japonica.
A molecular epidemiology study reveals the presence of identical genotypes on grapevines and ground cover weeds and the existence of separate genetic groups in a Botrytis cinerea population
Authors: Toffolatti Silvia L. , Maddalena Giuliana , Marcianò Demetrio , Passera Alessandro , Quaglino Fabio
Published: August 2020

Botrytis cinerea, the grey mould agent, is one of the most important pathogens of grapevine, due to the great yield losses caused and the economic costs related to disease control. Ground cover plants are assumed to have a role in the complex epidemiology of the pathogen, even if no information on the genetic variability of the strains is available. In this study, a molecular epidemiology approach, based on the comparative analysis of the nucleotide sequences of multiple genes (ITS1‐ITS2, G3PDH, NEP1, NEP2, BC‐hch, and sdhB), was used to evaluate whether B. cinerea isolated from herbaceous species contributes to grey mould diffusion on grapevines. From 330 samples collected in two vineyards in Lombardy, Italy, 63 B. cinerea strains were isolated from tissues of grapevine with symptoms (50 strains) and spontaneous ground cover plants (13 strains). Capsella bursa‐pastoris, Cardamine impatiens, Lamium purpureum, and Crepis tectorum were identified as novel B. cinerea hosts. Sequence analysis and phylogeny showed that the same genotypes were present on both grapevines and herbaceous plants, with no fitness (estimated from growth and sporulation on potato dextrose agar) or pathogenicity (on grapevine leaves and berries, and tomato leaves) penalties. This confirms that ground cover plants can be a source of inoculum for B. cinerea on grapevine. Moreover, phylogenetic analysis of the BC‐hch gene allowed the identification of two genetically distinct clusters, characterized by vegetative incompatibility and different distributions of the mating types, fitness, and pathogenicity. Therefore, B. cinerea seems to be composed of two diverging subpopulations that do not differ for host specialization.
Testing the top‐down contingent capture of attention for abrupt‐onset cues: Evidence from cue‐elicited N2pc
Authors: Goller Florian , Schoeberl Tobias , Ansorge Ulrich
Published: August 2020

Many studies using N2pc as a marker of attentional capture have demonstrated top‐down contingent capture for salient color singletons: Among all salient cues that are not predictive of the target location, only cues similar to searched‐for target features, and thus, matching to the top‐down attentional control settings capture attention. This is reflected in matching cue's elicitation of an N2pc and a cueing effect in behavior, and the absence of the corresponding effects for non‐matching cues (with features dissimilar to that of the searched‐for targets). Yet, with abrupt‐onset cues, corresponding evidence is missing, inviting speculations about the potential of abrupt‐onset cues to capture attention followed by quick suppression within the target displays. Here, we used two types of abrupt‐onset cues to test if capture by such cues also adheres to the contingent‐capture principle: matching abrupt‐onset cues with a color similar to the top‐down control settings and non‐matching abrupt‐onset cues with a color different from all searched‐for targets. With the help of these cues, top‐down contingent capture was supported. Only matching abrupt‐onset cues elicited an N2pc and a behavioral cueing effect. Depending on the exact side conditions, non‐matching cues either elicited no N2pc or a PD (i.e., evidence of active suppression). Results are discussed against the background of competing theories on attention capture by abrupt‐onset cues.
The role of shelf morphology on storm‐bed variability and stratigraphic architecture, Lower Cretaceous, Svalbard
Authors: Grundvåg Sten‐Andreas , Jelby Mads E. , Olaussen Snorre , Śliwińska Kasia K.
Published: August 2020

The dominance of isotropic hummocky cross‐stratification, recording deposition solely by oscillatory flows, in many ancient storm‐dominated shoreface–shelf successions is enigmatic. Based on conventional sedimentological investigations, this study shows that storm deposits in three different and stratigraphically separated siliciclastic sediment wedges within the Lower Cretaceous succession in Svalbard record various depositional processes and principally contrasting sequence stratigraphic architectures. The lower wedge is characterized by low, but comparatively steeper, depositional dips than the middle and upper wedges, and records a change from storm‐dominated offshore transition – lower shoreface to storm‐dominated prodelta – distal delta front deposits. The occurrence of anisotropic hummocky cross‐stratification sandstone beds, scour‐and‐fill features of possible hyperpycnal‐flow origin, and wave‐modified turbidites within this part of the wedge suggests that the proximity to a fluvio‐deltaic system influenced the observed storm‐bed variability. The mudstone‐dominated part of the lower wedge records offshore shelf deposition below storm‐wave base. In the middle wedge, scours, gutter casts and anisotropic hummocky cross‐stratified storm beds occur in inferred distal settings in association with bathymetric steps situated across the platform break of retrogradationally stacked parasequences. These steps gave rise to localized, steeper‐gradient depositional dips which promoted the generation of basinward‐directed flows that occasionally scoured into the underlying seafloor. Storm‐wave and tidal current interaction promoted the development and migration of large‐scale, compound bedforms and smaller‐scale hummocky bedforms preserved as anisotropic hummocky cross‐stratification. The upper wedge consists of thick, seaward‐stepping successions of isotropic hummocky cross‐stratification‐bearing sandstone beds attributed to progradation across a shallow, gently dipping ramp‐type shelf. The associated distal facies are characterized by abundant lenticular, wave ripple cross‐laminated sandstone, suggesting that the basin floor was predominantly positioned above, but near, storm‐wave base. Consequently, shelf morphology and physiography, and the nature of the feeder system (for example, proximity to deltaic systems) are inferred to exert some control on storm‐bed variability and the resulting stratigraphic architecture.
A model to predict SARS‐CoV‐2 infection based on the first three‐month surveillance data in Brazil
Authors: Diaz‐Quijano Fredi A. , da Silva José M. N. , Ganem Fabiana , Oliveira Silvano , Vesga‐Varela Andrea L. , Croda Julio
Published: August 2020

Objective

COVID‐19 diagnosis is a critical problem, mainly due to the lack or delay in the test results. We aimed to obtain a model to predict SARS‐CoV‐2 infection in suspected patients reported to the Brazilian surveillance system.

Methods

We analysed suspected patients reported to the National Surveillance System that corresponded to the following case definition: patients with respiratory symptoms and fever, who travelled to regions with local or community transmission or who had close contact with a suspected or confirmed case. Based on variables routinely collected, we obtained a multiple model using logistic regression. The area under the receiver operating characteristic curve (AUC) and accuracy indicators were used for validation.

Results

We described 1468 COVID‐19 cases (confirmed by RT‐PCR) and 4271 patients with other illnesses. With a data subset including 80% of patients from Sao Paulo (SP) and Rio Janeiro (RJ), we obtained a function which reached an AUC of 95.54% (95% CI: 94.41–96.67%) for the diagnosis of COVID‐19 and accuracy of 90.1% (sensitivity 87.62% and specificity 92.02%). In a validation dataset including the other 20% of patients from SP and RJ, this model exhibited an AUC of 95.01% (92.51–97.5%) and accuracy of 89.47% (sensitivity 87.32% and specificity 91.36%).

Conclusion

We obtained a model suitable for the clinical diagnosis of COVID‐19 based on routinely collected surveillance data. Applications of this tool include early identification for specific treatment and isolation, rational use of laboratory tests, and input for modelling epidemiological trends.
Subclinical bacteriuria and surgical site infections in dogs with cranial cruciate ligament disease
Authors: Garcia Cheslymar , Benitez Marian E. , Grant David C. , Barry Sabrina L.
Published: August 2020

Objective

To determine the prevalence of subclinical bacteriuria (SBU) in dogs with cranial cruciate ligament (CCL) disease, the clinical variables and clinicopathologic data associated with SBU, and the incidence of surgical site infections (SSI) in dogs with and without SBU.

Study design

Prospective, clinical cohort study.

Animals

One hundred fifty‐five dogs with CCL disease.

Methods

Dogs had a urinalysis, sediment examination, and aerobic urine culture performed. Age, breed, sex, body weight, body condition score, clinical history, and physical examination findings were recorded. Dogs with SBU were not treated for bacteriuria or with postoperative antibiotics. Standard perioperative antimicrobials were provided for all dogs. Dogs that received nonsteroidal anti‐inflammatory drugs were not excluded. Dogs that underwent an osteotomy were followed for at least 1 year to determine incidence of SSI. Outcomes and variables associated with SBU were assessed.

Results

In 155 dogs with CCL disease, the prevalence of SBU was 6.5%, and SBU occurred exclusively in female dogs (11.4%). The incidence of SSI was 22.3% (25/112). Two of six dogs with SBU and 23/106 dogs without SBU developed SSI. Organisms isolated from SSI were different from those isolated from urine.

Conclusion

The prevalence of SBU in dogs with CCL disease was similar to that in other studies in which SBU was evaluated in various populations of dogs.

Clinical significance

Screening for and treatment of SBU may not be beneficial prior to tibial osteotomy for CCL disease. Additional studies are required to determine whether dogs with SBU have a greater risk of SSI.
Tetraspanin‐7 regulation of L‐type voltage‐dependent calcium channels controls pancreatic β‐cell insulin secretion
Authors: Dickerson Matthew T. , Dadi Prasanna K. , Butterworth Regan B. , Nakhe Arya Y. , Graff Sarah M. , Zaborska Karolina E. , Schaub Charles M. , Jacobson David A.
Published: August 2020

Key points

Tetraspanin (TSPAN) proteins regulate many biological processes, including intracellular calcium (Ca2+) handling. TSPAN‐7 is enriched in pancreatic islet cells; however, the function of islet TSPAN‐7 has not been identified.

Here, we characterize how β‐cell TSPAN‐7 regulates Ca2+ handling and hormone secretion. We find that TSPAN‐7 reduces β‐cell glucose‐stimulated Ca2+ entry, slows Ca2+ oscillation frequency and decreases glucose‐stimulated insulin secretion.

TSPAN‐7 controls β‐cell function through a direct interaction with L‐type voltage‐dependent Ca2+ channels (CaV1.2 and CaV1.3), which reduces channel Ca2+ conductance. TSPAN‐7 slows activation of CaV1.2 and accelerates recovery from voltage‐dependent inactivation; TSPAN‐7 also slows CaV1.3 inactivation kinetics.

These findings strongly implicate TSPAN‐7 as a key regulator in determining the set‐point of glucose‐stimulated Ca2+ influx and insulin secretion.

Glucose‐stimulated insulin secretion (GSIS) is regulated by calcium (Ca2+) entry into pancreatic β‐cells through voltage‐dependent Ca2+ (CaV) channels. Tetraspanin (TSPAN) transmembrane proteins control Ca2+ handling, and thus they may also modulate GSIS. TSPAN‐7 is the most abundant islet TSPAN and immunostaining of mouse and human pancreatic slices shows that TSPAN‐7 is highly expressed in β‐ and α‐cells; however, the function of islet TSPAN‐7 has not been determined. Here, we show that TSPAN‐7 knockdown (KD) increases glucose‐stimulated Ca2+ influx into mouse and human β‐cells. Additionally, mouse β‐cell Ca2+ oscillation frequency was accelerated by TSPAN‐7 KD. Because TSPAN‐7 KD also enhanced Ca2+ entry when membrane potential was clamped with depolarization, the effect of TSPAN‐7 on CaV channel activity was examined. TSPAN‐7 KD enhanced L‐type CaV currents in mouse and human β‐cells. Conversely, heterologous expression of TSPAN‐7 with CaV1.2 and CaV1.3 L‐type CaV channels decreased CaV currents and reduced Ca2+ influx through both channels. This was presumably the result of a direct interaction of TSPAN‐7 and L‐type CaV channels because TSPAN‐7 coimmunoprecipitated with both CaV1.2 and CaV1.3 from primary human β‐cells and from a heterologous expression system. Finally, TSPAN‐7 KD in human β‐cells increased basal (5.6 mM glucose) and stimulated (45 mM KCl + 14 mM glucose) insulin secretion. These findings strongly suggest that TSPAN‐7 modulation of β‐cell L‐type CaV channels is a key determinant of β‐cell glucose‐stimulated Ca2+ entry and thus the set‐point of GSIS.
Application of kurtosis to underwater sound
Authors: Müller Roel A. J. , von Benda-Beckmann Alexander M. , Halvorsen Michele B. , Ainslie Michael A.
Published: August 2020

Regulations for underwater anthropogenic noise are typically formulated in terms of peak sound pressure, root-mean-square sound pressure, and (weighted or unweighted) sound exposure. Sound effect studies on humans and other terrestrial mammals suggest that in addition to these metrics, the impulsiveness of sound (often quantified by its kurtosis β) is also related to the risk of hearing impairment. Kurtosis is often used to distinguish between ambient noise and transients, such as echolocation clicks and dolphin whistles. A lack of standardization of the integration interval leads to ambiguous kurtosis values, especially for transient signals. In the current research, kurtosis is applied to transient signals typical for high-power underwater noise. For integration time (t2−t1), the quantity (t2−t1)/β is shown to be a robust measure of signal duration, closely related to the effective signal duration, τeff for sounds from airguns, pile driving, and explosions. This research provides practical formulas for kurtosis of impulsive sounds and compares kurtosis between measurements of transient sounds from different sources.
The Relationship Between Neurocognitive Function and Biomechanics: A Critically Appraised Topic
Authors: Porter Ke’La , Quintana Carolina , Hoch Matthew
Published: August 2020

Clinical Scenario: Neurocognitive performance may put individuals at a greater risk for lower-extremity musculoskeletal injuries. Research has observed the relationship between lower-extremity musculoskeletal injury and baseline neurocognitive performance; however, the understanding of this relationship is lacking. Exploring this relationship may give further insight into musculoskeletal injury and provide innovative directions for musculoskeletal injury prevention. Clinical Question: Is there a relationship between neurocognitive performance and lower-extremity biomechanics during a jumping or cutting task in healthy adult athletes? Summary of Key Findings: The literature was searched for articles that examined the relationship of a baseline neurocognitive test and a biomechanical analysis following a sports-related task. A total of 3 cross-sectional articles were included. All 3 studies concluded that poorer neurocognitive performance was associated with biomechanical faults that are linked to increased risk or rate of lower-extremity musculoskeletal injury. Clinical Bottom Line: Based on the evidence included, there is a moderate-level evidence to support the relationship between neurocognition and lower-extremity biomechanics in healthy adult athletes. Strength of Recommendation: In accordance with the van Tulder approach, there is a moderate level of evidence due to consistent findings from a combination of high- and limited-quality articles.
Influenza vaccine–induced human bone marrow plasma cells decline within a year after vaccination
Authors: Davis Carl W. , Jackson Katherine J. L. , McCausland Megan M. , Darce Jaime , Chang Cathy , Linderman Susanne L. , Chennareddy Chakravarthy , Gerkin Rebecca , Brown Shantoria J. , Wrammert Jens , Mehta Aneesh K. , Cheung Wan Cheung , Boyd Scott D. , Waller Edmund K. , Ahmed Rafi
Published: August 2020

Immunity after the flu shot

The seasonal flu shot is currently recommended each year because the influenza viral strains in circulation are continuously changing and because the antibody responses produced by the vaccine decline over time. In a human study of healthy volunteers, Davis
et al.
tracked antibody responses after flu vaccination. They investigated whether the vaccine led to the generation of antibody-secreting plasma cells in the bone marrow, a lymphoid organ that supports the survival of these cells for years. Although vaccination did generate influenza-specific cells, most were short-lived and lost within 1 year. The fact that a small number did persist over 1 year raises prospects that the longevity of flu vaccines can be improved and provides key information for the development of universal vaccines against influenza.

Science
, this issue p.
237
Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy
Authors: Mager Lukas F. , Burkhard Regula , Pett Nicola , Cooke Noah C. A. , Brown Kirsty , Ramay Hena , Paik Seungil , Stagg John , Groves Ryan A. , Gallo Marco , Lewis Ian A. , Geuking Markus B. , McCoy Kathy D.
Published: August 2020

Inosine modulates antitumor immunity

Checkpoint blockade immunotherapy harnesses the immune system to kill cancer cells and has been used with great success to treat certain tumors, but not all cancer patients respond. The efficacy of checkpoint blockade immunotherapy has been shown to depend on the presence of distinct, beneficial bacteria residing in the gut of patients, but how the microbiome mediates such beneficial effects is unclear. Mager
et al.
found that specific bacteria produce a metabolite called inosine that enhances the effect of checkpoint blockade immunotherapy (see the Perspective by Shaikh and Sears). In mouse models, inosine, together with proinflammatory stimuli and immunotherapy, strongly enhanced the antitumor capacities of T cells in multiple tumor types, including colorectal cancer, bladder cancer, and melanoma.

Science
, this issue p.
1481
; see also p.
1427