bluuebunny/crossref_metadata_2025 huggingface dataset:
UVA influenced the SIRT1‐miR‐27a‐5p‐SMAD2‐MMP1/COL1/BCL2 axis in human skin primary fibroblasts
Authors: Jiang Shi‐Bin , Lu Yan‐Song , Liu Tao , Li Liang‐Man , Wang He‐Xiao , Wu Yan , Gao Xing‐Hua , Chen Hong‐duo
Published: August 2020

Both SIRT1 and UVA radiation are involved in cellular damage processes such as apoptosis, senescence and ageing. MicroRNAs (miRNAs) have been reported to be closely related to UV radiation, as well as to SIRT1. In this study, we investigated the connections among SIRT1, UVA and miRNA in human skin primary fibroblasts. Our results showed that UVA altered the protein level of SIRT1 in a time point–dependent manner. Using miRNA microarray, bioinformatics analysis, we found that knocking down SIRT1 could cause up‐regulation of miR‐27a‐5p and the latter could down‐regulate SMAD2, and these results were verified by qRT‐PCR or Western blot. Furthermore, UVA radiation (5 J/cm2), knocking down SIRT1 or overexpression of miR‐27a‐5p led to increased expression of MMP1, and decreased expressions of COL1 and BCL2. We also found additive impacts on MMP1, COL1 and BCL2 under the combination of UVA radiation + Sirtinol (SIRT1 inhibitor), or UVA radiation + miR‐27a‐5p mimic. SIRT1 activator resveratrol could reverse damage changes caused by UVA radiation. Besides, absent of SIRT1 or overexpression of miR‐27a‐5p increased cell apoptosis and induced cell arrest in G2/M phase. Taken together, these results demonstrated that UVA could influence a novel SIRT1‐miR‐27a‐5p‐SMAD2‐MMP1/COL1/BCL2 axis in skin primary fibroblasts, and may provide potential therapeutic targets for UVA‐induced skin damage.
Recommendations for skin cancer consultation and surgery during COVID‐19 pandemic
Authors: Brochez L. , Baurain J.F. , Del Marmol V. , Nikkels A. , Kruse V. , Sales F. , Stas M. , Van Laethem A. , Garmyn M.
Published: August 2020

Linked articles: COVID‐19 SPECIAL FORUM. J Eur Acad Dermatol Venereol 2020; 34: e433–e466.
Extrahepatic autoimmune diseases in primary biliary cholangitis: Prevalence and significance for clinical presentation and disease outcome
Authors: Efe Cumali , Torgutalp Murat , Henriksson Ida , Alalkim Fatema , Lytvyak Ellina , Trivedi Hirsh , Eren Fatih , Fischer Janett , Chayanupatkul Maneerat , Coppo Claudia , Purnak Tugrul , Muratori Luigi , Werner Mårten , Muratori Paolo , Rorsman Fredrik , Onnerhag Kristina , Nilsson Emma , Heurgué‐Berlot Alexandra , Demir Nurhan , Semela David , Kıyıcı Murat , Schiano Thomas D , Montano‐Loza Aldo J , Berg Thomas , Ozaslan Ersan , Yoshida Eric M , Bonder Alan , Marschall Hanns‐Ulrich , Beretta‐Piccoli Benedetta Terziroli , Wahlin Staffan
Published: August 2020

Background and Aim

The prevalence and clinical significance of extrahepatic autoimmune diseases (EHAIDs) have not been evaluated in a large cohort of primary biliary cholangitis (PBC).

Methods

The medical records of 1554 patients with PBC from 20 international centers were retrospectively reviewed. Development of decompensated cirrhosis (ascites, variceal bleeding, and/or hepatic encephalopathy) and hepatocellular carcinoma were considered clinical endpoints.

Results

A total of 35 different EHAIDs were diagnosed in 440 (28.3%) patients with PBC. Patients with EHAIDs were more often female (92.5% vs 86.1%, P < 0.001) and seropositive for anti‐mitochondrial antibodies (88% vs 84%, P = 0.05) and antinuclear antibodies and/or smooth muscle antibodies (53.8% vs 43.6%, P = 0.005). At presentation, patients with EHAIDs had significantly lower levels of alkaline phosphatase (1.76 vs 1.98 × upper limit of normal [ULN], P = 0.006), aspartate aminotransferase (1.29 vs 1.50 × ULN, P < 0.001), and total bilirubin (0.53 vs 0.58 × ULN, P = 0.002). Patients with EHAIDs and without EHAIDs had similar rates of GLOBE high‐risk status (12.3% vs 16.1%, P = 0.07) and Paris II response (71.4% vs 69.4%, P = 0.59). Overall, event‐free survival was not different in patients with and without EHAIDs (90.8% vs 90.7%, P = 0.53, log rank). Coexistence of each autoimmune thyroid diseases (10.6%), Sjögren disease (8.3%), systemic sclerosis (2.9%), rheumatoid arthritis (2.7%), systemic lupus erythematosus (1.7%), celiac disease (1.7%), psoriasis (1.5%), and inflammatory bowel diseases (1.3%) did not influence the outcome.

Conclusions

Our study confirms that EHAIDs are frequently diagnosed in patients with PBC. The presence of EHAIDs may influence the clinical phenotype of PBC at presentation but has no impact on PBC outcome.
Reply to: Antidepressants and Fracture Risk: Is There a Real Connection?
Authors: Tamblyn Robyn , Girard Nadyne , Habib Bettina , Iqbal Usman
Published: August 2020

This letter comments on the letter by Vishnu Sundaresh.
Fiber type composition of contiguous palmaris longus and abductor pollicis brevis muscles: Morphological evidence of a functional synergy
Authors: Moore Colin W. , Fanous Jacob , Rice Charles L.
Published: August 2020

The palmaris longus (PL) tendon is used in surgical opponensplasty to restore functional hand movements in thenar paralysis. Although successful PL autologous tendon transfer has been attributed to an established synergistic relationship between the PL and abductor pollicis brevis (APB) muscles in vivo, this functional relationship may be dependent on the quality of their spatial relationship and properties of their constituent muscle fibers. The purpose was to compare the proportion of type I and type II muscle fibers in the APB based on its contiguous morphological relationship with the PL tendon for indirect insight into their functional synergy, contractile capacity, and digastric arrangement. Twenty‐four contiguous PL and APB specimens were harvested from the upper limbs (12 right and 12 left) of twelve formalin‐embalmed cadavers (mean age: 74 ± 10 years). The fiber type composition of these muscles was determined by labeling serial cross sections with myosin heavy chain (MyHC) type I and type II monoclonal antibodies. The PL consisted of a relatively heterogeneous fiber type composition irrespective of the presence of a discrete (type I: 41 ± 11%; type II: 55 ± 12%; hybrid: 4 ± 3%) or rudimentary (type I: 49 ± 10%; type II: 45 ± 9%; hybrid: 6 ± 4%) tendinous connection with the APB. The APB fascicles arranged contiguously with the PL through a discrete tendon had significantly greater proportions of type II fibers (41 ± 19%) compared to those with rudimentary PL connections (type II: 15 ± 8%). Therefore, the APB fascicles arranged in a digastric relationship with the PL may have the capacity to produce more powerful contractions than those with rudimentary PL tendons based on the known contractile properties of type II muscle fibers. Knowledge of the spatial relationship between the PL and thenar musculature prior to PL autologous tendon transfer may be a useful indicator of the quality of established synergy in vivo.
Subordinated masculinities: A critical inquiry into reproduction of gender norms in handovers and rounds in a forensic psychiatric care
Authors: Eivergård Kristina , Enmarker Ingela , Livholts Mona , Aléx Lena , Hellzén Ove
Published: August 2020

Aims and objectives

To examine how gendered discursive norms and notions of masculinity are (re)produced in professional conversations about men cared for as patients in forensic psychiatric care, with a particular focus on the centrality of language and gender.

Background

During verbal handovers and ward rounds, care staff converse to share information about patients and make decisions about their mental status. Spoken language is thus a pivotal tool in verbal handovers and ward rounds, one able to reproduce discourses and gender norms.

Design

Qualitative. Data collected from audio recordings of verbal handovers and ward rounds in a forensic psychiatric clinic were subjected to discourse analysis. The COREQ checklist was used.

Results

While discussing patients, staff subordinated them by reproducing a discourse typical of heteronormative, family‐oriented care. The overarching discourse, which we labelledsubordinated masculinities, was supported by three other discourses:being unable to take responsibility,being drug‐addictedandperforming masculinity. Such discourse was identified as a disciplining practice that subordinate's patients as a means to maintain order, rules and gender norms.

Conclusion

The study reveals a caring practice that position male patients as children or disabled individuals and, in that way, as subordinated other men within a context were staff reproduces a heteronormative family structured care. The process also reveals a practice were downplaying aggressive and deviant behaviour could disempower and reduce patients´ responsibility for personal actions and their possibilities to participate in their care. That finding especially seems to contradict previous findings that patients want to be able to act responsibly and, to that end, want care staff to help them.

Relevance to clinical practice

Nurses need to deepen their understanding of how language (re)produces discursive norms of gender and masculinity in forensic care and that process's consequences for such care.
Marketing of breast milk substitutes on the internet and television in Mexico
Authors: Lozada‐Tequeanes Ana Lilia , Hernández‐Cordero Sonia , Shamah‐Levy Teresa
Published: August 2020

Aim

We aimed to examine the advertising and marketing of breast milk substitutes (BMS) through the internet, social media and television in Mexico.

Methods

We recorded the programming of four main TV channels at peak times to identify BMS advertisements. In addition, we identified the main BMS products and companies present on the internet, as well as related home pages and social networks (Facebook, Twitter and YouTube). After that, we examined current BMS' marketing practices using the International Code of Marketing of Breast‐milk Substitutes (‘the Code’) as a framework for ethical marketing. Qualitative and statistical analyses are presented.

Results

BMS manufacturers have a presence on television, social media and the internet. Violations of the Code, as well as promotional practices unforeseen by the Code, were identified in all the studied media. These include text and images idealising the use of BMS, as well as mechanisms for boosting sales and making contact with consumers.

Conclusions

The Mexican population is exposed to BMS advertisements that breach the Code on the internet, on social networks and on television. Emerging challenges related to the use of electronic means to market BMS may call for new strategies for monitoring and enforcing the Code through local regulations.
The pretreatment of rats with nebivolol ameliorates bladder contractile dysfunction caused by ischemia‐reperfusion injury
Authors: Altunkaynak‐Camca Hande O. , Yazihan Nuray
Published: August 2020

Objective

The present study aimed to investigate the protective effect of nebivolol in the bladder isolated from rats exposed to ischemia‐reperfusion (IR) injury.

Methods

Sprague‐Dawley rats were divided into control, IR, and nebivolol+IR groups. In the nebivolol+IR group, nebivolol was administered (0.4 mg/kg, subcutaneous) in rats prior to IR insult. At the end of the experimental protocol, the urinary bladder was rapidly isolated and bladder strips were mounted in an organ bath. After the equilibration period, potassium chloride (KCl, 20‐100 mM) or carbachol (0.01‐10 μM) was cumulatively added to the organ bath to generate cumulative concentration‐response curves (CCRCs). Oxidative stress and interleukin 6 (IL‐6) levels were also evaluated in the bladder tissue.

Results

The CCRCs of KCl and carbachol were significantly reduced in the IR group compared to those of the control, and this inhibition was reversed by the pretreatment of rats with nebivolol (P < .05). The IR group's total antioxidant status was significantly lower with a concomitant increase in IL‐6 levels than that of the control and nebivolol+IR groups (P < .05).

Conclusions

The present study indicates that pretreatment of rats with nebivolol (0.4 mg/kg) could improve bladder contractile dysfunction caused by IR injury through suppression of increased oxidative stress and IL‐6 levels.
The hornworts: morphology, evolution and development
Authors: Frangedakis Eftychios , Shimamura Masaki , Villarreal Juan Carlos , Li Fay‐Wei , Tomaselli Marta , Waller Manuel , Sakakibara Keiko , Renzaglia Karen S. , Szövényi Péter
Published: August 2020

Extant land plants consist of two deeply divergent groups, tracheophytes and bryophytes, which shared a common ancestor some 500 million years ago. While information about vascular plants and the two of the three lineages of bryophytes, the mosses and liverworts, is steadily accumulating, the biology of hornworts remains poorly explored. Yet, as the sister group to liverworts and mosses, hornworts are critical in understanding the evolution of key land plant traits. Until recently, there was no hornwort model species amenable to systematic experimental investigation, which hampered detailed insight into the molecular biology and genetics of this unique group of land plants. The emerging hornwort model species, Anthoceros agrestis, is instrumental in our efforts to better understand not only hornwort biology but also fundamental questions of land plant evolution. To this end, here we provide an overview of hornwort biology and current research on the model plant A. agrestis to highlight its potential in answering key questions of land plant biology and evolution.
Prediction of 3‐month treatment outcome of IgG4‐DS based on BP artificial neural network
Authors: Shao Yanxiong , Wang Zhijun , Cao Ningning , Shi Huan , Xie Lisong , Fu Jiayao , Zheng Lingyan , Yu Chuangqi
Published: August 2020

Objective

The study aimed to establish an effective back‐Propagation artificial neural network (BP‐ANN) model for automatic prediction of 3‐month treatment outcome of IgG4‐DS.

Methods

A total of 26 IgG4‐DS patients at Shanghai Ninth People's Hospital from January 2018 to December 2019 were involved in the study. They were all followed for >3 months. The primary outcome was reduction of serum IgG4 (sIgG4) after 3‐month treatment. The association between risk factors and reduction of sIgG4 was analyzed by Spearman's rank correlation test. According to the R values, we built a BP‐ANN model by MATLAB R2019b.

Results

The average reduction of sIgG4 was 5.55 ± 5.03. After Spearman's rank correlation test, ESR, sIgG4, and sIgG were independently associated with reduction of sIgG4 (p < .05) and were selected as input variables. Take into account these parameters, BP‐ANN model was developed and the coefficient of determination (R2) model was 0.95512.

Conclusion

The BP‐ANN model based on ESR, sIgG4, and sIgG could predict the 3‐month reduction of sIgG4 for IgG4‐DS patients. It showed potential clinical application value.
Oropharyngeal cancer and osteoradionecrosis in a novel radiation era: a single institution analysis
Authors: Patel D. , Haria S. , Patel V.
Published: August 2020

Aim

This study investigates the incidence of osteoradionecrosis (ORN) in patients with oropharyngeal cancer (OPC) since the use of intensity‐modulating radiation therapy (IMRT).

Materials and methods

The multi‐disciplinary log for head and neck cancer (HNC) at Guys & St Thomas’ NHS Foundation Trust was used to identify and collect data on all patients with OPC and treated with a curative intent. Basic and oncology‐related demographic data were collected retrospectively. The presence and absence of ORN along with the causative factor was recorded.

Results

A total of 361 patients were available for analysis 1‐year post‐IMRT with the number decreasing to 129 patients at ≥5 years post‐IMRT. Thirty‐eight cases of ORN were identified from which 29 patients had necrotic areas in the region of pre‐RT dental extractions. The occurrence of spontaneous ORN was most evident within the first 2 years following RT while induced causes appear a steady lifelong threat particularly in the human papilloma virus (HPV)‐positive OPC group.

Conclusions

The introduction of novel targeted IMRT has not seen a significant reduction in the incidence of ORN with the condition of concern particularly evident in the HPV‐positive OPC group. These patients present with a relatively intact dentition receiving RT doses above the threshold for development of ORN. Additionally, the favourable long‐term survival of the HPV‐positve OPC population is likely to be contributory to the rise of cases seen which provides a clinical challenge the dental sector will have to proactively manage.
Difference Between Posterior Monteggia Fractures and Posterior Fracture‐Dislocation of Proximal Ulna in Adults
Authors: Liu Jun‐yang , Zhang Ji‐zheng , Wang Ye‐ming , Tian Xu , Dong Jing‐ming
Published: August 2020

Objective

To figure out the difference between patients with posterior Monteggia fractures which were concomitant with proximal radioulnar joint (PRUJ) dislocation and posterior fracture‐dislocation of the proximal ulna that were not concomitant with PRUJ.

Methods

From January 2016 to January 2019, 37 consecutive adult patients who had posterior fracture‐dislocation of proximal ulna (no PRUJ dislocation, n = 16) and posterior Monteggia fractures (PRUJ dislocation, n = 21) were included. All patients had intraoperative fluoroscopy, computed tomography (CT) scans, and standard radiography (anteroposterior view and lateral view). The mechanism of injury, the cases with open fracture, sustained multiple injuries and classification of fracture was recorded. The clinical details of the patients such as the final range of motion (ROM) and the Broberg–Morrey scores were described.

Results

Patients with PRUJ dislocation (ten type A, five type B, and six type D) and those without concomitant PRUJ dislocation (fifteen type A and one type C) exhibited an obvious difference according to the classifications of Jupiter et al. (P = 0.010). Ninety‐five percent of patients who had PRUJ dislocation were accompanied by a metaphyseal fracture, while only 50% of the patients who did not have PRUJ dislocation were accompanied by a metaphyseal fracture (P = 0.002). Meanwhile, 16 of 20 metaphyseal fractures had more than one fragment in the group of dislocations, but five of eight metaphyseal fractures were comminuted in the control group. The two groups exhibited an obvious difference (P = 0.009). The 21 patients who sustained a radioulnar dislocation had less mean arc of flexion, pronation, and Broberg–Morrey scores were significantly less than the patients of the control group (flexion: 117.38 ± 14.46 vs 127.50 ± 13.416, P = 0.035; pronation: 59.76 ± 11.88 vs 67.50 ± 6.58, P = 0.017; Broberg–Morrey: 80.48 ± 12.17 vs 88.19 ± 10.28, P = 0.040).

Conclusions

Patients suffering posterior Monteggia fractures had more metaphyseal fractures, more comminuted fractures of the metaphysis, and worse ultimate ulnohumeral motion than patients of posterior fracture‐dislocation of proximal ulna.
Act Consequentialism without Free Rides
Authors: Greene Preston , Levinstein Benjamin A.
Published: August 2020

Consequentialist theories determine rightness solely based on real or expected consequences. Although such theories are popular, they often have difficulty with generalizing intuitions, which demand concern for questions like “What if everybody did that?” Rule consequentialism attempts to incorporate these intuitions by shifting the locus of evaluation from the consequences of acts to those of rules. However, detailed rule‐consequentialist theories seem ad hoc or arbitrary compared to act consequentialist ones. We claim that generalizing can be better incorporated into consequentialism by keeping the locus of evaluation on acts but adjusting the decision theory behind act selection. Specifically, we should adjust which types of dependencies the theory takes to be decision‐relevant. Using this strategy, we formulate a new theory, generalized act consequentialism, which we argue is more compelling than rule consequentialism both in modeling the actual reasoning of generalizers and in delivering correct verdicts.
Subjective ratings of fear are associated with frontal late positive potential asymmetry, but not with early brain activity over the occipital and centro‐parietal cortices
Authors: Grassini Simone , Sikka Pilleriin , Revonsuo Antti , Koivisto Mika
Published: August 2020

The human frontal cortex is asymmetrically involved in motivational and affective processing. Several studies have shown that the left‐frontal hemisphere is related to positive and approach‐related affect, whereas the right‐frontal hemisphere is related to negative and withdrawal‐related affect. The present study aimed to investigate whether evolutionarily threatening stimuli modulate asymmetrical frontal activity. We examined hemispheric differences in frontal late positive potentials (f‐LPP asymmetry) and frontal alpha power activation (frontal alpha asymmetry, FAA) in response to images depicting snakes, spiders, butterflies, and birds. Results showed that the late component of f‐LPP asymmetry, but not FAA, was modulated by the category of stimuli. Specifically, threatening stimuli (snakes and spiders) evoked a relatively large late f‐LPP over the right‐frontal hemisphere than non‐threatening stimuli (birds and butterflies). Moreover, this relatively great right‐frontal activity was positively associated with the subjective ratings of fear. Importantly, the subjective ratings of fear were not associated with early brain activity over the occipital or centro‐parietal cortices. These results suggest that late f‐LPP asymmetry may reflect higher order affective processes, specifically the subjective appraisal of threatening stimuli and the subjective experience of fear, that are independent of the fast and automatic processing of evolutionarily significant and affectively arousing stimuli.
Materiality and Global Spiritual Networks: Old and new sacred places and objects
Authors: Rocha Cristina
Published: August 2020

In this article, I am interested in how belief and religious materiality—sacred objects, places, infrastructures and digital media—are entangled in globalisation processes. Drawing on a case study of the John of God spiritual movement, I analyse the ways in which places and objects that have recently acquired sacred status enter into older, more established global spiritual networks, and by doing so are able to travel and ‘settle’ elsewhere. I argue that if we want to make sense of the place of religion in the world today, we need to link two fields of research on religion which have mostly developed separately: the fields of Material Religion and Globalisation of Religion. Furthermore, I contend that it is precisely because of its (mostly mobile) materiality that the John of God movement was able to survive somewhat after its charismatic leader was sentenced and jailed for sexual crimes in 2019.
Characterization of the novel HLA‐C*06:283 allele by next‐generation sequencing
Authors: Genebrier Steve , Elsermans Vincent , Texeraud Emeric , Bertrand Gerald , Renac Virginie
Published: August 2020

C*06:283 differs from C*06:02:01:01 by one nucleotide substitution at position 764 in exon 4.
Retrospective case analysis of antiviral therapies for HHV‐6 encephalitis after hematopoietic stem cell transplantation
Authors: Toomey Danny , Phan Tuan L. , Nguyen Vanessa , Phan Thommas T. , Ogata Masao
Published: August 2020

Human herpesvirus 6 (HHV‐6) is one of the most common causes of encephalitis in allogeneic hematopoietic stem cell transplant (HCT) recipients and is associated with significant morbidity and mortality. There are no FDA‐approved treatments specifically for HHV‐6 encephalitis; HHV‐6 disease is typically treated with CMV antivirals. A review of antiviral medications used to treat HHV‐6 encephalitis was conducted by aggregating data from case reports found on PubMed. Articles were included if they examined at least one HCT patient diagnosed with HHV‐6 encephalitis and described their treatment course and outcome. Key data were abstracted from 123 cases described in 52 studies. The proportion of patients with encephalitis who died or developed sequelae was 63.6% among ganciclovir monotherapy recipients (n = 44), 55.3% among foscarnet monotherapy recipients (n = 47), and 37.5% among recipients of combination therapy with foscarnet and ganciclovir (n = 32). Logistic regression revealed that recipients of foscarnet (OR 4.286, 95% CI 1.235‐14.877, P = .022) and ganciclovir (OR 5.625, 95% CI 1.584‐19.975, P = .008) monotherapies were more likely to develop sequelae compared to recipients of combination therapy, respectively. In multivariate analyses, non‐cord blood transplant was identified as an independent risk factor for developing sequelae after receiving ganciclovir monotherapy (OR 5.999, 95% CI 1.274‐28.254, P = .023). There was no difference in mortality between patients who received combination therapy and those who received monotherapy. In conclusion, combination therapy with foscarnet and ganciclovir may reduce sequelae, but not mortality, secondary to HHV‐6 encephalitis.
Epidemiological characteristics of de novo hepatitis B infection in liver transplant recipients—An experience from a tertiary care centre in Qatar
Authors: Nair Arun P. , Sasi Sreethish , Al‐Maslamani Muna S. , Chandra Prem , Hashim Samar A. , Abu Jarir Sulieman , Derbala Moutaz
Published: August 2020

Background

The emergence of hepatitis B surface antigen in a patient with previously negative hepatitis B virus (HBV) serology post‐orthotropic liver transplant (OTLX) is known as de novo hepatitis B (DNHB). As there are no data on patients with DNHB available from Qatar, we aim to do a pioneer study indexing their clinical profile and epidemiology of patients with DNHB in Qatar.

Materials and Methods

This descriptive epidemiological study was done by retrospectively reviewing records of 159 post‐OTLX patients. HBV serology of these patients post‐OTLX was reviewed, and 17 were identified as DNHB cases. Baseline epidemiological characteristics were defined and compared between DNHB cases and the rest. DNHB cases were analyzed statistically using the chi‐square test and Kaplan‐Meier curve.

Results

The majority of the subjects were men (65%) and Qataris (40%). Mean age was 57.4 ± 12.5 years. Bulk of them underwent OTLX in China (44%). The overall incidence of DNHB was 10.7%, with transplants in China having significantly higher incidence than transplants from all other countries. The mortality rate was 23.5% in DNHB cases compared to 2.8% in non‐DNHB. 67% of patients survived at least 64 months after the diagnosis of DNHB. Five‐year survival did not vary significantly between those with DNHB and those without.

Conclusion

Orthotropic liver transplant in centers selecting donors liberally without screening for HBV poses the risk of DNHB. We recommend having protective levels of HBs antibodies before OTLX. Prophylactic antiviral treatment should be considered until peri‐operative HBV transmission has been excluded by screening hepatic tissue for HBV DNA.
Optimization of multiplexed CRISPR/Cas9 system for highly efficient genome editing in Setaria viridis
Authors: Weiss Trevor , Wang Chunfang , Kang Xiaojun , Zhao Hui , Elena Gamo Maria , Starker Colby G. , Crisp Peter A. , Zhou Peng , Springer Nathan M. , Voytas Daniel F. , Zhang Feng
Published: August 2020

In recent years, Setaria viridis has been developed as a model plant to better understand the C4 photosynthetic pathway in major crops. With the increasing availability of genomic resources for S. viridis research, highly efficient genome editing technologies are needed to create genetic variation resources for functional genomics. Here, we developed a protoplast assay to rapidly optimize the multiplexed clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated (Cas9) system in S. viridis. Targeted mutagenesis efficiency was further improved by an average of 1.4‐fold with the exonuclease, Trex2. Distinctive mutation profiles were found in the Cas9_Trex2 samples, with 94% of deletions larger than 10 bp, and essentially no insertions at all tested target sites. Further analyses indicated that 52.2% of deletions induced by Cas9_Trex2, as opposed to 3.5% by Cas9 alone, were repaired through microhomology‐mediated end joining (MMEJ) rather than the canonical non‐homologous end joining DNA repair pathway. Combined with a robust Agrobacterium‐mediated transformation method with more than 90% efficiency, the multiplex CRISPR/Cas9_Trex2 system was demonstrated to induce targeted mutations in two tightly linked genes, svDrm1a and svDrm1b, at a frequency ranging from 73% to 100% in T0 plants. These mutations were transmitted to at least 60% of the transgene‐free T1 plants, with 33% of them containing bi‐allelic or homozygous mutations in both genes. This highly efficient multiplex CRISPR/Cas9_Trex2 system makes it possible to create a large mutant resource for S. viridis in a rapid and high throughput manner, and has the potential to be widely applicable in achieving more predictable and deletion‐only MMEJ‐mediated mutations in many plant species.
Potential markers of healing from near infrared spectroscopy imaging of venous leg ulcer. A randomized controlled clinical trial comparing conventional with hyperbaric oxygen treatment
Authors: Longobardi Pasquale , Hartwig Valentina , Santarella Luigi , Hoxha Klarida , Campos Jhonny , Laurino Marco , Salvo Pietro , Trivella Maria Giovanna , Coceani Flavio , Rocco Monica , L'Abbate Antonio
Published: August 2020

The aim of this study is to ascertain whether the simultaneous measurement of hemoglobin O2 saturation (StO2) and dimension of venous leg ulcers (VLU) by near infrared spectroscopy (NIRS) imaging can predict the healing course with protocols employing a conventional treatment alone or in combination with hyperbaric oxygen therapy (HBOT). NIRS 2D images of wound region were obtained in 81 patients with hard‐to‐heal VLU that had been assigned, in a randomized controlled clinical trial, to the following protocols: 30 HBOT sessions, adjunctive to the conventional therapy, either twice daily over 3 weeks (group A) or once daily over 6 weeks (group B), and conventional therapy without HBOT (group C). Seventy‐three patients completed the study with a total of 511 NIRS images being analyzed. At the end of treatment, wound area was significantly smaller in all three groups. However, at the 3‐week mark the wound area reduction tended to be less evident in group A than in the other groups. This trend continued up to the 6‐week end‐point when a significantly greater area reduction was found with group B (65.5%) and group C (56.8%) compared to group A (29.7%) (P < .01). Furthermore, a higher incidence of complete healing was noted with group B (20%) than with group A (4.5%) and group C (3.8%). When using a final wound reduction in excess of 40% to distinguish healing from nonhealing ulcers, it was found that only the former present NIRS StO2 values abating over the study period both at center and edge of lesions. In conclusion, NIRS analysis of StO2 and wound area can predict the healing course of VLU. Adjunctive HBOT significantly facilitates VLU healing compared to the conventional treatment alone. This positive action, however, becomes manifest only with a longer and less intensive treatment schedule.
Stereotypical Views of Beauty and Boys STILL Not Letting Girls Play: A Student-Centered Curriculum for Young Girls Through an After-School Activist Approach
Authors: Marttinen Risto , Meza Brianna , Flory Sara B.
Published: August 2020

Purpose: The purpose of this study was to explore how a student-centered curriculum engaged participants in critical analysis of the “female ideal” and to identify perceived barriers to physical activity. Method: Participants were nine fifth and sixth grade Hispanic/Latina or mixed race girls, and two researchers at an urban elementary school in Southern California. Participants met one to two times per week in an after-school program. Data sources included researcher and participant journals, field notes, and semistructured interviews. Trustworthiness and credibility were established through prolonged engagement, member checks, and peer reviewer. Results: Two themes permeated the data. The first theme involved boys acting as a barrier to physical activity. The second theme involved alignment with the ideal female body. Discussion: This study highlights how boys still act as barriers to girls’ physical activity in many school settings, but also identifies how role models for girls have increased girls’ ability to critically examine media messages.
Jay-Z and O.J.: Sport and the Performance of Race in Hip-Hop Music
Authors: Northcutt Kellen Jamil , Henderson Kayla , Chicoski Kaylee
Published: August 2020

The purpose of this study was to understand the symbolic messaging in hip-hop music as it relates to the lived experiences and realities of Black Americans in the United States. The study examined the song and music video titled “The Story of O.J.,” by hip-hop artist Jay-Z to gain a better understanding of how Jay-Z interpreted the impact of Black Americans’ lived experiences in the United States on their identity and ability to progress economically and socially, regardless of social standing, within subcultures such as sport. Employing a content analysis method, data were collected and analyzed using critical race theory. The results of the analysis of lyrical and video data identified three major themes: (a) battle with Blackness, (b) economic enslavement and financial freedom, and (c) systematic subjugation.
Identification of Small-Molecule Inhibitors Targeting Porphyromonas gingivalis Interspecies Adherence and Determination of Their
In Vitro
and
In Vivo
Efficacies
Authors: Roky Mohammad , Tan Jinlian , Sztukowska Maryta N. , Trent John O. , Demuth Donald R.
Published: August 2020

Porphyromonas gingivalis
is one of the primary causative agents of periodontal disease and initially colonizes the oral cavity by adhering to commensal streptococci. Adherence requires the interaction of a minor fimbrial protein (Mfa1) of
P. gingivalis
with streptococcal antigen I/II (AgI/II). Our previous work identified an AgI/II peptide that potently inhibited adherence and significantly reduced
P. gingivalis
virulence
in vivo
, suggesting that this interaction represents a potential target for drug discovery.
Assessing the Safety, Tolerability, Pharmacokinetics, and Biodistribution of Novel Oral Formulations of Amphotericin B following Single- and Multiple-Dose Administration to Beagle Dogs
Authors: Wasan Kishor M. , Wasan Ellen K. , Hnik Peter
Published: August 2020

The purpose of this study was to assess the safety, tolerability, pharmacokinetics (PK), and biodistribution of novel oral amphotericin B (AmpB) formulations following single- and multiple-oral-dose administration to healthy beagle dogs. The liquid formulation of AmpB was administered to three male dogs, and the capsule formulations of AmpB were administered to each of two groups of six male dogs. Blood was collected for pharmacokinetic evaluation on days 1, 2, and 3 (up to 72 h postdosing).
Comparative
In Vitro
Activities of Ceftaroline and Tedizolid against Clinical Strains of Staphylococcus aureus and
Enterococcus
: Results from the China Antimicrobial Surveillance Network (CHINET) in 2018
Authors: Guo Yan , Yang Yang , Zheng Yonggui , Wu Shi , Yin Dandan , Zhu Demei , Hu Fupin
Published: August 2020

The
in vitro
activities of ceftaroline and tedizolid were compared against
Staphylococcus aureus
,
Enterococcus faecalis
, and
Enterococcus faecium
clinical isolates collected from the China Antimicrobial Surveillance Network. Ceftaroline demonstrated potent activity against
S. aureus
isolates (MIC
50/90
, ≤0.25/1 mg/liter). Tedizolid was also highly active against
S. aureus
(MIC
50/90
, 0.
Overproduction of a Dominant Mutant of the Conserved Era GTPase Inhibits Cell Division inEscherichia coli
Authors: Zhou Xiaomei , Peters Howard K. , Li Xintian , Costantino Nina , Kumari Vandana , Shi Genbin , Tu Chao , Cameron Todd A. , Haeusser Daniel P. , Vega Daniel E. , Ji Xinhua , Margolin William , Court Donald L.
Published: August 2020

Cell growth and division are coordinated, ensuring homeostasis under any given growth condition, with division occurring as cell mass doubles. The signals and controlling circuit(s) between growth and division are not well understood; however, it is known inEscherichia colithat the essential GTPase Era, which is growth rate regulated, coordinates the two functions and may be a checkpoint regulator of both. We have isolated a mutant of Era that separates its effect on growth and division. When overproduced, the mutant protein Era647 is dominant to wild-type Era and blocks division, causing cells to filament. Multicopy suppressors that prevent the filamentation phenotype of Era647 either increase the expression of FtsZ or decrease the expression of the Era647 protein. Excess Era647 induces complete delocalization of Z rings, providing an explanation for why Era647 induces filamentation, but this effect is probably not due to direct interaction between Era647 and FtsZ. The hypermorphicftsZ* allele at the native locus can suppress the effects of Era647 overproduction, indicating that extra FtsZ is not required for the suppression, but another hypermorphic allele that accelerates cell division through periplasmic signaling,ftsL*, cannot. Together, these results suggest that Era647 blocks cell division by destabilizing the Z ring.

IMPORTANCEAll cells need to coordinate their growth and division, and small GTPases that are conserved throughout life play a key role in this regulation. One of these, Era, provides an essential function in the assembly of the 30S ribosomal subunit inEscherichia coli, but its role in regulatingE. colicell division is much less well understood. Here, we characterize a novel dominant negative mutant of Era (Era647) that uncouples these two activities when overproduced; it inhibits cell division by disrupting assembly of the Z ring, without significantly affecting ribosome production. The unique properties of this mutant should help to elucidate how Era regulates cell division and coordinates this process with ribosome biogenesis.
Men and Women Have Similar Neisseria gonorrhoeae Bacterial Loads: a Comparison of Three Anatomical Sites
Authors: van der Veer Brian M. J. W. , Hoebe Christian J. P. A. , Dukers-Muijrers Nicole H. T. M. , van Alphen Lieke B. , Wolffs Petra F. G.
Published: August 2020

Neisseria gonorrhoeae
is a common bacterial sexually transmitted infection (STI). Currently, there are limited data on the bacterial load in both men and women and on both genital and extragenital sites. Therefore, we quantified
N. gonorrhoeae
bacterial loads in a large population of women, heterosexual men, and men who have sex with men (MSM) at three different anatomical sites.
N. gonorrhoeae
-positive samples (
n
 = 1265) of STI clinic consultations (
n
 = 944) were tested for
N. gonorrhoeae
with the Roche Cobas 4800 system, and quantification cycle (
Cq
) values were used as an inversely proportional measure for
N. gonorrhoeae
bacterial load after interpolation from a standard curve.
Enhancement of Culture of Legionella longbeachae from Respiratory Samples by Use of Immunomagnetic Separation and Antimicrobial Decontamination
Authors: Mohammadi Ali , Chambers Stephen T. , Scott-Thomas Amy , Lewis John G. , Anderson Trevor , Podmore Ros , Williman Jonathan , Murdoch David , Slow Sandy
Published: August 2020

Legionella longbeachae
is the commonest
Legionella
species identified in patients with community-acquired pneumonia in New Zealand. Isolation of the organism on culture is the gold standard for the diagnosis of Legionnaires disease, but it has poor sensitivity (40%) compared with quantitative PCR (qPCR). We have developed a selective decontamination process using glycine, vancomycin, polymyxin, and cycloheximide (GVPC) with immunomagnetic separation (IMS) for culturing
L. longbeachae
.
A Mechanism-Based Targeted Screen To Identify Epstein-Barr Virus-Directed Antiviral Agents
Authors: Li Xiaofan , Akinyemi Ibukun A. , You Jeehyun Karen , Rezaei Mohammad Ali , Li Chenglong , McIntosh Michael T. , Del Poeta Maurizio , Bhaduri-McIntosh Sumita
Published: August 2020

Epstein-Barr virus, which is nearly ubiquitous in humans, is causal to infectious mononucleosis, chronic active EBV infection, and lymphoid and epithelial cancers. However, EBV-specific antiviral agents are not yet available. To aid in the identification of compounds that may be developed as antivirals, we pursued a mechanism-based approach. Since many of these diseases rely on EBV’s lytic phase, we developed a high-throughput assay that is able to measure a key step that is essential for successful completion of EBV’s lytic cascade. We used this assay to screen a library of small-molecule compounds and identified inhibitors that may be pursued for their anti-EBV and possibly even antiherpesviral potential, as this key mechanism appears to be common to several human herpesviruses. Given the prominent role of this mechanism in both herpesvirus biology and cancer, our screening assay may be used as a platform to identify both antiherpesviral and anticancer drugs.
Heterogeneous trends in burden of heart disease mortality by subtypes in the United States, 1999-2018: observational analysis of vital statistics
Authors: Shah Nilay S , Molsberry Rebecca , Rana Jamal S , Sidney Stephen , Capewell Simon , O’Flaherty Martin , Carnethon Mercedes , Lloyd-Jones Donald M , Khan Sadiya S
Published: August 2020

Objective

To describe trends in the burden of mortality due to subtypes of heart disease from 1999 to 2018 to inform targeted prevention strategies and reduce disparities.

Design

Serial cross sectional analysis of cause specific heart disease mortality rates using national death certificate data in the overall population as well as stratified by race-sex, age, and geography.

Setting

United States, 1999-2018.

Participants

12.9 million decedents from total heart disease (49% women, 12% black, and 19% <65 years old).

Main outcome measures

Age adjusted mortality rates (AAMR) and years of potential life lost (YPLL) for each heart disease subtype, and respective mean annual percentage change.

Results

Deaths from total heart disease fell from 752 192 to 596 577 between 1999 and 2011, and then increased to 655 381 in 2018. From 1999 to 2018, the proportion of total deaths from heart disease attributed to ischemic heart disease decreased from 73% to 56%, while the proportion attributed to heart failure increased from 8% to 13% and the proportion attributed to hypertensive heart disease increased from 4% to 9%. Among heart disease subtypes, AAMR was consistently highest for ischemic heart disease in all subgroups (race-sex, age, and region). After 2011, AAMR for heart failure and hypertensive heart disease increased at a faster rate than for other subtypes. The fastest increases in heart failure mortality were in black men (mean annual percentage change 4.9%, 95% confidence interval 4.0% to 5.8%), whereas the fastest increases in hypertensive heart disease occurred in white men (6.3%, 4.9% to 9.4%). The burden of years of potential life lost was greatest from ischemic heart disease, but black-white disparities were driven by heart failure and hypertensive heart disease. Deaths from heart disease in 2018 resulted in approximately 3.8 million potential years of life lost.

Conclusions

Trends in AAMR and years of potential life lost for ischemic heart disease have decelerated since 2011. For almost all other subtypes of heart disease, AAMR and years of potential life lost became stagnant or increased. Heart failure and hypertensive heart disease account for the greatest increases in premature deaths and the largest black-white disparities and have offset declines in ischemic heart disease. Early and targeted primary and secondary prevention and control of risk factors for heart disease, with a focus on groups at high risk, are needed to avoid these suboptimal trends beginning earlier in life.
Resistance training in advanced cancer: a phase II safety and feasibility trial—home versus hospital
Authors: Ribeiro Catarina , Santos Rui , Correia Pedro , Maddocks Matthew , Gomes Barbara
Published: August 2020

Background

Resistance training (RT) is an effective way to increase muscle mass but little is known about its role to prevent sarcopenia in advanced cancer. Furthermore, the preferred setting for this training is not known. Considering home is frequently the place of care and death preferred by cancer patients, it is important to find out whether this would also be the best training setting as opposed to the most common one, hospital.

Objectives

We aimed to test if RT at home and in hospital is feasible (primary outcome) and safe in advanced cancer, with a view to inform a phase III trial.

Methods

Phase II randomised controlled trial including adults (≥18 years) with incurable solid tumours, randomised into one of three arms: (1) supervised RT at home; (2) supervised RT in hospital; (3) standard care with information leaflet. Both training programmes were similar, ran one-to-one with therapists and planned to last 12 weeks (three sessions/week). Feasibility included adherence (proportion of completed sessions) and acceptability (proportion of completed exercises), compared using Fisher’s test.

Results

We included 15 patients (53% men, median age 68), 5 per arm. The home intervention had higher adherence (49% vs 9% in hospital; p<0.001). Acceptability was similar (93% in home and 95% in hospital; p=0.179). No adverse events were recorded.

Conclusions

RT is a safe intervention, more feasible at home than in hospital in advanced cancer. Ways to increase adherence to the home intervention could further improve its potential benefit.

Trial registration number

NCT02930876.
Oral mucositis induced by risperidone: rare side effect of a frequently prescribed medication
Authors: Aguglia Andrea , Amerio Andrea , Proietti Luca , Costanza Alessandra , Serafini Gianluca , Amore Mario
Published: August 2020

Risperidone is a safe second-generation antipsychotic which is rarely associated with the emergence of a few adverse effects, such as oral lesions and stomatitis. We report the case of a 77-year-old woman affected by a neurocognitive disorder with psychotic features and treated with risperidone 2 mg/day. After 1 week, she showed a burning mouth syndrome with oral lesions and risperidone was discontinued. Antipsychotic-induced oral ulcerations may be caused by the reduction of saliva protection with minor adverse effects related to oral movement disorders or impairment of the bacterial flora of saliva.
Albanerpetontids (Lissamphibia, Albanerpetontidae) from the Aguja Formation (lower Campanian) of West Texas, USA
Authors: Wick Steven L.
Published: August 2020

The Lowerverse local fauna of West Texas, USA, preserves a rare, early Campanian assemblage of microvertebrates from Laramidia. The recovery of 137 fragmentary specimens reveals that albanerpetontids were locally abundant here and also widespread throughout much of the Western Interior of North America by early Campanian time. Both gracile- and robust-snouted species are represented within the assemblage. Among these, the occurrence of Albanerpeton nexuosum is consistent with its occurrence in paracontemporaneous deposits elsewhere in the Western Interior. The referral of two specimens to Albanerpeton sp., cf. Albanerpeton galaktion, strongly suggests that this long-lived taxon was far more widespread during the early Campanian than previously known and its likely occurrence in West Texas represents a significant geotemporal range extension for the species. However, Albanerpeton gracile is seemingly restricted to Judithian “age” deposits in North America and was not identified at Lowerverse. The Lowerverse assemblage supports the current paradigm involving the occurrence of these three named albanerpetontids during middle Campanian – Maastrichtian time in the Western Interior of North America.