bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in complement alternative pathway components, factor B and factor H during dengue virus infection in the AG129 mouse
Authors: Cabezas-Falcon Sheila , Norbury Aidan J. , Hulme-Jones Jarrod , Klebe Sonja , Adamson Penelope , Rudd Penny A. , Mahalingam Suresh , Ong Li-Ching , Alonso Sylvie , Gordon David L. , Carr Jillian M.
Published: January 2021

The complement alternative pathway (AP) is tightly regulated and changes in two important AP components, factor B (FB) and factor H (FH) are linked to severe dengue in humans. Here, a mouse model of dengue was investigated to define the changes in FB and FH and assess the utility of this model to study the role of the AP in severe dengue. Throughout the period of viremia in the AG129 IFN signalling-deficient mouse, an increase in FB and a decrease in FH was observed following dengue virus (DENV) infection, with the former only seen in a model of more severe disease associated with antibody-dependent enhancement (ADE). Terminal disease was associated with a decrease in FB and FH, with greater changes during ADE, and accompanied by increased C3 degradation consistent with complement activation. In silico analysis of NFκΒ, signal transducer and activator of transcription (STAT) and IFN-driven FB and FH promoter elements to reflect the likely impact of the lack of IFN-responses in AG129 mice, demonstrated that these elements differed markedly between human and mouse, notably with mouse FH lacking NFκΒ and key IFN-stimulated response elements (ISRE), and FB with many more NFκΒ and STAT-responsive elements than human FB. Thus, the AG129 mouse offers utility in demonstrating changes in FB and FH that, similar to humans, are associated with severe disease, but lack predicted important human-specific and IFN-dependent responses of FB and FH to DENV-infection that are likely to regulate the subtleties of the overall AP response during dengue disease in humans.
Sampling challenges in diagnosis of chronic bacterial infections
Authors: Jakobsen Tim Holm , Xu Yijuan , Bay Lene , Schønheyder Henrik Carl , Jakobsen Thomas , Bjarnsholt Thomas , Thomsen Trine Rolighed
Published: January 2021

In recent decades there has been an increase in knowledge of the distribution, species diversity and growth patterns of bacteria in human chronic infections. This has challenged standard diagnostic methods, which have undergone a development to both increase the accuracy of testing as well as to decrease the occurrence of contamination. In particular, the introduction of new technologies based on molecular techniques into the clinical diagnostic process has increased detection and identification of infectious pathogens. Sampling is the first step in the diagnostic process, making it crucial for obtaining a successful outcome. However, sampling methods have not developed at the same speed as molecular identification. The heterogeneous distribution and potentially small number of pathogenic bacterial cells in chronic infected tissue makes sampling a complicated task, and samples must be collected judiciously and handled with care. Clinical sampling is a step in the diagnostic process that may benefit from innovative methods based on current knowledge of bacteria present in chronic infections. In the present review, we describe and discuss different aspects that complicate sampling of chronic infections. The purpose is to survey representative scientific work investigating the presence and distribution of bacteria in chronic infections in relation to various clinical sampling methods.
Expression levels of HLA-DRB and HLA-DQ are associated with MHC Class II haplotypes in healthy individuals and rheumatoid arthritis patients
Authors: Houtman Miranda , Dzebisashvili Anna , Hesselberg Espen , Dubnovitsky Anatoly , Kozhukh Genadiy , Rönnblom Lars , Klareskog Lars , Malmström Vivianne , Padyukov Leonid
Published: January 2021

HLA-DRB1 alleles have been associated with several autoimmune diseases. In anti-citrullinated protein antibody positive rheumatoid arthritis (ACPA-positive RA), HLA-DRB1 shared epitope (SE) alleles are the major genetic risk factors. In order to investigate whether expression of different alleles of major histocompatibility complex (MHC) Class II genes influence functions of immune cells, we investigated transcriptomic profiles of a variety of immune cells from healthy individuals carrying different HLA-DRB1 alleles. Sequencing libraries from peripheral blood mononuclear cells, CD4+ T cells, CD8+ T cells, and CD14+ monocytes of 32 genetically pre-selected healthy female individuals were generated, sequenced and reads were aligned to the standard reference. For the MHC region, reads were mapped to available MHC reference haplotypes and AltHapAlignR was used to estimate gene expression. Using this method, HLA-DRB and HLA-DQ were found to be differentially expressed in different immune cells of healthy individuals as well as in whole blood samples of RA patients carrying HLA-DRB1 SE-positive versus SE-negative alleles. In contrast, no genes outside the MHC region were differentially expressed between individuals carrying HLA-DRB1 SE-positive and SE-negative alleles. Existing methods for HLA-DR allele-specific protein expression were evaluated but were not mature enough to provide appropriate complementary information at the protein level. Altogether, our findings suggest that immune effects associated with different allelic forms of HLA-DR and HLA-DQ may be associated not only with differences in the structure of these proteins, but also with differences in their expression levels.
Understanding apparel brand evolution patterns in Bangladesh: an industry life cycle perspective
Authors: Bari Md Sadaqul , Jin Byoungho Ellie
Published: January 2021

Purpose

The purpose of this study is to identify the emergence of apparel brands in Bangladesh: their timing, order and the reasons behind the patterns. This study also examined whether these evolution patterns followed the same path in Korea and India.

Design/methodology/approach

By employing secondary research method, this study gathered and analyzed data from companies, trade organizations, news media and academic articles to determine the socioeconomic backgrounds and underlying dynamics that propelled the evolution patterns. Following Jin et al.'s (2013) approach, we analyzed three types of apparel brands (international, national and private) in Bangladesh.

Findings

The findings indicated that in contrast with Korea and India, in Bangladesh (a) the emergence of international brands occurred after the national brands' appearance in the More Advanced Production of Fabric and Apparel stage, (b) national brands also emerged at the same stage and earlier than the international brands developed, and (c) internationalization of national brands and emergence of private brands were not observed. The differences in the emergent timing and order were explained by socioeconomic and cultural aspects, along with industry life cycle perspectives.

Practical implications

Findings indicate that the Bangladeshi market is dominated by national apparel brands. Therefore, international brands are advised to consider the business strategies of local competitors and develop their own pricing and merchandising strategies to maintain their supremacy as premium brands.

Originality/value

This study addressed apparel brand evolution patterns in a lower middle-income country. The results revealed some unique aspects. Unlike in other developing countries, national brand development in Bangladesh was initiated by entrepreneurs.
Morphological decomposition supports word recognition in primary school children learning to read: evidence from masked priming of German derived words
Authors: Fleischhauer Elisabeth , Bruns Gunnar , Grosche Michael
Published: January 2021

Background

When reading a word, skilled adult readers automatically decompose the word into its separate morphemes by processing the word's morpho‐orthography. In children, however, it still remains unclear when and how they start to automatically decompose words into morphemes.

Methods

To better understand how primary school children learn and integrate automatic morphological processes into their reading, we conducted a masked priming experiment withn = 218 first to fourth graders and a control group of 36 adult readers. Participants saw prime words on a computer screen for 67 ms, followed by a lexical decision task. For each target word, we constructed three prime words: an unrelated control prime, a semantic control prime and a test prime. The test prime was either morpho‐semantically, morpho‐orthographically or purely orthographically related to the target word. We analysed error rates and reaction times with linear mixed‐effects models and linear combinations.

Results

The error analysis revealed one significant interaction in the morpho‐semantic condition for fourth graders. The reaction time analysis revealed different priming effects depending on age group: first and second graders showed no priming effects, while third graders showed priming in the morpho‐semantic condition, and fourth graders and adults showed priming both in the morpho‐semantic and morpho‐orthographic condition.

Conclusions

We conclude that (i) fourth graders automatically decompose written words into morphemes based on the words' morpho‐orthography, (ii) third graders automatically detect stems in morphologically complex forms but do not rely on morpho‐orthographic representations while (iii) first and second graders show no indication of either of these processes. Our results are theoretically consistent with the ‘semantic view’ within a localist account and can be explained by edge‐aligned embedded word activation.
Genome analysis of the metabolically versatile Pseudomonas umsongensis GO16: the genetic basis for PET monomer upcycling into polyhydroxyalkanoates
Authors: Narancic Tanja , Salvador Manuel , Hughes Graham M. , Beagan Niall , Abdulmutalib Umar , Kenny Shane T. , Wu Huihai , Saccomanno Marta , Um Jounghyun , O'Connor Kevin E. , Jiménez José I.
Published: January 2021

The throwaway culture related to the single‐use materials such as polyethylene terephthalate (PET) has created a major environmental concern. Recycling of PET waste into biodegradable plastic polyhydroxyalkanoate (PHA) creates an opportunity to improve resource efficiency and contribute to a circular economy. We sequenced the genome of Pseudomonas umsongensis GO16 previously shown to convert PET‐derived terephthalic acid (TA) into PHA and performed an in‐depth genome analysis. GO16 can degrade a range of aromatic substrates in addition to TA, due to the presence of a catabolic plasmid pENK22. The genetic complement required for the degradation of TA via protocatechuate was identified and its functionality was confirmed by transferring the tph operon into Pseudomonas putida KT2440, which is unable to utilize TA naturally. We also identified the genes involved in ethylene glycol (EG) metabolism, the second PET monomer, and validated the capacity of GO16 to use EG as a sole source of carbon and energy. Moreover, GO16 possesses genes for the synthesis of both medium and short chain length PHA and we have demonstrated the capacity of the strain to convert mixed TA and EG into PHA. The metabolic versatility of GO16 highlights the potential of this organism for biotransformations using PET waste as a feedstock.
Celecoxib treatment dampens LPS‐induced periapical bone resorption in a mouse model
Authors: Petean I. B. F. , Almeida‐Junior L. A. , Arnez M. F. M. , Queiroz A. M. , Silva R. A. B , Silva L. A. B. , Faccioli L. H. , Paula‐Silva F. W. G.
Published: January 2021

Aim

To evaluate the efficacy of selective and nonselective inhibitors of cyclooxygenase‐2 enzymes in the treatment of experimental apical periodontitis induced by bacterial lipopolysaccharide (LPS) in vivo in a mouse model.

Methodology

Thirty‐six C57BL/6 mice were used. After access cavity preparation, a solution containing E. coli LPS (1.0 µg µL−1) was inoculated into the root canals of the mandibular and maxillary right first molars (n = 72) After 30 days, apical periodontitis was established and the animals were systemically treated with celecoxib, a selective COX‐2 inhibitor (15 mg kg−1), or indomethacin, a nonselective COX‐2 inhibitor (5 mg kg−1), for 7 and 14 days. Blocks containing teeth and bone were removed for histopathological and histometric analyses (haematoxylin and eosin), evaluation of osteoclasts numbers (tartrate‐resistant acid phosphatase enzyme – TRAP) and immunohistochemistry for RANK, RANKL and OPG. Gene expression was performed using reverse transcription and real‐time polymerase chain reaction (qRT‐PCR) for RANK, RANKL, OPG, TRAP, MMP‐9, cathepsin K and calcitonin receptor. Histopathological, histometric, TRAP, immunohistochemistry and qRT‐PCR data were evaluated using Kruskal–Wallis followed by Dunn’s test (α = 0.05).

Results

Systemic administration of celecoxib for 7 and 14 days prevented periapical bone resorption (P < 0.0001), differently from indomethacin that exacerbated bone resorption at 7 days (P < 0.0001) or exerted no effect at 14 days (P = 0.8488). Celecoxib treatment reduced osteoclast formation in apical periodontitis, regardless of the period of treatment (P < 0.0001 for 7 days and P = 0.026 for 14 days). Administration of celecoxib or indomethacin differentially modulated the expression of genes involved in bone resorption. At 7 days, celecoxib and indomethacin treatment significantly inhibited expression of mRNA for cathepsin K (P = 0.0005 and P = 0.016, respectively) without changing TRAP, MMP‐9 and calcitonin receptor gene expression. At 14 days, celecoxib significantly inhibited expression of mRNA for MMP‐9 (P < 0.0001) and calcitonin receptor (P = 0.004), whilst indomethacin exerted no effect on MMP‐9 (P = 0.216) and calcitonin receptor (P = 0.971) but significantly augmented cathepsin K gene expression (P = 0.001).

Conclusions

The selective COX‐2 inhibitor celecoxib reduced osteoclastogenic signalling and activity that dampened bone resorption in LPS‐induced apical periodontitis in mice, with greater efficacy than the nonselective inhibitor indomethacin.
Concordance of the Adaptive Behavior Assessment System, second and third editions
Authors: von Buttlar A. M. , Zabel T. A. , Pritchard A. E. , Cannon A. D.
Published: January 2021

Background

Adaptive functioning is an important area of assessment with implications for differential diagnosis, educational placement, service eligibility and criminal sentencing. While periodic normative and content updates of adaptive functioning measures are necessary to keep measures relevant, knowledge of equivalence between versions is also required if adaptive measures are to be used to track the stability of adaptive functioning skills over time.

Method

This paper presents two studies that used between‐group and within‐group comparison designs to examine the equivalence of the second and third editions of the Adaptive Behavior Assessment System (ABAS) in a mixed clinical sample. In study 1, ABAS‐2 scores for children assessed between 2014 and 2015 (n = 1036; mean age = 10.24, SD = 3.44) were compared with ABAS‐3 scores for children assessed between 2015 and 2016 (n = 1291; mean age = 10.51, SD = 3.70). Study 2 examined a separate sample of clinically referred children (n = 572) for whom parent ratings had been obtained on both the ABAS‐2 (mean age = 9.65, SD = 2.80) and ABAS‐3 (mean age = 13.33, SD = 2.95) in the course of repeated assessment.

Results

For Study 1, while no intelligence quotient score differences were observed between the ABAS‐2 group (mean Verbal Comprehension Index = 93.67, SD = 16.95) and the ABAS‐3 group (mean Verbal Comprehension Index = 93.08, SD = 17.42), ABAS‐2 scores were lower than ABAS‐3 scores on the Conceptual, Practical, and General Adaptive Composite scales. In study 2, a similar pattern was observed (ABAS‐2 < ABAS‐3 on the Conceptual, Practical, and General Adaptive Composite scales), and concordance correlation coefficients ranged from 0.54 [0.49, 0.58] (Practical composite) to 0.68 [0.64, 0.72] (Conceptual composite). The Practical composite had the lowest concordance correlation coefficient value and the largest mean score difference between ABAS versions.

Conclusions

The ABAS‐3 scores may be higher than ABAS‐2 scores in clinical populations. Knowledge of these potential discrepancies will be critical when interpreting standard score changes across ABAS versions in the course of clinical, educational and forensic assessments.
Contributions of the dark triad to moral disengagement among incarcerated and community adults
Authors: Navas María Patricia , Maneiro Lorena , Cutrín Olalla , Gómez‐Fraguela José Antonio , Sobral Jorge
Published: January 2021

Previous research has revealed a strong association between moral disengagement (MD) and criminal behaviour. However, few studies have attempted to examine the contribution of dark personalities to MD. This study aims to first analyse the differences between forensic and community samples in the use of MD strategies and then replicate the factorial structure of the Dark Triad Dirty Dozen scale in an incarcerated sample as a pre‐condition to examine the relationship between dark triad (DT) traits (i.e. Machiavellianism, psychopathy and narcissism) and MD. The sample comprised 160 incarcerated and 160 community adults. Comparisons between these two groups demonstrate that the incarcerated sample scored higher in MD and DT than the community sample. Furthermore, different MD strategies were related to each of the DT traits in the forensic and community samples. The results of exploratory factor analysis for the incarcerated sample indicate adequate fit indices for a bifactorial model of the DT (a latent factor of the shared variance of these constructs named the global DT and three specific latent factors for each component of the DT). The SEM analysis for this bifactorial model and MD disclosed direct and significant relationships between the global DT and MD in the incarcerated adults, while the Machiavellianism factor was directly and significantly related to MD in the community adults. These results highlight the relevance of cognitive (i.e. MD) strategies in forensic contexts, especially in incarcerated adults who present high levels of this DT profile.
Maintaining human milk bank services throughout the COVID‐19 pandemic: A global response
Authors: Shenker Natalie , Staff Marta , Vickers Amy , Aprigio Joao , Tiwari Satish , Nangia Sushma , Sachdeva Ruchika Chugh , Clifford Vanessa , Coutsoudis Anna , Reimers Penny , Israel‐Ballard Kiersten , Mansen Kimberly , Mileusnic‐Milenovic Radmila , Wesolowska Aleksandra , Goudoever Johannes B. van , Hosseini Mohammadbagher , Klotz Daniel , Grøvslien Anne Hagen , Weaver Gillian ,   Virtual Collaborative Network of Milk Banks and Associations
Published: January 2021

If maternal milk is unavailable, the World Health Organization recommends that the first alternative should be pasteurised donor human milk (DHM). Human milk banks (HMBs) screen and recruit milk donors, and DHM principally feeds very low birth weight babies, reducing the risk of complications and supporting maternal breastfeeding where used alongside optimal lactation support. The COVID‐19 pandemic has presented a range of challenges to HMBs worldwide. This study aimed to understand the impacts of the pandemic on HMB services and develop initial guidance regarding risk limitation. A Virtual Collaborative Network (VCN) comprising over 80 HMB leaders from 36 countries was formed in March 2020 and included academics and nongovernmental organisations. Individual milk banks, national networks and regional associations submitted data regarding the number of HMBs, volume of DHM produced and number of recipients in each global region. Estimates were calculated in the context of missing or incomplete data. Through open‐ended questioning, the experiences of milk banks from each country in the first 2 months of the pandemic were collected and major themes identified. According to data collected from 446 individual HMBs, more than 800,000 infants receive DHM worldwide each year. Seven pandemic‐related specific vulnerabilities to service provision were identified, including sufficient donors, prescreening disruption, DHM availability, logistics, communication, safe handling and contingency planning, which were highly context‐dependent. The VCN now plans a formal consensus approach to the optimal response of HMBs to new pathogens using crowdsourced data, enabling the benchmarking of future strategies to support DHM access and neonatal health in future emergencies.
Pigmented purpuric dermatosis in an infant
Authors: Martos‐Cabrera Luisa , López‐Balboa Pablo , Ramírez‐Lluch Mar , Colmenero Isabel , Mateos‐Mayo Ana , Torrelo Antonio , Hernández‐Martin Ángela
Published: January 2021

Pigmented purpuric dermatoses (PPDs) are a group of idiopathic, chronic, and self‐resolving conditions easily recognizable in adults but extremely uncommon in infants. We present the youngest patient with PPD reported to date.
Evaluation of antimicrobial photodynamic activities of 5‐aminolevulinic acid derivatives
Authors: Sajjad Faiza , Sun Ning‐Ning , Chen Ting , Yan Yi‐Jia , Margetić Davor , Chen Zhi‐Long
Published: January 2021

Background

Antibiotic resistance is increasing day by day, thereby increase the chances of more infections by resistant bacteria. In this situation, antimicrobial photodynamic therapy (aPDT) is gaining more attraction.

Objective

To evaluate the antimicrobial effect of ALA derivatives using photodynamic therapy.

Materials and methods

In this study, we evaluated the aPDT effect of different derivatives of 5‐ALA. In vivo and in vitro studies were performed to measure the antimicrobial activity. Different light doses and different concentrations of drugs were used to test anti‐bacterial effect of drugs as well as to detect any physiological changes in animal model after the treatment.

Results

In vivo studies revealed that ALA‐methyl ester, ALA‐hexyl ester, and ALA‐13A are potent photosensitizers. In vitro studies involved wound healing rate, body weight, and dietary intake were evaluated, and results showed that ALA, ALA‐methyl ester, ALA‐hexyl ester, and ALA‐13A had good anti‐bacterial effects, fast healing rate, and no effect on other physical parameters.

Conclusion

Photodynamic therapy is increasingly used to treat different types of skin infections caused by bacterial strains. Our studies revealed that ALA‐methyl ester, ALA‐hexyl ester, and ALA‐13A are promising photosensitizers for photodynamic therapy to inhibit the growth of resistant bacterial strains.
High‐frequency (22‐MHz) ultrasound for assessing the depth of basal cell carcinoma invasion
Authors: Barcaui Elisa de Oliveira , Carvalho Antonio Carlos Pires , Valiante Paulo Marcos , Piñeiro‐Maceira Juan , Barcaui Carlos Baptista
Published: January 2021

Background

High‐frequency ultrasound (HFUS) has been studied in the diagnosis and therapeutic management of basal cell carcinoma (BCC). The accuracy of this method for location of deep margins remains unknown. This study evaluates HFUS for localization of deep surgical margins in BCC.

Materials and Methods

Ultrasound images of 83 lesions from 67 patients with clinical and dermoscopic diagnosis of BCC were compared with histopathological findings. Pearson's correlation coefficient was used to assess the relationship between thickness as measured by HFUS and histopathology.

Results

A strong correlation between HFUS and histopathological measurements was identified (r = 0.9744, P < .001). HFUS had sensitivity of 96%, specificity of 84%, and accuracy of 91% for measurement of deep tumor margins. Factors affecting tumor measurement on HFUS include marked basophilic degeneration of collagen, presence of peritumoral hypertrophic glands or hair follicles, fibrosis, and dense inflammatory changes related to the tumor itself or to prior procedures.

Conclusion

High‐frequency ultrasound was effective in localizing deep tumor margins in BCC. Therefore, we believe that this diagnostic imaging method is important when selecting a therapeutic approach, considering Mohs micrographic surgery, and evaluating the surgical site.
Tubulin glycylation controls axonemal dynein activity, flagellar beat, and male fertility
Authors: Gadadhar Sudarshan , Alvarez Viar Gonzalo , Hansen Jan Niklas , Gong An , Kostarev Aleksandr , Ialy-Radio Côme , Leboucher Sophie , Whitfield Marjorie , Ziyyat Ahmed , Touré Aminata , Alvarez Luis , Pigino Gaia , Janke Carsten
Published: January 2021

Glycylation regulates axonemal dyneins

Physiological functions of the microtubule cytoskeleton are expected to be regulated by a variety of posttranslational tubulin modifications. For instance, tubulin glycylation is almost exclusively found in cilia and flagella, but its role in the function of these organelles remains unclear. Gadadhar
et al.
now demonstrate in mice that glycylation, although nonessential for the formation of cilia and flagella, coordinates the beat waveform of sperm flagella. This activity is a prerequisite for progressive sperm swimming and thus for male fertility. At the ultrastructural level, lack of glycylation perturbed the distribution of axonemal dynein conformations, which may explain the observed defects in flagellar beat.

Science
, this issue p.
eabd4914
Crossover from hydrogen to chemical bonding
Authors: Dereka Bogdan , Yu Qi , Lewis Nicholas H. C. , Carpenter William B. , Bowman Joel M. , Tokmakoff Andrei
Published: January 2021

The nature of short hydrogen bonds

Hydrogen bonding (H-bonding) unquestionably plays an important role in chemical and biological systems and is responsible for some of their unusual properties. Strong, short H-bonds constitute a separate class that, owing to their elusive characterization, has remained a point of contention over the past several decades. Using femtosecond two-dimensional infrared spectroscopy in conjunction with quantum chemical calculations, Dereka
et al.
demonstrate a powerful way to investigate the nature of short H-bonding (see the Perspective by Bonn and Hunger). Their quantitative characterization of multiple coupled motions in the model system of bifluoride anion [F-H-F]
−
in aqueous solution reveals several distinctive features of a crossover from conventional to short, strong H-bonding.

Science
, this issue p.
160
see also p.
123
Categorizing Susceptibility of Clinical Isolates of
Candida auris
to Amphotericin B, Caspofungin, and Fluconazole by Use of the CLSI M44-A2 Disk Diffusion Method
Authors: Nunnally Natalie S. , Damm Tajah , Lockhart Shawn R. , Berkow Elizabeth L.
Published: January 2021

We evaluated the CLSI M44ed3E disk diffusion method compared with the CLSI M27ed4 broth microdilution method for caspofungin and fluconazole and the Etest method for amphotericin B to categorize susceptibility of 347 clinical isolates of
Candida auris
. Utilizing the zone diameter cutoffs established here, we observed overall categorical agreement between the two methods.
Unusual presentation of sarcoidosis, requiring a positron emission tomography/CT (PET/CT) for diagnosis
Authors: O'Riordan Kenneth , Mohyuddin Tauseef , Moloney Manus
Published: January 2021

A 43-year-old man presented to hospital after routine laboratory tests showed an acute kidney injury and hypercalcaemia. He had no relevant medical history and normal physical examination, other than a 6-week history of lower back pain for which he had been taking naproxen. Low parathyroid hormone (PTH) levels indicated a PTH-independent hypercalcaemia. Investigations including CT of thorax, abdomen and pelvis and subsequent bone biopsy and renal biopsy were unremarkable. Positron emission tomography/CT (PET/CT) scan was ultimately considered as a diagnostic test and showed abnormalities in the right subpectoral and portacaval region with intense fluorodeoxyglucose F 18 uptake in local lymph nodes. A biopsy of the right subpectoral node showed granulomatous change consistent with sarcoidosis. PET/CT scanning can play an important role in the investigation of suspected malignancy, infection and inflammatory disease and in this case, was required to diagnose an atypical presentation of sarcoidosis.
Extra-Levator AbdominoPerineal excision (eLAPE): a complicated postoperative perineal hernia
Authors: Harris Holly , Ray Kausik , Swaminathan Christie
Published: January 2021

A 75-year-old woman presented with perineal wound dehiscence and small bowel prolapse of a perineal hernia, 6 years after extra-Levator AbdominoPerineal Excision (eLAPE) procedure for rectal cancer. She underwent emergency wound refashioning and perineal hernia repair with Parmacol mesh. Her postoperative recovery was complicated by long-standing ileus, wound infection, and she was discharged to community palliative care services. In this case report, we raise awareness of postoperative eLAPE complications and describe an unfortunate case where a postoperative perineal hernia was not repaired in a patient with multiple comorbidities.
Steroid-refractory PD-(L)1 pneumonitis: incidence, clinical features, treatment, and outcomes
Authors: Balaji Aanika , Hsu Melinda , Lin Cheng Ting , Feliciano Josephine , Marrone Kristen , Brahmer Julie R , Forde Patrick M , Hann Christine , Zheng Lei , Lee Valerie , Illei Peter B , Danoff Sonye K , Suresh Karthik , Naidoo Jarushka
Published: January 2021

Background

Immune-checkpoint inhibitor (ICI)-pneumonitis that does not improve or resolve with corticosteroids and requires additional immunosuppression is termed steroid-refractory ICI-pneumonitis. Herein, we report the clinical features, management and outcomes for patients treated with intravenous immunoglobulin (IVIG), infliximab, or the combination of IVIG and infliximab for steroid-refractory ICI-pneumonitis.

Methods

Patients with steroid-refractory ICI-pneumonitis were identified between January 2011 and January 2020 at a tertiary academic center. ICI-pneumonitis was defined as clinical or radiographic lung inflammation without an alternative diagnosis, confirmed by a multidisciplinary team. Steroid-refractory ICI-pneumonitis was defined as lack of clinical improvement after high-dose corticosteroids for 48 hours, necessitating additional immunosuppression. Serial clinical, radiologic (CT imaging), and functional features (level-of-care, oxygen requirement) were collected preadditional and postadditional immunosuppression.

Results

Of 65 patients with ICI-pneumonitis, 18.5% (12/65) had steroid-refractory ICI-pneumonitis. Mean age at diagnosis of ICI-pneumonitis was 66.8 years (range: 35–85), 50% patients were male, and the majority had lung carcinoma (75%). Steroid-refractory ICI-pneumonitis occurred after a mean of 5 ICI doses from PD-(L)1 start (range: 3–12 doses). The most common radiologic pattern was diffuse alveolar damage (DAD: 50%, 6/12). After corticosteroid failure, patients were treated with: IVIG (n=7), infliximab (n=2), or combination IVIG and infliximab (n=3); 11/12 (91.7%) required ICU-level care and 8/12 (75%) died of steroid-refractory ICI-pneumonitis or infectious complications (IVIG alone=3/7, 42.9%; infliximab alone=2/2, 100%; IVIG + infliximab=3/3, 100%). All five patients treated with infliximab (5/5; 100%) died from steroid-refractory ICI-pneumonitis or infectious complications. Mechanical ventilation was required in 53% of patients treated with infliximab alone, 80% of those treated with IVIG + infliximab, and 25.5% of those treated with IVIG alone.

Conclusions

Steroid-refractory ICI-pneumonitis constituted 18.5% of referrals for multidisciplinary irAE care. Steroid-refractory ICI-pnuemonitis occurred early in patients’ treatment courses, and most commonly exhibited a DAD radiographic pattern. Patients treated with IVIG alone demonstrated an improvement in both level-of-care and oxygenation requirements and had fewer fatalities (43%) from steroid-refractory ICI-pneumonitis when compared to treatment with infliximab (100% mortality).
Add-on azithromycin reduces sputum cytokines in non-eosinophilic asthma: an AMAZES substudy
Authors: Shukla Shakti D , Taylor Steven L , Gibson Peter G , Barker Daniel , Upham John W , Yang Ian A , Reynolds Paul N , Hodge Sandra , James Alan L , Rogers Geraint B , Simpson Jodie L
Published: January 2021

Add-on azithromycin (AZM) significantly reduces exacerbations in poorly controlled asthma irrespective of disease phenotype. In a predefined substudy of the original AMAZES protocol (500 mg, three times a week for 48 weeks), we report that AZM treatment reduces key sputum inflammatory proteins (interleukin (IL)-6, IL-1β and extracellular DNA), which is more evident in non-eosinophilic asthma (NEA). Moreover, AZM reduced
Haemophilus influenzae
load only in NEA. Our data support the anti-inflammatory effects of AZM in poorly controlled asthma. Prospective studies are required to identify patients that derive greatest benefit from AZM add-on therapy.
Shortening of Proof Length is Elusive for Theorem Provers
Authors: Hernández-Orozco Santiago , Hernández-Quiroz Francisco , Zenil Hector , Sieg Wilfried
Published: January 2021

There are many examples of failed strategies whose intention is to optimize a process but instead they produce worse results than no strategy at all. Many fall under the loose umbrella of the “no free lunch theorem”. In this paper we present an example in which a simple (but assumedly naive) strategy intended to shorten proof lengths in the propositional calculus produces results that are significantly worse than those achieved without any method to try to shorten proofs.This contrast with what was to be expected intuitively, namely no improvement in the length of the proofs. Another surprising result is how early the naive strategy failed. We set up a experiment in which we sample random classical propositional theorems and then feed them to two very popular automatic theorem provers (AProS and Prover9). We then compared the length of the proofs obtained under two methods: (1) the application of the theorem provers with no additional information; (2) the addition of new (redundant) axioms to the provers. The second method produced even longer proofs than the first one.
Relaxation behaviors of star polymers in the grid model
Authors: Yu Xu-Chen , Hou Ji-Xuan
Published: January 2021

The tube theory has made a detailed description for the linear polymer entangled system, while the behavior of entangled star polymers is still determined by a qualitative prediction. In this paper, the dynamical simulation of a three-arms star polymer in the grid model is presented. We record the diffusion coefficient [Formula: see text], the relaxation time for the arms of star polymer [Formula: see text] and some other parameters corresponding to different branch length. Therefore, results that are inconsistent with the theoretical begin to emerge.
Origin of megacrysts by carbonate-bearing metasomatism: a case study for the Muskox kimberlite, Slave craton, Canada
Authors: Cone Dylan , Kopylova Maya
Published: January 2021

Low-Cr and high-Cr clinopyroxene, garnet, olivine and ilmenite megacrysts from the Muskox kimberlite (Canada) were analysed for major and trace elements, as well as Sr, Nd and Pb isotopes. Samples display compositional overlap with respective phases in websterites, and clinopyroxene isotope systematics reveal similarities to both websteritic and metasomatic clinopyroxene in peridotites from the same kimberlite, in addition to Muskox and Jericho kimberlites. All lithologies may represent the products of mixing between EM1 mantle, relict Proterozoic enriched mantle and HIMU carbonatitic fluid. Equilibrium melts calculated from clinopyroxene trace element data using experimental distribution coefficients for feasible proto-kimberlitic melts yield a range of metasomatic agents. Conclusion on the carbonate-bearing nature of the metasomatism is based on the presence of a HIMU isotopic signature and results obtained from thermodynamic modelling using the Deep Earth Water model. Modelling was carried out with three fluid compositions; asthenospheric, eclogitic and kimberlitic. Our results suggest mineral compositions analogous to megacrysts cannot be produced by metasomatism of mantle peridotite by carbonate-free hydrous fluids. Isotope systematics argue against a strictly cognate relationship between megacrysts and their host kimberlite, instead suggesting that megacrysts and websterites may represent products of regional metasomatism by carbonatitic HIMU fluids shortly predating kimberlite magmatism.

Supplementary material:
A table containing parameters used in isotopic mixing models is available at
https://doi.org/10.6084/m9.figshare.c.5255825
New Drugs, Old Targets: Tweaking the Dopamine System to Treat Psychostimulant Use Disorders
Authors: Newman Amy Hauck , Ku Therese , Jordan Chloe J. , Bonifazi Alessandro , Xi Zheng-Xiong
Published: January 2021

The abuse of illicit psychostimulants such as cocaine and methamphetamine continues to pose significant health and societal challenges. Despite considerable efforts to develop medications to treat psychostimulant use disorders, none have proven effective, leaving an underserved patient population and unanswered questions about what mechanism(s) of action should be targeted for developing pharmacotherapies. As both cocaine and methamphetamine rapidly increase dopamine (DA) levels in mesolimbic brain regions, leading to euphoria that in some can lead to addiction, targets in which this increased dopaminergic tone may be mitigated have been explored. Further, understanding and targeting mechanisms underlying relapse are fundamental to the success of discovering medications that reduce the reinforcing effects of the drug of abuse, decrease the negative reinforcement or withdrawal/negative affect that occurs during abstinence, or both. Atypical inhibitors of the DA transporter and partial agonists/antagonists at DA D3receptors are described as two promising targets for future drug development.
A Serendipitous Path to Pharmacology
Authors: Olivera Baldomero M.
Published: January 2021

My path to research in neuropharmacology has been a coalescing of my training as a molecular biologist and my intense interest in an esoteric group of animals, the fish-hunting cone snails. Attempting to bridge these two disparate worlds has led me to an idiosyncratic career as a pharmacologist.
Cholinergic Capsules and Academic Admonitions
Authors: Taylor Palmer
Published: January 2021

Herein, I intend to capture highlights shared with my academic and research colleagues over the 60 years I devoted initially to my graduate and postdoctoral training and then to academic endeavors starting as an assistant professor in a new medical school at the University of California, San Diego (UCSD). During this period, the Department of Pharmacology emerged from a division within the Department of Medicine to become the first basic science department, solely within the School of Medicine at UCSD in 1979. As part of the school's plans to reorganize and to retain me at UCSD, I was appointed as founding chair. Some years later in 2002, faculty, led largely within the Department of Pharmacology and by practicing pharmacists within UCSD Healthcare, started the independent Skaggs School of Pharmacy and Pharmaceutical Sciences with a doctor of pharmacy (PharmD) program, where I served as the founding dean. My career pathway, from working at my family-owned pharmacy to chairing a department in a school of medicine and then becoming the dean of a school of pharmacy at a research-intensive, student-centered institution, involved some risky decisions. But the academic, curricular, and accreditation challenges posed were met by a cadre of creative faculty colleagues. I offer my experiences to individuals confronted with a multiplicity of real or imagined opportunities in academic health sciences, the related pharmaceutical industry, and government oversight agencies.
Effect of muscle stimulation intensity on the heterogeneous function of regions within an architecturally complex muscle
Authors: Tijs Chris , Konow Nicolai , Biewener Andrew A.
Published: January 2021

We show that muscle compartmentalization can influence whole muscle contractile properties, with slower-fibered proximal rat medial gastrocnemius undergoing larger changes in pennation angle and architectural gearing, whereas the faster-fibered distal region achieves greater peak and optimal shortening velocity, and power output. Consequently, regional variation in motor recruitment can fundamentally influence functional patterns within a single muscle.
Effect of Sodium Aluminate Dosage as a Solid Alkaline Activator on the Properties of Alkali‐Activated Slag Paste
Authors: Chen Bin , Wang Jun , Zhao Jinyou
Published: January 2021

Extensive research into alkali‐activated slag as a green gel material to substitute for cement has been done because of the advantages of low‐carbon dioxide emissions and recycling of industrial solid waste. Alkali‐activated slag usually has good mechanical properties, but the too fast setting time restricted its application and promotion. Changing the composition of alkaline activator could optimize setting time, usually making it by adding sodium carbonate or sodium sulfate but this would cause insufficient hydration reaction power and hinder compressive strength growth. In this paper, the effect of sodium aluminate dosage as an alkaline activator on the setting time, fluidity, compressive strength, hydration products, and microstructures was studied through experiments. It is fair to say that an appropriate amount of sodium aluminate could obtain a suitable setting time and better compressive strength. Sodium aluminate provided enough hydroxyl ions for the paste to promote the hydration reaction process that ensured obtaining high compressive strength and soluble aluminium formed precipitate wrapped on the surface of slag to inhibit the hydration reaction process in the early phase that prolonged setting time. The hydration mechanism research found that sodium aluminate played a key role in the formation of higher cross‐linked gel hydration products in the late phase of the process. Preparing an alkali‐activated slag with excellent mechanical properties and suitable setting time will significantly contribute to its application and promotion.
Conditions for Setting Exclusive Pedestrian Phases at Two-Phase Signalized Intersections considering Pedestrian-Vehicle Interaction
Authors: Wang Jiawen , Yang Chengcheng , Zhao Jing
Published: January 2021

In order to analyze the effectiveness of setting exclusive pedestrian phase (EPP) under different vehicle yielding rates, the effect of EPPs on traffic efficiency is studied and a setting condition of EPP considering pedestrian-vehicle interaction is proposed in this paper. First, the main factors influencing the behavior of vehicles and pedestrians during pedestrian-vehicle interaction are analyzed, and a pedestrian-vehicle interaction (PVI) model at the crosswalk of urban road is established. Second, assuming that vehicle arrival obeys the Poisson distribution, the delay models of vehicle passengers and pedestrians crossing the street at the intersection are established, and taking the total delay of traffic participants as the main index, the setting condition of EPP are proposed. Third, based on the video of pedestrian-vehicle interaction at crosswalks, the parameters of the proposed model are calibrated. Through sensitivity analysis, the change of the total delay of traffic participants is analyzed under different conditions of pedestrian and vehicle arrival rates. Finally, by introducing pedestrian-vehicle interaction rules, a cellular automata (CA) simulation platform of pedestrian-vehicle interaction in crosswalk is established; based on the field data of Shanghai, a simulation model of intersection is established, and the total delay, queue length, and vehicle throughput under conventional signal control plan and EPP plan are compared. The results show that the pedestrian-vehicle interaction process has a great influence on the total delay of traffic participants at intersections, and pedestrian-vehicle interaction should be considered in the setting conditions of EPP. Under the same condition of vehicular flow, the more the pedestrian flow is, the smaller the delay increment will be. The higher the vehicle yielding rate is, the smaller the delay increment will be after setting EPP.
The Effectiveness of Scutellaria baicalensis on Migraine: Implications from Clinical Use and Experimental Proof
Authors: Liao Chung-Chih , Liao Ke-Ru , Lin Cheng-Li , Li Jung-Miao
Published: January 2021

Background. Scutellaria baicalensis (SB), a traditional Chinese medicine, is commonly used for the treatment of inflammatory and painful conditions. The purpose of the present study was to examine the effects of SB on migraine. Materials and Methods. We examined the clinical applications of SB based on the data obtained from Taiwan’s National Health Insurance Research Database and confirmed that it was frequently used in Taiwan for the treatment of headaches. An experimental migraine model was established in rats by an intraperitoneal injection of nitroglycerin (NTG, 10 mg/kg). Pretreatment with SB was given orally 30 min before NTG administration. The rats were subjected to migraine-related behaviour tests that were video-recorded and analysed using EthoVision XT 12.0 software. Results. The frequency of exploratory and locomotor behaviour was comparatively lower in the NTG group than that in the control group, while the frequency of resting and grooming behaviour increased. These phenomena were ameliorated by pretreatment with 1.0 g/kg SB. The total time spent on the smooth surface was longer in the NTG group than that in the control group, but the time was shortened by pretreatment with 1.0 g/kg SB. Conclusions. Pretreatment with 1.0 g/kg SB relieved migraine-related behaviours in the experimental NTG-induced migraine model. The outcome therefore demonstrated that pretreatment with 1.0 g/kg SB is beneficial for migraine treatment.
Patients’ and Health Professionals’ Experiences of Group Training to Increase Intensity of Training after Acquired Brain Injury: A Focus Group Study
Authors: Hansen Gunhild Mo , Brunner Iris , Pallesen Hanne
Published: January 2021

Background. Increased intensity of training in the subacute phase after acquired brain injury facilitates plasticity and enhances better function. Group training can be a motivating factor and an effective means of increasing intensity. Reports on patients’ and health care professionals’ experiences on increasing the amount of active practice through group training during in-patient rehabilitation after acquired brain injury have been limited. Methods. Two focus groups, patients and health care professionals, participated each in two interviews, before and after implementation of the Activity block, i.e., 2-hour daily intensive group training. The data from the interviews were analyzed from a phenomenological perspective. Results. Three categories emerged from the data analyzes (i) training intensity, (ii) motivation and meaningfulness, and (iii) expectations and concerns. Both groups experienced that the training after implementation of the Activity block had become more intense and that motivation was increased induced by the group setting. Also, both groups found self-management enhanced. Some challenges were also reported. Patients expressed concerns to finding a balance between rest and activity, while the health professionals mentioned practical challenges, i.e., planning the content of the day and finding their role in the Activity block. Conclusion. Activity block benefitted a heterogeneous group of patients with acquired brain injury and was perceived as an overall positive experience by patients and health personnel. Matching the training to the individuals’ need for support, finding a balance between rest and activity and using tasks that support patients’ motivation, appeared important.