bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunotherapy choice and maintenance for generalized myasthenia gravis in China
Authors: Zhang Chao , Bu Bitao , Yang Huan , Wang Lihua , Liu Weibin , Duan Rui‐Sheng , Zhang Meini , Zeng Pei , Du Chen , Yang Li , Shi Fu‐Dong
Published: October 2020

Aims

To compare long‐term efficacy and safety of immunotherapeutic strategies as maintenance to prevent disease relapses of generalized myasthenia gravis (MG) in real‐world settings.

Methods

This is a retrospective cohort study on generalized MG conducted in seven major neurological centers across China. Eligible participants were patients with generalized MG who were under minimal manifestation status or better. Main outcome measures were probability of patients free of relapses and causes of drug discontinuation.

Results

Among 1064 patients enrolled, the median (interquartile range) age was 50.3 (37.0‐62.5) years and 641 (60.2%) were women. Disease relapse was significantly lower for rituximab (6.1%) compared with all the other monotherapies (hazard ratio [HR] = 0.18, 95% confidence interval [CI] 0.06 to 0.56, P = .0030). As combination therapies, tacrolimus in combination with corticosteroids reduced risk of disease relapses compared with azathioprine with corticosteroids (HR = 0.45, 95% CI 0.25 to 0.81, P = .0077) or mycophenolate mofetil with corticosteroids (HR = 0.32, 95% CI 0.15 to 0.67, P = .0020). Otherwise, lower‐dose corticosteroids or azathioprine as monotherapy significantly increased risk of disease relapses (HR = 2.78, 95% CI 1.94 to 3.99, P < .0001; HR = 2.14, 95% CI 1.42 to 3.23, P = .0003, respectively). The proportion of discontinuation was lowest in patients with rituximab (20.4%) as monotherapy and tacrolimus with corticosteroids (23.6%). Overall, combination treatment of immunosuppressants with corticosteroids had a lower rate of discontinuation compared with corresponding monotherapy (HR = 0.51, 95% CI 0.36 to 0.71, P < .0001).

Conclusions

Rituximab as monotherapy and tacrolimus with corticosteroids displayed better clinical efficacy as well as drug maintenance to prevent disease relapses in patients with generalized MG.
When a sentence loses semantics: Selective involvement of a left anterior temporal subregion in semantic processing
Authors: Iwabuchi Toshiki , Makuuchi Michiru
Published: October 2020

Although the left anterior temporal lobe (ATL) has been associated with semantic processing, the role of this region in syntactic structure building of sentences remains a subject of debate. Functional neuroimaging studies contrasting well‐formed sentences with word lists lacking syntactic structure have produced mixed results. The current functional magnetic resonance imaging study examined whether the left ATL is selectively involved in semantic processing or also plays a role in syntactic structure building by manipulating syntactic complexity and meaningfulness in a novel way. To deprive semantic/pragmatic information from a sentence, we replaced all content words with pronounceable meaningless placeholders. We conducted an experiment with a 2 × 2 factorial design with factors of SEMANTICS (natural sentences [NAT]; sentences with placeholders [SPH]) and SYNTAX (the basic Japanese Subject‐Object‐Verb [SOV] word order; a changed Object‐Subject‐Verb [OSV] word order). A main effect of SEMANTICS (NAT > SPH) was found in the left ATL, as well as in the ventral occipitotemporal regions. The opposite contrast (SPH > NAT) revealed activation in the dorsal regions encompassing Brodmann area 44, the premotor area, and the parietal cortex in the left hemisphere. We found no main effect of SYNTAX (OSV > SOV) in a subregion of the left ATL that was more responsive to natural sentences than meaningless sentences. These results indicate selective involvement of a subregion of the left ATL in semantic/pragmatic processing.
Fatigue crack growth in micro specimens as a tool to measure crack–microstructure interactions
Authors: Grünewald Patrick , Rauber Jonas , Marx Michael , Motz Christian , Schaefer Florian
Published: October 2020

The process of short fatigue crack growth plays a significant role for the lifetime of materials in the high and very high cycle regimes. Fatigue crack growth is strongly influenced by interactions with microstructural obstacles, such as grain boundaries or phase boundaries, requiring a better understanding of these interactions to enhance the lifetime in these load regimes and improve lifetime calculations. Although it is possible to obtain crack growth rates from fatigue cracks in the lower micrometre range, further information like the exact position and type of the obstacle are mostly unavailable during the experiment. To overcome this issue, we propose a testing methodology of fatigue crack growth in micro specimens, which allows for an exact positioning of the crack relative to the obstacles and for monitoring the crack behaviour in a scanning electron microscope. The capabilities of this method are demonstrated for the interaction of fatigue cracks with grain boundaries.
Patient reactions to witnessed medical events in the dialysis center or to the sudden absence of other patients from the center: A qualitative study
Authors: Ramer Sarah J. , Reid M. Carrington , Unruh Mark L.
Published: October 2020

Introduction

Patients receiving in‐center maintenance hemodialysis (HD) spend a significant amount of time together. To date, little or no research has examined how these patients perceive and process other patients' medical events in and absences from their centers. We therefore undertook this qualitative study using semi‐structured interviews to explore these phenomena from the patient perspective.

Methods

Patients at a suburban Pittsburgh HD center participated in semi‐structured interviews in April to May 2011, reporting on their impressions of their relationships with other patients in the center; their experiences of witnessing clinical decompensations in the center; and their reactions to absences of fellow patients from the center. Trained coders developed a codebook and applied it to interview transcripts.

Findings

There were 17 participants, 47% women, 29% black, with median age 63 years. Almost every participant had witnessed other patients' medical events during HD. Three main themes emerged in analysis of interviews: (1) incomplete knowledge of many aspects of witnessed events and patient absences in the HD center; (2) a process of “filling in the blanks”: Participants used their own past events and absences to help process other patients' events and absences and used other patients' events and absences to help process their own future events and absences; and (3) participants' broad support for HD center staff being able to share with other patients basic information about their whereabouts if they themselves are absent from the center.

Discussion

Witnessed medical events in and patients' absences from the HD center are not only common but are also important to patients, who struggle to process these events and absences due to limited information about what actually happened. Interventions, such as providing patients with more information, could improve patients' experience of witnessed events and fellow patients' absences and potentially impact other patient‐centered outcomes.
Cost analysis of two modalities of continuous renal replacement therapy
Authors: Duriseti Parikshit , Idrees Najia , Aldairem Atheer , Jaber Bertrand L. , Balakrishnan Vaidyanathapuram S.
Published: October 2020

Background

Continuous veno‐venous hemofiltration (CVVH) and continuous veno‐venous hemodialysis (CVVHD) are costly therapies reserved for use in critically ill patients with kidney failure.

Design

Quality improvement study at St. Elizabeth's Medical Center, Boston, MA, USA.

Setting and participants

Members of nephrology and pharmacy department, working alongside intensive care unit nursing staff and hospital administration, undertook an initiative to transition from CVVH to CVVHD, to simplify therapy administration, lessen need for electrolyte repletion, and reduce total treatment‐related costs.

Quality improvement plan

We postulated that conversion from CVVH to CVVHD would result in fewer filter clotting events, longer filter use (up to 72 hours), lower resource utilization, and confer overall cost benefit. Over 12 months, patients initiated on CVVH were identified. Following conversion to CVVHD, patients initiated on CVVHD over 9 months were identified. Patient characteristics, comorbidities, and hospital‐related outcomes, as well as CRRT‐related information including treatment modality, treatment duration, and treatment‐related costs were obtained.

Measures

Daily treatment‐related costs, intensive care unit and hospital length of stay (LOS), and in‐hospital mortality.

Results

During the baseline period, 77 patients were initiated on CVVH, and during the intervention period, 60 patients were initiated on CVVHD. Following conversion from CVVH to CVVHD, mean (±SD) daily total treatment cost decreased from $1813 ± $2143 to $775 ± $766 (P < 0.001). Conversion from CVVH to CVVHD had no impact on intensive care unit LOS (11.8 ± 9.7 vs. 12.4 ± 9.5 days; P = 0.53), hospital LOS (15.0 ± 11.1 vs. 16.4 ± 14.0 days; P = 0.89), or in‐hospital mortality (58% vs. 60%; P = 0.85).

Limitations

Nursing costs, costs of dialysis machine utilization, phosphate repletion, and systemic anti‐coagulation were not studied.

Conclusion

Transition from CVVH to CVVHD resulted in a significant cost benefit and reduced resource utilization. There was no difference in LOS and in‐hospital mortality between the two treatment modalities.
Uterine plexiform tumourlets: multifocal and solitary cases with subsets expressing melanocytic markers
Authors: Stewart Colin J R , McCluggage W Glenn , Chua Yee J , Texler Michael , Rabban Joseph T
Published: October 2020

Aims

Uterine plexiform tumourlets are traditionally regarded as microscopic epithelioid leiomyomas. They are typically solitary incidental findings, but may be multifocal (plexiform leiomyomatosis). We aim to report novel immunohistochemical and morphological findings, specifically the presence of spindled and epithelioid cell nodules, in these lesions.

Methods and results

Three cases of plexiform leiomyomatosis and 16 solitary plexiform tumourlets were included. Two cases of plexiform leiomyomatosis and four solitary plexiform tumourlets demonstrated spindled and epithelioid cell nodules which, in one of the former cases, formed expansile masses up to 15 mm. The nodules demonstrated mild cytological atypia and occasional mitotic activity, and they were associated with a myxoid stroma and a lymphohistiocytic infiltrate which imparted a granulomatous appearance to the microscopic lesions. The plexiform tumourlets (solitary and multifocal) consistently expressed desmin, smooth muscle actin, ER and PR, and they commonly co‐expressed melanocytic and perivascular epithelioid cell (PEC) markers HMB45, MiTF and cathepsin K. The spindled and epithelioid cell nodules were generally negative for myoid markers and hormone receptors, but expressed p16, cyclin D1 and TFE3. All lesions tested were negative for cytokeratin, S100, melanA, inhibin, EMA, ALK and BCOR; fluorescence in‐situ hybridisation was negative for ALK, TFE3 and BCOR rearrangements in one of the larger spindled and epithelioid cell nodules.

Conclusions

Plexiform tumourlets commonly co‐express myoid and melanocytic markers and may represent part of the spectrum of gynaecological PEC‐related lesions. Some cases are associated with spindled and epithelioid cell nodules that could potentially mimic other uterine myxoid neoplasms.
Reduction in flippase activity contributes to surface presentation of phosphatidylserine in human senescent erythrocytes
Authors: Seki Momoko , Arashiki Nobuto , Takakuwa Yuichi , Nitta Kosaku , Nakamura Fumio
Published: October 2020

Mature human erythrocytes circulate in blood for approximately 120 days, and senescent erythrocytes are removed by splenic macrophages. During this process, the cell membranes of senescent erythrocytes express phosphatidylserine, which is recognized as a signal for phagocytosis by macrophages. However, the mechanisms underlying phosphatidylserine exposure in senescent erythrocytes remain unclear. To clarify these mechanisms, we isolated senescent erythrocytes using density gradient centrifugation and applied fluorescence‐labelled lipids to investigate the flippase and scramblase activities. Senescent erythrocytes showed a decrease in flippase activity but not scramblase activity. Intracellular ATP and K+, the known influential factors on flippase activity, were altered in senescent erythrocytes. Furthermore, quantification by immunoblotting showed that the main flippase molecule in erythrocytes, ATP11C, was partially lost in the senescent cells. Collectively, these results suggest that multiple factors, including altered intracellular substances and reduced ATP11C levels, contribute to decreased flippase activity in senescent erythrocytes in turn to, present phosphatidylserine on their cell membrane. The present study may enable the identification of novel therapeutic approaches for anaemic states, such as those in inflammatory diseases, rheumatoid arthritis, or renal anaemia, resulting from the abnormally shortened lifespan of erythrocytes.
Periodontal disease and emotional disorders: A meta‐analysis
Authors: Zheng De‐Xiu , Kang Xiao‐Ning , Wang Yi‐Xi , Huang Yi‐Na , Pang Chun‐Feng , Chen Yu‐Xuan , Kuang Zhi‐Li , Peng Yun
Published: October 2020

Objective

The objective of this study was to evaluate the relationship of periodontal disease with depression and anxiety via a systematic review and meta‐analysis.

Method

We systematically searched the EMBASE, PubMed, Web of Science, PsycINFO, and SinoMed databases (until August 4, 2019) with language restricted to English and Chinese. Case–control, cross‐sectional, and cohort studies that calculated the risk ratio (RR), odds ratio (OR)/prevalence OR (POR), and hazard ratio (HR) of depression/anxiety with periodontal disease or the OR/POR/RR/HR of periodontal disease caused by depression/anxiety were included. Observational studies that reported the depression/anxiety scale score of patients with periodontal disease and healthy periodontal subjects aged ≥14 years were also included.

We used the standard format to extract the following information from each included study: author/s, survey year, study design, age of participants, periodontal disease definition, depression/anxiety measurement, and summary of results. The Newcastle–Ottawa scale was used to ascertain the quality of the included citations.

Results

After screening, 40 studies were included. A meta‐analysis of the case–control studies showed that periodontal disease was positively associated with depression (OR = 1.70, 95% confidence interval [CI]  = 1.01–2.83). A meta‐analysis of 12 studies showed that periodontal disease was significantly correlated with anxiety (OR = 1.36, 95% CI = 1.11–1.66). A meta‐analysis of 18 studies showed that subjects with periodontal disease had higher depression scale score (standardized mean difference [SMD] = 1.05, 95% CI = 0.68–1.41) and anxiety scale score (SMD = 0.70, 95% CI = 0.44–0.96).

Conclusion

Periodontal disease is associated with emotional disorders. However, the high degree of heterogeneity among studies should be considered. More high‐quality prospective studies are required to confirm the relationship.
Randomized controlled study for the anti‐aging effect of human adipocyte‐derived mesenchymal stem cell media combined with niacinamide after laser therapy
Authors: Lee Young In , Kim Soomin , Kim Jihee , Kim Jemin , Chung Kyung Bae , Lee Ju Hee
Published: October 2020

Background

Recent advancements in laser‐assisted drug delivery have emphasized the importance of post‐laser use of active ingredients.

Aims

We evaluated the effect of topical post‐laser treatment with adipocyte‐derived stem cell‐containing medium (ADSC‐CM) in combination with niacinamide through a double‐blind, randomized, vehicle‐controlled study.

Patients/Methods

Twenty‐five patients with aging skin underwent ablative fractional laser (AFL) treatment on both sides of the face for skin rejuvenation. Moisturizers with or without ADSC‐CM plus 2% niacinamide was applied to the designated sides of faces for 3 weeks. The wrinkle and the melanin indices were assessed using a specialized digital photography analyzer. Additional in vitro assays were performed.

Results

The wrinkle index, melanin index, patient satisfaction score, and the investigator's global esthetic improvement scale (GAIS) after use of ADSC‐CM plus niacinamide were significantly higher than after use of the vehicle cream. The in vitro UVB irradiation assays with human keratinocytes showed decreased levels of pro‐inflammatory cytokines upon incubation with ADSC‐CM plus niacinamide, and the cell scratch assay displayed decreased MMP‐1 and MMP‐2 expression as well as increased Type 1 collagen expression.

Conclusions

We demonstrated that post‐laser topical application of ADSC‐CM in combination with niacinamide has anti‐aging effect on skin.
Hydrocolloid dressings can be used to treat hypertrophic scars: An outpatient dermatology service devoted to treat keloids and challenging scars
Authors: de Oliveira Gisele Viana , Gold Michael H.
Published: October 2020

Since we first described the rationale for the use of hydrocolloid dressings to treat keloids and hypertrophic scars, this technique has been used as an occlusive therapy alternative to the use of silicone sheets in our outpatient clinic. In this paper, we describe the use of these dressings on two patients with challenging scars: a large postburn hypertrophic scar on a young patient's hand and arm, with a growing keloid on the wrist, and a progressive scar on the lower eyelid, developing after a complication of a cosmetic blepharoplasty procedure, leading to ectropium. The methods on the proper use of these dressings are reviewed here in detail. Larger clinical trials are needed to further evaluate this technique in the treatment of hypertrophic scars and keloids.
MORE Care: an evaluation of an interprofessional oral health quality improvement initiative
Authors: Kanan Christine , Ohrenberger Kelli , Bayham Mary , Raskin Sarah E. , Tranby Eric P. , Boynes Sean
Published: October 2020

Objective

This evaluation assesses the Medical Oral Expanded Care (MORE Care) initiative in four states that focused on oral health integration into primary care practices located in dental shortage areas.

Methods

This analysis is conducted using self‐reported primary data collected from each of the participating MORE Care clinics in South Carolina, Pennsylvania, Colorado and Oregon. Three measures: the percentage of pediatric patients with a) fluoride varnish applied, b) self‐management goals reviewed, and c) risk assessed, were evaluated to compare the impact and timing of change tactics on participating teams. An engagement dashboard tool was also hand coded with inductive codes using an adapted grounded theory approach common in applied health services research, to iteratively identify themes that could illuminate or explain quantitative findings.

Results

The average proportion of pediatric patients receiving fluoride varnish increased from 25 percent after the first collaborative learning session to 40 percent after the third collaborative learning session. The proportion of pediatric patients with self‐management goals reviewed also improved, increasing from 25 percent to 62 percent. There was more variation in the proportion of pediatric patients with oral health risk assessments completed increasing from 47 percent to 77 percent. Qualitative analysis of MORE Care open text data produced three themes related to facilitators and barriers of project implementation and criteria for project success.

Conclusions

The results of this analysis demonstrated that MORE Care is effective in creating an operational structure for integrating oral health care into primary care practices and most successful when participating clinics meet success criteria.
Intra‐specific trait variation remains hidden in the environment
Authors: Ahrens Collin W. , Rymer Paul D. , Tissue David T.
Published: October 2020

This article is a Commentary on Anderegg et al. (2021), 229: 1375–1387.
Human papillomavirus infection in esophageal squamous cell carcinoma and esophageal adenocarcinoma: a concise review
Authors: Rajendra Shanmugarajah , Pavey Darren , McKay Owen , Merrett Neil , Gautam Shweta Dutta
Published: October 2020

The causal link between high‐risk human papillomavirus (hr‐HPV) infection and cervical, anogenital, and some oropharyngeal malignancies has been established by both molecular and epidemiological data. The association between HPV and esophageal squamous cell carcinoma (ESCC) remains controversial, as is the true prevalence of HPV infection in ESCC. The wide range in reported rates reflects variability in the primary literature, with some larger scale case–control studies suggesting the infection rates range from 0% to 78%. Interactions between HPV and the Barrett's metaplasia–dysplasia–carcinoma sequence have been explored, and these studies have shown some conflicting data. Overall, systematic reviews have reported the prevalence of HPV‐positive DNA in esophageal adenocarcinoma patients of between 13% and 35%. Postulated reasons for discrepancies in HPV prevalence rates in esophageal cancer include variations in testing methodology and assay sensitivities; technical issues, including the lack of a gold‐standard primer; types of specimens utilized (fresh‐frozen versus formalin‐fixed tissue); geographical variation; cross‐contamination; and small sample sizes. Thus, efforts must be undertaken to (1) standardize HPV testing, ideally in a central laboratory and utilizing tests that detect viral transcriptional activity; (2) avoid cross‐contamination; and (3) recruit large numbers of patients to accurately ascertain HPV rates in esophageal malignancy.
Molecular hydrogen–induced salinity tolerance requires melatonin signalling inArabidopsis thaliana
Authors: Su Jiuchang , Yang Xinghao , Shao Yudong , Chen Ziping , Shen Wenbiao
Published: October 2020

Melatonin (MT) plays positive roles in salinity stress tolerance. However, the upstream signalling components that regulate MT are poorly understood. Here, we report that endogenous MT acts downstream of molecular hydrogen (H2) in the salinity response inArabidopsis. The addition of hydrogen‐rich water and expression of the hydrogenase1 gene (CrHYD1) fromChlamydomonas reinhardtiiincreased endogenous H2and MT levels and enhanced salinity tolerance. These results were not observed in the absence of serotoninN‐acetyltransferase gene (SNAT). H2increased the levels ofSNATtranscripts in the wild‐type andCrHYD1lines, which had lower Na+/K+ratios and higher levels of ion transport–related gene transcripts. These changes were not observed inatsnat/CrHYD1‐4hybrids. The increased MT‐dependent Na+extrusion observed in theCrHYD1plants resulted, at least in part, from enhanced Na+/H+antiport across the plasma membrane. The endogenous H2‐induced MT‐dependent regulation of ion and redox homeostasis was impaired in theatsnat/CrHYD1‐4hybrids. Taken together, these results demonstrate that MT‐induced salinity tolerance is induced by a H2signalling cascade that regulates ion and redox homeostasis in response to salinity.
Optimal Bayesian Demand Learning over Short Horizons
Authors: Wang Jue
Published: October 2020

We investigate the optimal Bayesian dynamic pricing and demand learning policy over short selling horizons, where the pricing decisions are time‐sensitive. The seller fine‐tunes the price near an incumbent price in order to maximize the total revenue. The existing literature focuses on policies that are asymptotically optimal, that is, near optimal when the selling horizons are sufficiently long, but little is known about the optimal Bayesian policies, especially over short horizons. We formulate the problem as a finite‐horizon stochastic dynamic program and identify a connection between the optimality equations and the generalized Weierstrass transform (GWT). We fully characterize the structure of the Bayesian optimal policy for the linear Gaussian demand model and prove that the optimal policy adjusts the myopic price away from the incumbent price. A notable exception occurs when the two prices coincide and the precision of the posterior belief exceeds a threshold, in which case it is optimal to forgo learning and use a fixed‐price policy. Exploiting the structural results makes it possible to compute the optimal policy efficiently on an ordinary computer.
Reflections on Continuity of Care and Risk of Readmission
Authors: Senot Claire
Published: October 2020

The article “Continuity of Care and Risk of Readmission: An Investigation into the Healthcare Journey of Heart Failure Patients” won the 2020 Ralph Gomory Best Industry Studies Paper Award. This award recognizes the valuable contributions provided by academic research that is anchored in a deep understanding of industries. In this article, I discuss how my interactions with practitioners challenged me and ultimately shaped many critical aspects of the awarded study.
Importance of Distributional Forms for the Assessment of Protozoan Pathogens Concentrations in Drinking‐Water Sources
Authors: Sylvestre Émile , Prévost Michèle , Smeets Patrick , Medema Gertjan , Burnet Jean‐Baptiste , Cantin Philippe , Villion Manuela , Robert Caroline , Dorner Sarah
Published: October 2020

The identification of appropriately conservative statistical distributions is needed to predict microbial peak events in drinking water sources explicitly. In this study, Poisson and mixed Poisson distributions with different upper tail behaviors were used for modeling source water Cryptosporidium and Giardia data from 30 drinking water treatment plants. Small differences (<0.5‐log) were found between the “best” estimates of the mean Cryptosporidium and Giardia concentrations with the Poisson–gamma and Poisson–log‐normal models. However, the upper bound of the 95% credibility interval on the mean Cryptosporidium concentrations of the Poisson–log‐normal model was considerably higher (>0.5‐log) than that of the Poisson–gamma model at four sites. The improper choice of a model may, therefore, mislead the assessment of treatment requirements and health risks associated with the water supply. Discrimination between models using the marginal deviance information criterion (mDIC) was unachievable because differences in upper tail behaviors were not well characterized with available data sets (). Therefore, the gamma and the log‐normal distributions fit the data equally well but may predict different risk estimates when they are used as an input distribution in an exposure assessment. The collection of event‐based monitoring data and the modeling of larger routine monitoring data sets are recommended to identify appropriately conservative distributions to predict microbial peak events.
Income inequality and macroeconomic instability
Authors: Memon Sonan , Qureshi Irfan A.
Published: October 2020

This paper examines the relationship between macroeconomic instability, as measured by the variance of inflation and output, and income inequality. We develop a panel data set consisting of 61 developed and developing economies for 1990–2019. Our results highlight a positive relationship between past inflation variance and subsequent inequality. We find that this relationship is nonexistent in developed countries but is strong for developing economies. Developing countries that have adopted an inflation targeting (IT) regime are insulated from the regressive effect of inflation volatility. From the point of view of achieving an even income distribution, IT may be consistent with better equity and efficiency outcomes simultaneously. The main findings are robust to a rich set of controls, alternative measures of volatility and inequality, various subsample checks, and dynamic panel specifications.
Development of a New Algorithm for Modeling Viscous Transonic Flow on Unstructured Grids at High Reynolds Numbers
Authors: Zangeneh Rozie
Published: October 2020

This study investigates a new algorithm for modeling viscous transonic flow at high Reynolds number cases suitable for unstructured grids. The challenge of modeling viscous transonic flow around airfoils becomes intense at high Reynolds number cases due to a variety of flow regimes encountered, such as boundary layer growth and the shockwave/turbulent boundary-layer interaction, accompanied by large separation bubble. Therefore, it is highly demanded to develop robust and efficient models that can capture the shock-induced problems of turbulent flows for aircraft design purposes. The new model is essentially a hybrid algorithm to address the conflict between turbulence modeling and shock-capturing requirements. A skew-symmetric form of a collocated finite volume scheme with minimum aliasing errors was implemented to model the turbulent region in the combination of a semidiscrete, central difference scheme to capture discontinuities with adequately low numerical dissipation for the minimal effect on turbulent flows. To evaluate the effectiveness of the model, it was tested in three conventional cases. The computational results are close to measured data for predicting the shock locations. This implies that the model is able to predict the scale of the separation bubble and the main characteristics of turbulent transonic flow adequately.
Annual Partitioning Patterns of Labyrinthulomycetes Protists Reveal Their Multifaceted Role in Marine Microbial Food Webs
Authors: Xie Ningdong , Hunt Dana E. , Johnson Zackary I. , He Yaodong , Wang Guangyi
Published: October 2020

Increasing evidence has shown that heterotrophic microeukaryotes are an important component in global marine ecosystems, while their diversity and ecological functions remain largely unknown. Without appropriately incorporating these organisms into the food web models, our current understanding of marine microbial community ecology is incomplete, which may further hamper broader studies of biogeochemistry and climate change. This study focuses on a major group of unicellular fungus-like protists (Labyrinthulomycetes) and reveals their distinct annual community patterns relative to fungi and bacteria. Results of our observations provide new information on the community structure and ecology of this protistan group and shed light on the intricate ecological roles of unicellular heterotrophic eukaryotes in the coastal oceans.
Contact with the CsrA Core Is Required for Allosteric Inhibition by FliW in Bacillus subtilis
Authors: Oshiro Reid T. , Dunn Caroline M. , Kearns Daniel B.
Published: October 2020

CsrA is a small dimeric protein that binds RNA and is one of the few known examples of transcript-specific protein regulators of translation in bacteria. A protein called FliW binds to and antagonizes CsrA to govern flagellin homeostasis and flagellar assembly. Despite having a high-resolution three-dimensional structure of the FliW-CsrA complex, the mechanism of noncompetitive inhibition remains unresolved. Here, we identify FliW residues required for antagonism and we find that the residues make a linear connection in the complex from initial binding interaction with CsrA to a critical salt bridge near the core of the CsrA dimer. We propose that the salt bridge represents an allosteric contact that distorts the CsrA core to prevent RNA binding.
A Clinical Epidemiology and Molecular Attribution Evaluation of Adenoviruses in Pediatric Acute Gastroenteritis: a Case-Control Study
Authors: Pabbaraju Kanti , Tellier Raymond , Pang Xiao-Li , Xie Jianling , Lee Bonita E. , Chui Linda , Zhuo Ran , Vanderkooi Otto G. , Ali Samina , Tarr Phillip I. , Funk Anna , Freedman Stephen B.
Published: October 2020

The objective of this study was to characterize the etiological role of human adenovirus (HAdV) serotypes in pediatric gastroenteritis. Using a case-control design, we compared the frequencies of HAdV serotypes between children with ≥3 episodes of vomiting or diarrhea within 24 h and <7 days of symptoms (i.e., cases) and those with no infectious symptoms (i.e., controls). Stool samples and/or rectal swabs underwent molecular serotyping with cycle threshold (Ct) values provided by multiplex real-time reverse transcription-PCR testing.
A Parainfluenza Virus Vector Expressing the Respiratory Syncytial Virus (RSV) Prefusion F Protein Is More Effective than RSV for Boosting a Primary Immunization with RSV
Authors: Liang Bo , Matsuoka Yumiko , Le Nouën Cyril , Liu Xueqiao , Herbert Richard , Swerczek Joanna , Santos Celia , Paneru Monica , Collins Peter L. , Buchholz Ursula J. , Munir Shirin
Published: October 2020

Immune responses to RSV in infants can be reduced due to immunological immaturity and immunosuppression by RSV-specific maternal antibodies. In infants and young children, two infections with wild-type RSV typically are needed to achieve the titers of RSV-specific serum antibodies and protection against illness that are observed in adults. Therefore, a boost might substantially improve the performance of live pediatric RSV vaccines presently being developed. Hamsters and African green monkeys received a primary intranasal infection with RSV and were given a boost with RSV or a parainfluenza virus (PIV) vector expressing RSV fusion protein engineered for enhanced immunogenicity. The RSV boost was highly restricted but induced a significant increase in serum RSV-neutralizing antibodies. The PIV vectors replicated efficiently and induced significantly higher antibody responses. The use of an attenuated PIV vector expressing RSV antigen to boost a primary immunization with an attenuated RSV warrants further evaluation.
Histone Loaders CAF1 and HIRA Restrict Epstein-Barr Virus B-Cell Lytic Reactivation
Authors: Zhang Yuchen , Jiang Chang , Trudeau Stephen J. , Narita Yohei , Zhao Bo , Teng Mingxiang , Guo Rui , Gewurz Benjamin E.
Published: October 2020

Epstein-Barr virus (EBV) was discovered as the first human tumor virus in endemic Burkitt lymphoma, the most common childhood cancer in sub-Saharan Africa. In Burkitt lymphoma and in 200,000 EBV-associated cancers per year, epigenetic mechanisms maintain viral latency, during which lytic cycle factors are silenced. This property complicated EBV’s discovery and facilitates tumor immunoevasion. DNA methylation and chromatin-based mechanisms contribute to lytic gene silencing. Here, we identified histone chaperones CAF1 and HIRA, which have key roles in host DNA replication-dependent and replication-independent pathways, respectively, as important for EBV latency. EBV strongly upregulates CAF1 in newly infected B-cells, where viral genomes acquire histone 3.1 and 3.3 variants prior to the first mitosis. Since histone chaperones ATRX and DAXX also function in maintenance of EBV latency, our results suggest that EBV coopts multiple histone pathways to reprogram viral genomes and highlight targets for lytic induction therapeutic strategies.
Aberrant Intracellular pH Regulation Limiting Glyceraldehyde-3-Phosphate Dehydrogenase Activity in the Glucose-Sensitive Yeast
tps1
Δ Mutant
Authors: Van Leemputte Frederik , Vanthienen Ward , Wijnants Stefanie , Van Zeebroeck Griet , Thevelein Johan M.
Published: October 2020

Glucose catabolism is the backbone of metabolism in most organisms. In spite of numerous studies and extensive knowledge, major controls on glycolysis and its connections to the other metabolic pathways remain to be discovered. A striking example is provided by the extreme glucose sensitivity of the yeast
tps1
Δ mutant, which undergoes apoptosis in the presence of just a few millimolar glucose. Previous work has shown that the conspicuous glucose-induced hyperaccumulation of the glycolytic metabolite fructose-1,6-bisphosphate (Fru1,6bisP) in
tps1
Δ cells triggers apoptosis through activation of the Ras-cAMP-protein kinase A (PKA) signaling pathway. However, the molecular cause of this Fru1,6bisP hyperaccumulation has remained unclear. We now provide evidence that the persistent drop in intracellular pH upon glucose addition to
tps1
Δ cells likely compromises the activity of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a major glycolytic enzyme downstream of Fru1,6bisP, due to its unusually high pH optimum. Our work highlights the potential importance of intracellular pH fluctuations for control of major metabolic pathways.
A CozE Homolog Contributes to Cell Size Homeostasis of Streptococcus pneumoniae
Authors: Stamsås Gro Anita , Restelli Marine , Ducret Adrien , Freton Céline , Garcia Pierre Simon , Håvarstein Leiv Sigve , Straume Daniel , Grangeasse Christophe , Kjos Morten
Published: October 2020

Penicillin-binding proteins (PBPs), the proteins catalyzing the last steps of peptidoglycan assembly, are critical for bacteria to maintain cell size, shape, and integrity. PBPs are consequently attractive targets for antibiotics. Resistance to antibiotics in
Streptococcus pneumoniae
(the pneumococcus) are often associated with mutations in the PBPs. In this work, we describe a new protein, CozEb, controlling the cell size of pneumococcus. CozEb is a highly conserved integral membrane protein that works together with other proteins to regulate PBPs and peptidoglycan synthesis. Deciphering the intricate mechanisms by which the pneumococcus controls peptidoglycan assembly might allow the design of innovative anti-infective strategies, for example, by resensitizing resistant strains to PBP-targeting antibiotics.
A Small-Molecule Modulator of Metal Homeostasis in Gram-Positive Pathogens
Authors: Juttukonda Lillian J. , Beavers William N. , Unsihuay Daisy , Kim Kwangho , Pishchany Gleb , Horning Kyle J. , Weiss Andy , Al-Tameemi Hassan , Boyd Jeffrey M. , Sulikowski Gary A. , Bowman Aaron B. , Skaar Eric P.
Published: October 2020

Staphylococcus aureusis a leading agent of antibiotic-resistant bacterial infections in the world.S. aureustightly controls metal homeostasis during infection, and disruption of metal uptake systems impairs staphylococcal virulence. We identified small molecules that interfere with metal handling inS. aureusto develop chemical probes to investigate metallobiology in this organism. Compound VU0026921 was identified as a small molecule that killsS. aureusboth aerobically and anaerobically. The activity of VU0026921 is modulated by metal supplementation, is enhanced by genetic inactivation of Mn homeostasis genes, and correlates with increased cellular reactive oxygen species. Treatment with VU0026921 causes accumulation of multiple metals withinS. aureuscells and concomitant upregulation of genes involved in metal detoxification. This work defines a small-molecule probe for further defining the role of metal toxicity inS. aureusand validates future antibiotic development targeting metal toxicity pathways.
DDX56 Binds to Chikungunya Virus RNA To Control Infection
Authors: Taschuk Frances , Tapescu Iulia , Moy Ryan H. , Cherry Sara
Published: October 2020

Arthropod-borne viruses are diverse pathogens and include the emerging virus chikungunya virus, which is associated with human disease. Through genetic screening, we found that the conserved RNA binding protein DDX56 is antiviral against chikungunya virus in insects and humans. DDX56 relocalizes from the nucleus to the cytoplasm, where it binds to a stem-loop in the viral genome and destabilizes incoming genomes. Thus, DDX56 is an evolutionarily conserved antiviral factor that controls alphavirus infection.
Fifteen-minute consultation: Does this child have COVID-19 (and does it matter)?
Authors: Ponmani Caroline , Roland Damian
Published: October 2020

SARS-CoV-2 was identified as a new virus in January 2020 following reports of pneumonia of unknown aetiology from China. Since then, the virus has spread rapidly throughout the world. While evidence accumulates on the collateral damage to children as a result of system changes, SARS-CoV-2 appears to rarely cause serious illness in younger age groups. However, the emergence of an inflammatory condition associated with COVID-19 has complicated initial assessment. We present a summary of how the virus has affected children with a synopsis of testing and treatment to help acute paediatricians make informed decisions.
Differential DNA methylation profile in infants born small-for-gestational-age: association with markers of adiposity and insulin resistance from birth to age 24 months
Authors: Diaz Marta , Garde Edurne , Lopez-Bermejo Abel , de Zegher Francis , Ibañez Lourdes
Published: October 2020

Introduction

Prenatal growth restraint followed by rapid postnatal weight gain increases lifelong diabetes risk. Epigenetic dysregulation in critical windows could exert long-term effects on metabolism and confer such risk.

Research design and methods

We conducted a genome-wide DNA methylation profiling in peripheral blood from infants born appropriate-for-gestational-age (AGA, n=30) or small-for-gestational-age (SGA, n=21, with postnatal catch-up) at age 12 months, to identify new genes that may predispose to metabolic dysfunction. Candidate genes were validated by bisulfite pyrosequencing in the entire cohort. All infants were followed since birth; cord blood methylation profiling was previously reported. Endocrine-metabolic variables and body composition (dual-energy X-ray absorptiometry) were assessed at birth and at 12 and 24 months.

Results

GPR120(cg14582356,cg01272400,cg23654127,cg03629447),NKX6.1(cg22598426,cg07688460,cg17444738,cg12076463,cg10457539),CPT1A (cg14073497, cg00941258, cg12778395) andIGFBP 4(cg15471812) genes were hypermethylated (GPR120,NKX6.1were also hypermethylated in cord blood), whereasCHGA (cg13332653,cg15480367,cg05700406),FABP5(cg00696973,cg10563714,cg16128701),CTRP1(cg19231170,cg19472078,cg0164309,cg07162665,cg17758081,cg18996910,cg06709009),GAS6(N/A),ONECUT1(cg14217069,cg02061705,cg26158897,cg06657050,cg15446043) andSLC2A8(cg20758474,cg19021975,cg11312566,cg12281690,cg04016166,cg03804985) genes were hypomethylated in SGA infants. These genes were related to β-cell development and function, inflammation, and glucose and lipid metabolism and associated with body mass index, body composition, and markers of insulin resistance at 12 and 24 months.

Conclusion

In conclusion, at 12 months, abnormal methylation ofGPR120andNKX6.1persists and new epigenetic marks further involved in adipogenesis and energy homeostasis arise in SGA infants. These abnormalities may contribute to metabolic dysfunction and diabetes risk later in life.
Practising what we preach: clinical ethicists’ professional perspectives and personal use of advance directives
Authors: Wasserman Jason Adam , Navin Mark Christopher , Drzyzga Victoria , Gibb Tyler S
Published: October 2020

The field of clinical bioethics strongly advocates for the use of advance directives to promote patient autonomy, particularly at the end of life. This paper reports a study of clinical bioethicists’ perceptions of the professional consensus about advance directives, as well as their personal advance care planning practices. We find that clinical bioethicists are often sceptical about the value of advance directives, and their personal choices about advance directives often deviate from what clinical ethicists acknowledge to be their profession’s recommendations. Moreover, our respondents identified a pluralistic set of justifications for completing treatment directives and designating surrogates, even while the consensus view focuses on patient autonomy. Our results suggest important revisions to academic discussion and public-facing advocacy about advance care planning.
Fisher information and the weak equivalence principle of a quantum particle in a gravitational wave
Authors: Quach James Q.
Published: October 2020

We show that the weak equivalence principle (WEP) is violated for a quantum particle in a gravitational wave (GW) background, in the sense that extra mass information can be extracted in the presence of the GW. We quantify the degree of violation with the Fisher information of mass. This provides a precise characterisation of WEP violation by quantum systems in a GW, that should be useful in formalising other works that have argued for such violations heuristically.
Digital contact tracing
Authors: Trivedi Amee , Vasisht Deepak
Published: October 2020

Since the start of the COVID-19 pandemic, technology enthusiasts have pushed for digital contact tracing as a critical tool for breaking the COVID-19 transmission chains. Motivated by this push, many countries and companies have created apps that enable digital contact tracing with the goal to identify the chain of transmission from an infected individual to others and enable early quarantine. Digital contact tracing applications like AarogyaSetu in India, TraceTogether in Singapore, SwissCovid in Switzerland, and others have been downloaded hundreds of millions of times. Yet, this technology hasn't seen the impact that we envisioned at the start of the pandemic. Some countries have rolled back their apps, while others have seen low adoption [12, 17].

Therefore, it is prudent to ask what the technology landscape of contact-tracing looks like and what are the missing pieces. We attempt to undertake this task in this paper. We present a high-level review of technologies underlying digital contact tracing, a set of metrics that are important while evaluating different contact tracing technologies, and evaluate where the different technologies stand today on this set of metrics. Our hope is two fold: (a) Future designers of contact tracing applications can use this review paper to understand the technology landscape, and (b) Researchers can identify and solve the missing pieces of this puzzle, so that we are ready to face the rest of the COVID-19 pandemic and any future pandemics. A majority of this discussion is focused on the ability to identify contact between individuals. The questions of ethics, privacy, and security of such contact tracing are briefly mentioned but not discussed in detail.
Contact tracing
Authors: Mokbel Mohamed , Abbar Sofiane , Stanojevic Rade
Published: October 2020

As pandemic wide spread results in locking down vital facilities, digital contact tracing is deemed as a key for re-opening. However, current efforts in digital contact tracing, running as mobile apps on users' smartphones, fall short in being effective and present two major weaknesses related to accessibility and apparent privacy concern augmentation. Indeed, accessibility is affected by several factors such as smartphone penetration, age, or socio-economic conditions. The privacy concern on the other hand comes from the fear of having a piece of technology that is monitoring us all the time, everywhere, even when contact tracing is irrelevant. This paper lays out the vision and guidelines for the next era of digital contact tracing, where the contact tracing functionality is moved from being personal responsibility to be the responsibility of facilities that users visit daily. Our proposal tackles the two aforementioned shortcomings by disengaging users from using their own smartphones and requiring facilities to provide the technological devices needed for contact tracing. By doing so, we reassure users that their contacts are only considered in places where manual contact tracing is not effective, and cease being recorded as soon as they leave the facilities they visit. A privacy-preserving architecture is proposed, which can be mandated as a prerequisite for any facility to re-open during or after the pandemic. We finally outline research opportunities and challenges revolving around contact tracing system design and data management.