bluuebunny/crossref_metadata_2025 huggingface dataset:
Botulinum toxin type A for preventing and treating cleft lip scarring—A systematic review and meta‐analysis
Authors: Ji Qiang , Tang Jun , Hu Hua , Chen Junjie , Cen Ying
Published: March 2022

Background

Cleft lip and/or palate (CL/P) are congenital cleft facial deformities that are abnormal developments caused by errors in the fusion process of the embryo's face. Surgery is an important treatment, but postoperative scars will still cause psychological shadows to patients. This study aimed to systematically evaluate the efficacy of Botulinum toxin type A (BTXA) in preventing and treating postoperative CL/P scars and improving scar quality.

Methods

A systematic review was performed by searching PubMed, EMBASE, the Cochrane Library, and Web of Science for relevant trials. All relevant trials were performed before June 30, 2021. The data were entered into Revman 5.3 software, and a meta‐analysis was conducted by using the random‐effects model or fixed‐effects model.

Results

Four randomized controlled trials involving 161 cases were included. Through quantitative analysis, BTXA showed significant differences in preventing and treating postoperative CL/P scars in terms of scar width (MD: −0.20; [95% CI, −0.30, –0.10], p < 0.0001) and the Visual Analog Scale (VAS) (MD: 1.30; [95% CI, 1.06, 1.55], p < 0.0001), although no significant difference was noted on the Vancouver Scar Scale (VSS) (MD: −0.75; [95% CI, −1.68, 0.19], p = 0.12) between the two groups.

Conclusion

In preventing and treating postoperative CL/P scar hypertrophy, we found that BTXA injection can show better results. There was no statistically significant difference between the results after omitting Navarro's study or Chang's study because of the time of injection—before/during surgery or adult CL/P scars.
Resource Allocation in Bank Supervision: Trade‐Offs and Outcomes
Authors: EISENBACH THOMAS M. , LUCCA DAVID O. , TOWNSEND ROBERT M.
Published: March 2022

We estimate a structural model of resource allocation on work hours of Federal Reserve bank supervisors to disentangle how supervisory technology, preferences, and resource constraints impact bank outcomes. We find a significant effect of supervision on bank risk and large technological scale economies with respect to bank size. Consistent with macroprudential objectives, revealed supervisory preferences disproportionately weight larger banks, especially post‐2008 when a resource reallocation to larger banks increased risk on average across all banks. Shadow cost estimates show tight resources around the financial crisis and counterfactuals indicate that binding constraints have large effects on the distribution of bank outcomes.
Marketing Logics and the Politics of Public Spheres: On Discursive Engineering and Enclosure
Authors: Graan Andrew
Published: March 2022

Scholarship on publics has proliferated during the past two decades, especially in linguistic anthropology. Drawing on Michael Warner’s famous formulation, publics are now routinely theorized as a social form predicated on the reflexive circulation of discourse. This article, however, identifies a tension within Warner’s conception of publics. On the one hand, Warner levels a critique of liberal publicity, noting its exclusions and contradictions, but on the other hand, he models his own account of publics on the liberal public sphere and assumptions of voluntaristic, free speech. Working from ethnographic research on a government‐sponsored nation‐branding project undertaken in Macedonia, the article develops a different perspective on publics and their politics. It examines how practices of marketing and strategic communication now pervade public spheres and valorize not voluntaristic participation but discursive engineering, that is, concerted efforts to determine how discourse can and will circulate in some public. When tethered to projects of centralized political control, as happened in Macedonia during Nikola Gruevski’s prime ministership (2006‐2016), practices of discursive engineering can result in enclosed public spheres. Ultimately, the article asks, what can attention to elite efforts to engineer and enclose public spheres teach about struggles over participation in contemporary contexts of mass publicity?
Decoloniality as a social issue for psychological study
Authors:   Readsura Decolonial Editorial Collective
Published: March 2022

This article provides a theoretical introduction to a two‐installment special issue on decolonial approaches to the psychological study of social issues. Decolonial approaches propose that colonial violence is not confined to the distant past (i.e., colonialism); instead, it persists as coloniality: racialized ways of thinking and being associated with Eurocentric global domination. Rather than characterizing modernity and its individualist psychological manifestations as progress, decolonial theorists use modernity/coloniality to illuminate the colonial violence inherent in the modern order and inseparable from modern individualist development. One implication of a decolonial framework is that colonial violence extends beyond physical space to psychological space, such that complete liberation requires forms of psychological decolonization. Accordingly, articles in this first installment consider decoloniality as a social issue for psychological analysis not only to address historical trauma, internalized inferiority, and other forms of psychological violence among the (formerly) colonized but also to recognize the coloniality in features of Eurocentric modernity—e.g., mainstream environmentalism, prevailing articulations of human rights education, or modern individualist lifeways—that appear liberal or progressive.
Prevalence of functional abdominal pain disorders and functional constipation in adolescents
Authors: Siajunboriboon Sakonkarn , Tanpowpong Pornthep , Empremsilapa Suthatip , Lertudomphonwanit Chatmanee , Nuntnarumit Pracha , Treepongkaruna Suporn
Published: March 2022

Aim

Functional abdominal pain disorders (FAPDs) and functional constipation (FC) are the common functional gastrointestinal disorders in adolescents. We aimed to determine the prevalence of FAPDs and FC in adolescents using the Rome IV Questionnaire of Pediatric Gastrointestinal Symptoms and the factors associated with these two functional gastrointestinal disorders.

Methods

A survey for the prevalence of FAPDs and FC in adolescents was carried out at two high schools. A translated and validated Thai version of Rome IV Questionnaire of Pediatric Gastrointestinal Symptoms was used. Potential associated factors were also collected. Psychosocial problems were evaluated by using the Strengths and Difficulties Questionnaire.

Results

A total of 1700 adolescents (55.5% females) with a mean age (SD) of 16.1 (0.9) years were enrolled. The prevalence of FAPDs and FC was 5.3% and 8.1%, respectively. The subtypes of FAPDs were functional dyspepsia (4.7%; postprandial distress syndrome 3.9% and epigastric pain syndrome 0.8%), irritable bowel syndrome (0.6%), abdominal migraine (0.4%) and functional abdominal pain not otherwise specified (0.3%). Multiple logistic regression analysis revealed that FAPDs were associated with female gender (odds ratio (OR) 3.3, 95% confidence interval (CI): 1.7–6.4), underlying allergic diseases (OR 3.2, 95% CI: 1.6–6.6) and concomitant emotional problem (OR 2.7, 95% CI: 1.2–5.9). No significant associated factors with FC were found.

Conclusion

FAPDs and FC are common in adolescents. Postprandial distress syndrome is the most common subtype of FAPD. Associated factors for FAPDs may suggest hormonal, immune‐related and psychological involvement in the disease pathogenesis.
PK/PD modelling of enrofloxacin againstGlaesserella parasuisinfection in pigs
Authors: Yang Bo , Li Xiao Dong , Chen Xun , Hong Juan , Liu Can , Zheng Jin Ping , Ou Zheng Yang , Yu Dao Jin
Published: March 2022

A pharmacokinetic/pharmacodynamic (PK/PD) model was developed to optimize the dosing regimen of enrofloxacin (EN) againstGlaesserella parasuisin pigs. EN (2.5 mg/kg) was administered intramuscularly to eight healthy pigs and eight pigs that were experimentally infected withG. parasuisSW124. Blood samples were collected at predetermined time points. Plasma EN concentrations were determined, and the main PK parameters were estimated. The PD of EN againstG. parasuisSW124 was also investigated in vitro and ex vivo. The dynamic behaviour of EN in pigs was consistent with a one‐compartment model. Significant differences were observed between healthy and infected pigs in the area under the curve (AUC) (3.58 ± 0.94 and 5.39 ± 1.01 μg h/ml, respectively) and the systemic clearance (CL) (736.32 ± 171.46 and 479.36 ± 96.81 ml/h/kg, respectively), suggesting that the pathogenicity ofG. parasuisSW124 to pigs might alter the PK profile of EN, and therefore should be considered in dose optimization. Both the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were 0.125 μg/ml in tryptone soya broth (TSB) medium or plasma. The mutant prevention concentration (MPC) was 0.6 μg/ml. EN inhibited or killedG.parasuisSW124 in a concentration‐dependent manner. The targeted endpoints of AUC24 h/MIC for bacteriostasis, bactericidal action, and eradication were 5.10, 7.34, and 8.65 h and 5.91, 9.01, and 10.90 h in healthy and infected pigs, respectively. The optimal doses were 3.58−6.08 mg/kg in healthy pigs and 2.71−4.99 mg/kg in infected pigs from the point of view of preventing drug resistance.
An infinite‐dimensional affine stochastic volatility model
Authors: Cox Sonja , Karbach Sven , Khedher Asma
Published: March 2022

We introduce a flexible and tractable infinite‐dimensional stochastic volatility model. More specifically, we consider a Hilbert space valued Ornstein–Uhlenbeck‐type process, whose instantaneous covariance is given by a pure‐jump stochastic process taking values in the cone of positive self‐adjoint Hilbert–Schmidt operators. The tractability of our model lies in the fact that the two processes involved are jointly affine, that is, we show that their characteristic function can be given explicitly in terms of the solutions to a set of generalized Riccati equations. The flexibility lies in the fact that we allow multiple modeling options for the instantaneous covariance process, including state‐dependent jump intensity. Infinite dimensional volatility models arise, for example, when considering the dynamics of forward rate functions in the Heath–Jarrow–Morton–Musiela (HJMM) modeling framework using the Filipović space. In this setting, we discuss various examples: an infinite‐dimensional version of the Barndorf–Nielsen–Shephard stochastic volatility model, as well as covariance processes with a state dependent intensity.
The humanities as conceptual practices: The formation and development of high‐impact concepts in philosophy and beyond
Authors: Haueis Philipp , Slaby Jan
Published: March 2022

This paper proposes an analysis of the discursive dynamics of high‐impact concepts in the humanities. These are concepts whose formation and development have a lasting and wide‐ranging effect on research and our understanding of discursive reality in general. The notion of a conceptual practice, based on a normative conception of practice, is introduced, and practices are identified, on this perspective, according to the way their respective performances are held mutually accountable. This normative conception of practices is then combined with recent work from philosophy of science that characterizes concepts in terms of conceptual capacities that are productive, open‐ended, and applicable beyond the original context they were developed in. It is shown that the formation of concepts can be identified by changes in how practitioners hold exercise of their conceptual capacities accountable when producing knowledge about a phenomenon. In a manner similar to the use of operational definitions in scientific practices, such concepts can also be used to intervene in various discourses within or outside the conceptual practice. Using the formation of the concepts “mechanism” and “performative” as examples, the paper shows how high‐impact concepts reconfigure what is at issue and at stake in conceptual practices. As philosophy and other humanities disciplines are its domain of interest, it is a contribution to the methodology of the humanities.
Locating Autonomous Abortion Accompanied by Feminist Activists in the Spectrum of Self‐Managed Medication Abortion
Authors: Veldhuis Suzanne , Sánchez‐Ramírez Georgina , Darney Blair G.
Published: March 2022

Diverse models of self‐managed medication abortion exist—ranging from some interaction with medical personnel to completely autonomous abortion. In this commentary, we propose a new classification of self‐managed medication abortion and describe the different modalities. We highlight autonomous abortion accompanied by feminist activists, called “acompañantes,” as a community‐ and rights‐based strategy that can be a safe alternative to clinical abortion services in clandestine as well as legal settings. To improve access, abortion needs to be decriminalized and governments must acknowledge and facilitate the diversity of safe abortion options so women may choose where, when, how, and with whom to abort.
Acute intermittent hypercapnic‐hypoxia elicits central neural respiratory motor plasticity in humans
Authors: Welch Joseph F. , Nair Jayakrishnan , Argento Patrick J. , Mitchell Gordon S. , Fox Emily J.
Published: March 2022

Acute intermittent hypoxia (AIH) elicits long‐term facilitation (LTF) of respiration. Although LTF is observed when CO2 is elevated during AIH in awake humans, the influence of CO2 on corticospinal respiratory motor plasticity is unknown. Thus, we tested the hypotheses that acute intermittent hypercapnic‐hypoxia (AIHH): (1) enhances cortico‐phrenic neurotransmission (reflecting volitional respiratory control); and (2) elicits ventilatory LTF (reflecting automatic respiratory control). Eighteen healthy adults completed four study visits. Day 1 consisted of anthropometry and pulmonary function testing. On Days 2, 3 and 4, in a balanced alternating sequence, participants received: AIHH, poikilocapnic AIH, and normocapnic‐normoxia (Sham). Protocols consisted of 15, 60 s exposures with 90 s normoxic intervals. Transcranial (TMS) and cervical (CMS) magnetic stimulation were used to induce diaphragmatic motor‐evoked potentials and compound muscle action potentials, respectively. Respiratory drive was assessed via mouth occlusion pressure (P0.1), and minute ventilation measured at rest. Dependent variables were assessed at baseline and 30–60 min after exposures. Increases in TMS‐evoked diaphragm potential amplitudes were observed following AIHH vs. Sham (+28 ± 41%, P = 0.003), but not after AIH. No changes were observed in CMS‐evoked diaphragm potential amplitudes. Mouth occlusion pressure also increased after AIHH (+21 ± 34%, P = 0.033), but not after AIH. Ventilatory LTF was not observed after any treatment. We demonstrate that AIHH elicits central neural mechanisms of respiratory motor plasticity and increases resting respiratory drive in awake humans. These findings may have important implications for neurorehabilitation after spinal cord injury and other neuromuscular disorders compromising breathing.

Key points

The occurrence of respiratory long‐term facilitation following acute exposure to intermittent hypoxia is believed to be dependent upon CO2 regulation – mechanisms governing the critical role of CO2 have seldom been explored.

We tested the hypothesis that acute intermittent hypercapnic‐hypoxia (AIHH) enhances cortico‐phrenic neurotransmission in awake healthy humans.

The amplitude of diaphragmatic motor‐evoked potentials induced by transcranial magnetic stimulation was increased after AIHH, but not the amplitude of compound muscle action potentials evoked by cervical magnetic stimulation.

Mouth occlusion pressure (P0.1, an indicator of neural respiratory drive) was also increased after AIHH, but not tidal volume or minute ventilation.

Thus, moderate AIHH elicits central neural mechanisms of respiratory motor plasticity, without measurable ventilatory long‐term facilitation in awake humans.
Engineering Document Summarization: A Bidirectional Language Model-Based Approach
Authors: Qiu Yunjian , Jin Yan
Published: March 2022

In this study, the extractive summarization using sentence embeddings generated by the finetuned Bidirectional Encoder Representations from Transformers (BERT) models and the k-means clustering method has been investigated. To show how the BERT model can capture the knowledge in specific domains like engineering design and what it can produce after being finetuned based on domain-specific data sets, several BERT models are trained, and the sentence embeddings extracted from the finetuned models are used to generate summaries of a set of papers. Different evaluation methods are then applied to measure the quality of summarization results. Both the machine evaluation method Recall-Oriented Understudy for Gisting Evaluation (ROUGE) and a human-based evaluation method are used for the comparison study. The results indicate that the BERT model finetuned with a larger dataset can generate summaries with more domain terminologies than the pretrained BERT model. Moreover, the summaries generated by BERT models have more contents overlapping with original documents than those obtained through other popular non-BERT-based models. The experimental results indicate that the BERT-based method can provide better and more informative summaries to engineers. It has also been demonstrated that the contextualized representations generated by BERT-based models can capture information in text and have better performance in applications like text summarizations after being trained by domain-specific data sets.
Design, Modeling, and Kinematics Analysis of a Modular Cable-Driven Manipulator
Authors: Ju Renjie , Zhang Dong , Xu Jiakai , Yuan Hao , Miao Zhiwen , Zhou Mengchu , Cao Zhengcai
Published: March 2022

Modular manipulators have broad application prospects in the field of narrow confined space owing to their characteristics of superior dexterity. However, compared with traditional ones, their mechanism design, modeling, and inverse kinematics (IK) are challenging due to their special structures and redundant degrees-of-freedom. In this paper, a modular cable-driven manipulator (CDM) is designed. A lightweight and expandable structure is proposed to reduce weight of the whole manipulator and improve its environmental adaptability. To calibrate its global posture, angle sensors are equipped with its joints. Its kinematics are rigorously analyzed. To obtain the IK of a hyper-redundant CDM in real-time, a fast heuristic method with adaptive joint constraints is introduced. Then, a segmented IK strategy is proposed by extending the IK solver to local CDM, which realizes the local joint migration motion under the stable overall configuration. Finally, numerical simulations are conducted and a physical prototype is developed to carry out experiments. The results show that the designed CDM has great performance in dexterity and accuracy.
Stakeholders, Prototypes, and Settings of Front-End Medical Device Design Activities
Authors: Coulentianos Marianna , Rodriguez-Calero Ilka , Daly Shanna , Burridge Jocelyn , Sienko Kathleen
Published: March 2022

Successful medical device design entails an understanding of stakeholder-driven requirements early in the process to assure device safety and usability and support successful and positive patient experiences. Prototypes can be used during stakeholder engagement in the design front end to gather information to inform design decisions. However, an understanding of medical device industry practices of front-end stakeholder engagement with prototypes is lacking. Through interviews with medical device design practitioners, this study explored the variety of stakeholder groups engaged by design practitioners, prototype types used during stakeholder engagements, and settings in which engagements took place during front-end design activities. This study describes the 14 types of stakeholders, 14 types of prototypes, and six types of settings described by practitioners as well as patterns across engagement strategies, stakeholders, prototypes, and/or settings in front-end activities. These outcomes can contribute to broadening designers' stakeholder engagement planning and practices.
Neutronic Evaluation of Light Water Reactor-Based Small Modular Reactor With Transuranic Fuel and Comparison With Different Core Configuration of UO2 and Mixed Oxide Fuel
Authors: Biswas Sushanta , Sahadath Md. Hossain , Ananya Nazia Rahim
Published: March 2022

Neutronic and burnup assessment of a light water reactor (LWR)-based small modular reactor (SMR) core with transuranic fuel (TRU) was carried out and compared with UO2 fuel and mixed oxide fuel (MOX) for different core composition and configurations. Eight different cores were modeled by changing the fuel composition and loading pattern of four different fuel assemblies, namely, UO2, MOX, TRU, and annular UO2 fuel and simulated in open-source Monte Carlo code OpenMC. The radial neutron flux distribution and maximum to average flux ratio were studied. The lowest flux ratio was found in annular-2 models, whereas TRU models showed the highest value. The effect of enrichment, fuel burnup, moderator to fuel ratio, and soluble boron concentration on effective multiplication factor (keff) was investigated. Burnup analysis of fissionable materials and neutron poison was performed. Burnup-dependent fission rate of U-235, Pu-239, and Pu-241 was also studied. The composition of spent fuel at end of the cycle (EOC) was investigated and lower minor actinides (MAs) production was observed for TRU models. This analysis would help to determine the effectiveness and feasibility of these potential core configurations and to predict their neutronic behavior.
Numerical Model of the Railway Brake Disk for the Temperature and Axial Thermal Stress Analyses
Authors: Cati Yusuf , aus der Wiesche Stefan , Düzgün Mesut
Published: March 2022

Increases in travel speeds and traffic density in railway sector impose challenges on the modern disk-pad brake systems such as higher temperatures and stresses resulting in cracks/hot spots and a degraded system performance. The prediction of disk thermal behavior under challenging conditions has become an important engineering issue. In this study, a model is developed using the finite difference method with realistic time-dependent boundary conditions and different experimental convection correlations with non-uniform time-step size features. A previous numerical/experimental study on the thermal behavior of railway disk brake is partly adopted and enhanced. The results of the developed model agree well with the results of the previous study. A practical prediction method for thermal stresses in the disk is applied using the axial temperature distributions at several time instants from locations with highest temperature. Apart from that, same configuration of the disk with the pad is modeled in simcenter star-ccm+ which is a well-validated commercial computational fluid dynamics software to compare the results and computation times with that of the developed model. Using this model, an investigation has been conducted on the effect of temperature-dependent material properties on thermal behavior of the disk. The developed numerical model can simulate the conditions experienced by a railway disk in a relatively new standard (EN 14535-3) considering the transient thermal behavior and axial thermal stress distribution with relatively low computational time and reasonable accuracy. Also, in this study, valuable insights are obtained on the effect of variable thermal properties of the disk and convection correlations on the disk thermal behavior.
Experimental and Numerical Investigations of Extended Jet Effects on Multiple-Jet Impingement Heat Transfer Characteristics
Authors: Yang Xing , Wu Hang , Feng Zhenping
Published: March 2022

A jet impingement system equipped with extended jet holes was experimentally evaluated in this study. To reproduce a strong crossflow condition, the jet impingement configuration featured a multiple-jet array of 16 × 5 rows in the streamwise and pitchwise directions, respectively, and the crossflow was exhausted from one open side of the impingement channel only. The transient thermochromic liquid crystal (TLC) technique was used to measure heat transfer on the target surface for different extended lengths of 1.0–2.5 jet hole diameters with Reynolds numbers from 1.0 × 104 to 3.0 × 104. To provide complementary flow physics for elaborating the heat transfer patterns observed from the experiments, well-validated numerical simulations were carried out. Comparisons with a baseline jet hole configuration showed that the extended jet holes helped to significantly improve the heat transfer levels as well as to generate a more uniform distribution pattern by suppressing the crossflow. Despite an aerodynamic penalty, the extended jet holes provided much higher heat transfer levels at equal pumping power consumption. The flow fields obtained by the numerical simulations revealed that the jets issued from the extended jet holes were straighter and had less mixing with the crossflow, resulting in a higher jet momentum impinging onto the target. Most importantly, it was found that the dominated flow mechanism of the extended jet holes was to prevent the jets from being redirected by the crossflow in strong crossflow conditions, rather than reducing the jet-to-target distance.
Longitudinal Tibia Stress Fracture Risk During High-Volume Training: A Multiscale Modeling Pipeline Incorporating Bone Remodeling
Authors: Pyles Connor O. , Dunphy Melissa , Vavalle Nicholas A. , Vignos Michael F. , Luong Quang T. , Ott Kyle , Drewry David G.
Published: March 2022

Tibia stress fractures are prevalent during high-intensity training, yet a mechanistic model linking longitudinal training intensity, bone health, and long-term injury risk has yet to be demonstrated. The objective of this study was to develop and validate a multiscale model of gross and tissue level loading on the tibia including bone remodeling on a timescale of week. Peak tensile tibial strain (3517 μstrain) during 4 m/s running was below injury thresholds, and the peak anteromedial tibial strain (1248 μstrain) was 0.17 standard deviations away from the mean of reported literature values. An initial study isolated the effects of cortical density and stiffness on tibial strain during a simulated eight week training period. Tibial strains and cortical microcracking correlated with initial cortical modulus, with all simulations presenting peak anteromedial tensile strains (1047–1600 μstrain) near day 11. Average cortical densities decreased by 7–8% of their nominal value by day 11, but the overall density change was <2% by the end of the simulated training period, in line with reported results. This study demonstrates the benefits of multiscale models for investigating stress fracture risk and indicates that peak tibial strain, and thus injury risk, may increase early in a high intensity training program. Future studies could optimize training volume and recovery time to reduce injury risk during the most vulnerable training periods.
Palmitoylation couples the kinases DLK and JNK3 to facilitate prodegenerative axon-to-soma signaling
Authors: Niu Jingwen , Holland Sabrina M. , Ketschek Andrea , Collura Kaitlin M. , Hesketh Natasha L. , Hayashi Takashi , Gallo Gianluca , Thomas Gareth M.
Published: March 2022

Dual leucine-zipper kinase (DLK; a MAP3K) mediates neuronal responses to diverse injuries and insults through the c-Jun N-terminal kinase (JNK) family of mitogen-activated protein kinases (MAPKs). Here, we identified two ways through which DLK is coupled to the neural-specific isoform JNK3 to control prodegenerative signaling. JNK3 catalyzed positive feedback phosphorylation of DLK that further activated DLK and locked the DLK-JNK3 module in a highly active state. Neither homologous MAP3Ks nor a homologous MAPK could support this positive feedback loop. Unlike the related JNK1 isoform JNK2 and JNK3 promote prodegenerative axon-to-soma signaling and were endogenously palmitoylated. Moreover, palmitoylation targeted both DLK and JNK3 to the same axonal vesicles, and JNK3 palmitoylation was essential for axonal retrograde signaling in response to optic nerve crush injury in vivo. These findings provide previously unappreciated insights into DLK-JNK signaling relevant to neuropathological conditions and answer long-standing questions regarding the selective prodegenerative roles of JNK2 and JNK3.
mRNA-1273 and BNT162b2 COVID-19 vaccines elicit antibodies with differences in Fc-mediated effector functions
Authors: Kaplonek Paulina , Cizmeci Deniz , Fischinger Stephanie , Collier Ai-ris , Suscovich Todd , Linde Caitlyn , Broge Thomas , Mann Colin , Amanat Fatima , Dayal Diana , Rhee Justin , de St. Aubin Michael , Nilles Eric J. , Musk Elon R. , Menon Anil S. , Saphire Erica Ollmann , Krammer Florian , Lauffenburger Douglas A. , Barouch Dan H. , Alter Galit
Published: March 2022

The successful development of several coronavirus disease 2019 (COVID-19) vaccines has substantially reduced morbidity and mortality in regions of the world where the vaccines have been deployed. However, in the wake of the emergence of viral variants that are able to evade vaccine-induced neutralizing antibodies, real-world vaccine efficacy has begun to show differences across the two approved mRNA platforms, BNT162b2 and mRNA-1273; these findings suggest that subtle variation in immune responses induced by the BNT162b2 and mRNA-1273 vaccines may confer differential protection. Given our emerging appreciation for the importance of additional antibody functions beyond neutralization, we profiled the postboost binding and functional capacity of humoral immune responses induced by the BNT162b2 and mRNA-1273 vaccines in a cohort of hospital staff. Both vaccines induced robust humoral immune responses to wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to variants of concern. However, differences emerged across epitope-specific responses, with higher concentrations of receptor binding domain (RBD)– and N-terminal domain–specific IgA observed in recipients of mRNA-1273. Antibodies eliciting neutrophil phagocytosis and natural killer cell activation were also increased in mRNA-1273 vaccine recipients as compared to BNT162b2 recipients. RBD-specific antibody depletion highlighted the different roles of non–RBD-specific antibody effector functions induced across the mRNA vaccines. These data provide insights into potential differences in protective immunity conferred by these vaccines.
RetS Regulates Phage Infection in Pseudomonas aeruginosa via Modulating the GacS/GacA Two-Component System
Authors: Xuan Guanhua , Lin Hong , Li Xiaoyan , Kong Jiuna , Wang Jingxue
Published: March 2022

Our knowledge on the molecular mechanisms behind bacterium-phage interactions remains limited. Our study reported that the complex multisensing regulatory networks RetS-GacS/GacA of
Pseudomonas aeruginosa
PAO1 play key roles in controlling phage infection.
Structural Studies Reveal the Role of Helix 68 in the Elongation Step of Protein Biosynthesis
Authors: Cimicata Giuseppe , Fridkin Gil , Bose Tanaya , Eyal Zohar , Halfon Yehuda , Breiner-Goldstein Elinor , Fox Tara , Zimmerman Ella , Bashan Anat , de Val Natalia , Wlodawer Alexander , Yonath Ada
Published: March 2022

The mechanism that regulates the translocation step in ribosomes during protein synthesis is not fully understood. In this work, cryo-EM techniques used to image ribosomes from
Staphylococcus aureus
after incubation at physiological temperature allowed the identification of a conformation of the helix 68 that has never been observed so far.
SARS-CoV-2 Point Mutation and Deletion Spectra and Their Association with Different Disease Outcomes
Authors: Martínez-González Brenda , Soria María Eugenia , Vázquez-Sirvent Lucía , Ferrer-Orta Cristina , Lobo-Vega Rebeca , Mínguez Pablo , de la Fuente Lorena , Llorens Carlos , Soriano Beatriz , Ramos Ricardo , Cortón Marta , López-Rodríguez Rosario , García-Crespo Carlos , Gallego Isabel , de Ávila Ana Isabel , Gómez Jordi , Enjuanes Luis , Salar-Vidal Llanos , Esteban Jaime , Fernandez-Roblas Ricardo , Gadea Ignacio , Ayuso Carmen , Ruíz-Hornillos Javier , Verdaguer Nuria , Domingo Esteban , Perales Celia
Published: March 2022

The study shows that mutant spectra of SARS-CoV-2 from diagnostic samples differ in point mutation abundance and complexity and that significantly larger values were observed in virus from patients who developed mild COVID-19 symptoms. Mutant spectrum complexity is not a uniform trait among isolates. The nature and location of low-frequency amino acid substitutions present in mutant spectra anticipate great potential for phenotypic diversification of SARS-CoV-2.
Eradication of Biofilm-Mediated Methicillin-Resistant Staphylococcus aureus Infections
In Vitro
: Bacteriophage-Antibiotic Combination
Authors: Kebriaei Razieh , Lev Katherine L. , Shah Rahi M. , Stamper Kyle C. , Holger Dana J. , Morrisette Taylor , Kunz Coyne Ashlan J. , Lehman Susan M. , Rybak Michael J.
Published: March 2022

Biofilm-associated multidrug-resistant infections pose significant challenges for antibiotic therapy. The extracellular polymeric matrix of biofilms presents an impediment for antibiotic diffusion, facilitating the emergence of multidrug-resistant populations.
Clarification of the Dynamic Autothermal Thermophilic Aerobic Digestion Process Using Metagenomic Analysis
Authors: Ishida Natsumi , Kawano Yoshihisa , Fukui Ryo , Zhang Min , Tashiro Yukihiro , Sakai Kenji
Published: March 2022

Metagenome analysis was performed to determine the microbial dynamics of the unique autothermal thermophilic aerobic digestion process of human excreta, which includes initial, middle, and final phases. In this study, we revealed the details of functional genes related to physicochemical and bacterial characteristics in the ATAD process.
Bioaugmentation of Anammox Activated Sludge with a Nitrifying Bacterial Community as a Way to Increase the Nitrogen Removal Efficiency
Authors: Pimenov N. V. , Nikolaev Yu. A. , Dorofeev A. G. , Grachev V. A. , Kallistova A. Yu. , Mironov V. V. , Vanteeva A. V. , Grigor’eva N. V. , Berestovskaya Yu. Yu. , Gruzdev E. V. , Begmatov Sh. A. , Ravin N. V. , Mardanov A. V.
Published: March 2022

Abstract—

Bioaugmentation, i.e., increasing the abundance of certain microorganisms in the community by adding appropriate cells or establishing the conditions promoting their growth, is widely used in environmental technologies. Its application for launching of the anammox reactors is usually limited to introduction of anammox bacteria. We expected addition of nitrifiers during anammox bioreactor launching to stimulate the anammox process due to rapid production of nitrite, which anammox bacteria use for ammonium oxidation. The present work investigated the effect of introduction of a nitrifying community on the composition and activity of the microbial community in an anammox reactor. At the time of inoculation of a laboratory SBR reactor, an active nitrifying community (5 days old) (ASB) (bioaugmenting activated sludge, ASB) containing group I nitrifiers, primarily Nitrosospira, was added (1 : 100 by biomass) to anammox activated sludge (ASA) stored for 1 month at 4°C and exhibiting low metabolic activity. The use of ASB resulted in increased efficiency of nitrogen removal. While noticeable nitrogen removal in the control (7%) was observed since day 11 of incubation, nitrogen removal in the experimental reactor began on day 4 at the level of 20%. Nitrogen removal after 30 days of incubation was ~60% in the experiment and 20% in the control. The rate of ammonium oxidation in the presence of ASB increased due to activity of nitrifying bacteria (during the first 10 days of operation) and anammox bacteria of the genus Brоcadia, which were already present in ASA (throughout all period of operation). Activity of group II nitrifiers (genera Nitrobacter and Nitrococcus), which were present in ASB, prevented accumulation of nitrite, which in high concentrations is toxic to both nitrifiers and anammox bacteria. High activity of the Nitrosospira nitrifiers introduced with ASB probably provided the anammox bacteria with one of the substrates (nitrite), promoting their rapid growth. During subsequent operation of the reactor, nitrifiers of the genus Nitrosomonas from the initial ASA community were mainly responsible for growth of the anammox bacteria. Thus, ASA bioaugmentation at the loading of the anammox reactor by active nitrifiers resulted in significantly improved efficiency of ammonium removal via the anammox process and accelerated transition of the reactor to the working mode.
Rapidly enlarging pulmonary mass due to immune reconstitution inflammatory syndrome (IRIS) in an immunocompetent host with pulmonaryCryptococcus neoformans
Authors: Tucker Mollie , Sheikh Abdul Majeed , Villanueva Merceditas S
Published: March 2022

An immunocompetent man presented withCryptococcus neoformansdisease manifesting as a large pulmonary mass (cryptococcoma). Despite an initial induction course of 4 weeks of liposomal amphotericin B (LAmB), followed by 8 weeks of fluconazole, the cryptococcoma enlarged in size. Ten days into a second course of induction therapy with LAmB and flucytosine, the cryptococcoma markedly increased in size with encroachment on critical vascular structures. Due to concern for immune reconstitution inflammatory syndrome (IRIS), prednisone was added with significant decrease in the size of the mass. To our knowledge, this is the first reported case of pulmonary cryptococcal-IRIS in an immunocompetent host.
Antisynthetase syndrome sine myositis presenting as severe acute respiratory failure
Authors: Archer Christian , Nazim Khola , Panchatsharam Selva
Published: March 2022

A female in her late 40s presented to the emergency department during the COVID-19 pandemic with shortness of breath, fever and productive cough following a recent diagnosis of bilateral non-massive pulmonary emboli. She had elevated inflammatory markers and her chest X-ray revealed bilateral infiltrates. Her SARS-CoV-2 PCR was negative, and she was treated for community-acquired pneumonia. However, despite treatment she rapidly deteriorated and developed severe respiratory failure, requiring mechanical ventilation.

On further investigation, she tested positive for anti-Jo-1 antibodies and a diagnosis of antisynthetase syndrome sine myositis was made. This led to successful treatment with high dose corticosteroids and intravenous immunoglobulin.

This case highlights an uncommon presentation of a rare condition, as well as the benefits of working in a multidisciplinary team on the intensive care unit.
Comparison of cognitive function in older adults with type 1 diabetes, type 2 diabetes, and no diabetes: results from the Study of Longevity in Diabetes (SOLID)
Authors: Lacy Mary E , Moran Chris , Gilsanz Paola , Beeri Michal S , Karter Andrew J , Whitmer Rachel A
Published: March 2022

Introduction

The incidence of both type 1 diabetes (T1D) and type 2 diabetes (T2D) is increasing. Life expectancy is improving in T1D, resulting in a growing population of elderly adults with diabetes. While it is well established that older adults with T2D are at increased risk of cognitive impairment, little is known regarding cognitive aging in T1D and how their cognitive profiles may differ from T2D.

Research design and methods

We compared baseline cognitive function and low cognitive function by diabetes status (n=734 T1D, n=232 T2D, n=247 without diabetes) among individuals from the Study of Longevity in Diabetes (mean age=68). We used factor analysis to group cognition into five domains and a composite measure of total cognition. Using linear and logistic regression models, we examined the associations between diabetes type and cognitive function, adjusting for demographics, comorbidities, depression, and sleep quality.

Results

T1D was associated with lower scores on total cognition, language, executive function/psychomotor processing speed, and verbal episodic memory, and greater odds of low executive function/psychomotor processing speed (OR=2.99, 95% CI 1.66 to 5.37) and verbal episodic memory (OR=1.92, 95% CI 1.07 to 3.46), compared with those without diabetes. T2D was associated with lower scores on visual episodic memory. Compared with T2D, T1D was associated with lower scores on verbal episodic memory and executive function/psychomotor processing speed and greater odds of low executive function/psychomotor processing speed (OR=1.74, 95% CI 1.03 to 2.92).

Conclusions

Older adults with T1D had significantly poorer cognition compared with those with T2D and those without diabetes even after accounting for a range of comorbidities. Future studies should delineate how to reduce risk in this vulnerable population who are newly surviving to old age.
FreeStyle Libre Flash Glucose Monitoring system for people with type 1 diabetes in the UK: a budget impact analysis
Authors: Blissett Robert , Blissett Deirdre , Levrat-Guillen Fleur , Deshmukh Harshal , Wilmot Emma G , Ryder Robert E J , Walton Chris , Sathyapalan Thozhukat
Published: March 2022

Introduction

This study aims to estimate the budget impact of increased uptake of the FreeStyle Libre Flash Glucose Monitoring system in people with type 1 diabetes mellitus (T1DM) in the UK.

Research design and methods

A budget impact model was developed, applying real-world data collected in the Association of British Clinical Diabetologists (ABCD) FreeStyle Libre Nationwide Audit. Costs of diabetes glucose monitoring in a T1DM population (n=1790) using self-monitoring of blood glucose (SMBG) or the FreeStyle Libre system were compared with a scenario with increased use of the FreeStyle Libre system.

Results

The ABCD audit demonstrates FreeStyle Libre system use reduces diabetes-related resource utilization. The cost analysis found that higher acquisition costs are offset by healthcare costs avoided (difference £168 per patient per year (PPPY)). Total costs were £1116 PPPY with FreeStyle Libre system compared with £948 PPPY with SMBG. In an average-sized UK local health economy, increasing FreeStyle Libre system uptake from 30% to 50% increased costs by 3.4% (£1 787 345–£1 847 618) and when increased to 70% increased by a further 3.3%.

Conclusion

Increased uptake of the FreeStyle Libre system in the T1DM population marginally increases the cost to UK health economies and offers many system benefits.
Empowering consumers to PREVENT diet-related diseases through OMICS sciences (PREVENTOMICS): protocol for a parallel double-blinded randomised intervention trial to investigate biomarker-based nutrition plans for weight loss
Authors: Aldubayan Mona Adnan , Pigsborg Kristina , Gormsen Sophia M O , Serra Francisca , Palou Mariona , Mena Pedro , Wetzels Mart , Calleja Alberto , Caimari Antoni , Del Bas Josep , Gutierrez Biotza , Magkos Faidon , Hjorth Mads Fiil
Published: March 2022

Introduction

Personalised nutrition holds immense potential over conventional one-size-fits-all approaches for preventing and treating diet-related diseases, such as obesity. The current study aims to examine whether a personalised nutritional plan produces more favourable health outcomes than a standard approach based on general dietary recommendations in subjects with overweight or obesity and elevated waist circumference.

Methods and analysis

This project is a 10-week parallel, double-blinded randomised intervention trial. We plan to include 100 adults aged 18–65 years interested in losing weight, with body mass index ≥27 but<40 kg/m2 and elevated waist circumference (males >94 cm; females >80 cm). Participants will be categorised into one of five predefined ‘clusters’ based on their individual metabolic biomarker profile and genetic background, and will be randomised in a 1:1 ratio to one of two groups: (1) personalised plan group that will receive cluster-specific meals every day for 6 days a week, in conjunction with a personalised behavioural change programme via electronic push notifications; or (2) control group that will receive meals following the general dietary recommendations in conjunction with generic health behaviour prompts. The primary outcome is the difference between groups (personalised vs control) in the change in fat mass from baseline. Secondary outcomes include changes in weight and body composition, fasting blood glucose and insulin, lipid profile, adipokines, inflammatory biomarkers, and blood pressure. Other outcomes involve measures of physical activity and sleep patterns, health-related quality of life, dietary intake, eating behaviour, and biomarkers of food intake. The effect of the intervention on the primary outcome will be analysed by means of linear mixed models.

Ethics and dissemination

The protocol has been approved by the Ethics Committee of the Capital Region, Copenhagen, Denmark. Study findings will be disseminated through peer-reviewed publications, conference presentations and media outlets.

Trial registration number

NCT04590989.
Burden of cancer in the general surgical population in the eastern region of Ghana
Authors: Olecki Elizabeth Josephine , Ssentongo Paddy , Dao Joseph , Wong William G , Stahl Kelly A , Ofosu-Akromah Richard , Amponsah-Manu Foster , Pameijer Colette
Published: March 2022

Objective

To estimate the surgical burden of malignant disease in the Eastern Region of Ghana.

Design

Descriptive cross-sectional study.

Setting

Regional hospital in the eastern region of Ghana.

Participants

Patients treated by the surgery department at Eastern Regional Hospital in Koforidua, Ghana.

Interventions

None.

Primary and secondary outcome measures

Primary outcome was incidence of malignancy and secondary outcome descriptive differences between patients who had a benign indication for surgery compared with those with a malignant indication for surgery.

Results

A total of 1943 inpatient surgical procedures were performed from 2015 to 2017 with 13.4% (261) of all procedures ultimately performed for malignancy. Of all breast procedures performed, 95.2% of procedures resulted in a malignant diagnosis. The remaining subtypes of procedures had rates ranging from <1% to 41.2% of procedures performed for malignant disease. Additionally, this study found over 13% of patients admitted to the surgical service for breast cancer ultimately did not undergo a surgical procedure.

Conclusion

This is the first study investigating the burden of malignant disease in the Eastern Region of Ghana. We found a substantial prevalence of malignant disease in the surgical population in this region. This information can be used to aid in future medical resource planning in this region.