bluuebunny/crossref_metadata_2025 huggingface dataset:
Sliding bifurcations of a two DOF self-excited SD oscillator with Coulomb friction
Authors: Li Zhixin , Li Zhiguo , Zhang Ke , Lu Jiaqi
Published: March 2023

In this study, on the basis of the SD (smooth and discontinuous) oscillator, we analyze the sliding bifurcations of a two DOF self-excited system driven by the classical conveyor belt friction. In order to elaborate the nonsmooth model named the self-excited SD oscillator, we model the friction of the conveyor belt of this system as Coulomb friction. Switching surfaces and sliding regions of this nonsmooth system are obtained based on the Filippov theory. The numerical simulations are performed to present the various scenarios of sliding bifurcation and chaotic attractors in the system. The results of this study give us an opportunity to understand clearly the bifurcation mechanism of the rich nonlinear frictional dynamics in machinery field.
Dynamic modeling and analysis of compound pendulum motion of projectile
Authors: Hang Zhang , Dong Chen , Binan Jiang , Qi Meng
Published: March 2023

The influence of air lift on the stability of inaccurate precision strike ammunition is studied, and the mechanical analysis of projectile and its flight stage is carried out. The dynamic equation of projectile under the action of air lift is established and simulated. The angular velocity and angular time-history curve of the compound pendulum motion of the projectile are obtained, and the correctness of the mechanical analysis of compound pendulum motion during flight is verified.
Analytic solution on force analysis of tripod in arbitrary space
Authors: Li Yun , Song Yumin
Published: March 2023

Tripod is a common support structure. The key to tripod design is to accurately analyze the force, select appropriate materials, and design the angle according to the size of the axial force. To study the stress condition and application performance of a tripod, this paper takes any tripod in space as the research object, through the combination of mathematics and mechanics, establishes a space rectangular coordinate system, solves the internal force of the tripod member, and verifies the correctness of the solution results. The evolution from arbitrary tripod structure to special tripod structure demonstrates the correctness of the reasoning method from general to special. An arbitrary space tripod is a common engineering application structure. Taking it as the research object, mechanical analysis has certain practical significance.
Performance of a spherical high pressure gas TPC for neutrino magnetic moment measurement
Authors: Bouet R. , Busto J. , Cecchini V. , Cerna C. , Charpentier P. , Dastgheibi-Fard A. , Druillole F. , Jollet C. , Hellmuth P. , Katsioulas I. , Knights P. , Giomataris I. , Gros M. , Lautridou P. , Meregaglia A. , Navick X.F. , Neep T. , Nikolopoulos K. , Perrot F. , Piquemal F. , Roche M. , Thomas B. , Ward R.
Published: March 2023

The measurement of neutrino magnetic moment larger than
10-19
μB
would be a clear signature of physics beyond the
standard model other than the existence of massive Dirac
neutrinos. The use of a spherical proportional counter detector
filled with gas at 40 bar located near a nuclear reactor would be a
simple way to perform such a measurement exploiting the developments
made on such a technology for the search of dark matter and
neutrinoless double beta decay. Different targets can be used just
by replacing the gas: xenon, CF4 and argon were compared and the
sensitivity in one year of data taking could reach the level of
4.3 × 10-12
μB
, 6.5 × 10-12
μB
, and
8.5 × 10-12
μB
, respectively.
Abelian sandpiles on cylinders
Authors: Eckmann Jean-Pierre , Nagnibeda Tatiana , Perriard Aymeric
Published: March 2023

We study the Abelian sandpile model on a special playground, a cylinder of width w and of circumference c. When

c
≪
w

, we describe a phenomenon which has not been observed in other geometries: the probability distribution of avalanche sizes has a ladder structure, with the first step consisting of avalanches of size up to

w
⋅
c

/

2

that are essentially equiprobable, except for a small exponential tail of order about 10 c. We explain this phenomenon and describe subsequent steps.
DeepFormer: a hybrid network based on convolutional neural network and flow-attention mechanism for identifying the function of DNA sequences
Authors: Yao Zhou , Zhang Wenjing , Song Peng , Hu Yuxue , Liu Jianxiao
Published: March 2023

Identifying the function of DNA sequences accurately is an essential and challenging task in the genomic field. Until now, deep learning has been widely used in the functional analysis of DNA sequences, including DeepSEA, DanQ, DeepATT and TBiNet. However, these methods have the problems of high computational complexity and not fully considering the distant interactions among chromatin features, thus affecting the prediction accuracy. In this work, we propose a hybrid deep neural network model, called DeepFormer, based on convolutional neural network (CNN) and flow-attention mechanism for DNA sequence function prediction. In DeepFormer, the CNN is used to capture the local features of DNA sequences as well as important motifs. Based on the conservation law of flow network, the flow-attention mechanism can capture more distal interactions among sequence features with linear time complexity. We compare DeepFormer with the above four kinds of classical methods using the commonly used dataset of 919 chromatin features of nearly 4.9 million noncoding DNA sequences. Experimental results show that DeepFormer significantly outperforms four kinds of methods, with an average recall rate at least 7.058% higher than other methods. Furthermore, we confirmed the effectiveness of DeepFormer in capturing functional variation using Alzheimer’s disease, pathogenic mutations in alpha-thalassemia and modification in CCCTC-binding factor (CTCF) activity. We further predicted the maize chromatin accessibility of five tissues and validated the generalization of DeepFormer. The average recall rate of DeepFormer exceeds the classical methods by at least 1.54%, demonstrating strong robustness.
Topical tacrolimus versus corticosteroids in childhood moderate-to-severe atopic dermatitis and the impact on airway inflammation: a long-term randomized open-label study
Authors: Perälä Miia , Salava Alexander , Malmberg Pekka , Pelkonen Anna S , Mäkelä Mika J , Remitz Anita
Published: March 2023

Background

Childhood atopic dermatitis (AD) is often followed by other atopic comorbidities such as asthma.

Aim

To compare the effectiveness of topical tacrolimus (TAC) and topical corticosteroids (TCSs) and their impact on airway inflammation and bronchial hyperresponsiveness in patients with paediatric AD.

Methods

This was a 3-year randomized open-label comparative follow-up study of 152 1–3-year-old children with moderate-to-severe AD (trial registration: EudraCT2012-002412-95). Frequent study visits including clinical examinations, laboratory investigations (total IgE, specific IgEs, blood eosinophils), skin prick and respiratory function tests to assess airway inflammation and bronchial hyperresponsiveness (exhaled nitric oxide, airway responsiveness to exercise and methacholine) were performed.

Results

Changes in eczema parameters at 36 months were similar in the TCS and TAC groups for mean body surface area (BSA) difference 1.4 [95% confidence interval (CI) –1.48 to 4.19); P = 0.12], mean Eczema Area and Severity Index (EASI) difference 0.2 (95% CI –1.38 to 1.82; P = 0.2), mean Investigator’s Global Assessment (IGA) difference, 0.3 (95% CI –0.12 to 0.67; P = 0.12) and mean transepidermal water loss (TEWL) difference at the eczema site, –0.3 (95% CI –4.93 to 4.30; P = 0.96) and at the control site, 1.4 (95% CI –0.96 to 3.60, P = 0.19). The control-site TEWL increased more towards the end of follow-up in the TCS vs. TAC group (mean change difference –4.2, 95% CI –8.14 to –0.29; P = 0.04). No significant impact on development of airway inflammation or bronchial hyperresponsiveness occurred in early effective eczema-treatment responders vs. others (‘early’ vs. ‘other’ response was defined as the difference in treatment response to airway outcomes in BSA, EASI or IGA at 3 months).

Conclusion

Children with moderate-to-severe AD benefit from long-term treatment with TCS or TAC. There were no significant differences in treatment efficacy. No differences in the impact on airways occurred between early effective treatment responders vs. others.
Pipelined Decision Trees for Online Traffic Classification on FPGAs
Authors: Erdem Oğuzhan , Soylu Tuncay , Carus Aydın
Published: March 2023

Decision tree (DT)-based machine learning (ML) algorithms are one of the preferred solutions for real-time internet traffic classification in terms of their easy implementation on hardware. However, the rapid increase in today’s newly developed applications and the resulting diversity in internet traffic greatly increases the size of DTs. Therefore, the tree-based hardware classifiers cannot keep up with this growth in terms of resource usage and classification speed. To alleviate the problem, we propose to group application classes by certain rules and create an individual small DT per each group. In this article, a pipelined organization of multiple DT data structures, called pipelined decision trees, is proposed as a scalable solution to tree-based traffic classification. We also propose two distinct algorithms, namely confusion matrix-based class aggregation and leaf count-based class aggregation algorithms, to set group creation rules that allows traffic classification on pipelined smaller DTs in a hierarchical order. We further designed an hardware engine on field programmable gate arrays, which can search those pipelined trees within a single clock cycle by transforming them into bit vectors and implementing multiple range comparisons in parallel. Our architecture with 12 classes can run in 928.88 giga bit per second and achieve 96.04% accuracy.
Hybrid inferiority and genetic incompatibilities drive divergence of fungal pathogens infecting the same host
Authors: Yuzon Jennifer D , Wyatt Nathan A , Vasighzadeh Asieh , Clare Shaun , Navratil Emma , Friesen Timothy L , Stukenbrock Eva H
Published: March 2023

Agro-ecosystems provide environments that are conducive for rapid evolution and dispersal of plant pathogens. Previous studies have demonstrated that hybridization of crop pathogens can give rise to new lineages with altered virulence profiles. Currently, little is known about either the genetics of fungal pathogen hybridization or the mechanisms that may prevent hybridization between related species. The fungus Pyrenophora teres is a global pathogen of barley. The pathogenic fungus P. teres exists as two distinct lineages P. teres f. teres and P. teres f. maculata (Ptt and Ptm, respectively), which both infect barley but produce very distinct lesions and rarely interbreed. Interestingly, Ptt and Ptm can, by experimental mating, produce viable progenies. Here, we addressed the underlying genetics of reproductive barriers of P. teres. We hypothesize that Ptt and Ptm diverged in the past, possibly by adapting to distinct hosts, and only more recently colonized the same host in agricultural fields. Using experimental mating and in planta phenotyping in barley cultivars susceptible to both P. teres forms, we demonstrate that hybrids produce mixed infection phenotypes but overall show inferior pathogenic fitness relative to the pure parents. Based on analyses of 104 hybrid genomes, we identify signatures of negative epistasis between parental alleles at distinct loci (Dobzhansky–Müller incompatibilities). Most DMI regions are not involved in virulence but certain genes are predicted or known to play a role in virulence. These results potentially suggest that divergent niche adaptation—albeit in the same host plant—contributes to speciation in P. teres.
Genetic modifiers modulate phenotypic expression of tafazzin deficiency in a mouse model of Barth syndrome
Authors: Wang Suya , Yazawa Erika , Keating Erin M , Mazumdar Neil , Hauschild Alexander , Ma Qing , Wu Haiyan , Xu Yang , Shi Xu , Strathdee Douglas , Gerszten Robert E , Schlame Michael , Pu William T
Published: March 2023

Barth syndrome is an X-linked disorder caused by loss-of-function mutations in Tafazzin (TAZ), an acyltransferase that catalyzes remodeling of cardiolipin, a signature phospholipid of the inner mitochondrial membrane. Patients develop cardiac and skeletal muscle weakness, growth delay and neutropenia, although phenotypic expression varies considerably between patients. Taz knockout mice recapitulate many of the hallmark features of the disease. We used mouse genetics to test the hypothesis that genetic modifiers alter the phenotypic manifestations of Taz inactivation. We crossed TazKO/X females in the C57BL6/J inbred strain to males from eight inbred strains and evaluated the phenotypes of first-generation (F1) TazKO/Y progeny, compared to TazWT/Y littermates. We observed that genetic background strongly impacted phenotypic expression. C57BL6/J and CAST/EiJ[F1] TazKO/Y mice developed severe cardiomyopathy, whereas A/J[F1] TazKO/Y mice had normal heart function. C57BL6/J and WSB/EiJ[F1] TazKO/Y mice had severely reduced treadmill endurance, whereas endurance was normal in A/J[F1] and CAST/EiJ[F1] TazKO/Y mice. In all genetic backgrounds, cardiolipin showed similar abnormalities in knockout mice, and transcriptomic and metabolomic investigations identified signatures of mitochondrial uncoupling and activation of the integrated stress response. TazKO/Y cardiac mitochondria were small, clustered and had reduced cristae density in knockouts in severely affected genetic backgrounds but were relatively preserved in the permissive A/J[F1] strain. Gene expression and mitophagy measurements were consistent with reduced mitophagy in knockout mice in genetic backgrounds intolerant of Taz mutation. Our data demonstrate that genetic modifiers powerfully modulate phenotypic expression of Taz loss-of-function and act downstream of cardiolipin, possibly by altering mitochondrial quality control.
Psychometric Performance of Fatigue Scales in Inflammatory Bowel Disease
Authors: Marrie Ruth Ann , Fisk John D , Dolovich Casandra , Lix Lisa M , Graff Lesley A , Patten Scott B , Bernstein Charles N
Published: March 2023

Background

Fatigue is highly prevalent in people with inflammatory bowel disease (IBD). Fatigue scales are important for studies testing fatigue interventions, but information about psychometric properties of many scales is insufficient in IBD. We compared the psychometric properties of multiple generic fatigue scales in participants with IBD.

Methods

Individuals with IBD (N = 216) completed the Daily Fatigue Impact Scale (DFIS), the vitality subscale of the RAND-36, and the Patient Health Questionnaire-9 (PHQ-9) fatigue item twice. A subgroup (n = 84) also completed the Fatigue Impact Scale (FIS) once, from which we also scored the 21 items from the Modified Fatigue Impact Scale (MFIS-IBD). We assessed floor/ceiling effects, construct validity, and internal consistency reliability. Using relative efficiency (RE), we compared discriminating ability and comparative responsiveness of the measures regarding disease activity and employment status and changes.

Results

The FIS, MFIS, and RAND-36-vitality scales did not exhibit floor or ceiling effects. The DFIS showed mild floor effects (19.4%), and the PHQ-9 fatigue item showed floor (18.1%) and ceiling (20.8%) effects. Internal consistency reliability exceeded 0.93 for FIS, MFIS-IBD, and DFIS and was 0.81 for the RAND-36-vitality scale. In the subgroup analysis, the FIS, MFIS-IBD, and DFIS were strongly correlated with each other (r ≥ 0.90). The ability to discriminate between disease activity groups was highest for the FIS and MFIS-IBD, followed by the DFIS. The FIS, MFIS-IBD, and DFIS were responsive to changes in work impairment.

Conclusions

The FIS, MFIS-IBDs and DFIS had adequate validity and reliability for assessing fatigue in IBD.
The Curious Case of Judicial Interpretation and Labour Flexibility in India
Authors: Balasubramanian Girish , Talluri Surendra Babu , Sarkar Santanu
Published: March 2023

The economic liberalisation of the 1990s in India led to calls for increased labour flexibility. As achieving legislative reform proved difficult, the focus shifted to judicial interpretation of existing labour statutes. We present evidence that Indian courts changed their interpretations of labour laws over time, favouring flexibility at the expense of the protective purposes underlying the legislation. Our study is based on analysis of a sample of 196 judgments of senior appellate courts between 1999 and 2019 on protective provisions of the Contract Labour (Regulation and Abolition) Act 1970. The tendency of the Indian courts to support interpretations consistent with the goal of labour flexibility may be said to illustrate the role of the judiciary in promoting market-led economic development, but it also suggests a degree of bias in the courts’ approach to questions of labour law adjudication.
Where Should Multinationals Pay Taxes?
Authors: Arel-Bundock Vincent , Blais André
Published: March 2023

The international tax system is a pillar of the post-war economic order, but it faces major challenges with the rise of global value chains, digitalization, and tax avoidance. Debates over international tax reform usually occur within a small epistemic community of experts and technocrats. In this article, we step outside this restricted circle to assess the sources of bottom-up legitimacy and support for the rules that govern where multinationals must report profits and which governments are entitled to tax those profits. We conduct survey experiments in Brazil, France, and the United States to assess mass attitudes toward the allocation of the tax base across countries. We find that people’s views clash with the core principles of the current regime, but are aligned with reform proposals that allocate more taxing rights to market jurisdictions. These findings are strikingly consistent across three countries and three distinct studies. At first glance, the consistency of attitudes across countries could spell good things for international cooperation in this arena. However, we also find a significant level of “home bias” in the public’s views on tax allocation. These results shed new light on the legitimacy of tax reform and on the prospects for cooperation in a key area of international economic relations.
Brevicillin, a novel lanthipeptide from the genusBrevibacilluswith antimicrobial, antifungal, and antiviral activity
Authors: Singh Shelley Sardul , Sharma Deepika , Singh Charandeep , Kumar Sahil , Singh Prashant , Sharma Anshul , Das Deepjyoti Kumar , Pinnaka Anil Kumar , Thakur Krishan Gopal , Ringe Rajesh P , Korpole Suresh
Published: March 2023

Aim

This study was aimed to determine antimicrobial and antiviral activity of a novel lanthipeptide from a Brevibacillus sp. for disinfectant application.

Methods and results

The antimicrobial peptide (AMP) was produced by a bacterial strain AF8 identified as a member of the genus Brevibacillus representing a novel species. Whole genome sequence analysis using BAGEL identified a putative complete biosynthetic gene cluster involved in lanthipeptide synthesis. The deduced amino acid sequence of lanthipeptide named as brevicillin, showed >30% similarity with epidermin. Mass determined by MALDI-MS and Q-TOF suggested posttranslational modifications like dehydration of all Ser and Thr amino acids to yield Dha and Dhb, respectively. Amino acid composition determined upon acid hydrolysis is in agreement with core peptide sequence deduced from the putative biosynthetic gene bvrAF8. Biochemical evidence along with stability features ascertained posttranslational modifications during formation of the core peptide. The peptide showed strong activity with 99% killing of pathogens at 12 μg ml−1 within 1 minute. Interestingly, it also showed potent anti-SARS-CoV-2 activity by inhibiting ∼99% virus growth at 10 μg ml−1 in cell culture-based assay. Brevicillin did not show dermal allergic reactions in BALB/c mice.

Conclusion

This study provides detailed description of a novel lanthipeptide and demonstrates its effective antibacterial, antifungal and anti-SARS-CoV-2 activity.
Congenital diverticulum of the vermiform appendix: a rare finding of a routine operation
Authors: Padar Maria , Mudalige Vijitha P
Published: March 2023

Congenital diverticulum of the appendix as well as diverticulitis of the vermiform appendix remain a rare, mainly retrospective diagnosis, reported by the pathologist, post-appendicectomy. In clinical practice, however, it is important to be aware of this entity, the different types, diagnosis, association with malignancy and treatment options. We are presenting a young female case of pathologically proved true diverticulum of the appendix with associated uncomplicated appendicitis and an overview of the literature.
Utility of a Viral Vesicular Panel Multiplex Polymerase Chain Reaction Assay for the Diagnosis of Monkeypox, Herpes Simplex, and Varicella Zoster Viruses
Authors: Wilber Eli , Rebolledo Paulina A , Kasinathan Vyjayanti , Merritt Stephanie , Titanji Boghuma K , Aldred Bruce , Kandiah Sheetal , Ray Susan M , Sheth Anandi N , Colasanti Jonathan A , Wang Yun F
Published: March 2023

Mpox (monkeypox) represents a diagnostic challenge due to varied clinical presentations and multiple mimics. A commercially available multiplex polymerase chain reaction panel accurately detects mpox virus as well as common mimics (herpes simplex virus, varicella zoster virus) in clinical specimens and could be used in routine clinical, surveillance, and outbreak settings.
Volatile Organic Compounds of Bacillus pumilus Strain S1-10 Exhibit Fumigant Activity Against Meloidogyne incognita
Authors: Dai Ming-ming , Liu Rui , Jiang Hao , Zhang Xiao-ping , Song Wen-wen , Zhang Jie , Liang Chen , Zhao Hong-hai , Shi Qian-qian
Published: March 2023

Root-knot nematodes (RKNs) are highly specialized parasites that cause significant yield losses worldwide. In this study, we isolated Bacillus pumilus strain S1-10 from the rhizosphere soil of Zingiber officinale Rosc. plants and evaluated its fumigant activity against Meloidogyne incognita. S1-10 exhibited a strong repellent effect on second-stage juveniles (J2s) of M. incognita, and in vitro assays indicated that S1-10 volatile organic compounds (VOCs) suppressed J2 activity and egg hatching. Under greenhouse conditions, 71 and 79% reductions of nematodes and eggs were detected on plants treated with S-10 VOCs compared with controls. Ten VOCs were identified through gas chromatography and mass spectrometry (GC-MS), of which 2-(methylamino)-ethanol (2-ME) had strong fumigant activity against J2s of M. incognita, with an LC50 value of 1.5 mM at 12 h. These results indicate that S1-10 represents a potential novel biocontrol agent for RKNs.
Biological Control Efficacy of Bacillus sp. REB711 on Sheath Blight of Rice
Authors: Maharjan Ateet , Bruno Jobelle , Osti Surendra , Barphagha Inderjit K. , Ham Jong Hyun
Published: March 2023

Sheath blight (ShB), caused by Rhizoctonia solani, is one of the economically important rice diseases in Louisiana and other rice-growing regions. Fungicides are used to manage ShB, but such chemical methods are not economically or ecologically sustainable. To develop new biological control agents for the management of ShB, bacteria isolated from rice plants in the field were initially screened in the laboratory based on their antagonistic activities against R. solani through plate assays that exhibit growth inhibition of the fungal pathogen. The efficacy of three selected strains of Bacillus spp. (RAB14R, REB711, and RRB985) in suppression of ShB was further evaluated under the greenhouse and field conditions. In field trials conducted in 2017 and 2018, foliar spray of Bacillus sp. REB711 significantly reduced the development of ShB compared with the nontreated control, although it was less effective than the azoxystrobin fungicide Quadris. In greenhouse tests, Bacillus sp. REB711 significantly reduced ShB development (disease severity and lesion length) through seed treatment, whereas the other two strains of Bacillus spp. did not. The observed efficacy of Bacillus sp. REB711 could result from competition, antibiosis, and/or induction of the plant defense system and suggests that this bacterial strain could be used as a potential biological agent for managing ShB by itself or in combination with fungicides to reduce the risk of fungicide resistance.
Plasticity of mitochondrial function safeguards phosphorylating respiration during in vitro simulation of rest‐phase hypothermia
Authors: García‐Díaz Carmen C. , Chamkha Imen , Elmér Eskil , Nord Andreas
Published: March 2023

Many animals downregulate body temperature to save energy when resting (rest‐phase hypothermia). Small birds that winter at high latitudes have comparatively limited capacity for hypothermia and so pay large energy costs for thermoregulation during cold nights. Available evidence suggests this process is fueled by adenosine triphosphate (ATP)‐dependent mechanisms. Most ATP is produced by oxidative phosphorylation in the mitochondria, but mitochondrial respiration may be lower during hypothermia because of the temperature dependence of biological processes. This can create conflict between increased organismal ATP demand and a lower mitochondrial capacity to provide it. We studied this in blood cell mitochondria of wild great tits (Parus major) by simulating rest‐phase hypothermia via a 6°C reduction in assay temperature in vitro. The birds had spent the night preceding the experiment in thermoneutrality or in temperatures representing mild or very cold winter nights, but night temperatures never affected mitochondrial respiration. However, across temperature groups, endogenous respiration was 14% lower in hypothermia. This did not reflect general thermal suppression of mitochondrial function because phosphorylating respiration was unaffected by thermal state. Instead, hypothermia was associated with a threefold reduction of leak respiration, from 17% in normothermia to 4% in hypothermia. Thus, the coupling of total respiration to ATP production was 96% in hypothermia, compared to 83% in normothermia. Our study shows that the thermal insensitivity of phosphorylation combined with short‐term plasticity of leak respiration may safeguard ATP production when endogenous respiration is suppressed. This casts new light on the process by which small birds endure harsh winter cold and warrants future tests across tissues in vivo.
Predicting Deformity Correction of Growth Modulation in Late-onset Tibia Vara
Authors: Walker Janet L. , Dueber David M. , Powell Kenneth P. , Stephenson Lindsay P. , Scott Allison C. , Lerman Joel A. , Nossov Sarah B. , Franklin Corinna C. , Westberry David E.
Published: March 2023

Background:

Growth modulation in late-onset tibia vara (LOTV) has been reported to yield variable results. We hypothesized that parameters of deformity severity, skeletal maturity, and body weight could predict the odds of a successful outcome.

Methods:

A retrospective review of tension band growth modulation for LOTV (onset ≥8 y) was performed at 7 centers. Tibial/overall limb deformity and hip/knee physeal maturity were assessed on preoperative anteroposterior standing lower-extremity digital radiographs. Tibial deformity change with first-time lateral tibial tension band plating (first LTTBP) was assessed by medial proximal tibia angle (MPTA). Effects of a growth modulation series (GMS) on overall limb alignment were assessed by mechanical tibiofemoral angle (mTFA) and included changes from implant removal, revision, reimplantation, subsequent growth, and femoral procedures during the study period. The successful outcome was defined as radiographic resolution of varus deformity or valgus overcorrection. Patient demographics, characteristics, maturity, deformity, and implant selections were assessed as outcome predictors using multiple logistic regression.

Results:

Fifty-four patients (76 limbs) had 84 LTTBP procedures and 29 femoral tension band procedures. For each 1-degree decrease in preoperative MPTA or 1-degree increase in preoperative mTFA the odds of their successful correction decreased by 26% in the first LTTBP and 6% by GMS, respectively, controlling for maturity. The change in odds of success for GMS assessed by mTFA was similar when controlling for weight. Closure of a proximal femoral physis decreased the odds of success for postoperative-MPTA by 91% with first LTTBP and for final-mTFA by 90% with GMS, controlling for preoperative deformity. Preoperative weight ≥100 kg decreased the odds of success for final-mTFA with GMS by 82%, controlling for preoperative mTFA. Age, sex, race/ethnicity, type of implant, and knee center peak value adjusted age (a method for bone age) were not predictive of outcome.

Conclusions:

Resolution of varus alignment in LOTV using first LTTBP and GMS, as quantified by MPTA and mTFA, respectively, is negatively impacted by deformity magnitude, hip physeal closure, and/or body weight ≥100 kg. The presented table, utilizing these variables, is helpful in the prediction of the outcome of the first LTTBP and GMS. Even if complete correction is not predicted, growth modulation may still be appropriate to reduce deformity in high-risk patients.

Level of Evidence:

Level III.
Subgroups of Idiopathic Clubfoot Can Predict Short-term Outcomes
Authors: Quinlan Rachal , Pacey Verity , Ilhan Emre , Gibbons Paul , Gray Kelly
Published: March 2023

Background:

The Pirani scale is used for the assessment of Ponseti-managed clubfoot. Predicting outcomes using the total Pirani scale score has varied results, however, the prognostic value of midfoot and hindfoot components remains unknown. The purpose was to (1) determine the existence of subgroups of Ponseti-managed idiopathic clubfoot based on the trajectory of change in midfoot and hindfoot Pirani scale scores, (2) identify time points, at which subgroups can be distinguished, and (3) determine whether subgroups are associated with the number of casts required for correction and need for Achilles tenotomy.

Methods:

Medical records of 226 children with 335 idiopathic clubfeet, over a 12-year period, were reviewed. Group-based trajectory modeling of the Pirani scale midfoot score and hindfoot score identified subgroups of clubfoot that followed statistically distinct patterns of change during initial Ponseti management. Generalized estimating equations determined the time point, at which subgroups could be distinguished. Comparisons between groups were determined using the Kruskal-Wallis test for the number of casts required for correction and binary logistic regression analysis for the need for tenotomy.

Results:

Four subgroups were identified based on the rate of midfoot-hindfoot change: (1) fast-steady (61%), (2) steady-steady (19%), (3) fast-nil (7%), and (4) steady-nil (14%). The fast-steady subgroup can be distinguished at the removal of the second cast and all other subgroups can be distinguished at the removal of the fourth cast [H (3) = 228.76, P < 0.001]. There was a significant statistical, not clinical, difference in the total number of casts required for correction across the 4 subgroups [median number of casts 5 to 6 in all groups, H (3) = 43.82, P < 0.001]. Need for tenotomy was significantly less in the fast-steady (51%) subgroup compared with the steady-steady (80%) subgroup [H (1) = 16.23, P < 0.001]; tenotomy rates did not differ between the fast-nil (91%) and steady-nil (100%) subgroups [H (1) = 4.13, P = 0.04].

Conclusions:

Four distinct subgroups of idiopathic clubfoot were identified. Tenotomy rate differs between the subgroups highlighting the clinical benefit of subgrouping to predict outcomes in Ponseti-managed idiopathic clubfoot.

Level of Evidence:

Level II, prognostic.
Fibrin Glue is a Viable Alternative to Fat Graft for Interposition After Tarsal Coalition Resection
Authors: Swonger Ronald M. , Bernstein Jessica M. , Perez Olivia F. , Syros Alina , Horowitz Kevin S. , Schreiber Verena M.
Published: March 2023

Background:

Tarsal coalition is one of the most common foot and ankle pathologies in children, yet there is no consensus regarding what to interpose after resection. Fibrin glue could be considered, but the literature comparing fibrin glue to other interposition types is sparse. The purpose of this study was to evaluate the effectiveness of fibrin glue for interposition compared with fat graft by analyzing the rate of coalition recurrence and wound complications. We hypothesized that fibrin glue would have similar rates of coalition recurrence and fewer wound complications compared with fat graft interposition.

Methods:

A retrospective cohort study was performed examining all patients who underwent a tarsal coalition resection at a free-standing children’s hospital in the United States from 2000 to 2021. Only patients undergoing isolated primary tarsal coalition resection with interposition of fibrin glue or fat graft were included. Wound complications were defined as any concern for an incision site that prompted the use of antibiotics. Comparative analyses were conducted using χ2 and Fisher exact test to examine relationships among interposition type, coalition recurrence, and wound complications.

Results:

One hundred twenty-two tarsal coalition resections met our inclusion criteria. Fibrin glue was used for interposition in 29 cases and fat graft was used in 93 cases. The difference in the coalition recurrence rate between fibrin glue and fat graft interposition was not statistically significant (6.9% vs. 4.3%, P=0.627). The difference in wound complication rate between fibrin glue and fat graft interposition was not statistically significant (3.4% vs 7.5%, P = 0.679).

Conclusion:

Fibrin glue interposition after tarsal coalition resection is a viable alternative to fat graft interposition. Fibrin glue has similar rates of coalition recurrence and wound complications when compared with fat grafts. Given our results and the lack of tissue harvesting required with fibrin glue, fibrin glue may be superior to fat grafts for interposition after tarsal coalition resection.

Level of Evidence:

Level III, a retrospective comparative study between treatment groups.
Current applications for magnetic resonance-guided focused ultrasound in the treatment of Parkinson's disease
Authors: Lu Haoxuan , Wang Xiaoyu , Lou Xin
Published: March 2023

Magnetic resonance-guided focused ultrasound (MRgFUS) is a novel and minimally invasive technology. Since the US Food and Drug Administration approved unilateral ventral intermediate nucleus-MRgFUS for medication-refractory essential tremor in 2016, studies on new indications, such as Parkinson's disease (PD), psychiatric diseases, and brain tumors, have been on the rise, and MRgFUS has become a promising method to treat such neurological diseases. Currently, as the second most common degenerative disease, PD is a research hotspot in the field of MRgFUS. The actions of MRgFUS on the brain range from thermoablation, blood-brain barrier (BBB) opening, to neuromodulation. Intensity is a key determinant of ultrasound actions. Generally, high intensity can be used to precisely thermoablate brain targets, whereas low intensity can be used as molecular therapies to modulate neuronal activity and open the BBB in conjunction with injected microbubbles. Here, we aimed to summarize advances in the application of MRgFUS for the treatment of PD, with a focus on thermal ablation, BBB opening, and neuromodulation, in the hope of informing clinicians of current applications.
Low-dose aspirin in the prevention of pre-eclampsia in China: postpartum hemorrhage in subgroups of women according to their characteristics and potential bleeding risk
Authors: Chen Jiahui , Huai Jing , Lin Li , Li Boya , Zhu Yuchun , Yang Huixia
Published: March 2023

Background:

The APPEC study is a large-population randomized controlled trial in China evaluating the role of low-dose aspirin prophylactic treatment for pre-eclampsia. There was no statistically significant difference in postpartum hemorrhage (PPH) incidence between the aspirin and control groups. This study aimed to evaluate the potential bleeding risk of 100 mg aspirin in high-risk pregnant women and the difference in the incidence of PPH according to maternal characteristics.

Methods:

This is a secondary data analysis of the APPEC study. Platelet counts and coagulation test results were collected at five follow-up visits. Subgroups defined by maternal age (<35 years and ≥35 years), pre-pregnancy body mass index (pre-BMI, <28 kg/m2 and ≥28 kg/m2), parity, gestational age at enrollment, and medical history, including pre-eclampsia, chronic hypertension, and diabetes mellitus, were analyzed. Logistic regression analysis was used to determine the statistical significance of the difference in the incidence of PPH after aspirin administration in pregnant women in each subgroup. Adjustment using multiple logistic regression models followed these analyses. Binary logistic regression was used to determine the relationship between pre-BMI and PPH.

Results:

There was no significant difference between the aspirin and control groups in bleeding risk (3.4% [16/464] vs. 3.0% [13/434], T = 0.147, P = 0.701). No significant difference was found in the incidence of PPH in total (relative risk  = 1.220, 95% confidence interval [CI] = 0.720–2.067, P = 0.459; aspirin group vs. control group, 6.5% [30/464] vs. 5.3% [23/434], P = 0.459) or in subgroup analysis. A significant correlation between pre-BMI and PPH was found in the aspirin group, while in the control group there was no significant correlation (aspirin group, odds ratio [OR] = 1.086, 95% CI = 1.004–1.175, P = 0.040; control group, OR = 1.060, 95% CI = 0.968–1.161, P = 0.209).

Conclusions:

A dosage of 100 mg of aspirin per day, initiated from 12 to 20 gestational weeks until 34 weeks of gestation, did not increase the risk of potential bleeding and PPH regardless of the maternal characteristic. In the aspirin group, the positive correlation between BMI and PPH was significant.

Trial Registration:

ClinicalTrials.gov, NCT01979627.
Long-term outcomes of additional surgery versus non-gastrectomy treatment for early gastric cancer after non-curative endoscopic submucosal dissection: a meta-analysis
Authors: Li Sixuan , Tian Xueli , Wei Jingyao , Shi Yanyan , Zhang Hua , Huang Yonghui
Published: March 2023

Background:

Endoscopic resection is increasingly used in the treatment for early gastric cancer (EGC); however, about 15% of endoscopic submucosal dissection (ESD) cases report non-curative resection. The efficacy of different remedial interventions after non-curative ESD for EGC remains controversial. This meta-analysis aimed to compare the long-term outcomes of additional surgery and non-gastrectomy treatment for EGC patients who underwent non-curative ESD.

Methods:

All relevant studies published up to October 2021 were systematically searched in the PubMed, Web of Science, and Embase databases. The medical subject headings terms “early gastric cancer,” “gastrectomy,” “endoscopic submucosal dissection,” and their related free keywords were used to search relevant articles without restrictions on regions, publication types, or languages. The Newcastle–Ottawa Quality Assessment Scale was used to evaluate the quality of the included studies. Odds ratios (ORs) with 95% confidence intervals (CIs) of 5-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS) and hazard ratios (HRs) with 95% CIs of OS were calculated using a random- or fixed-effects model.

Results:

This meta-analysis included 17 retrospective cohort studies with 5880 patients, of whom 3167 underwent additional surgery and 2713 underwent non-gastrectomy. We found that patients receiving additional gastrectomy had better 5-year OS (OR = 3.63, 95% CI = 3.05–4.31), DSS (OR = 3.22, 95% CI = 2.22–4.66), and DFS (OR = 4.39, 95% CI = 1.78–10.82) outcomes than those receiving non-gastrectomy treatments. The pooled HR also showed that gastrectomy following non-curative ESD significantly improved OS (HR = 0.40, 95% CI = 0.33–0.48). In addition, elderly patients benefited from additional surgery in consideration of the 5-year OS (HR = 0.54, 95% CI = 0.41–0.72).

Conclusions:

Compared with non-gastrectomy treatments, additional surgery offered better long-term survival outcomes for patients with EGC who underwent non-curative ESD.
Stereotactic Body Radiation Therapy for Sarcoma Pulmonary Metastases
Authors: Asha Wafa , Koro Sami , Mayo Zachary , Yang Kailin , Halima Ahmed , Scott Jacob , Scarborough Jessica , Campbell Shauna R. , Budd G. Thomas , Shepard Dale , Stephans Kevin , Videtic Gregory M. , Shah Chirag
Published: March 2023

Background:

Lung metastases are the most common form of distant failure for patients diagnosed with sarcoma with metastasectomy considered for some patients with limited metastatic disease and good performance status. Alternatives to surgery such as stereotactic body radiation therapy (SBRT) can be considered, though data are limited. We present outcomes after SBRT for sarcoma lung metastases.

Methods:

Fifty sarcoma patients with 109 lung metastases were treated with SBRT between 2005 and 2021. Outcomes evaluated included local control (LC), overall survival (OS), and toxicity including lung pneumonitis/fibrosis, chest wall toxicity, dermatitis, brachial plexus, and esophageal toxicity. Systemic therapy receipt before and after SBRT was recorded.

Results:

SBRT schedules were divided into 3 cohorts: 30 to 34 Gy/1fx (n=10 [20%]), 48 to 50 Gy/4 to 5fx (n=24[48%]), and 60 Gy/5fx (n=16[32%]). With a median follow-up of 19.5 months, 1/3-year LC rates were 96%/88% and 1/3-year OS 77%/50%, respectively. There was no differences between the 3 regimens in terms of LC, OS, or toxicity. Size >4 cm was a predictor of worse LC (P=0.031) and worse OS (P= 0.039) on univariate analysis. The primary pattern of failure was new metastases (64%) of which the majority were in the contralateral lung (52%). One-year chemotherapy-free survival was 85%. Overall, 76% of patients did not require chemotherapy initiation or change of chemotherapy regimen after lung SBRT. Toxicity was reported in 16% of patients overall, including 25%, 20%, and 14% in the 30 to 34 Gy/1fx, 48 to 50 Gy/4 to 5fx, and 60 Gy/5fx cohorts, respectively.

Conclusions:

SBRT outcomes for lung metastases from sarcoma demonstrate high rates of LC and are similar with different dose/fractionation regimens. Lung SBRT is associated with prolonged chemotherapy-free survival. Prospective validation of these results is warranted.
Applications of Volumetric Absorptive Microsampling Technique: A Systematic Critical Review
Authors: Dodeja Prerna , Giannoutsos Spiros , Caritis Steve , Venkataramanan Raman
Published: March 2023

Background:

Microsampling is a technique that utilizes a very small volume of biological matrix, typically less than 50 µL, for quantitatively analyzing chemicals, drugs, and biologics. The use of filter paper for blotting blood samples, usually referred to “Dried Blood Spots”, is an example of a microsampling approach, which has been established since the early 1960s. However, non-homogeneous sample spread, the influence of hematocrit, improper volume measurement, and environmental degradation are major bottlenecks to the widespread adoption of this technique in routine clinical sample analysis. Novel methods have overcome several of these issues; however, assays using these microsampling tools involve variable steps/approaches.

Methods:

A novel microsampling device called Volumetric Absorptive microsampling (VAMS), developed in 2014, appears to have resolved the sample inhomogeneity inherent to dried blood spots, with improved precision in the volume of sample collected for measuring drug concentration. A literature search was conducted to identify several analytical and pharmacokinetic studies that have used VAMS in recent years.

Results:

The key factors for proper experimental design and optimization of the extraction of drugs and metabolites of interest from the device were summarized. This review focuses on VAMS and elaborates on bioanalytical factors, method validation steps, and scope of this technique in clinical practice.

Conclusions:

The promising microsampling method VAMS is especially suited for conducting pharmacokinetic studies with very small volumes of blood, especially in special patient populations. Clinical validation of every VAMS assay must be conducted prior to the routine practical implementation of this method.
Development of a Therapeutic Drug Monitoring Strategy for the Optimization of Vincristine Treatment in Pediatric Oncology Populations in Africa
Authors: Van der Heijden Lisa T. , Nijstad A. Laura , Uittenboogaard Aniek , Beijnen Jos H. , Dorlo Thomas P.C. , Kaspers Gertjan J.L. , Huitema Alwin D.R.
Published: March 2023

Background:

Recent studies have reported ethnic differences in vincristine exposure and outcomes such as toxicity. This resulted in the hypothesis of subtherapeutic dosing in African children. To optimize individual treatment, a strategy to identify subtherapeutic exposure using therapeutic drug monitoring is essential. The aim of the current study was to develop a strategy for therapeutic drug monitoring of vincristine in African children to meet the following criteria: (1) identify patients with low vincristine exposure with sufficient sensitivity (>70%), (2) determine vincristine exposure with a limited sampling strategy design of 3 samples, and (3) allow all samples to be collected within 4 hours after administration.

Methods:

An in silico simulation study was performed using a previously described population pharmacokinetic model and real-life demographic dataset of Kenyan and Malawian pediatric oncology patients. Two different therapeutic drug monitoring strategies were evaluated: (1) Bayesian approach and (2) pharmacometric nomogram. The sampling design was optimized using the constraints described above. Sensitivity analysis was performed to investigate the influence of missing samples, erroneous sampling times, and different boundaries on the nomogram weight bands.

Results:

With the Bayesian approach, 43.3% of the estimated individual exposure values had a prediction error of ≥20% owing to extremely high shrinkage. The Bayesian approach did not improve with alternative sampling designs within sampling constraints. However, the pharmacometric nomogram could identify patients with low vincristine exposure with a sensitivity, specificity, and accuracy of 75.1%, 76.4%, and 75.9%, respectively. The pharmacometric nomogram performed similarly for different weight bands.

Conclusions:

The pharmacometric nomogram was able to identify patients with low vincristine exposure with high sensitivity, with 3 blood samples collected at 1, 1.5, and 4 hours after administration. Missing samples should be avoided, and the 3 scheduled samples should be collected within 15, 5, and 15 minutes of 1, 1.5, and 4 hours after administration, respectively.