bluuebunny/crossref_metadata_2025 huggingface dataset:
Early prevention of maxillary canine impaction: a randomized clinical trial
Authors: Willems Guy , Butaye Charlotte , Raes Margot , Zong Chen , Begnoni Giacomo , Cadenas de Llano-Pérula Maria
Published: June 2023

Objectives

To investigate the effect of three interceptive measures (slow maxillary expansion (SME) with removable plates (1), extraction of both upper deciduous canines (DC) (2) and no intervention (3)) on maxillary canine (MC) position in patients with early mixed dentition (EMD) and lack of upper arch space. These three groups were additionally compared to a control group (4) with adequate upper arch space.

Null hypothesis

None of the studied strategies outperforms the others regarding improvement of MC position.

Trial design

Four-arm parallel group prospective randomized controlled trial.

Participants

Patients in EMD with at least one impacted MC, non-resorbed DC, and no crossbite.

Interventions

Patients with a lack of space were randomly distributed to protocols (1), (2), and (3).

Primary objective

To assess the change in MC position after 18 months follow up.

Secondary objectives

To assess canine eruption and need for orthodontic intervention within 18–60 month follow up.

Outcome assessment

Five variables defined canine position: sector, canine-to-midline angle, canine-to-first-premolar angle, canine-cusp-to-midline distance, and canine-cusp-to-occlusal-plane distance on two panoramic radiographs at 0 (T1) and 18 months (T2). Mean differences between groups were compared with linear mixed models, corrected for age and sex.

Randomization

The patient allocation sequence was generated by an electronic randomization list.

Blinding

The operator taking the measurements was blinded to the groups.

Results

Seventy-six patients were included (142 canines, mean age 9.2 years, 60.5 per cent male, mean follow up 1.9 years), 19, 17, 14, and 26 patients in groups 1–4, respectively. In absence of dental crossbite in patients with lack of space and impacted MC, SME improved the canine sector (P = 0.040), compared to no intervention (P = 0.028). Canine-to-midline angle and canine-to-occlusal-plane distance significantly decreased in all groups at T2. Extraction improved the canine-to-first-premolar angle at T2 more than other strategies in EMD (P = 0.015–0.000).

Conclusions

Early SME improves the canine sector and reduces the need for major orthodontic intervention in the long term. Taking a first panoramic radiograph in EMD allows timely intervention in case of MC impaction.

Trial Registration Number

NCT05629312 (Clinical Trials.org). Trial status: follow up ongoing.
Three-dimensional comparison of tooth-borne and tooth-bone-borne RME appliances: a randomized controlled trial with 5-year follow-up
Authors: Bazargani Farhan , Knode Vanessa , Plaksin Alexander , Magnuson Anders , Ludwig Björn
Published: May 2023

Objectives

To compare the long-term skeletal effects of tooth-borne (TB) and tooth-bone-borne (TBB) rapid maxillary expansion in growing children, using 3D imaging.

Materials and methods

In total, 52 consecutive patients who met the eligibility criteria were recruited and allocated to either the TB group, mean age 9.3 years (SD 1.3), or the TBB group, mean age 9.5 years (SD 1.2). Cone-beam computed tomography records and plaster models were taken before (T0), directly after (T1), 1 year after (T2), and 5 years after expansion (T3).

Randomization

Participants were randomly allocated in blocks of different sizes, using the concealed allocation principle in a 1:1 ratio. The randomization list was also stratified by sex to ensure homogeneity between groups.

Blinding

Due to clinical limitations, only the outcome assessors were blinded to the groups to which the patients were allocated.

Results

At T1, the midpalatal suture at its anterior part showed a statistically significant difference between the groups with a mean of 0.6 mm (CI 0.2–1.1) more expansion in the TBB group (P < 0.01). This difference was also more evident in boys at T1 with a mean of 0.8 mm (CI 0.2–1.4) (P < 0.01). These differences, however, blotted out at T2 and T3. The nasal width also showed similar differences between the groups, with a significantly larger expansion in the TBB group by a mean of 0.7 mm (CI 0.1–1.4) (P = 0.03). This group difference in favour of the TBB group was maintained at T2 (1.6 mm) and T3 (2.1 mm) (P < 0.01 T2 and T3, respectively).

Conclusions

Skeletal expansion in the midpalatal suture was significantly higher in the TBB group; however, the magnitude of this expansion was around 0.6 mm more and may not be clinically significant. Skeletal expansion at the level of the nasal cavity was significantly higher in the TBB group. There were no differences between boys and girls with regard to skeletal expansion.

Trial registration

This trial was not registered on any external sites.
Ribosomal protein mutations and cell competition: autonomous and nonautonomous effects on a stress response
Authors: Kiparaki Marianthi , Baker Nicholas E
Published: June 2023

Ribosomal proteins (Rps) are essential for viability. Genetic mutations affecting Rp genes were first discovered in Drosophila, where they represent a major class of haploinsufficient mutations. One mutant copy gives rise to the dominant “Minute” phenotype, characterized by slow growth and small, thin bristles. Wild-type (WT) and Minute cells compete in mosaics, that is, Rp+/− are preferentially lost when their neighbors are of the wild-type genotype. Many features of Rp gene haploinsufficiency (i.e. Rp+/− phenotypes) are mediated by a transcriptional program. In Drosophila, reduced translation and slow growth are under the control of Xrp1, a bZip-domain transcription factor induced in Rp mutant cells that leads ultimately to the phosphorylation of eIF2α and consequently inhibition of most translation. Rp mutant phenotypes are also mediated transcriptionally in yeast and in mammals. In mammals, the Impaired Ribosome Biogenesis Checkpoint activates p53. Recent findings link Rp mutant phenotypes to other cellular stresses, including the DNA damage response and endoplasmic reticulum stress. We suggest that cell competition results from nonautonomous inputs to stress responses, bringing decisions between adaptive and apoptotic outcomes under the influence of nearby cells. In Drosophila, cell competition eliminates aneuploid cells in which loss of chromosome leads to Rp gene haploinsufficiency. The effects of Rp gene mutations on the whole organism, in Minute flies or in humans with Diamond-Blackfan Anemia, may be inevitable consequences of pathways that are useful in eliminating individual cells from mosaics. Alternatively, apparently deleterious whole organism phenotypes might be adaptive, preventing even more detrimental outcomes. In mammals, for example, p53 activation appears to suppress oncogenic effects of Rp gene haploinsufficiency.
Clinical Validation of a Capillary Blood Home-Based Self-Sampling Technique for Monitoring of Infliximab, Vedolizumab, and C-Reactive Protein Concentrations in Patients With Inflammatory Bowel Disease
Authors: Otten Antonius T , van der Meulen Hedwig H , Steenhuis Maurice , Loeff Floris C , Touw Daan J , Kosterink Jos G W , Frijlink Henderik W , Rispens Theo , Dijkstra Gerard , Visschedijk Marijn C , Bourgonje Arno R
Published: June 2023

Background

Therapeutic drug monitoring provides important guidance for treatment of patients with inflammatory bowel disease (IBD) and could help to early identify treatment failure. This study aimed to validate a finger prick–based capillary blood sampling technique to measure biological trough levels and C-reactive protein (CRP) and evaluate patient performance and -support.

Methods

In this prospective cohort study, patients with IBD receiving infliximab (IFX) or vedolizumab (VEDO) therapy performed finger prick–based capillary blood sampling at home. Additionally, blood was collected through routinely performed in-hospital venepuncture prior to biological infusion. IFX, VEDO, and CRP concentrations were measured by enzyme-linked immunosorbent assay. The concordance between methods was statistically evaluated and a survey was conducted to assess practicality and patient support.

Results

In total, 81 patients (46 IFX, 35 VEDO) were enrolled. Mean differences between both methods were 0.42 (95% confidence interval, -1.74 to 2.58) μg/mL for IFX and 0.72 (95% confidence interval, -5.50 to 6.94) μg/mL for VEDO. Passing-Bablok regressions demonstrated no evidence for systematic or proportional biases. Venous and capillary IFX (ρ = 0.96, P < .001) and VEDO (ρ = 0.97, P < .001) levels strongly correlated and showed high intermethod agreement (Cohen’s kappa: IFX = 0.82; VEDO = 0.94). Similarly, venous and capillary CRP levels were strongly correlated (ρ = 0.99, P < .001). Most patients (>95%) were able to successfully perform the self-sampling at home without prior instructions.

Conclusions

This study clinically validated a finger prick–based capillary blood self-sampling technique allowing concomitant home monitoring of biological levels and CRP for patients with IBD, who reported substantial support, tolerability, and practicality.
Leptin Resistance Does Not Facilitate Migratory Fattening in Ruby-Throated Hummingbirds (Archilochus Colubris)
Authors: Rossi Giulia S , Welch Kenneth C
Published: May 2023

Synopsis

In mammals, leptin is an important energy homeostasis hormone produced by adipose tissue. Circulating leptin concentrations correlate positively with fat mass and act in a negative feedback fashion to inhibit food intake and increase energy expenditure, thereby preventing fat gain. For some species, leptin resistance is advantageous during times of year where fat gain is necessary (e.g., prior to hibernation). While the function of leptin in birds remains controversial, seasonal leptin resistance may similarly benefit migratory species. Here, we used the ruby-throated hummingbird (Archilochus colubris) to test the hypothesis that leptin resistance promotes fattening prior to migration. We predicted that during the migratory fattening period, leptin levels should correlate positively with fat mass but should not inhibit food intake or increase energy expenditure, resulting in fattening. We tracked the body (fat) mass, the concentration of leptin-like protein in the urine, and the food intake of 12 captive hummingbirds from August 2021 to January 2022. In a subset of hummingbirds, we also quantified voluntary physical activity as a proxy for energy expenditure. We found remarkable age-related variation in fattening strategies, with juveniles doubling their body fat by mid-September and adults exhibiting only a 50% increase. Changes in fat mass were strongly associated with increased food intake and reduced voluntary activity. However, we found no correlation between leptin-like protein concentration and fat mass, food intake, or voluntary activity. Since increased torpor use has been shown to accelerate migratory fattening in ruby-throated hummingbirds, we also hypothesized that leptin is a mediator of torpor use. In an experimental manipulation of circulating leptin, however, we found no change in torpor use, body fat, or food intake. Overall, our findings suggest that leptin may not act as an adipostat in hummingbirds, nor does leptin resistance regulate how hummingbirds fatten prior to migration.
Ionizing radiation and solid cancer mortality among US nuclear facility workers
Authors: Kelly-Reif Kaitlin , Bertke Steven J , Daniels Robert D , Richardson David B , Schubauer-Berigan Mary K
Published: May 2023

Background

The risk of solid cancers from low-level protracted ionizing radiation is not well characterized. Nuclear workers provide valuable information on the effects of ionizing radiation in contemporary exposure scenarios relevant to workers and the public.

Methods

We evaluated the association between penetrating ionizing radiation exposure and solid cancer mortality among a pooled cohort of nuclear workers in the USA, with extended follow-up to examine cancers with long latencies. This analysis includes 101 363 workers from five nuclear facilities, with 12 069 solid cancer deaths between 1944 and 2016. The association between cumulative equivalent dose measured in sieverts (Sv) and solid cancer subtypes were modelled as the excess relative rate per Sv (ERR Sv–1) using Cox regression.

Results

For the association between ionizing radiation exposure and all solid cancer mortality we observed an elevated rate (ERR Sv–1=0.19; 95% CI: –0.10, 0.52), which was higher among a contemporary sub-cohort of workers first hired in 1960 or later (ERR Sv–1= 2.23; 95% CI: 1.13, 3.49). Similarly, we observed an elevated rate for lung cancer mortality (ERR Sv–1= 0.65; 95% CI: 0.09, 1.30) that was higher among contemporary hires (ERR Sv–1= 2.90; 95% CI: 1.00, 5.26).

Conclusions

Although concerns remain about confounding, measurement error and precision, this analysis strengthens the evidence base indicating there are radiogenic risks for several solid cancer types.
High-titer convalescent plasma plus nirmatrelvir/ritonavir treatment for non-resolving COVID-19 in six immunocompromised patients
Authors: Huygens Sammy , Gharbharan Arvind , Serroukh Yasmina , Snoek Britt , Franken Bas , Oude Munnink Bas B , Van Hagen P Martin , Bogers Susanne , Geurtsvankessel Corine H , Rijnders Bart J A
Published: May 2023

Objectives

Immunocompromised patients have an increased risk of severe or prolonged COVID-19. Currently available drugs are registered to treat COVID-19 during the first 5 to 7 days after symptom onset. Data on the effectivity in immunocompromised patients with chronic non-resolving COVID-19 are urgently needed. Here, we report the outcome of patients treated with nirmatrelvir/ritonavir together with high-titer convalescent plasma (CP) in six immunocompromised patients with non-resolving COVID-19.

Methods

Immunocompromised patients with persisting COVID-19 (positive PCR with Ct values <30 for ≥20 days) received off-label therapy with nirmatrelvir/ritonavir. It was combined with CP containing BA.5 neutralizing titers of ≥1/640 whenever available. Follow-up was done by PCR and sequencing on nasopharyngeal swabs on a weekly basis until viral genome was undetectable consecutively.

Results

Five immunocompromised patients were treated with high-titer CP and 5 days of nirmatrelvir/ritonavir. One patient received nirmatrelvir/ritonavir monotherapy. Median duration of SARS-CoV-2 PCR positivity was 70 (range 20–231) days before nirmatrelvir/ritonavir treatment. In four patients receiving combination therapy, no viral genome of SARS-CoV-2 was detected on day 7 and 14 after treatment while the patient receiving nirmatrelvir/ritonavir monotherapy, the day 7 Ct value increased to 34 and viral genome was undetectable thereafter. Treatment was unsuccessful in one patient. In this patient, sequencing after nirmatrelvir/ritonavir treatment did not show protease gene mutations.

Conclusions

In immunocompromised patients with non-resolving COVID-19, the combination of nirmatrelvir/ritonavir and CP may be an effective treatment. Larger prospective studies are needed to confirm these preliminary results and should compare different treatment durations.
Implementation of WGS analysis of ESBL-producing Escherichia coli within EU AMR monitoring in livestock and meat
Authors: Brouwer Michael S M , Zandbergen Van Essen Alieda , Kant Arie , Rapallini Michel , Harders Frank , Bossers Alex , Wullings Bart , Wit Ben , Veldman Kees T
Published: May 2023

Background

As WGS comes of age, changes in EU legislation implemented in 2021 allow its usage for systematic monitoring of ESBL-producing Escherichia coli from livestock and meat, replacing phenotypic testing. Presently, phenotypic testing correlates well with antimicrobial resistance predicted from WGS data. WGS has added value in the wealth of additional information that is present in the data.

Objectives

In this study we have detected the resistance phenotypes for a panel of antimicrobials while also analysing the molecular epidemiology of ESBL-producing E. coli.

Methods

Susceptibility testing was performed with broth microdilution of selectively isolated E. coli. Short-read WGS was performed in parallel and phenotypes predicted based on the sequence data, which was also used to determine the phylogeny of the isolates.

Results

The phenotypically determined resistance and the predicted resistance correlated 90%–100% for the different antimicrobial classes. Furthermore, clonal relationships were detected amongst ESBL-producing E. coli within livestock sectors and the meat produced by this sector.

Conclusions

Further implementation of WGS analysis of ESBL/AmpC-producing E. coli within the AMR monitoring programme of EU member states and global surveillance programmes will contribute to determining the attribution of livestock in the prevalence of ESBL/AmpC-encoding E. coli in humans.
In vitro dynamics and mechanisms of cefiderocol resistance development in wild-type, mutator and XDR Pseudomonas aeruginosa
Authors: Gomis-Font María A , Sastre-Femenia Miquel À , Taltavull Biel , Cabot Gabriel , Oliver Antonio
Published: May 2023

Objectives

To analyse the dynamics and mechanisms of stepwise resistance development to cefiderocol in Pseudomonas aeruginosa.

Methods

Cefiderocol resistance evolution was analysed in WT PAO1, PAOMS (mutS mutator derivate) and three XDR clinical isolates belonging to ST111, ST175 and ST235 clones. Strains were incubated in triplicate experiments for 24 h in iron-depleted CAMHB with 0.06–128 mg/L cefiderocol. Tubes from the highest antibiotic concentration showing growth were reinoculated into fresh medium containing concentrations up to 128 mg/L for 7 consecutive days. Two colonies per strain and experiment were characterized by determining the susceptibility profiles and WGS.

Results

Evolution of resistance was significantly enhanced in PAOMS, but was variable for the XDR strains, including levels similar to PAOMS (ST235), similar to PAO1 (ST175) or even below PAO1 (ST111). WGS revealed 2–5 mutations for PAO1 lineages and 35–58 for PAOMS. The number of mutations in the XDR clinical strains ranged from 2 to 4 except for one of the ST235 experiments in which a mutL lineage was selected, thus increasing the number of mutations. The most frequently mutated genes were piuC, fptA and pirR, related to iron uptake. Additionally, an L320P AmpC mutation was selected in multiple lineages and cloning confirmed its major impact on cefiderocol (but not ceftolozane/tazobactam or ceftazidime/avibactam) resistance. Mutations in CpxS and PBP3 were also documented.

Conclusions

This work deciphers the potential resistance mechanisms that may emerge upon the introduction of cefiderocol into clinical practice, and highlights that the risk of resistance development might be strain-specific even for XDR high-risk clones.
Chlorpyrifos and chlorfenapyr resistance in Spodoptera frugiperda (Lepidoptera: Noctuidae) relies on UDP-glucuronosyltransferases
Authors: Su Xiang-ning , Li Chuan-ying , Zhang Yu-ping
Published: May 2023

Fall armyworm, Spodoptera frugiperda (J. E. Smith), has become an important agricultural pest worldwide. S. frugiperda is mainly controlled by the chemical insecticides, whereas the frequent application of insecticides would result in the resistance development. Insect uridine diphosphate-glucuronosyltransferases (UGTs), as phase II metabolism enzymes, play vital roles in the breakdown of endobiotic and xenobiotics. In this study, 42 UGT genes were identified by RNA-seq, including 29 UGT genes were elevated compared to the susceptible population, and the transcript levels of 3 UGTs (UGT40F20, UGT40R18, and UGT40D17) were increased by more than 2.0-fold in the field populations. Expression pattern analysis revealed that S. frugiperda UGT40F20, UGT40R18, and UGT40D17 were increased by 6.34-, 4.26-, and 8.28-fold, compared the susceptible populations, respectively. The expression of UGT40D17, UGT40F20, and UGT40R18 was affected after exposure to phenobarbital, chlorpyrifos, chlorfenapyr, sulfinpyrazone, and 5-nitrouracil. The induced expression of UGT genes may have improved UGT enzymatic activity, while the inhibition of UGTs genes expression may decreased UGT enzymatic activity. Sulfinpyrazone, and 5-nitrouracil, significantly increased the toxicity of chlorpyrifos and chlorfenapyr, as well as phenobarbital significantly reduced the toxicity of chlorpyrifos and chlorfenapyr against the susceptible populations and field populations of S. frugiperda. The suppression of UGTs (UGT40D17, UGT40F20, and UGT40R18) significantly increased the insensitivity of the field populations to chlorpyrifos and chlorfenapyr. These findings strongly supported our viewpoint that UGTs may play a critical role in insecticide detoxification. This study provides a scientific basis for the management of S. frugiperda.
Chromosome-length genome assembly and karyotype of the endangered black-footed ferret (Mustela nigripes)
Authors: Kliver Sergei , Houck Marlys L , Perelman Polina L , Totikov Azamat , Tomarovsky Andrey , Dudchenko Olga , Omer Arina D , Colaric Zane , Weisz David , Aiden Erez Lieberman , Chan Saki , Hastie Alex , Komissarov Aleksey , Ryder Oliver A , Graphodatsky Alexander , Johnson Warren E , Maldonado Jesús E , Pukazhenthi Budhan S , Marinari Paul E , Wildt David E , Koepfli Klaus-Peter
Published: May 2023

The black-footed ferret (Mustela nigripes) narrowly avoided extinction to become an oft-cited example of the benefits of intensive management, research, and collaboration to save a species through ex situ conservation breeding and reintroduction into its former range. However, the species remains at risk due to possible inbreeding, disease susceptibility, and multiple fertility challenges. Here, we report the de novo genome assembly of a male black-footed ferret generated through a combination of linked-read sequencing, optical mapping, and Hi-C proximity ligation. In addition, we report the karyotype for this species, which was used to anchor and assign chromosome numbers to the chromosome-length scaffolds. The draft assembly was ~2.5 Gb in length, with 95.6% of it anchored to 19 chromosome-length scaffolds, corresponding to the 2n = 38 chromosomes revealed by the karyotype. The assembly has contig and scaffold N50 values of 148.8 kbp and 145.4 Mbp, respectively, and is up to 96% complete based on BUSCO analyses. Annotation of the assembly, including evidence from RNA-seq data, identified 21,406 protein-coding genes and a repeat content of 37.35%. Phylogenomic analyses indicated that the black-footed ferret diverged from the European polecat/domestic ferret lineage 1.6 million yr ago. This assembly will enable research on the conservation genomics of black-footed ferrets and thereby aid in the further restoration of this endangered species.
Reranking cancer mortality using years of life lost
Authors: Radkiewicz Cecilia , Andersson Therese M-L , Lagergren Jesper
Published: May 2023

Incidence and mortality are default measures to describe cancer trends. Mortality compounds incidence and survival but not age at death. We calculated years of life lost (YLL) due to 1 of the 10 solid tumors causing most deaths (lung, colorectal, prostate, pancreatic, breast, hepatobiliary, urinary, central nervous system, gastric, melanoma) using Swedish National Cancer and Cause of Death Registers. Comparing YLL with mortality in 2019, lung (43 152 YLL) and colorectal (32 340 YLL) cancer remained at the top, pancreatic cancer was upranked fourth to third (22 592 YLL) and breast cancer fifth to fourth (21 810 YLL), while prostate cancer was downranked third to fifth (17 380 YLL). Assessing YLL over 2010-2019, women lost consistently more life years because of lung and pancreatic cancer. A downward colorectal cancer mortality trend was reflected as a YLL decline only in women. YLL is simple to calculate, is intuitive to interpret, and expands the understanding of the cancer burden on society.
Complications of surgical management of osteopetrosis. A case report of multiple surgeries performed on one patient
Authors: Lamut Anže , Kovač Simon
Published: May 2023

Osteopetrosis is a rare form of sclerosing bone dysplasias which in some cases requires orthopedic surgical management of its complications. It is characterized by osteosclerosis, brittle bones and obliteration of the medullary cavity. Therefore, surgery in these cases is difficult and results can be compromised by postoperative complications. We present a case of a 73-year-old patient treated at our institution in a period of 24 years. In this period, the patient had bilateral primary hip arthroplasty (THA), total knee arthroplasty, revision surgeries of both THA’s and lumbar spine surgeries. The treatment of infected THA and periprosthetic fractures ended with satisfactory results but complications of the spinal surgery resulted in a poor clinical outcome.
Drop impact dynamics on the hydrophobic leaf surface of an aquatic plant: a case study of Pistia stratiotes
Authors: Papierowska Ewa , Beczek Michał , Mazur Rafał , Szatyłowicz Jan , Szewińska Joanna , Polakowski Cezary , Ryżak Magdalena , Stańczyk Tomasz , Sochan Agata , Frankowska-Łukawska Justyna , Bieganowski Andrzej
Published: May 2023

Pistia stratiotes is an aquatic plant with a complex structure that allows it to stay afloat. It grows quickly, and in large numbers becomes an undesirable plant as an invasive species. Describing the dynamics of a water drop splash on P. stratiotes leaves can contribute to increasing knowledge of its behavior and finding alternative methods for eradicating it or using it for the benefit of the environment. The non-wettable surface of P. stratiotes presents a complex structure—simple uniseriate trichomes and also ridges and veins. We analyzed the drop impact on a leaf placed on the water surface and recorded it by high-speed cameras. Based on the recordings, quantitative and qualitative analyses were performed. After impacting the leaf, the water drop spread until it reached its maximum surface area accompanied by the ejection of early droplets in the initial stage. Thereafter, three scenarios of water behavior were observed: (i) drop receding and stabilization; (ii) drop receding and ejection of late droplets formed in the later stage as an effect of elastic deformation of the leaf; and (iii) drop breaking apart and ejection of late droplets. The results indicated that the increasing kinetic energy of the impacting drops expressed by the Weber number and the complex leaf surface have an effect on the course of the splash. The simple uniseriate trichomes of the P. stratiotes leaf and the high energy of the falling drops were responsible for the formation and characteristics of the early droplets. The presence of ridges and veins and the leaf’s mechanical response had an impact on the occurrence of late droplets.
The value of metagenomic next-generation sequencing for the diagnosis of pulmonary tuberculosis using bronchoalveolar lavage fluid
Authors: Gao Jiali , Zhao Lu , Chen Gongqi , Huang Chunli , Kong Weiqiang , Feng Yuchen , Zhen Guohua
Published: June 2023

Objective

The aim of this study was to compare metagenomic next-generation sequencing (mNGS) with other methods, including Xpert MTB/RIF, Mycobacterium tuberculosis (MTB) culture, and acid-fast bacillus (AFB) staining in the diagnosis of pulmonary tuberculosis (PTB) using bronchoalveolar lavage fluid (BALF).

Methods

The data of 186 patients with suspected PTB were retrospectively collected from January 2020 to May 2021 at Tongji Hospital. BALF samples were collected from all patients and analyzed using AFB staining, MTB culture, Xpert MTB/RIF, and mNGS.

Results

Of the 186 patients, 38 patients were ultimately diagnosed as PTB. Metagenomic next-generation sequencing exhibited a sensitivity of 78.95%, which was higher than AFB staining (27.59%) and MTB culture (44.12%) but similar to Xpert MTB/RIF (72.73%). Utilization of combined methods demonstrates improvement for PTB diagnosis. In support of this, the area under the receiver operating characteristic curve for the combination of mNGS and MTB culture (0.933, 95% CI: 0.871, 0.995) was larger than those of mNGS, Xpert MTB/RIF, MTB culture, and the combination of Xpert MTB/RIF and MTB culture.

Conclusion

The sensitivity of mNGS in the diagnosis of PTB using BALF specimen is similar to Xpert MTB/RIF. Metagenomic next-generation sequencing in combination with MTB culture may further improve the diagnosis of pulmonary tuberculosis.
Comparison of Sampson and extended Martin/Hopkins methods of low-density lipoprotein cholesterol calculations with direct measurement in pediatric patients with hypertriglyceridemia
Authors: Touhidul Islam SM , Muthukumar Alagar R , Mary Jones Patricia , Hashim Ibrahim , Cao Jing
Published: May 2023

Objective

The Friedewald equation is the commonly used method of low-density lipoprotein cholesterol (LDL-C) calculation, requiring reflex to direct LDL-C measurement when triglycerides (TG) ≥ 400 mg/dL. Recently formulated Sampson and extended Martin/Hopkins methods have been validated with TG up to 800 mg/dL and thus have the potential to replace direct LDL-C measurement. Given the growing prevalence of childhood dyslipidemia, the objective of this study was to compare Sampson and extended Martin/Hopkins methods of LDL-C calculation with the direct measurement in a pediatric cohort with 400 ≤ TG ≤ 799 mg/dL.

Methods

This study retrieved standard lipid panels and corresponding direct LDL-C measurements of 131 patients with 400 ≤ TG ≤ 799 mg/dL from a pediatric population. Following the application of Sampson and extended Martin/Hopkins calculations, calculated values were compared with direct LDL-C measurements using ordinary least squares linear regression analysis and bias plotting.

Results

Both Sampson and extended Martin/Hopkins LDL-C calculations exhibited a strong correlation with the direct measurements (Pearson r = 0.89) in patients with 400 ≤ TG ≤ 800 mg/dL. Average percentages of bias of 45% and 21% were found between the direct LDL-C measurements and Sampson or extended Martin/Hopkins calculations, respectively. 

Conclusion

Both Sampson and extended Martin/Hopkins calculations are applicable as clinical alternatives of direct LDL-C measurement in pediatric patients given 400 ≤ TG ≤ 799 mg/dL.
Nitrogen enhancements 440 Myr after the big bang: supersolar N/O, a tidal disruption event, or a dense stellar cluster in GN-z11?
Authors: Cameron Alex J , Katz Harley , Rey Martin P , Saxena Aayush
Published: May 2023

Recent observations of GN-z11 with JWST/NIRSpec revealed numerous oxygen, carbon, nitrogen, and helium emission lines at z = 10.6. Using the measured line fluxes, we derive abundance ratios of individual elements within the interstellar medium (ISM) of this superluminous galaxy. Driven by the unusually-bright N iii] λ1750 and N iv] λ1486 emission lines (and by comparison, faint O iii] λλ1660, 1666 lines), our fiducial model prefers log (N/O) > −0.25, greater than four times solar and in stark contrast to lower-redshift star-forming galaxies. The derived log (C/O) > −0.78, (≈30 per cent solar) is also elevated with respect to galaxies of similar metallicity (12 + log (O/H) ≈ 7.82), although less at odds with lower-redshift measurements. We explore the feasibility of achieving these abundance ratios via several enrichment mechanisms using metal yields available in the literature. Given the long time-scale typically expected to enrich nitrogen with stellar winds, traditional scenarios require a very fine-tuned formation history to reproduce such an elevated N/O. We find no compelling evidence that nitrogen enhancement in GN-z11 can be explained by enrichment from metal-free Population III stars. Interestingly, yields from runaway stellar collisions in a dense stellar cluster or a tidal disruption event provide promising solutions to give rise to these unusual emission lines at z = 10.6, and explain the resemblance between GN-z11 and a nitrogen-loud quasar. These recent observations showcase the new frontier opened by JWST to constrain galactic enrichment and stellar evolution within 440 Myr of the big bang.
Studying the link between radio galaxies and AGN fuelling with relativistic hydrodynamic simulations of flickering jets
Authors: Whitehead Henry W , Matthews James H
Published: May 2023

We present two- and three-dimensional hydrodynamic simulations of ∼kpc-scale AGN jets with mean jet powers in the range 1–7 × 1045 erg s−1, in which the jet power varies (through variation of the Lorentz factor) according to a flicker or pink noise power spectrum. We find the morphology and dynamics of the jet–cocoon system depends on the amplitude of the variability with a clear correspondence between the shape of the cocoon and the historical activity. The jet advances quickly during high-power states, whereas quiescent periods instead produce passive periods of inflation resembling Sedov–Taylor blast waves. Periods of high activity preferentially produce hotspots and create stronger backflow as they maximize the pressure gradient between the jet head and cocoon. The variability can also lead to propagating internal shock structures along the jet. Our work suggests that variability and flickering in the jet power has important implications, which we discuss, for observations of radio galaxies, ultrahigh energy cosmic ray acceleration and jet power to luminosity correlations. We explore the link between morphology and fuelling, and suggest that chaotic cold accretion should introduce a relatively small scatter in radio luminosity (∼0.2 dex) and modest imprints on morphology; sources such as Hercules A and Fornax A, which show evidence for more dramatic variability, may therefore require redder power spectra, or be triggered by mergers or other discrete events. We suggest ways to search for jet flickering observationally and propose that radio galaxies may be an important diagnostic of Myr time-scale AGN fuelling, due to their ‘long-term memory’.
Evolution of the mass relation between supermassive black holes and dark matter halos across the cosmic time
Authors: Bansal Aryan , Ichiki Kiyotomo , Tashiro Hiroyuki , Matsuoka Yoshiki
Published: May 2023

A positive observational proof suggests that most galaxies contain a central supermassive black hole (SMBH) with mass in the range of 106 M⊙–1010 M⊙. It is suggested that the mass of SMBHs is proportionally related to that of the dark matter (DM) halo, even at z = 6. This implies that these SMBHs could coevolve with the host DM halos. Here, we investigate the mass evolution of SMBHs in a hierarchical structure formation by building halo merger trees using the extended Press–Schechter formalism. An SMBH with a mass that follows various power-law relations with the DM halo mass is assigned as an initial condition. Assuming that the mass growth of all black holes is due to mergers, we obtain the relation between SMBH and DM halo masses at the present epoch. By requiring that the mass of the SMBHs at z = 0 should not be greater than the currently observed SMBH-DM halo mass relation, a lower bound on the mass of the DM halo that can contain a SMBH can be imposed at z = 6 as Mlim > 3.6 × 1010 M⊙ × (1.4 − n)2.3, where n is the power-law index of the SMBH-DM halo mass relation at z = 6. Because we only consider mergers for the mass evolution of SMBHs, this model is simplistic and should underestimate the mass of SMBHs relative to the mass of the DM halo at the present epoch. Our work aims to constrain the SMBH-DM mass relation at z = 6 and not build a new model to explain the observations
Efficient radial migration by giant molecular clouds in the first several hundred Myr after the stellar birth
Authors: Fujimoto Yusuke , Inutsuka Shu-ichiro , Baba Junichi
Published: May 2023

Stars in the Galactic disc, including the Solar system, have deviated from their birth orbits and have experienced radial mixing and vertical heating. By performing hydrodynamical simulations of a galactic disc, we investigate how much tracer particles, which are initially located in the disc to mimic newborn stars and the thin and thick disc stars, are displaced from initial near-circular orbits by gravitational interactions with giant molecular clouds (GMCs). To exclude the influence of other perturbers that can change the stellar orbits, such as spiral arms and the bar, we use an axisymmetric form for the entire galactic potential. First, we investigate the time evolution of the radial and vertical velocity dispersion σR and σz by comparing them with a power-law relation of σ ∝ tβ. Although the exponents β decrease with time, they keep large values of 0.3 ∼ 0.6 for 1 Gyr, indicating fast and efficient disc heating. Next, we find that the efficient stellar scattering by GMCs also causes a change in angular momentum for each star and, therefore, radial migration. This effect is more pronounced in newborn stars than old disc stars; nearly 30 per cent of stars initially located on the galactic mid-plane move more than 1 kpc in the radial direction for 1 Gyr. The dynamical heating and radial migration drastically occur in the first several hundred Myr. As the amplitude of the vertical oscillation increases, the time spent in the galactic plane, where most GMCs are distributed, decreases, and the rate of an increase in the heating and migration slows down.
Alternative splicing analysis benchmark with DICAST
Authors: Fenn Amit , Tsoy Olga , Faro Tim , Rößler Fanny L M , Dietrich Alexander , Kersting Johannes , Louadi Zakaria , Lio Chit Tong , Völker Uwe , Baumbach Jan , Kacprowski Tim , List Markus
Published: May 2023

Alternative splicing is a major contributor to transcriptome and proteome diversity in health and disease. A plethora of tools have been developed for studying alternative splicing in RNA-seq data. Previous benchmarks focused on isoform quantification and mapping. They neglected event detection tools, which arguably provide the most detailed insights into the alternative splicing process. DICAST offers a modular and extensible framework for analysing alternative splicing integrating eleven splice-aware mapping and eight event detection tools. We benchmark all tools extensively on simulated as well as whole blood RNA-seq data. STAR and HISAT2 demonstrated the best balance between performance and run time. The performance of event detection tools varies widely with no tool outperforming all others. DICAST allows researchers to employ a consensus approach to consider the most successful tools jointly for robust event detection. Furthermore, we propose the first reporting standard to unify existing formats and to guide future tool development.
RFcaller: a machine learning approach combined with read-level features to detect somatic mutations
Authors: Díaz-Navarro Ander , Bousquets-Muñoz Pablo , Nadeu Ferran , López-Tamargo Sara , Beà Silvia , Campo Elias , Puente Xose S
Published: May 2023

The cost reduction in sequencing and the extensive genomic characterization of a wide variety of cancers are expanding tumor sequencing to a wide number of research groups and the clinical practice. Although specific pipelines have been generated for the identification of somatic mutations, their results usually differ considerably, and a common approach is to use several callers to achieve a more reliable set of mutations. This procedure is computationally expensive and time-consuming, and it suffers from the same limitations in sensitivity and specificity as other approaches. Expert revision of mutant calls is therefore required to verify calls that might be used for clinical diagnosis. This step could take advantage of machine learning techniques, as they provide a useful approach to incorporate expert-reviewed information for the identification of somatic mutations. Here we present RFcaller, a pipeline based on machine learning algorithms, for the detection of somatic mutations in tumor–normal paired samples that does not require large computing resources. RFcaller shows high accuracy for the detection of substitutions and insertions/deletions from whole genome or exome data. It allows the detection of mutations in driver genes missed by other approaches, and has been validated by comparison to deep and Sanger sequencing.
GammaTile® (GT) as a brachytherapy platform for rapidly growing brain metastasis
Authors: Dharnipragada Rajiv , Ferreira Clara , Shah Rena , Reynolds Margaret , Dusenbery Kathryn , Chen Clark C
Published: May 2023

Background

A subset of brain metastasis (BM) shows rapid recurrence post-initial resection or aggressive tumor growth between interval scans. Here we provide a pilot experience in the treatment of these BM with GammaTile® (GT), a collagen tile-embedded Cesium 131 (131Cs) brachytherapy platform.

Methods

We identified ten consecutive patients (2019–2023) with BM that showed either (1) symptomatic recurrence while awaiting post-resection radiosurgery or (2) enlarged by >25% of tumor volume on serial imaging and underwent surgical resection followed by GT placement. Procedural complication, 30-day readmission, local control, and overall survival were assessed.

Results

For this cohort of ten BM patients, 3 patients suffered tumor progression while awaiting radiosurgery and 7 showed >25% tumor growth prior to surgery and GT placement. There were no procedural complications or 30-day mortality. All patients were discharged home, with a median hospital stay of 2 days (range: 1–9 days). 4/10 patients experienced symptomatic improvement while the remaining patients showed stable neurologic conditions. With a median follow-up of 186 days (6.2 months, range: 69–452 days), no local recurrence was detected. The median overall survival (mOS) for the newly diagnosed BM was 265 days from the time of GT placement. No patients suffered from adverse radiation effects.

Conclusion

Our pilot experience suggests that GT offers favorable local control and safety profile in patients suffering from brain metastases that exhibit aggressive growth patterns and support the future investigation of this treatment paradigm.
Deep vein thrombosis as thrombotic sequelae of vaccine-induced thrombotic thrombocytopenia
Authors: Osei Racheal , Ahmed Saad , Morrow David , Hamid Sarbast , Hawkins Peter , Mohan Mahalakshmi
Published: May 2023

Administration of the ChAdOx1 nCoV-19 (AstraZeneca) vaccination has recently been associated with rare, unusual cases of thrombotic events. We report a case of a 55-year-old woman who presented to hospital with headaches, petechial rashes and bruising—7 days after receiving her first vaccine dose. Blood tests showed low platelets, a markedly high d-dimer and positive anti-platelet factor 4 antibodies. Computed tomography (CT) of head and venogram showed features consistent with venous sinus thrombosis. She was immediately started on IV pooled immunoglobulin therapy, high-dose prednisolone and full anticoagulation. Subsequent magnetic resonance imaging of head and venogram supported the initial CT findings, with features suggestive of a small-volume venous sinus thrombosis. Additionally, CT pulmonary angiogram revealed a right-sided segmental pulmonary embolism. Our case highlights the importance of increased awareness of this complication after covid vaccination and how searching for distal thrombotic events and liaison with tertiary centres influence clinical outcomes.
A successful management of refractory immune thrombocytopenic purpura with Eltrombopag during pregnancy complicated with superimposed preeclampsia
Authors: Miyashita Dai , Sayama Seisuke , Iriyama Takayuki , Nakazaki Kumi , Toshimitsu Masatake , Seyama Takahiro , Kumasawa Keiichi , Nagamatsu Takeshi , Kurokawa Mineo , Osuga Yutaka
Published: May 2023

Eltrombopag, a thrombopoietin receptor agonist, is approved for treating patients with immune thrombocytopenic purpura (ITP) refractory to corticosteroids and intravenous immunoglobulin (IVIg) therapy.

We report a 32-years-old nulliparous Japanese woman with ITP and chronic hypertension who developed pulmonary edema due to superimposed preeclampsia at 27 weeks of gestation. She received therapy with corticosteroids, IVIg and Eltrombopag, but her platelet level was fluctuating and was difficult to achieve a well sustained response. A transient leukocytosis was noted but resolved by Eltrombopag dose reduction. Her pregnancy was complicated with preeclampsia with severe features required a prompt delivery. Although recent evidence supports the safety and efficacy of Eltrombopag use during pregnancy, unreported risks may underlie its use during pregnancy.
Acute febrile illness in a teenage female with history of Graves’ disease
Authors: Rushing Mark W , Rebolledo Michael A , Lahoti Amit , Alemzadeh Ramin
Published: May 2023

Thyroid storm is a rare, life-threatening condition that is usually precipitated by Graves’ disease in children and adolescents. COVID-19 (SARS-CoV-2) can cause multisystem inflammatory syndrome in children (MIS C), which shares some features of Graves’ disease. We present a case of acute thyroid storm following SARS-CoV-2 infection in a 16-year-old female with poorly controlled Graves’ disease. She initially presented to the emergency department for fever and palpitations. Initial laboratory results suggested thyroid storm, for which she was started on propranolol. She remained tachycardic with new gallop rhythm on exam. An echocardiogram demonstrated a depressed left ventricular ejection fraction and mild pulmonary hypertension. Her SARS-CoV-2 antibodies were positive. She was started on intravenous immunoglobulin for suspected MIS-C. She responded to combined treatment of thyroid storm and MIS-C. She was discharged home on propranolol, methimazole, cholestyramine and aspirin.
Social Power and the Movement System: Why and How Physical Therapists Might Influence the Upstream Currents of Health
Authors: Davenport Todd E , Griech Sean F , VanDeCarr Terri , Rethorn Zachary D , Magnusson Dawn M
Published: May 2023

Social determinants of health are an emerging focus within physical therapist practice, research, education, and advocacy as a necessary condition for movement system health disparities. Fundamental cause theory suggests that the sociopolitical environment sets the context for individuals’ socioeconomic positioning, which determines the availability of resources that are necessary for groups and individuals to maintain health. These resources include knowledge, money, power, prestige, and social connections. Yet, it is the hierarchical organization of society that dictates both the availability of socioeconomic resources and the ability of patients and clients to use those resources to promote and maintain movement system health. The presence of social hierarchies indicates the need for physical therapists to consider social power as a key determinant of movement system health. Consideration of social power in clinical initiatives and advocacy agendas would provide a framework for physical therapists to begin the dynamic, and often, adversarial process of breaking down social hierarchies and redistributing social power, rather than simply redistributing socioeconomic resources, in pursuit of societal transformation and community-building. This Perspective discusses social power as the fundamental driver of movement system health inequalities and explores the effects of social power on exposure, susceptibility, experience, and recovery related to movement system pathology—including the influence of social power on the ability of people to acquire socioeconomic resources and convert them to health-relevant resources. This perspective concludes with recommendations for physical therapists to identify and dismantle inequalities in social power through structural competency.