bluuebunny/crossref_metadata_2025 huggingface dataset:
Activating Killer-Cell Immunoglobulin-Like Receptors Are Associated With the Severity of Coronavirus Disease 2019
Authors: Bernal Enrique , Gimeno Lourdes , Alcaraz María J , Quadeer Ahmed A , Moreno Marta , Martínez-Sánchez María V , Campillo José A , Gomez Jose M , Pelaez Ana , García Elisa , Herranz Maite , Hernández-Olivo Marta , Martínez-Alfaro Elisa , Alcaraz Antonia , Muñoz Ángeles , Cano Alfredo , McKay Matthew R , Muro Manuel , Minguela Alfredo
Published: April 2021

Background

Etiopathogenesis of the clinical variability of the coronavirus disease 2019 (COVID-19) remains mostly unknown. In this study, we investigate the role of killer cell immunoglobulin-like receptor (KIR)/human leukocyte antigen class-I (HLA-I) interactions in the susceptibility and severity of COVID-19.

Methods

We performed KIR and HLA-I genotyping and natural killer cell (NKc) receptors immunophenotyping in 201 symptomatic patients and 210 noninfected controls.

Results

The NKcs with a distinctive immunophenotype, suggestive of recent activation (KIR2DS4low CD16low CD226low CD56high TIGIThigh NKG2Ahigh), expanded in patients with severe COVID-19. This was associated with a higher frequency of the functional A-telomeric activating KIR2DS4 in severe versus mild and/or moderate patients and controls (83.7%, 55.7% and 36.2%, P < 7.7 × 10−9). In patients with mild and/or moderate infection, HLA-B*15:01 was associated with higher frequencies of activating B-telomeric KIR3DS1 compared with patients with other HLA-B*15 subtypes and noninfected controls (90.9%, 42.9%, and 47.3%; P < .002; Pc = 0.022). This strongly suggests that HLA-B*15:01 specifically presenting severe acute respiratory syndrome coronavirus 2 peptides could form a neoligand interacting with KIR3DS1. Likewise, a putative neoligand for KIR2DS4 could arise from other HLA-I molecules presenting severe acute respiratory syndrome coronavirus 2 peptides expressed on infected an/or activated lung antigen-presenting cells.

Conclusions

Our results support a crucial role of NKcs in the clinical variability of COVID-19 with specific KIR/ligand interactions associated with disease severity.
Stepwise generation of AID knock-in and conditional knockout mice from a single gene-targeting event
Authors: Kinoshita Kazuo , Uemura Munehiro , Shimizu Takahiro , Kinoshita Shun , Marusawa Hiroyuki
Published: April 2021

Activation-induced cytidine deaminase (AID) encoded by the Aicda gene initiates class-switch recombination and somatic hypermutation of immunoglobulin genes. In addition to this function, AID is also implicated in the epigenetic regulation in pluripotent stem cells and in the oncogenesis of lymphoid and non-lymphoid origins. To examine AID’s role in specific cell types, we developed mouse strains of conditional knockout (Aicda-FL) and knock-in with a red fluorescent protein gene (RFP) inserted into the Aicda locus (Aicda-RFP). These two strains were obtained from a single targeting event in embryonic stem cells by a three-loxP or tri-lox strategy. Partial and complete recombination among the three loxP sites in the Aicda-RFP locus gave rise to Aicda-FL and AID-deficient loci (Aicda-KO), respectively, after mating Aicda-RFP mice with Cre-expressing mice driven by tissue-non-specific alkaline phosphate promoter. We confirmed RFP expression in B cells of germinal centers of intestine-associated lymphoid tissue. Mice homozygous for each allele were obtained and were checked for AID activity by class-switch and hypermutation assays. AID activity was normal for Aicda-FL but partially and completely absent for Aicda-RFP and Aicda-KO, respectively. Aicda-FL and Aicda-RFP mice would be useful for studying AID function in subpopulations of B cells and in non-lymphoid cells.
Single- and Multiple-Laboratory Validation of LC-MS/MS Method for Simultaneous Determination of Fosetyl-Al and Phosphonic Acid in Cereal Grains and Analysis of Rice, Wheat, and Barley
Authors: Sekiyama Atsushi , Toriumi Eisuke , Yamada Yukiko
Published: April 2021

Background

In Japan, the residue definition for fosetyl-Al is “sum of fosetyl-Al and phosphonic acid expressed as fosetyl-Al” and its current provisional maximum residue limit (MRL) in cereals is under review.

Objective

For establishment and enforcement of fosetyl-Al MRL in cereals, a new analytical method for fosetyl-Al and phosphonic acid in cereals should be developed and validated.

Method

The new method involves water extraction, cleanup using tandem cation- and anion-exchange mini columns, and determination by LC-MS/MS. It was validated in a single laboratory and multiple laboratories. Using the method, 41 samples of rice, wheat, and barley were analyzed.

Results

In the multiple-laboratory validation: repeatability and reproducibility for three concentrations of fosetyl-Al and phosphonic acid were in ranges of 4.8–20 and 5.9–34%; calculated sum of fosetyl-Al and phosphonic acid, expressed as fosetyl-Al, showed good recoveries; linearity was observed for fosetyl-Al and phosphonic acid in ranges of 0.005–0.4 and 0.025–2.0 mg/kg; and specificity was sufficient. The method was verified for rice matrixes. In 41 samples, phosphonic acid was detected up to 0.2 mg/kg while fosetyl was not.

Conclusions

The method was successfully validated with high precision, accuracy, linearity, and specificity and capable of analyzing fosetyl-Al and phosphonic acid with a practical LOQ of 0.01 and 0.05 mg/kg. The LOQs and concentrations of phosphonic acid in samples indicate that a potential MRL would be 0.5 mg/kg for fosetyl-Al in cereals.

Highlights

The validated method was simpler than many methods and did not require derivatization, matrix-matched orisotopically-labeled internal standards.
Delayed Neurological Sequelae in an Infant After Carbon Monoxide Intoxication
Authors: Lai Yeu-Her , Chen Li-Wen , Hsueh Yuan-Yu
Published: April 2021

Delayed neurological sequelae are symptoms that appear over a period of time after an acute event of carbon monoxide poisoning. The incidence of delayed neurological sequelae is lower in children than in adults and is even more uncommon in infants. Here, we present a case of a 4-month-old infant who developed delayed neurological sequelae after carbon monoxide intoxication. She presented with neurological symptoms, including opisthotonus, athetoid movements, anterior tongue thrust, and opsoclonus. Because these symptoms are starkly different from those of adults, they should be compared with age-appropriate developmental milestones. Because of their faster metabolic rate and presence of fetal hemoglobin, infants with developing brains may be especially vulnerable to carbon monoxide toxicity. Therefore, thorough neurological examination and prompt treatment are critical for infants who experience carbon monoxide intoxication.
Vernacular Design: A History of Hong Kong Neon Signs
Authors: Kwok Brian Sze-Hang
Published: April 2021

Neon signs dominated Hong Kong’s urban landscape from the 1950s to the early 2000s. This visual vernacular, however, has begun to vanish from Hong Kong’s streets over the past decade due to stricter regulations and the emergence of cheaper alternatives. As a result, scholars, the media and the general public have become more engaged in recording and preserving neon signs, and have begun to recognize them as an aspect of Hong Kong’s vernacular design. This engagement serves as an entry point for investigating the application of western views of vernacular design to Hong Kong, using neon signs as a case study. A collection of 218 original neon sign designs was donated by the Nam Wah Neonlight & Electrical Factory to the Information Design Lab at Hong Kong Polytechnic University. Using these original designs and photos of neon signs taken in different districts in Hong Kong, this article provides historical and socio-cultural perspectives with which to examine vernacular design, to identify other attributes that should be taken into account, such as aesthetics, bottom-up participation, architecture and the urban environment. The article aims to contribute to the study of vernacular design and the design history of neon signs.
Effects ofHelicobacter pylorieradication on gastric cancer incidence in the Japanese population: a systematic evidence review
Authors: Lin Yingsong , Kawai Sayo , Sasakabe Tae , Nagata Chisato , Naito Mariko , Tanaka Keitaro , Sugawara Yumi , Mizoue Tetsuya , Sawada Norie , Matsuo Keitaro , Kitamura Tetsuhisa , Utada Mai , Ito Hidemi , Shimazu Taichi , Kikuchi Shogo , Inoue Manami ,   Research Group for the Development and Evaluation of Cancer Prevention Strategies in Japan
Published: April 2021

Background

In Japan, there are ongoing efforts to shift the gastric cancer prevention and control policy priorities from barium-based screening to Helicobacter pylori (H. pylori)-oriented primary prevention. A comprehensive summary of the evidence regarding the effects of H. pylori eradication on the risk of gastric cancer could inform policy decisions.

Methods

We conducted a systematic review and meta-analysis of published studies evaluating the effectiveness of H. pylori eradication for the prevention of gastric cancer in otherwise healthy individuals (primary prevention) and early gastric cancer patients (tertiary prevention).

Results

In total, 19 studies were included. Three moderate-quality observational cohort studies showed that H. pylori eradication may be associated with a decreased risk of gastric cancer in healthy asymptomatic Japanese people. There is moderate certainty regarding the effectiveness of H. pylori eradication in patients with gastrointestinal diseases, such as peptic ulcers. A meta-analysis of 10 observational studies with otherwise healthy individuals (mainly peptic ulcer patients) yielded an overall risk ratio of 0.34 (95% CI: 0.25–0.46). Regarding tertiary prevention, the overall risk ratio for developing metachronous gastric cancer was 0.50 (95% CI: 0.39–0.66) in the eradication group in a meta-analysis of nine studies involving early gastric cancer patients who underwent endoscopic resection.

Conclusion

H. pylori eradication is effective in preventing gastric cancer in the Japanese population, regardless of symptoms. Well-designed, large cohort studies are warranted to determine the long-term efficacy and safety of H. pylori eradication in the context of reducing the gastric cancer burden through population-based screening and treatment.
The current status of inpatient cancer rehabilitation provided by designated cancer hospitals in Japan
Authors: Fukushima Takuya , Tsuji Tetsuya , Watanabe Noriko , Sakurai Takuro , Matsuoka Aiko , Kojima Kazuhiro , Yahiro Sachiko , Oki Mami , Okita Yusuke , Yokota Shota , Nakano Jiro , Sugihara Shinsuke , Sato Hiroshi , Kawakami Juichi , Kagaya Hitoshi , Tanuma Akira , Sekine Ryuichi , Mori Keita , Zenda Sadamoto , Kawai Akira
Published: April 2021

Objective

This survey was conducted to clarify the current status of inpatient cancer rehabilitation provided by designated cancer hospitals in Japan.

Methods

A survey questionnaire was sent to 427 designated cancer hospitals in Japan. Information was sought regarding whether inpatient cancer rehabilitation was provided by the center, and if so, whether respondents regarded such provision as satisfactory.

Results

Responses were obtained from 235/427 surveyed institutions (55.0%). Cancer rehabilitation was provided in inpatient settings by 97.4%. Two-thirds of respondents (67.7%) regarded inpatient cancer rehabilitation provision as still inadequate. The primary reasons claimed for this inadequacy were a lack of human resources, a lack of rehabilitation professionals with the requisite knowledge/skills and patients who would benefit from cancer rehabilitation present but not prescribed. The total number of rehabilitation staff was identified as associated factor of inadequate inpatient cancer rehabilitation in multivariate analysis (odds ratio = 0.979, 95% confidence interval = 0.96–1.00, P = 0.009).

Conclusions

In order to provide adequate cancer rehabilitation, a sufficient supply of rehabilitation staff, education and recognition of the need for cancer rehabilitation within oncology units are necessary.
A flexible modelling of galaxy assembly bias
Authors: Contreras S , Angulo R E , Zennaro M
Published: April 2021

We use the illustris TNG300 magneto-hydrodynamic simulation, the sage semi-analytical model, and the subhalo abundance matching technique (SHAM) to examine the diversity in predictions for galaxy assembly bias (i.e. the difference in the large-scale clustering of galaxies at a fixed halo mass due to correlations with the assembly history and other properties of host haloes). We consider samples of galaxies selected according to their stellar mass or star formation rate at various redshifts. We find that all models predict an assembly bias signal of different magnitude, redshift evolution, and dependence with selection criteria and number density. To model these non-trivial dependences, we propose an extension to the standard SHAM technique so it can include arbitrary amounts of assembly bias. We do this by preferentially selecting subhaloes with the same internal property but different individual large-scale bias. We find that with this model, we can successfully reproduce the galaxy assembly bias signal in either sage or the tng, for all redshifts and galaxy number densities. We anticipate that this model can be used to constrain the level of assembly bias in observations and aid in the creation of more realistic mock galaxy catalogues.
Formation of chiral CO polyhedral crystals on icy interstellar grains
Authors: Kouchi Akira , Tsuge Masashi , Hama Tetsuya , Niinomi Hiromasa , Nakatani Naoki , Shimonishi Takashi , Oba Yasuhiro , Kimura Yuki , Sirono Sin-iti , Okuzumi Satoshi , Momose Munetake , Furuya Kenji , Watanabe Naoki
Published: April 2021

The crystallinity and morphology of solid carbon monoxide (CO) on icy interstellar grains were examined by observing the deposition, crystallization, and UV and electrons irradiation of solid CO using transmission electron microscopy. Herein, we found that solid CO deposited in molecular clouds was crystalline, and that even if amorphous CO was deposited, amorphous CO crystallized within 103 yr at 10 K. Conversely, crystalline CO was not amorphized by UV rays or electron beam at 10 K. These results indicated the occurrence of chiral crystalline CO instead of amorphous CO in space. Furthermore, the large surface diffusion coefficients of CO on eamorphous H2O and crystalline CO at 10 K facilitated the morphological equilibration of crystalline CO. Bad wetting of crystalline CO with amorphous H2O proved that the morphology of the ice grains was not spherical with an onion-like structure, as hitherto assumed, but rather it was a polyhedral crystalline CO attached to amorphous H2O. This has important implications for phenomena associated with the collision and subsequent sticking between ice grains, surface chemical reactions, non-thermal desorption of molecules and the origin of homochirality in interstellar biomolecules.
Impact of surface heterogeneity on IR line profiles of adsorbed carbon monoxide on models of interstellar grain surfaces
Authors: Taj S , Rosu-Finsen A , McCoustra M R S
Published: April 2021

Surface heterogeneity of model amorphous silica films used as a model for interstellar grain surfaces is revealed through the application of the pre-exponential optimized inversion method to previously reported sub-monolayer thermal desorption studies of carbon monoxide (CO) desorption. The impact of that surface heterogeneity, as represented by the coverage dependence of the CO activation energy for desorption from the amorphous silica surface, on the IR spectroscopy of the CO stretching vibration is explored through vibrational line profile synthesis. Comparison is then made to previous investigations of CO line profiles on this surface and on amorphous solid water as reported in Taj et al. (2017, 2019a). A tentative conclusion is drawn that CO vibrationally promoted desorption from, and diffusion on, the amorphous silica surface may be responsible for the correspondingly short vibrational excited state lifetime of CO on that surface. The contrast with CO on amorphous solid water, where direct and rapid vibrational relaxation into the solid water phonon bath occurs, is highlighted. The consequences of this from the standpoint of CO deposition on grain surfaces are discussed.
Testing the fossil field hypothesis: could strongly magnetized OB stars produce all known magnetars?
Authors: Makarenko Ekaterina I , Igoshev Andrei P , Kholtygin A F
Published: April 2021

Stars of spectral types O and B produce neutron stars (NSs) after supernova explosions. Most of NSs are strongly magnetized including normal radio pulsars with B ∝ 1012 G and magnetars with B ∝ 1014 G. A fraction of 7–12 per cent of massive stars are also magnetized with B ∝ 103 G and some are weakly magnetized with B ∝ 1 G. It was suggested that magnetic fields of NSs could be the fossil remnants of magnetic fields of their progenitors. This work is dedicated to study this hypothesis. First, we gather all modern precise measurements of surface magnetic fields in O, B, and A stars. Secondly, we estimate parameters for lognormal distribution of magnetic fields in B stars and found μB = 2.83 ± 0.1 log10 (G), σB = 0.65 ± 0.09 for strongly magnetized and μB = 0.14 ± 0.5 log10 (G), $\sigma =0.7_{-0.27}^{+0.57}$ for weakly magnetized. Third, we assume that the magnetic field of pulsars and magnetars have 2.7-dex difference in magnetic fields and magnetars represent 10 per cent of all young NSs and run population synthesis. We found that it is impossible to simultaneously reproduce pulsars and magnetars populations if the difference in their magnetic fields is 2.7 dex. Therefore, we conclude that the simple fossil origin of the magnetic field is not viable for NSs.
Matched filtering with non-Gaussian noise for planet transit detections
Authors: Robnik Jakob , Seljak Uroš
Published: April 2021

We develop a method for planet detection in transit data, which is based on the matched filter technique, combined with the Gaussianization of the noise outliers. The method is based on Fourier transforms and is as fast as the existing methods for planet searches. The Gaussianized matched filter (GMF) method significantly outperforms the standard baseline methods in terms of the false positive rate, enabling planet detections at up to 30 per cent lower transit amplitudes. Moreover, the method extracts all the main planet transit parameters, amplitude, period, phase, and duration. By comparison to the state-of-the-art Gaussian process methods on both simulations and real data, we show that all the transit parameters are determined with an optimal accuracy (no bias and minimum variance), meaning that the GMF method can be used for both the initial planet detection and the follow-up planet parameter analysis.
Structurally restricted Bi(III) metallation of apo-βMT1a: metal-induced tangling
Authors: Korkola Natalie C , Hudson Elyse , Stillman Martin J
Published: April 2021

Non-toxic bismuth salts are used in anti-ulcer medications and to protect against nephrotoxicity from anticancer drugs. Bismuth salts also induce metallothionein (MT), a metal-binding protein that lacks a formal secondary structure. We report the impact on the metallation properties of Bi(III) to the 9-cysteine β fragment of MT as a function of cysteine accessibility using electrospray ionization mass spectrometry. At pH 7.4, Bi2βMT formed cooperatively. Cysteine modification shows that each Bi(III) was terminally bound to three cysteinyl thiolates. Non-cooperative Bi(III) binding was observed at pH 2.3, where cysteine accessibility is increased. However, competition from H4EDTA inhibited Bi(III) binding. When GdmCl, a well-known denaturing agent, was used to increase cysteine accessibility of the apoβMT at pH 7.4, a greater fraction of Bi3βMT formed using all nine cysteines. The change in binding profile and equilibrium of Bi2βMT was determined as a function of acidification, which changed as a result of competition with H4EDTA. There was no Bi(III) transfer between Bi2βMT, Cd3βMT, and Zn3βMT. This lack of metal exchange and the resistance towards binding the third Bi(III) suggest a rigidity in the Bi2βMT binding sites that inhibits Bi(III) mobility. These experiments emphasize the conformational control of metallation that results in substantially different metallated products: at pH 7.4 (many cysteines buried) Bi2βMT, whereas at pH 7.4 (all cysteines accessible) enhanced formation of Bi3βMT. These data suggest that the addition of the first two Bi(III) crosslinks the protein, blocking access to the remaining three cysteines for the third Bi(III), as a result of tangle formation.
Structural recognition of the MYC promoter G-quadruplex by a quinoline derivative: insights into molecular targeting of parallel G-quadruplexes
Authors: Dickerhoff Jonathan , Dai Jixun , Yang Danzhou
Published: April 2021

DNA G-Quadruplexes (G4s) formed in oncogene promoters regulate transcription. The oncogene MYC promoter G4 (MycG4) is the most prevalent G4 in human cancers. However, the most studied MycG4 sequence bears a mutated 3′-residue crucial for ligand recognition. Here, we report a new drug-like small molecule PEQ without a large aromatic moiety that specifically binds MycG4. We determined the NMR solution structures of the wild-type MycG4 and its 2:1 PEQ complex, as well as the structure of the 2:1 PEQ complex of the widely used mutant MycG4. Comparison of the two complex structures demonstrates specific molecular recognition of MycG4 and shows the clear effect of the critical 3′-mutation on the drug binding interface. We performed a systematic analysis of the four available complex structures involving the same mutant MycG4, which can be considered a model system for parallel G4s, and revealed for the first time that the flexible flanking residues are recruited in a conserved and sequence-specific way, as well as unused potential for selective ligand-G4 hydrogen-bond interactions. Our results provide the true molecular basis for MycG4-targeting drugs and new critical insights into future rational design of drugs targeting MycG4 and parallel G4s that are prevalent in promoter and RNA G4s.
dSPRINT: predicting DNA, RNA, ion, peptide and small molecule interaction sites within protein domains
Authors: Etzion-Fuchs Anat , Todd David A , Singh Mona
Published: April 2021

Domains are instrumental in facilitating protein interactions with DNA, RNA, small molecules, ions and peptides. Identifying ligand-binding domains within sequences is a critical step in protein function annotation, and the ligand-binding properties of proteins are frequently analyzed based upon whether they contain one of these domains. To date, however, knowledge of whether and how protein domains interact with ligands has been limited to domains that have been observed in co-crystal structures; this leaves approximately two-thirds of human protein domain families uncharacterized with respect to whether and how they bind DNA, RNA, small molecules, ions and peptides. To fill this gap, we introduce dSPRINT, a novel ensemble machine learning method for predicting whether a domain binds DNA, RNA, small molecules, ions or peptides, along with the positions within it that participate in these types of interactions. In stringent cross-validation testing, we demonstrate that dSPRINT has an excellent performance in uncovering ligand-binding positions and domains. We also apply dSPRINT to newly characterize the molecular functions of domains of unknown function. dSPRINT’s predictions can be transferred from domains to sequences, enabling predictions about the ligand-binding properties of 95% of human genes. The dSPRINT framework and its predictions for 6503 human protein domains are freely available at http://protdomain.princeton.edu/dsprint.
InterEvDock3: a combined template-based and free docking server with increased performance through explicit modeling of complex homologs and integration of covariation-based contact maps
Authors: Quignot Chloé , Postic Guillaume , Bret Hélène , Rey Julien , Granger Pierre , Murail Samuel , Chacón Pablo , Andreani Jessica , Tufféry Pierre , Guerois Raphaël
Published: April 2021

The InterEvDock3 protein docking server exploits the constraints of evolution by multiple means to generate structural models of protein assemblies. The server takes as input either several sequences or 3D structures of proteins known to interact. It returns a set of 10 consensus candidate complexes, together with interface predictions to guide further experimental validation interactively. Three key novelties were implemented in InterEvDock3 to help obtain more reliable models: users can (i) generate template-based structural models of assemblies using close and remote homologs of known 3D structure, detected through an automated search protocol, (ii) select the assembly models most consistent with contact maps from external methods that implement covariation-based contact prediction with or without deep learning and (iii) exploit a novel coevolution-based scoring scheme at atomic level, which leads to significantly higher free docking success rates. The performance of the server was validated on two large free docking benchmark databases, containing respectively 230 unbound targets (Weng dataset) and 812 models of unbound targets (PPI4DOCK dataset). Its effectiveness has also been proven on a number of challenging examples. The InterEvDock3 web interface is available at http://bioserv.rpbs.univ-paris-diderot.fr/services/InterEvDock3/.
A novel bipartite antitermination system widespread in conjugative elements of Gram-positive bacteria
Authors: Miguel-Arribas Andrés , Val-Calvo Jorge , Gago-Córdoba César , Izquierdo José M , Abia David , Wu Ling Juan , Errington Jeff , Meijer Wilfried J J
Published: April 2021

Transcriptional regulation allows adaptive and coordinated gene expression, and is essential for life. Processive antitermination systems alter the transcription elongation complex to allow the RNA polymerase to read through multiple terminators in an operon. Here, we describe the discovery of a novel bipartite antitermination system that is widespread among conjugative elements from Gram-positive bacteria, which we named conAn. This system is composed of a large RNA element that exerts antitermination, and a protein that functions as a processivity factor. Besides allowing coordinated expression of very long operons, we show that these systems allow differential expression of genes within an operon, and probably contribute to strict regulation of the conjugation genes by minimizing the effects of spurious transcription. Mechanistic features of the conAn system are likely to decisively influence its host range, with important implications for the spread of antibiotic resistance and virulence genes.
Intracranial Meningiomas Decrease in Volume on Magnetic Resonance Imaging After Discontinuing Progestin
Authors: Voormolen Eduard H J , Champagne Pierre Olivier , Roca Elena , Giammattei Lorenzo , Passeri Thibault , di Russo Paolo , Sanchez Miguel Marigil , Bernat Anne Laure , Yoldjian Isabelle , Fontanel Sylvie , Weill Alain , Mandonnet Emmanuel , Froelich Sébastien
Published: April 2021

BACKGROUND

The behavior of meningiomas under influence of progestin therapy remains unclear.

OBJECTIVE

To investigate the relationship between growth kinetics of intracranial meningiomas and usage of the progestin cyproterone acetate (PCA).

METHODS

This study prospectively followed 108 women with 262 intracranial meningiomas and documented PCA use. A per-meningioma analysis was conducted. Changes in meningioma volumes over time, and meningioma growth velocities, were measured on magnetic resonance imaging (MRI) after stopping PCA treatment.

RESULTS

Mean follow-up time was 30 (standard deviation [SD] 29) mo. Ten (4%) meningiomas were treated surgically at presentation. The other 252 meningiomas were followed after stopping PCA treatment. Overall, followed meningiomas decreased their volumes by 33% on average (SD 28%). A total of 188 (72%) meningiomas decreased, 51 (20%) meningiomas remained stable, and 13 (4%) increased in volume of which 3 (1%) were surgically treated because of radiological progression during follow-up after PCA withdrawal. In total, 239 of 262 (91%) meningiomas regressed or stabilized during follow-up. Subgroup analysis in 7 women with 19 meningiomas with follow-up before and after PCA withdrawal demonstrated that meningioma growth velocity changed statistically significantly (P = .02). Meningiomas grew (average velocity of 0.25 mm3/day) while patients were using PCA and shrank (average velocity of −0.54 mm3/day) after discontinuation of PCA.

CONCLUSION

Ninety-one percent of intracranial meningiomas in female patients with long-term PCA use decrease or stabilize on MRI after stopping PCA treatment. Meningioma growth kinetics change significantly from growth during PCA usage to shrinkage after PCA withdrawal.
Transportation of AIE-visualized nanoliposomes is dominated by the protein corona
Authors: Wang Yi-Feng , Zhang Chunqiu , Yang Keni , Wang Yufei , Shan Shaobo , Yan Yan , Dawson Kenneth A , Wang Chen , Liang Xing-Jie
Published: April 2021

Liposomes, especially cationic liposomes, are the most common and well-investigated nanocarriers for biomedical applications, such as drug and gene delivery. Like other types of nanomaterials, once liposomes are incubated in a biological milieu, their surface can be immediately cloaked by biological components to form a protein corona, which confers a new ‘biological identity’ and modulates downstream interactions with cells. However, it remains unclear how the protein corona affects the transportation mechanism after liposomes interact with cells. Here, we employed home-made aggregation-induced-emission-visualized nanoliposomes TR4@Lipo as a model to investigate transportation with or without the protein corona by optical imaging techniques. The results show that the protein corona can change the cellular transportation mechanism of TR4@Lipo from energy-independent membrane fusion to energy-dependent endocytosis. The protein corona also modulates the intracellular distribution of loaded cargoes. This knowledge furthers our understanding of bio-nano interactions and is important for the efficient use of cationic liposomes.
The distinct morphological phenotypes of Southeast Asian aborigines are shaped by novel mechanisms for adaptation to tropical rainforests
Authors: Zhang Xiaoming , Liu Qi , Zhang Hui , Zhao Shilei , Huang Jiahui , Sovannary Tuot , Bunnath Long , Aun Hong Seang , Samnom Ham , Su Bing , Chen Hua
Published: April 2021

Southeast Asian aborigines, the hunter-gatherer populations living in tropical rainforests, exhibit distinct morphological phenotypes, including short stature, dark skin, curly hair and a wide and snub nose. The underlying genetic architecture and evolutionary mechanism of these phenotypes remain a long-term mystery. We conducted whole genome deep sequencing of 81 Cambodian aborigines from eight ethnic groups. Through a genome-wide scan of selective sweeps, we discovered key genes harboring Cambodian-enriched mutations that may contribute to their phenotypes, including two hair morphogenesis genes (TCHH and TCHHL1), one nasal morphology gene (PAX3) and a set of genes (such as ENTPD1-AS1) associated with short stature. The identified new genes and novel mutations suggest an independent origin of the distinct phenotypes in Cambodian aborigines through parallel evolution, refuting the long-standing argument on the common ancestry of these phenotypes among the worldwide rainforest hunter-gatherers. Notably, our discovery reveals that various types of molecular mechanisms, including antisense transcription and epigenetic regulation, contribute to human morphogenesis, providing novel insights into the genetics of human environmental adaptation.
Image-Guided Right T10 Costotransverse Joint Resection for Costotransversitis: Operative Technique and Nuances: 2-Dimensional Operative Video
Authors: De Biase Gaetano , Gassie Kelly , Abode-Iyamah Kingsley , Nottmeier Eric
Published: April 2021

We describe the operative approach and management for costotransverse joint inflammation in a 49-yr-old man with worsening midthoracic pain radiating to the right paraspinal area. He underwent physical therapy with no relief of his symptoms. Thoracic spine magnetic resonance imaging (MRI) revealed severe arthritic changes involving the right T10 costotransverse joint. Scoliosis X-rays showed a dextroconvex curvature in the midthoracic spine, without any significant imbalance. Single-photon emission computed tomography (SPECT) scan revealed focal increased uptake of the right T10 costotransverse joint. T10 costotransverse joint lidocaine injection did not provide any relief. We performed a computed tomography (CT)-guided biopsy, which was negative for malignancy and also cultures were negative. MRI revealed a significant enhancement in this area and the patient's C-reactive Protein was elevated. Decision was made to perform open biopsy and costotransverse joint resection. We present a case of minimally invasive, image-guided costotransverse joint resection, which has not been described in the literature. The right T10 costotransverse joint was dissected out with the image-guided dilator, and tubular retractors were inserted. Under the microscope, using the image-guided drill, the right T10 costotransverse joint was drilled out. The lateral aspect of the right T10 process was drilled out as well as the medial-dorsal aspect of the right T10 rib. The patient recovered from surgery well with abatement of his preoperative thoracic pain, which remained abated at 6-mo follow-up. This case highlights the complex technical nuances of this procedure, and the importance of a thorough preoperative evaluation with a bone SPECT scan to help localize the pain generator.

Patient consented for the procedures and for the publication of the video.
Erard
Authors: Adelson Robert
Published: April 2021

Sébastien Erard’s (1752–1831) inventions have had an enormous impact on instruments and musical life and are still at the foundation of piano building today. Drawing on an unusually rich set of archives from both the Erard firm and the Erard family, Robert Adelson shows how the Erard piano played an important and often leading role in the history of the instrument, beginning in the late eighteenth century and continuing into the final decades of the nineteenth. The Erards were the first piano builders in France to prioritise the more sonorous grand piano, sending gifts of their new model to both Haydn and Beethoven. Erard’s famous double-escapement action, which improved the instrument’s response while at the same time producing a more powerful tone, revolutionised both piano construction and repertoire. Thanks to these inventions, the Erard firm developed close relationships with the greatest pianist composers of the nineteenth century, including Hummel, Liszt, Moscheles, and Mendelssohn. The book also presents new evidence concerning Pierre Erard’s homosexuality, which helps us to understand his reluctance to found a family to carry on the Erard tradition, a reluctance that would spell the end of the golden era of the firm and lead to its eventual demise. The book closes with the story of Pierre’s widow Camille, who directed the firm from 1855 until 1889. Her influential position in the male-dominated world of instrument building was unique for a woman of her time.
The mechanism by which noncoding RNAs regulate muscle wasting in cancer cachexia
Authors: Zhou Xueer , Hu Shoushan , Zhang Yunan , Du Guannan , Li Yi
Published: April 2021

Cancer cachexia (CC) is a complex metabolic syndrome that accelerates muscle wasting and affects up to 80% of patients with cancer; however, timely diagnostic methods and effective cures are lacking. Although a considerable number of studies have focused on the mechanism of CC-induced muscle atrophy, few novel therapies have been applied in the last decade. In recent years, noncoding RNAs (ncRNAs) have attracted great attention as many differentially expressed ncRNAs in cancer cachectic muscles have been reported to participate in the inhibition of myogenesis and activation of proteolysis. In addition, extracellular vesicles (EVs), which function as ncRNA carriers in intercellular communication, are closely involved in changing ncRNA expression profiles in muscle and promoting the development of muscle wasting; thus, EV-related ncRNAs may represent potential therapeutic targets. This review comprehensively describes the process of ncRNA transmission through EVs and summarizes the pathways and targets of ncRNAs that lead to CC-induced muscle atrophy.
Predicting Recurrent Care Seeking of Physical Therapy for Musculoskeletal Pain Conditions
Authors: George Steven Z , Giczewska Anna , Alhanti Brooke , Lutz Adam D , Shanley Ellen , Thigpen Charles A , Bhavsar Nrupen A
Published: April 2021

Objective

Musculoskeletal pain conditions are a leading cause of pain and disability internationally and a common reason to seek health care. Accurate prediction of recurrence of health care seeking due to musculoskeletal conditions could allow for better tailoring of treatment. The aim of this project was to characterize patterns of recurrent physical therapy seeking for musculoskeletal pain conditions and to develop a preliminary prediction model to identify those at increased risk of recurrent care seeking.

Design

Retrospective cohort.

Setting

Ambulatory care.

Subjects

Patients (n = 578,461) seeking outpatient physical therapy (United States).

Methods

Potential predictor variables were extracted from the electronic medical record, and patients were placed into three different recurrent care categories. Logistic regression models were used to identify individual predictors of recurrent care seeking, and the least absolute shrinkage and selection operator (LASSO) was used to develop multivariate prediction models.

Results

The accuracy of models for different definitions of recurrent care ranged from 0.59 to 0.64 (c-statistic), and individual predictors were identified from multivariate models. Predictors of increased risk of recurrent care included receiving workers’ compensation and Medicare insurance, having comorbid arthritis, being postoperative at the time of the first episode, age range of 44–64 years, and reporting night sweats or night pain. Predictors of decreased risk of recurrent care included lumbar pain, chronic injury, neck pain, pregnancy, age range of 25–44 years, and smoking.

Conclusion

This analysis identified a preliminary predictive model for recurrence of care seeking of physical therapy, but model accuracy needs to improve to better guide clinical decision-making.
The yellow vests roundabout revolt, seen through the lens of household budgets
Authors: Blavier Pierre
Published: April 2021

The ‘yellow vest movement’ that emerged in France in Autumn 2018 raises a serious question for political economy, because many of those who participated did not come from the most fragile sectors of the population. Based on ethnographic fieldwork, but also quantitative data, this article takes an in-depth look at the household budget of one ‘yellow vest’ family. It reveals the increasing tensions lower middle-class peri-urban families are confronted with, and the different ways they address them. In order to understand how they make ends meet, various spheres like the labour and housing market, the transport system, and social mobility must absolutely be interconnected. Contemporary economic reforms impact heavily on these households, lending support to the argument of an ‘attack on household budgets’, particularly as far as road transport is concerned. This approach also allows us to observe the gap between the socio-economic reality of these people and the overly unidimensional statistical indicators available. This budgetary data paves the way for a fair comparison with other contemporary political changes—Brexit for example—to see if similar mechanisms are at work in those cases.
ALiEM Connect: Large-Scale, Interactive, Virtual Residency Programming in Response to COVID-19
Authors: Rose Christian C. , Haas Mary Rose Calderone , Yilmaz Yusuf , Alvarez Al’ai , Mott Sarah E. , Landry Adaira I. , Gisondi Michael A. , Ankel Felix , Lin Michelle , Chan Teresa M.
Published: April 2021

Problem

The COVID-19 pandemic restricted in-person gatherings, including residency conferences. The pressure to quickly reorganize educational conferences and convert content to a remote format overwhelmed many programs. This article describes the pilot event of a large-scale, interactive, virtual educational conference modeled, designed, and implemented by Academic Life in Emergency Medicine (ALiEM), called ALiEM Connect.

Approach

The pilot ALiEM Connect event was conceptualized and implemented within a 2-week period in March 2020. The pilot was livestreamed via a combination of Zoom and YouTube and was archived by YouTube. Slack was used as a backchannel to allow interaction with other participants and engagement with the speakers (via moderators who posed questions from the backchannel to the speakers live during the videoconference).

Outcomes

The RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework was used for program evaluation, showing that 64 U.S. Accreditation Council for Graduate Medical Education–accredited emergency medicine residency programs participated in the pilot event, with 1,178 unique users during the event (reach). For effectiveness, 93% (139/149) of trainees reported the pilot as enjoyable and 85% (126/149) reported it was equivalent to or better than their usual academic proceedings. Adoption for ALiEM Connect was fairly good with 64/237 (27%) of invited residency programs registering and participating in the pilot event. Implementation was demonstrated by nearly half of the livestream viewers (47%, 553/1,178) interacting in the backchannel discussion, sending a total of 4,128 messages in the first 4 hours.

Next Steps

The final component of the RE-AIM framework, maintenance, will take more time to evaluate. Further study is required to measure the educational impact of events like the ALiEM Connect pilot. The ALiEM Connect model could potentially be used to replace educational conferences that have been canceled or to implement and/or augment a large-scale, shared curriculum among residency programs in the future.
TrkB agonist 7,8-dihydroxyflavone reverses an induced prepulse inhibition deficit selectively in maternal immune activation offspring: implications for schizophrenia
Authors: Jaehne Emily J. , Chong Elaine Mei San , Sbisa Alyssa , Gillespie Brendan , Hill Rachel , Gogos Andrea , van den Buuse Maarten
Published: April 2021

Reduced brain-derived neurotrophic factor (BDNF) signalling has been implicated in schizophrenia endophenotypes, including deficits in prepulse inhibition (PPI). Maternal immune activation (MIA) is a widely used neurodevelopmental animal model for schizophrenia but it is unclear if BDNF and its receptor, tropomyosin receptor kinase B (TrkB), are involved in PPI regulation in this model. Pregnant Long Evans rats were treated with the viral mimetic, polyinosinic–polycytidylic acid (poly I:C; 4 mg/kg i.v.), and nine male offspring from these dams were compared in adulthood to 11 male Long Evans controls. Offspring underwent PPI testing following injection with the TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF) (10 mg/kg i.p.), with or without the dopamine receptor agonist, apomorphine (APO; 1 mg/kg s.c.), or the dopamine releasing drug, methamphetamine (METH; 2 mg/kg s.c.). Acute administration of APO and METH caused the expected significant reduction of PPI. Acute administration of 7,8-DHF did not alter PPI on its own; however, it significantly reversed the effect of APO on PPI in poly I:C rats, but not in controls. A similar trend was observed in combination with METH. Western blot analysis of frontal cortex revealed significantly increased levels of BDNF protein, but not TrkB or phosphorylated TrkB/TrkB levels, in poly I:C rats. These findings suggest that, selectively in MIA offspring, 7,8-DHF has the ability to reverse PPI deficits caused by dopaminergic stimulation. This effect could be associated with increased BDNF expression in the frontal cortex. These data suggest that targeting BDNF signalling may have therapeutic potential for the treatment of certain symptoms of schizophrenia.
Combination blood pressure lowering in the presence or absence of background statin and aspirin therapy: a combined analysis of PROGRESS and ADVANCE Trials
Authors: Wang Nelson , Harris Katie , Chalmers John , Harrap Stephen , Mancia Giuseppe , Marre Michel , Poulter Neil , Tzourio Christophe , Williams Bryan , Zoungas Sophia , Woodward Mark , Rodgers Anthony
Published: April 2021

Objectives:

To assess the effects of combination BP lowering on cardiovascular events and mortality in the presence of aspirin and/or statin therapy in a combined analysis of the ADVANCE and PROGRESS trials.

Methods:

We conducted an analysis of 14 682 participants allocated combination therapy with perindopril and indapamide or placebo followed up for a mean of 4.2 years. Participants were stratified into four groups defined by background use of medications at baseline: statin, aspirin, both or neither. Linear mixed effect models were used to assess differences in BP and Cox proportional hazard models were used to estimate the risks of major cardiovascular events, all-cause mortality and treatment discontinuation.

Results:

At baseline, 14% of patients were on both aspirin and statin, 35% on aspirin, 9% on statins and 42% on neither aspirin/statins. Compared with placebo, combination BP therapy reduced mean SBP by 5.7 mmHg in ADVANCE and 12.1 mmHg in PROGRESS, with no difference (P > 0.447) between patients by baseline use of aspirin/statin. Combination BP therapy reduced the risk of major cardiovascular events (hazard ratio 0.78, 95% CI 0.71–0.86), with no significant difference (P = 0.600) between aspirin/statin subgroups. Rates of treatment discontinuation were similar with combination BP therapy compared with placebo (18.4 versus 18%), with no evidence of difference across the subgroups (P = 0.340).

Conclusion:

BP lowering with perindopril and indapamide reduces the risk of major cardiovascular events independent of baseline use of aspirin and/or statins.
Ultrasound-guided dextrose solution perimysium dissection for posterior shoulder myofascial pain
Authors: Lai Yi-Chen , Tsai Sheng-Han , Chiou Hong-Jen
Published: April 2021

Background:

To assess the efficacy and safety of perimysium dissection for posterior shoulder myofascial pain.

Methods:

This retrospective single-arm study was performed at a medical center between April 2016 and August 2017. Fifty-seven participants with refractory chronic posterior shoulder pain of myofascial origin underwent ultrasound (US)-guided perimysium dissection with hypertonic dextrose solution. Visual analog scale (VAS) scores and complication rate were evaluated before treatment and 4 weeks after treatment.

Results:

US-guided perimysium dissection with dextrose solution resulted in excellent treatment efficacy and safety. Nineteen participants (33.3%) were free of pain after treatment, and 32 (56.1%) had >50% improvement in pain score. Forty-nine participants had complete VAS records. Overall mean pre- and posttreatment VAS scores were 7.18 ± 1.60 and 1.91 ± 2.04 (mean difference −5.27, 95% CI −5.99 to −4.55, p < 0.0001), respectively, including 7.26 ± 1.44 and 1.84 ± 1.98 (mean difference −5.43, 95% CI −6.33 to −4.52, p < 0.0001) for those with infraspinatus myofascial pain, and 7.00 ± 1.96 and 2.07 ± 2.26 (mean difference −4.93, 95% CI −6.23 to −3.62, p < 0.0001) for those in the teres minor subgroup. No complications were reported in any of the participants. One participant received retreatment for teres minor myofascial pain.

Conclusion:

US-guided perimysium dissection is an easy, safe, and effective injection method to manage posterior myofascial shoulder pain.