bluuebunny/crossref_metadata_2025 huggingface dataset:
SPCS: a spatial and pattern combined smoothing method for spatial transcriptomic expression
Authors: Liu Yusong , Wang Tongxin , Duggan Ben , Sharpnack Michael , Huang Kun , Zhang Jie , Ye Xiufen , Johnson Travis S
Published: March 2022

High-dimensional, localized ribonucleic acid (RNA) sequencing is now possible owing to recent developments in spatial transcriptomics (ST). ST is based on highly multiplexed sequence analysis and uses barcodes to match the sequenced reads to their respective tissue locations. ST expression data suffer from high noise and dropout events; however, smoothing techniques have the promise to improve the data interpretability prior to performing downstream analyses. Single-cell RNA sequencing (scRNA-seq) data similarly suffer from these limitations, and smoothing methods developed for scRNA-seq can only utilize associations in transcriptome space (also known as one-factor smoothing methods). Since they do not account for spatial relationships, these one-factor smoothing methods cannot take full advantage of ST data. In this study, we present a novel two-factor smoothing technique, spatial and pattern combined smoothing (SPCS), that employs the k-nearest neighbor (kNN) technique to utilize information from transcriptome and spatial relationships. By performing SPCS on multiple ST slides from pancreatic ductal adenocarcinoma (PDAC), dorsolateral prefrontal cortex (DLPFC) and simulated high-grade serous ovarian cancer (HGSOC) datasets, smoothed ST slides have better separability, partition accuracy and biological interpretability than the ones smoothed by preexisting one-factor methods. Source code of SPCS is provided in Github (https://github.com/Usos/SPCS).
DeepREAL: a deep learning powered multi-scale modeling framework for predicting out-of-distribution ligand-induced GPCR activity
Authors: Cai Tian , Abbu Kyra Alyssa , Liu Yang , Xie Lei
Published: March 2022

Motivation

Drug discovery has witnessed intensive exploration of predictive modeling of drug–target physical interactions over two decades. However, a critical knowledge gap needs to be filled for correlating drug–target interactions with clinical outcomes: predicting genome-wide receptor activities or function selectivity, especially agonist versus antagonist, induced by novel chemicals. Two major obstacles compound the difficulty on this task: known data of receptor activity is far too scarce to train a robust model in light of genome-scale applications, and real-world applications need to deploy a model on data from various shifted distributions.

Results

To address these challenges, we have developed an end-to-end deep learning framework, DeepREAL, for multi-scale modeling of genome-wide ligand-induced receptor activities. DeepREAL utilizes self-supervised learning on tens of millions of protein sequences and pre-trained binary interaction classification to solve the data distribution shift and data scarcity problems. Extensive benchmark studies on G-protein coupled receptors (GPCRs), which simulate real-world scenarios, demonstrate that DeepREAL achieves state-of-the-art performances in out-of-distribution settings. DeepREAL can be extended to other gene families beyond GPCRs.

Availability and implementation

All data used are downloaded from Pfam (Mistry et al., 2020), GLASS (Chan et al., 2015) and IUPHAR/BPS and the data from reference (Sakamuru et al., 2021). Readers are directed to their official website for original data. Code is available on GitHub https://github.com/XieResearchGroup/DeepREAL.

Supplementary information

Supplementary data are available at Bioinformatics online.
BridgeDPI: a novel Graph Neural Network for predicting drug–protein interactions
Authors: Wu Yifan , Gao Min , Zeng Min , Zhang Jie , Li Min
Published: March 2022

Motivation

Exploring drug–protein interactions (DPIs) provides a rapid and precise approach to assist in laboratory experiments for discovering new drugs. Network-based methods usually utilize a drug–protein association network and predict DPIs by the information of its associated proteins or drugs, called ‘guilt-by-association’ principle. However, the ‘guilt-by-association’ principle is not always true because sometimes similar proteins cannot interact with similar drugs. Recently, learning-based methods learn molecule properties underlying DPIs by utilizing existing databases of characterized interactions but neglect the network-level information.

Results

We propose a novel method, namely BridgeDPI. We devise a class of virtual nodes to bridge the gap between drugs and proteins and construct a learnable drug–protein association network. The network is optimized based on the supervised signals from the downstream task—the DPI prediction. Through information passing on this drug–protein association network, a Graph Neural Network can capture the network-level information among diverse drugs and proteins. By combining the network-level information and the learning-based method, BridgeDPI achieves significant improvement in three real-world DPI datasets. Moreover, the case study further verifies the effectiveness and reliability of BridgeDPI.

Availability and implementation

The source code of BridgeDPI can be accessed at https://github.com/SenseTime-Knowledge-Mining/BridgeDPI. The source data used in this study is available on the https://github.com/IBM/InterpretableDTIP (for the BindingDB dataset), https://github.com/masashitsubaki/CPI_prediction (for the C.ELEGANS and HUMAN) datasets, http://dude.docking.org/ (for the DUD-E dataset), repectively.
Clinical Risk Factors Associated With Late-Onset Invasive Group B Streptococcal Disease: Systematic Review and Meta-Analyses
Authors: Karampatsas Konstantinos , Davies Hannah , Mynarek Maren , Andrews Nick , Heath Paul T , Le Doare Kirsty
Published: March 2022

Background

Group B streptococcal (GBS) infection remains one of the most significant causes of late-onset sepsis and meningitis (LOGBS) among young infants. However, transmission routes and risk factors for LOGBS are not yet fully understood.

Methods

We conducted systematic reviews on clinical risk factors previously reported in the literature (prematurity, low birth weight [<2500 g], antenatal colonization, multiple-gestation pregnancy, maternal age <20 years, male infant sex, intrapartum fever, prolonged rupture of membranes) and meta-analyses to determine pooled estimates of risk.

Results

We included 27 articles, reporting 5315 cases. Prematurity (odds ratio [OR] 5.66; 95% confidence interval [CI]: 4.43–7.22), low birth weight (OR 6.73; 95% CI: 4.68–9.67), maternal colonization (2.67; [2.07–3.45]), and multiple-gestation pregnancies (OR 8.01; 95% CI: 5.19–12.38) were associated with an increased risk of LOGBS.

Conclusions

Prematurity/low birth weight and maternal colonization are major risk factors for LOGBS. Future GBS vaccine studies should try to establish the optimal time for vaccination during pregnancy to protect preterm infants.
Remote ECG monitoring to reduce complications following transcatheter aortic valve implantations: the Redirect TAVI study
Authors: Natarajan Madhu Kailash , Sheth Tej Narendra , Wijeysundera Harindra Channa , Chavarria Jorge , Rodes-Cabau Josep , Velianou James Louis , Radhakrishnan Sam , Newman Toni , Smith Amanda , Wong Jorge Alfredo , Schwalm Jon David , Duong Monica , Mian Rajibul Islam , Bishop Marsella Giuliana , Healey Jeffrey Sean
Published: March 2022

Aims

The optimal strategy of monitoring for conduction disturbances in patients undergoing transcatheter aortic valve implantation (TAVI) is uncertain. We evaluated a pre- and post-TAVI remote ambulatory cardiac monitoring (rACM) strategy for identification of conduction disturbances and to reduce unplanned pre-discharge post-TAVI permanent pacemaker implantation (PPMI).

Methods and results

REdireCT TAVI (NCT0381820) was a prospective cohort study of patients referred for outpatient TAVI. Patients with prior PPMI were excluded. Remote ambulatory cardiac monitoring consisted of 2 weeks of continuous electrocardiogram (ECG) monitoring (Pocket-ECGTM) both before and after TAVI. Compliance to monitoring, frequency of notifications, unplanned PPMI post-TAVI, and length of hospitalization were measured. Between June 2018 and March 2020, in 192 undergoing TAVI (mean age: 81.8 years; female sex 46%; balloon-expandable valve 95.3%), compliance to rACM was 91.7% pre-TAVI (mean duration: 12.8 days), and 87.5% post-TAVI (mean duration: 12.9 days). There were 24 (12.5%) rACM notifications (13 pre-TAVI; 11 post-TAVI) resulting in 14 (7.3%) planned PPMI: seven pre-TAVI [due to sinus pauses n = 2 or atrio-ventricular block (AVB) n = 5] and seven post-TAVI [due to sinus pauses n = 1 or AVB n = 5 or ventricular tachycardia (VT) n = 1]. In addition, nine (4.7%) patients received pre-TAVI PPMI due to high-risk baseline ECG (right bundle branch block with hemi-block or prolonged PR interval). Unplanned PPMI post-TAVI during index hospitalization occurred in six (3.1%) patients due to AVB and in one patient readmitted with AVB. The median length of stay post-TAVI was 1 day.

Conclusion

A strategy of routine rACM was feasible and frequently led to PPMI. Our approach of 2-week rACM both pre- and post-TAVI achieves both high patient compliance and sufficient surveillance.

Clinical trial registration

Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03810820
Imaging the Kanto Basin seismic basement with earthquake and noise autocorrelation functions
Authors: Viens Loïc , Jiang Chengxin , Denolle Marine A
Published: March 2022

Sedimentary basins can strongly amplify seismic waves from earthquakes. To better predict future ground motions, detailed knowledge of the sediment thickness and internal structure of basins is required. We image the sediment-to-bedrock interface of the Kanto Basin in Japan using the P-wave reflectivity response from earthquake and ambient seismic noise autocorrelation functions (ACFs) at 286 shallow borehole stations. Earthquake ACFs are computed using P-wave records from 50 Mw 6+ teleseismic events. Noise ACFs are obtained using 1 month of continuous data. Both methods are used to retrieve P-wave traveltimes between the surface and the bedrock interface and map the basin basement geometry. Our prediction of the basement depth agrees generally well with that from a reference velocity model, except for smoother variations in the central part of the basin. Using full-wavefield simulations, we show that the nature of the autocorrelated wavefield has a significant impact on the shape of the ACF waveforms and that earthquake ACFs yield more accurate results in the Kanto Basin.
Abelianization of Matrix Orthogonal Polynomials
Authors: Bertola M
Published: March 2022

The main goal of the paper is to connect matrix polynomial biorthogonality on a contour in the plane with a suitable notion of scalar, multi-point Padé approximation on an arbitrary Riemann surface endowed with a rational map to the Riemann sphere. To this end we introduce an appropriate notion of (scalar) multi-point Padé approximation on a Riemann surface and corresponding notion of biorthogonality of sections of the semi-canonical bundle (half-differentials). Several examples are offered in illustration of the new notions.
Finite axiomatizability of logics of distributive lattices with negation
Authors: Marcelino Sérgio , Rivieccio Umberto
Published: March 2022

This paper focuses on order-preserving logics defined from varieties of distributive lattices with negation, and in particular on the problem of whether these can be axiomatized by means Hilbert-style calculi that are finite (i.e. that contain a finite number of finitary rule schemata). On the negative side, we provide a syntactic condition on the equational presentation of a variety that entails failure of finite axiomatizability for the corresponding logic. An application of this result is that the logic of all distributive lattices with negation is not finitely axiomatizable; we likewise establish that the order-preserving logic of the variety of all Ockham algebras is also not finitely axiomatizable. On the positive side, we show that an arbitrary subvariety of semi-De Morgan algebras is axiomatized by a finite number of equations if and only if the corresponding order-preserving logic is axiomatized by a finite Hilbert-style calculus. This equivalence also holds for every subvariety of a Berman variety of Ockham algebras. We obtain, as a corollary, a new proof that the implication-free fragment of intuitionistic logic is finitely axiomatizable, as well as a new corresponding Hilbert-style calculus. Our proofs are constructive in that they allow us to effectively convert an equational presentation of a variety of algebras into a Hilbert-style calculus for the corresponding order-preserving logic, and vice versa. We also consider the assertional logics associated to the above-mentioned varieties, showing in particular that the assertional logics of finitely axiomatizable subvarieties of semi-De Morgan algebras are finitely axiomatizable as well.
CD4/CD8 Ratio and Cancer Risk Among Adults With HIV
Authors: Castilho Jessica L , Bian Aihua , Jenkins Cathy A , Shepherd Bryan E , Sigel Keith , Gill M John , Kitahata Mari M , Silverberg Michael J , Mayor Angel M , Coburn Sally B , Wiley Dorothy , Achenbach Chad J , Marconi Vincent C , Bosch Ronald J , Horberg Michael A , Rabkin Charles S , Napravnik Sonia , Novak Richard M , Mathews W Christopher , Thorne Jennifer E , Sun Jing , Althoff Keri N , Moore Richard D , Sterling Timothy R , Sudenga Staci L ,   the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) of the International Epidemiology Databases to Evaluate AIDS (IeDEA), Castilho Jessica L , Bian Aihua , Jenkins Cathy A , Shepherd Bryan E , Sigel Keith , John Gill M , Kitahata Mari M , Silverberg Michael J , Mayor Angel M , Coburn Sally B , Wiley Dorothy , Achenbach Chad J , Marconi Vincent C , Bosch Ronald J , Horberg Michael A , Rabkin Charles S , Napravnik Sonia , Novak Richard M , Christopher Mathews W , Thorne Jennifer E , Sun Jing , Althoff Keri N , Moore Richard D , Sterling Timothy R , Sudenga Staci L
Published: March 2022

Background

Independent of CD4 cell count, a low CD4/CD8 ratio in people with HIV (PWH) is associated with deleterious immune senescence, activation, and inflammation, which may contribute to carcinogenesis and excess cancer risk. We examined whether low CD4/CD8 ratios predicted cancer among PWH in the United States and Canada.

Methods

We examined all cancer-free PWH with 1 or more CD4/CD8 values from North American AIDS Cohort Collaboration on Research and Design observational cohorts with validated cancer diagnoses between 1998 and 2016. We evaluated the association between time-lagged CD4/CD8 ratio and risk of specific cancers in multivariable, time-updated Cox proportional hazard models using restricted cubic spines. Models were adjusted for age, sex, race and ethnicity, hepatitis C virus, and time-updated CD4 cell count, HIV RNA, and history of AIDS-defining illness.

Results

Among 83 893 PWH, there were 5628 incident cancers, including lung cancer (n = 755), Kaposi sarcoma (n = 501), non-Hodgkin lymphoma (n = 497), and anal cancer (n = 439). The median age at cohort entry was 43 years. The overall median 6-month lagged CD4/CD8 ratio was 0.52 (interquartile range = 0.30-0.82). Compared with a 6-month lagged CD4/CD8 of 0.80, a CD4/CD8 of 0.30 was associated with increased risk of any incident cancer (adjusted hazard ratio = 1.24 [95% confidence interval = 1.14 to 1.35]). The CD4/CD8 ratio was also inversely associated with non-Hodgkin lymphoma, Kaposi sarcoma, lung cancer, anal cancer, and colorectal cancer in adjusted analyses (all 2-sided P < .05). Results were similar using 12-, 18-, and 24-month lagged CD4/CD8 values.

Conclusions

A low CD4/CD8 ratio up to 24 months before cancer diagnosis was independently associated with increased cancer risk in PWH and may serve as a clinical biomarker.
A rare case of a large low-grade appendicular mucinous neoplasm causing compressive symptoms
Authors: Ekblad John R , Bhuller Sidra B , Weaver John , Bertocchi Michael E
Published: March 2022

Primary neoplasm of the appendix is often diagnosed incidentally after an appendectomy. Low-grade appendiceal mucinous neoplasms (LAMNs) make up a small portion of these neoplasms. We present a rare case of a patient with a slow-growing LAMN causing urinary retention and constipation. The mass was initially found incidentally 25 years prior, but the patient declined further workup since he was asymptomatic at that time. The patient experienced progressively worsening abdominal discomfort related to urinary retention and difficulty in evacuating his bowels. Imaging identified a large abdominal mass (19.3 × 8.7 × 13.5 cm). The mass was surgically resected. Pathology was consistent with a LAMN. In general, an incidental finding of an abdominal mass should be further investigated regardless of symptomology. Patients should be educated about the potential of malignancy and the need for a major abdominal surgery in the future if they choose not to have a mass further evaluated.
Rhamnogalacturonan-I forms mucilage: behind its simplicity, a cutting-edge organization
Authors: Saez-Aguayo Susana , Largo-Gosens Asier
Published: March 2022

Zhang Y, Yin Q, Qin W, Gao H, Du J, Chen J, Li H, Zhou G, Wu H, Wu A-M. 2022. The Class II KNOX family members KNAT3 and KNAT7 redundantly participate in Arabidopsis seed coat mucilage biosynthesis. Journal of Experimental Botany 73, 3477–3495.
Two Nineteenth-Century Copies of Joseph Prémare’s Notitia linguæ sinicæ
Authors: Kua Paul
Published: March 2022

French Jesuit Joseph Prémare, a missionary to Qing Dynasty China, had completed by the end of 1728 the draft of a book entitled Notitia linguæ sinicæ, intended to assist aspiring Catholic missionaries from Europe in learning the Chinese language. One of the original manuscripts sent from Canton to Paris, now held in the Bibliothæque nationale de France in Paris, was rediscovered in the 1810s by the French sinologist Jean-Pierre Abel-Rémusat, and became the source for some manuscript copies, made mostly before the work’s eventual publication in 1831. This paper examines two of these manuscript copies dated between 1825 and 1830, held respectively in the Archive of the School of Oriental and African Studies in London and the the Bayerische Staatsbibliothek in Munich, both important in their own ways, and both somewhat misunderstood and largely neglected by recent studies.
Avalanches of magnetic flux rope in the state of self-organized criticality
Authors: Wang W B , Li C , Tu Z L , Guo J H , Chen P F , Wang F Y
Published: March 2022

The self-organized criticality (SOC) is a universal theory to explain the ubiquitous power-law size distributions of astrophysical instabilities such as solar eruptions. One way to understand the dynamical processes of an SOC system is through cellular automaton (CA) simulations. Here, we develop a three-dimensional solar CA model that assumes a twisted magnetic flux rope (MFR), in which the avalanche takes place when a local magnetic vector potential exceeds a Gaussian distributed instability criterion, triggered by a global and space-dependent energy driving mechanism. To avoid non-physical released energies, an energy screening mechanism is applied to calculate the avalanche energies of each time-step. Our results show that the statistics of the CA simulated flaring events are comparable to the frequency distributions of observed solar flares originating from an individual active region. Due to the fact of the universality of MFRs, the CA model can be applied to many other astrophysical SOC systems.
Wide binaries from the H3 survey: the thick disc and halo have similar wide binary fractions
Authors: Hwang Hsiang-Chih , Ting Yuan-Sen , Conroy Charlie , Zakamska Nadia L , El-Badry Kareem , Cargile Phillip , Zaritsky Dennis , Chandra Vedant , Han Jiwon Jesse , Speagle Joshua S , Bonaca Ana
Published: March 2022

Due to the different environments in the Milky Way’s disc and halo, comparing wide binaries in the disc and halo is key to understanding wide binary formation and evolution. By using Gaia Early Data Release 3, we search for resolved wide binary companions in the H3 survey, a spectroscopic survey that has compiled ∼150 000 spectra for thick-disc and halo stars to date. We identify 800 high-confidence (a contamination rate of 4 per cent) wide binaries and two resolved triples, with binary separations mostly between 103 and 105 au and a lowest [Fe/H] of −2.7. Based on their Galactic kinematics, 33 of them are halo wide binaries, and most of those are associated with the accreted Gaia-Sausage-Enceladus galaxy. The wide binary fraction in the thick disc decreases toward the low metallicity end, consistent with the previous findings for the thin disc. Our key finding is that the halo wide binary fraction is consistent with the thick-disc stars at a fixed [Fe/H]. There is no significant dependence of the wide binary fraction on the α-captured abundance. Therefore, the wide binary fraction is mainly determined by the iron abundance, not their disc or halo origin nor the α-captured abundance. Our results suggest that the formation environments play a major role for the wide binary fraction, instead of other processes like radial migration that only apply to disc stars.
Explosive instability of dust settling in a protoplanetary disc
Authors: Zhuravlev V V
Published: March 2022

It is shown that gas-dust perturbations in a disc with dust settling to the disc mid-plane exhibit the non-linear three-wave resonant interactions between streaming dust wave (SDW) and two inertial waves (IW). In the particular case considered in this paper, SDW at the wavenumber k• = 2κ/(g$z$ts), where κ, g$z$, and ts are, respectively, epicyclic frequency, vertical gravitational acceleration, and particle’s stopping time, interacts with two IW at the lower wavenumbers k′ and k″ such that k′ < kDSI < k″ < k•, where kDSI = κ/(g$z$ts) is the wavenumber of the linear resonance between SDW and IW associated with the previously discovered linear dust settling instability. The problem is solved analytically in the limit of the small dust fraction. As soon as the dynamical dust back reaction on gas is taken into account, k•, k′, and k″ become slightly non-collinear and the emerging interaction of waves leads to simultaneous explosive growth of their amplitudes. This growth is explained by the conservative exchange with energy between the waves. The amplitudes of all three waves grow because the negative energy SDW transfers its energy to the positive energy IW. The product of the dimension-less amplitude of initially dominant wave and the time of explosion can be less than Keplerian time in a disc. It is shown that, generally, the three-wave resonance of an explosive type exists in a wide range of wavenumbers 0 < k• ≤ 2κ/(g$z$ts). An explosive instability of gas-dust mixture may facilitate the dust clumping and the subsequent formation of planetesimals in young protoplanetary discs.
The THOR + HELIOS general circulation model: multiwavelength radiative transfer with accurate scattering by clouds/hazes
Authors: Deitrick Russell , Heng Kevin , Schroffenegger Urs , Kitzmann Daniel , Grimm Simon L , Malik Matej , Mendonça João M , Morris Brett M
Published: March 2022

General circulation models (GCMs) provide context for interpreting multiwavelength, multiphase data of the atmospheres of tidally locked exoplanets. In the current study, the non-hydrostatic THOR GCM is coupled with the HELIOS radiative transfer solver for the first time, supported by an equilibrium chemistry solver (FastChem), opacity calculator (HELIOS-K), and Mie scattering code (LX-MIE). To accurately treat the scattering of radiation by medium-sized to large aerosols/condensates, improved two-stream radiative transfer is implemented within a GCM for the first time. Multiple scattering is implemented using a Thomas algorithm formulation of the two-stream flux solutions, which decreases the computational time by about 2 orders of magnitude compared to the iterative method used in past versions of HELIOS. As a case study, we present four GCMs of the hot Jupiter WASP-43b, where we compare the temperature, velocity, entropy, and streamfunction, as well as the synthetic spectra and phase curves, of runs using regular versus improved two-stream radiative transfer and isothermal versus non-isothermal layers. While the global climate is qualitatively robust, the synthetic spectra and phase curves are sensitive to these details. A THOR + HELIOS WASP-43b GCM (horizontal resolution of about 4 deg on the sphere and with 40 radial points) with multiwavelength radiative transfer (30 k-table bins) running for 3000 Earth days (864 000 time-steps) takes about 19–26 d to complete depending on the type of GPU.
Measuring weak lensing masses on individual clusters
Authors: Murray Calum , Bartlett James G , Artis Emmanuel , Melin Jean-Baptiste
Published: March 2022

We present weak lensing mass estimates for a sample of 458 galaxy clusters from the redMaPPer Sloan Digital Sky Survey DR8 catalogue using Hyper Suprime-Cam weak lensing data. We develop a method to quickly estimate cluster masses from weak lensing shear and use this method to estimate weak lensing masses for each of the galaxy clusters in our sample. Subsequently, we constrain the mass–richness relation as well as the intrinsic scatter between the cluster richness and the measured weak lensing masses. When calculating the mass–richness relation for all clusters with a richness λ > 20, we find a tension in the slope of the mass–richness relation with the Dark Energy Survey Year 1 stacked weak lensing analysis. For a reduced sample of clusters with a richness λ > 40, our results are consistent with the Dark Energy Survey Year 1 analysis.
Activating cryptic biosynthetic gene cluster through a CRISPR–Cas12a-mediated direct cloning approach
Authors: Liang Mindong , Liu Leshi , Xu Fei , Zeng Xiaoqian , Wang Ruijun , Yang Jinling , Wang Weishan , Karthik Loganathan , Liu Jiakun , Yang Zhiheng , Zhu Guoliang , Wang Shuliu , Bai Linquan , Tong Yaojun , Liu Xueting , Wu Min , Zhang Li-Xin , Tan Gao-Yi
Published: March 2022

Direct cloning of biosynthetic gene clusters (BGCs) from microbial genomes facilitates natural product-based drug discovery. Here, by combining Cas12a and the advanced features of bacterial artificial chromosome library construction, we developed a fast yet efficient in vitro platform for directly capturing large BGCs, named CAT-FISHING (CRISPR/Cas12a-mediated fast direct biosynthetic gene cluster cloning). As demonstrations, several large BGCs from different actinomycetal genomic DNA samples were efficiently captured by CAT-FISHING, the largest of which was 145 kb with 75% GC content. Furthermore, the directly cloned, 110 kb long, cryptic polyketide encoding BGC from Micromonospora sp. 181 was then heterologously expressed in a Streptomyces chassis. It turned out to be a new macrolactam compound, marinolactam A, which showed promising anticancer activity. Our results indicate that CAT-FISHING is a powerful method for complicated BGC cloning, and we believe that it would be an important asset to the entire community of natural product-based drug discovery.
The impact of different volumetric thresholds to determine progressive disease in patients with recurrent glioblastoma treated with bevacizumab
Authors: Gahrmann Renske , Smits Marion , Vernhout René Michel , Taal Walter , Kapsas Giorgios , de Groot Jan Cees , Hanse Monique , Vos Maaike , Beerepoot Laurens Victor , Buter Jan , Flach Zwenneke Hendrieke , van der Holt Bronno , van den Bent Martin
Published: March 2022

Background

The optimal volumetric threshold for determining progressive disease (PD) in recurrent glioblastoma is yet to be determined. We investigated a range of thresholds in association with overall survival (OS).

Methods

First recurrent glioblastoma patients treated with bevacizumab and/or lomustine were included from the phase II BELOB and phase III EORTC26101 trials. Enhancing and nonenhancing tumor volumes were measured at baseline, first (6 weeks), and second (12 weeks) follow-up. Hazard ratios (HRs) for the appearance of new lesions and several thresholds for tumor volume increase were calculated using cox regression analysis. Results were corrected in a multivariate analysis for well-established prognostic factors.

Results

At first and second follow-up, 138 and 94 patients respectively, were deemed eligible for analysis of enhancing volumes, while 89 patients were included in the analysis of nonenhancing volumes at first follow-up. New lesions were associated with a significantly worse OS (3.2 versus 11.2 months, HR = 7.03, P < .001). At first follow-up a threshold of enhancing volume increase of ≥20% provided the highest HR (5.55, p = .001. At second follow-up, any increase in enhancing volume (≥0%) provided the highest HR (9.00, p < .001). When measuring nonenhancing volume at first follow-up, only 6 additional patients were scored as PD with the highest HR of ≥25% increase in volume (HR=3.25, p = .008).

Conclusion

Early appearing new lesions were associated with poor OS. Lowering the volumetric threshold for PD at both first and second follow-up improved survival prediction. However, the additional number of patients categorized as PD by lowering the threshold was very low. The per-RANO added change in nonenhancing volumes to the analyses was of limited value.
Management of brain metastasis. Surgical resection versus stereotactic radiotherapy: a meta-analysis
Authors: Krist David T , Naik Anant , Thompson Charee M , Kwok Susanna S , Janbahan Mika , Olivero William C , Hassaneen Wael
Published: March 2022

Background

Treatment of metastatic brain tumors often involves radiotherapy with or without surgical resection as the first step. However, the indications for when to use surgery are not clearly defined for certain tumor sizes and multiplicity. This study seeks to determine whether resection of brain metastases versus exclusive radiotherapy provided improved survival and local control in cases where metastases are limited in number and diameter.

Methods

According to PRISMA guidelines, this meta-analysis compares outcomes from treatment of a median number of brain metastases ≤ 4 with a median diameter ≤ 4 cm with exclusive radiotherapy versus surgery followed by radiotherapy. Four randomized control trials and 11 observational studies (1693 patients) met inclusion criteria. For analysis, studies were grouped based on whether radiation involved stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT).

Results

In both analyses, there was no difference in survival between surgery ± SRS versus SRS alone two years after treatment (OR 1.89 (95% CI: 0.47–7.55, P = .23) or surgery + WBRT versus radiotherapy alone (either WBRT and/or SRS) (OR 1.18 (95% CI: 0.76–1.84, P = .46). However, surgical patients demonstrated greater risk for local tumor recurrence compared to SRS alone (OR 2.20 (95% CI: 1.49–3.25, P < .0001)) and compared to WBRT/SRS (OR 2.93; 95% CI: 1.68–5.13, P = .0002).

Conclusion

The higher incidence of local tumor recurrence for surgical patients suggests that more prospective studies are needed to clarify outcomes for treatment of 1-4 metastasis less than 4 cm diameter.
Flowering time runs hot and cold
Authors: Preston Jill C , Fjellheim Siri
Published: March 2022

Evidence suggests that anthropogenically-mediated global warming results in accelerated flowering for many plant populations. However, the fact that some plants are late flowering or unaffected by warming, underscores the complex relationship between phase change, temperature, and phylogeny. In this review, we present an emerging picture of how plants sense temperature changes, and then discuss the independent recruitment of ancient flowering pathway genes for the evolution of ambient, low, and high temperature-regulated reproductive development. As well as revealing areas of research required for a better understanding of how past thermal climates have shaped global patterns of plasticity in plant phase change, we consider the implications for these phenological thermal responses in light of climate change.
Exploring the disparity between inflammation and disability in the 10-year outcomes of people with rheumatoid arthritis
Authors: Gwinnutt James M , Norton Sam , Hyrich Kimme L , Lunt Mark , Combe Bernard , Rincheval Nathalie , Ruyssen-Witrand Adeline , Fautrel Bruno , McWilliams Daniel F , Walsh David A , Nikiphorou Elena , Kiely Patrick D W , Young Adam , Chipping Jacqueline R , MacGregor Alex , Verstappen Suzanne M M
Published: March 2022

Objectives

To identify groups of people with RA with different disability trajectories over 10 years, despite comparable levels of inflammation.

Methods

Data for this analysis came from three European prospective cohort studies of people with RA [Norfolk Arthritis Register (NOAR), Early RA Network (ERAN), Étude et Suivi des Polyarthrites Indifférenciées Récentes (ESPOIR)]. Participants were assessed regularly over 8 (ERAN) to 10 (NOAR/ESPOIR) years. Inclusion criteria were: recruited after 1 January 2000, <24 months baseline symptom duration, and disability (HAQ) and inflammation [two-component DAS28 (DAS28-2C)] recorded at baseline and at one other follow-up. People in each cohort also completed patient-reported outcome measures at each assessment (pain, fatigue, depressive symptoms). Group-based trajectory models were used to identify distinct groups of people with similar HAQ and DAS28-2C trajectories over follow-up.

Results

This analysis included 2500 people with RA (NOAR: 1000, ESPOIR: 766, ERAN: 734). ESPOIR included more women and the participants were younger [mean (standard deviation) age: NOAR: 57.1 (14.6), ESPOIR: 47.6 (12.5), ERAN: 56.8 (13.8); women: NOAR: 63.9%, ESPOIR: 76.9%, ERAN: 69.1%). Within each cohort, two pairs of trajectories following the hypothesized pattern (comparable DAS28-2Cs but different HAQs) were identified. Higher pain, fatigue and depressive symptoms were associated with increased odds of being in the high HAQ trajectories.

Conclusion

Excess disability is persistent in RA. Controlling inflammation may not be sufficient to alleviate disability in all people with RA, and effective pain, fatigue and mood management may be needed in some groups to improve long-term function.
Assessing Bayesian Phylogenetic Information Content of Morphological Data Using Knowledge From Anatomy Ontologies
Authors: Porto Diego S , Dahdul Wasila M , Lapp Hilmar , Balhoff James P , Vision Todd J , Mabee Paula M , Uyeda Josef
Published: March 2022

Morphology remains a primary source of phylogenetic information for many groups of organisms, and the only one for most fossil taxa. Organismal anatomy is not a collection of randomly assembled and independent “parts”, but instead a set of dependent and hierarchically nested entities resulting from ontogeny and phylogeny. How do we make sense of these dependent and at times redundant characters? One promising approach is using ontologies—structured controlled vocabularies that summarize knowledge about different properties of anatomical entities, including developmental and structural dependencies. Here, we assess whether evolutionary patterns can explain the proximity of ontology-annotated characters within an ontology. To do so, we measure phylogenetic information across characters and evaluate if it matches the hierarchical structure given by ontological knowledge—in much the same way as across-species diversity structure is given by phylogeny. We implement an approach to evaluate the Bayesian phylogenetic information (BPI) content and phylogenetic dissonance among ontology-annotated anatomical data subsets. We applied this to data sets representing two disparate animal groups: bees (Hexapoda: Hymenoptera: Apoidea, 209 chars) and characiform fishes (Actinopterygii: Ostariophysi: Characiformes, 463 chars). For bees, we find that BPI is not substantially explained by anatomy since dissonance is often high among morphologically related anatomical entities. For fishes, we find substantial information for two clusters of anatomical entities instantiating concepts from the jaws and branchial arch bones, but among-subset information decreases and dissonance increases substantially moving to higher-level subsets in the ontology. We further applied our approach to address particular evolutionary hypotheses with an example of morphological evolution in miniature fishes. While we show that phylogenetic information does match ontology structure for some anatomical entities, additional relationships and processes, such as convergence, likely play a substantial role in explaining BPI and dissonance, and merit future investigation. Our work demonstrates how complex morphological data sets can be interrogated with ontologies by allowing one to access how information is spread hierarchically across anatomical concepts, how congruent this information is, and what sorts of processes may play a role in explaining it: phylogeny, development, or convergence. [Apidae; Bayesian phylogenetic information; Ostariophysi; Phenoscape; phylogenetic dissonance; semantic similarity.]
Cardiovascular Diseases Following Breast Cancer
Authors: Mery Benoite , Rowinski Elise , Rivier Charlène , Bouleftour Wafa , Sotton Sandrine , Tinquaut Fabien , Bertoletti Laurent , Tredan Olivier , Magne Nicolas
Published: March 2022

Objectives:

To identify patients at high risk of developing cardiovascular disease through the identification of risk factors among a large population of breast cancer women and to assess the performance of Abdel-Qadir risk prediction model score.

Materials and Methods:

The medical records and baseline characteristics of all patients/tumors diagnosed with breast cancer from 2010 to 2011 in a French comprehensive cancer center were collected. Cardiovascular events were defined as arterial and cardiac events, atrial fibrillation and venous thromboembolism occurring during the 5-year follow-up. Abdel-Qadir multivariable prediction model for major adverse cardiovascular events were used with the concordance index (c-index) score to assess calibration by comparing predicted risks to observed probabilities.

Results:

Among the 943 breast cancer patients included, 83 patients (8.8%) presented with at least one cardiovascular event, leading to a cumulative incidence of 0.07 at 5 years (95% confidence interval [CI], 0.055-0.088). The cumulative incidence of atrial fibrillation at 5 years was 0.01 (95% CI, 0.005-0.018). Factors associated with the occurrence of cardiovascular events were pre-existing cardiovascular diseases including high blood pressure (hazard ratio [HR]=1.78, 95% CI=1.07-2.97, P=0.028), acute coronary syndrome (HR=5.28, 95% CI: 2.16-12.88, P<0.05) and grade 3 Scarff-Blool-Richardson (HR=1.95, 95% CI: 1.21-3.15, P=0.006). With a c-index inferior to 0.7, the Abdel-Qadir score was not fully validated in our population.

Conclusion:

These findings call for the assessment of the performance of risk prediction models such as Abdel-Qadir score coupled with other factors such as Scarff Bloom and Richardson grading in order to identify patients at high risk of experiencing cardiotoxicity.
Ketamine in the Treatment of Obsessive-Compulsive Disorder: A Systematic Review
Authors: Bandeira Igor D. , Lins-Silva Daniel H. , Cavenaghi Vitor Breseghello , Dorea-Bandeira Ingrid , Faria-Guimarães Daniela , Barouh Judah L. , Jesus-Nunes Ana Paula , Beanes Graziele , Souza Lucca S. , Leal Gustavo C. , Sanacora Gerard , Miguel Euripedes C. , Sampaio Aline S. , Quarantini Lucas C.
Published: March 2022

Introduction

First-line treatment for obsessive-compulsive disorder (OCD) includes exposure and response prevention behavioral therapy and serotonin reuptake inhibitors, particularly in combination. New and more effective treatments are needed, give that recent studies suggest that glutamatergic neurotransmission contributes to the pathophysiology of the disorder. In these circumstances, ketamine, as a potent N-methyl-D-aspartate receptor antagonist and glutamate modulator, offers alternative possibilities for OCD treatment.

Methods

This systematic review aims to investigate the effects of ketamine in OCD, following the Preferred Reporting Items for Systematic Review and Meta-analyses Protocols (PRISMA-P). Searches were carried out using the PubMed/MEDLINE, Embase, and PsycINFO databases.

Results

Nine articles were included, of which three were randomized controlled trials, three case reports, two open-label trials, and one a retrospective chart review. Reported data have shown a potential for fast onset of action and good tolerability of ketamine for OCD, even though the principal studies used only single-session racemic ketamine treatments, administered intravenously, and the results have been erratic. In addition, none of the available evidence demonstrates whether racemic ketamine, S-ketamine, or R-ketamine has the best efficacy in controlling OCD symptoms, and only sparse evidence suggests that a combination of ketamine and psychotherapy could benefit patients with OCD.

Conclusion

In order to advance clinical practice regarding the use of ketamine in treating OCD, future randomized, double-blind, placebo-controlled trials are required. These trials need to use larger samples to explore ketamine and its enantiomers, with different methods of administration, multiple sessions, and appropriate washout periods.
Monitoring of Leukemia Clones in B-cell Acute Lymphoblastic Leukemia at Diagnosis and During Treatment by Single-cell DNA Amplicon Sequencing
Authors: Meyers Sarah , Alberti-Servera Llucia , Gielen Olga , Erard Margot , Swings Toon , De Bie Jolien , Michaux Lucienne , Dewaele Barbara , Boeckx Nancy , Uyttebroeck Anne , De Keersmaecker Kim , Maertens Johan , Segers Heidi , Cools Jan , Demeyer Sofie
Published: March 2022

Acute lymphoblastic leukemia (ALL) is characterized by the presence of chromosomal changes, including numerical changes, translocations, and deletions, which are often associated with additional single-nucleotide mutations. In this study, we used single cell–targeted DNA sequencing to evaluate the clonal heterogeneity of B-ALL at diagnosis and during chemotherapy treatment. We designed a custom DNA amplicon library targeting mutational hotspot regions (in 110 genes) present in ALL, and we measured the presence of mutations and small insertions/deletions (indels) in bone marrow or blood samples from 12 B-ALL patients, with a median of 7973 cells per sample. Nine of the 12 cases showed at least 1 subclonal mutation, of which cases with PAX5 alterations or high hyperdiploidy (with intermediate to good prognosis) showed a high number of subclones (1 to 7) at diagnosis, defined by a variety of mutations in the JAK/STAT, RAS, or FLT3 signaling pathways. Cases with RAS pathway mutations had multiple mutations in FLT3, NRAS, KRAS, or BRAF in various clones. For those cases where we detected multiple mutational clones at diagnosis, we also studied blood samples during the first weeks of chemotherapy treatment. The leukemia clones disappeared during treatment with various kinetics, and few cells with mutations were easily detectable, even at low frequency (<0.1%). Our data illustrate that about half of the B-ALL cases show >2 subclones at diagnosis and that even very rare mutant cells can be detected at diagnosis or during treatment by single cell–targeted DNA sequencing.
Suicide Among American Indian and Alaska Native Veterans Who Use Veterans Health Administration Care
Authors: Mohatt Nathaniel V. , Hoffmire Claire A. , Schneider Alexandra L. , Goss Cynthia W. , Shore Jay H. , Spark Talia L. , Kaufman Carol E.
Published: March 2022

Background:

American Indian and Alaska Natives (AI/ANs) veterans may be at elevated risk for suicide, but little is known about suicide among this population.

Methods:

We conducted a retrospective cohort analysis of AI/AN veterans who received health care services provided or paid for by the Veterans Health Administration (VHA) between October 1, 2002, and September 30, 2014, and who were alive as of September 30, 2003. Age-specific and age-adjusted suicide rates through 2018, per 100,000 person-years (PY) at risk and 95% confidence intervals were computed.

Results:

Age-adjusted suicide rates among AI/AN veterans in this cohort more than doubled (19.1–47.0/100,000 PY) over the 15-year observation period. In the most recent observation period (2014–2018), the age-adjusted suicide rate was 47.0 per 100,000 PY, with the youngest age group (18–39) exhibiting the highest suicide rate (66.0/100,000 PY). The most frequently used lethal means was firearms (58.8%), followed by suffocation (19.3%), poisoning (17.2%), and other (4.7%).

Conclusions:

Results suggest that: (1) suicide is an increasing problem among AI/AN VHA veterans; and (2) younger AI/AN VHA veterans are at particularly high risk and warrant focused prevention efforts. Findings are similar to those observed in general AI/AN population. There is a compelling need to review and strengthen VHA suicide prevention efforts directed towards AI/AN veterans.
Reprint from AJN: Secondary Medication Administration and IV Smart Pump Setup
Authors: Giuliano Karen K. , Blake Jeannine W. C. , Butterfield Robert
Published: March 2022

Secondary infusion by large-volume iv smart pump is used extensively in the acute care setting for one-time or intermittent administration of medications such as antibiotics, electrolyte replacements, and some oncology drugs. Consistent and accurate delivery of secondary medications requires a full understanding of the system and setup requirements. Unfortunately, it is not uncommon for nurses to find a secondary medication only partially administered when their programming should have resulted in a complete infusion. This article discusses the technical requirements that every nurse should know when administering secondary medications using an iv smart pump.
Lipofilling in Osteoarthritis of the Finger Joints: Initial Prospective Long-Term Results
Authors: Meyer-Marcotty Max , Batsilas Ioannis , Sanders Agnes , Dahmann Sonja , Happe Caroline , Herold Christian
Published: March 2022

Background:

There is considerable interest in the possibility of offering an alternative and less invasive method of treatment for osteoarthritis that will preserve the joint. This article presents for the first time the long-term results of a prospective study following autologous fat transfer to arthritic finger joints.

Methods:

The authors report on 28 finger joints with osteoarthritis that they treated by injecting fatty tissue into the joints. The degree of pain, force of pinch grip, and fist closure were assessed and hand function was determined using the German version of the Disabilities of the Arm, Shoulder and Hand questionnaire.

Results:

The average follow-up period during the study was 44 months. The median force of pinch grip rose highly significantly from 2.00 kg (range, 0.00 to 11.00 kg) to 4.30 kg (range, 2.00 to 12.00 kg) (p < 0.001). The median force of fist closure rose from 15.00 kg (range, 2.00 to 44.00 kg) to 18.00 kg (range, 3.78 to 42.00 kg) (p = 0.082). The median Disabilities of the Arm, Shoulder and Hand value improved nonsignificantly from 50 (range, 3 to 72) to 25 (range, 0 to 85) (p = 0.129). The median level of pain experienced showed a highly significant improvement from 6.0 (range, 1.0 to 10.0) to 0.5 (range, 0.0 to 6.5) (p < 0.001).

Conclusions:

Even over a long-term study period, the transfer of fatty tissue to arthritic finger joints has shown itself to be a minimally invasive, safe and promising alternative treatment to conventional surgical procedures that offers significant improvements in terms of osteoarthritis symptoms. Because this method preserves the joint, conventional resection surgery still remains a later option.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.