bluuebunny/crossref_metadata_2025 huggingface dataset:
The adjunctive effect for left pulmonary vein isolation of vein of Marshall ethanol infusion in persistent atrial fibrillation
Authors: Huang Lihong , Gao Mingyang , Lai Yiwei , Guo Qi , Li Songnan , Li Changyi , Liu Nian , Wang Wei , Liu Xiaoxia , Zuo Song , Guo Xueyuan , Zhao Xin , Jiang Chenxi , Sang Caihua , Tang Ribo , Long Deyong , Du Xin , Dong Jianzeng , Ma Chang-sheng
Published: December 2022

Objective

This study sought to assess the effect of ethanol infusion into the vein of Marshall (EIVOM) on the acute success of left pulmonary vein (LPV) isolation in persistent atrial fibrillation (PeAF).

Methods and results

A total of 313 patients with drug-resistant PeAF were enrolled (135 in Group 1 and 178 in Group 2). In Group 1, EIVOM was firstly performed, followed by radiofrequency ablation (RFA) including bilateral pulmonary vein isolation (PVI) and linear ablation at roofline, cavotricuspid isthmus, and mitral isthmus (MI). In Group 2, PVI and linear ablations were completed with RFA. First-pass isolation of the LPV was achieved in 119 (88.1%) and 132 (74.2%) patients in Groups 1 and 2, respectively (P = 0.002). The rate of acute pulmonary vein reconnection (PVR) was significantly lower in Group 1 (9.6% vs. 22.5%, P = 0.003). About half of acute PVR occurred in the carina with or without EIVOM.

Conclusion

EIVOM is effective in achieving a higher first-pass isolation and a lower acute PVR of LPV in PeAF.
Multi-tissue RNA-Seq Analysis and Long-read-based Genome Assembly Reveal Complex Sex-specific Gene Regulation and Molecular Evolution in the Manila Clam
Authors: Xu Ran , Martelossi Jacopo , Smits Morgan , Iannello Mariangela , Peruzza Luca , Babbucci Massimiliano , Milan Massimo , Dunham Joseph P , Breton Sophie , Milani Liliana , Nuzhdin Sergey V , Bargelloni Luca , Passamonti Marco , Ghiselli Fabrizio
Published: December 2022

The molecular factors and gene regulation involved in sex determination and gonad differentiation in bivalve molluscs are unknown. It has been suggested that doubly uniparental inheritance (DUI) of mitochondria may be involved in these processes in species such as the ubiquitous and commercially relevant Manila clam, Ruditapes philippinarum. We present the first long-read-based de novo genome assembly of a Manila clam, and a RNA-Seq multi-tissue analysis of 15 females and 15 males. The highly contiguous genome assembly was used as reference to investigate gene expression, alternative splicing, sequence evolution, tissue-specific co-expression networks, and sexual contrasting SNPs. Differential expression (DE) and differential splicing (DS) analyses revealed sex-specific transcriptional regulation in gonads, but not in somatic tissues. Co-expression networks revealed complex gene regulation in gonads, and genes in gonad-associated modules showed high tissue specificity. However, male gonad-associated modules showed contrasting patterns of sequence evolution and tissue specificity. One gene set was related to the structural organization of male gametes and presented slow sequence evolution but high pleiotropy, whereas another gene set was enriched in reproduction-related processes and characterized by fast sequence evolution and tissue specificity. Sexual contrasting SNPs were found in genes overrepresented in mitochondrial-related functions, providing new candidates for investigating the relationship between mitochondria and sex in DUI species. Together, these results increase our understanding of the role of DE, DS, and sequence evolution of sex-specific genes in an understudied taxon. We also provide resourceful genomic data for studies regarding sex diagnosis and breeding in bivalves.
Prevalence and characterization of piperaquine, mefloquine and artemisinin derivatives triple-resistant Plasmodium falciparum in Cambodia
Authors: Mairet-Khedim Mélissa , Roesch Camille , Khim Nimol , Srun Sreynet , Bouillon Anthony , Kim Saorin , Ke Sopheakvatey , Kauy Chhayleang , Kloeung Nimol , Eam Rotha , Khean Chanra , Kul Chanvong , Chy Sophy , Leang Rithea , Ringwald Pascal , Barale Jean-Christophe , Witkowski Benoit
Published: December 2022

Background

In early 2016, in Preah Vihear, Northern Cambodia, artesunate/mefloquine was used to cope with dihydroartemisinin/piperaquine-resistant Plasmodium falciparum parasites. Following this policy, P. falciparum strains harbouring molecular markers associated with artemisinin, piperaquine and mefloquine resistance have emerged. However, the lack of a viable alternative led Cambodia to adopt artesunate/mefloquine countrywide, raising concerns about a surge of triple-resistant P. falciparum strains.

Objectives

To assess the prevalence of triple-resistant parasites after artesunate/mefloquine implementation countrywide in Cambodia and to characterize their phenotype.

Methods

For this multicentric study, 846 samples were collected from 2016 to 2019. Genotyping of molecular markers associated with artemisinin, piperaquine and mefloquine resistance was coupled with phenotypic analyses.

Results

Only four triple-resistant P. falciparum isolates (0.47%) were identified during the study period. These parasites combined the pfk13 polymorphism with pfmdr1 amplification, pfpm2 amplification and/or pfcrt mutations. They showed significantly higher tolerance to artemisinin, piperaquine and mefloquine and also to the mefloquine and piperaquine combination.

Conclusions

The use of artesunate/mefloquine countrywide in Cambodia has not led to a massive increase of triple-resistant P. falciparum parasites. However, these parasites circulate in the population, and exhibit clear resistance to piperaquine, mefloquine and their combination in vitro. This study demonstrates that P. falciparum can adapt to more complex drug associations, which should be considered in future therapeutic designs.
A MITE insertion abolishes theAP3-3self-maintenance regulatory loop in apetalous flowers ofNigella damascena
Authors: Conde e Silva Natalia , Leguilloux Martine , Bellec Arnaud , Rodde Nathalie , Aubert Juliette , Manicacci Domenica , Damerval Catherine , Berges Helene , Deveaux Yves
Published: December 2022

MADS-box transcription factors are important regulators of floral organ identity through their binding to specific motifs, termed CArG, in the promoter of their target genes. Petal initiation and development depend on class A and B genes, but MADS-box genes of the APETALA3 (AP3) clade are key regulators of this process. In the early diverging eudicot Nigella damascena, an apetalous [T] morph is characterized by the lack of expression of the NdAP3-3 gene, with its expression being petal-specific in the wild-type [P] morph. All [T] morph plants are homozygous for an NdAP3-3 allele with a Miniature Inverted-repeat Transposable Element (MITE) insertion in the second intron of the gene. Here, we investigated to which extent the MITE insertion impairs regulation of the NdAP3-3 gene. We found that expression of NdAP3-3 is initiated in the [T] morph, but the MITE insertion prevents its positive self-maintenance by affecting the correct splicing of the mRNA. We also found specific CArG features in the promoter of the NdAP3-3 genes with petal-specific expression. However, they are not sufficient to drive expression only in petals of transgenic Arabidopsis, highlighting the existence of Nigella-specific cis/trans-acting factors in regulating AP3 paralogs.
Improving machine learning-derived photometric redshifts and physical property estimates using unlabelled observations
Authors: Humphrey A , Cunha P A C , Paulino-Afonso A , Amarantidis S , Carvajal R , Gomes J M , Matute I , Papaderos P
Published: December 2022

In the era of huge astronomical surveys, machine learning offers promising solutions for the efficient estimation of galaxy properties. The traditional, ‘supervised’ paradigm for the application of machine learning involves training a model on labelled data, and using this model to predict the labels of previously unlabelled data. The semi-supervised ‘pseudo-labelling’ technique offers an alternative paradigm, allowing the model training algorithm to learn from both labelled data and as-yet unlabelled data. We test the pseudo-labelling method on the problems of estimating redshift, stellar mass, and star formation rate, using COSMOS2015 broad band photometry and one of several publicly available machine learning algorithms, and we obtain significant improvements compared to purely supervised learning. We find that the gradient-boosting tree methods CatBoost, XGBoost, and LightGBM benefit the most, with reductions of up to ∼15  per cent in metrics of absolute error. We also find similar improvements in the photometric redshift catastrophic outlier fraction. We argue that the pseudo-labelling technique will be useful for the estimation of redshift and physical properties of galaxies in upcoming large imaging surveys such as Euclid and LSST, which will provide photometric data for billions of sources.
Constraining galactic baryon cycle using the galaxy stellar-to-halo mass relations
Authors: Chen Yaoxin , Xu Yingzhong , Kang Xi
Published: December 2022

Galaxies display several well-behaved scaling relations between their properties, such as the star formation rate–stellar mass relation (the main sequence, MS) and the stellar mass–halo mass relation (SHMR). In principle, these scaling relations could imply different star formation histories (SFHs) of galaxies and different constraints on galaxy formation physics. In this paper, we derive the SFHs of galaxies by assuming that they always follow the SHMRs at different redshifts and use an empirical model to constrain key processes in their baryon cycle. It is found that, besides cold accretion due to halo growth, outflow of gas produced by stellar feedback has to be recycled to sustain the derived SFHs of galaxies. The recycled fraction is strongly affected by the baryon fraction in accreted low-mass haloes and the mass loading factor that quantifies the ratio between the galactic outflow rate and star formation rate. Our fiducial model predicts that around 20–60 per cent of outflow is recycled in $\sim 0.5\!-\!4\, \mathrm{Gyr}$, while simulations predict a slightly higher recycle fraction and a lower recycle time. We argue that strong constraints on the baryon cycle process can be obtained from future observation of the circum-galactic medium (CGM) of galaxies, such as the gas cooling rate of CGM. We also find that the implied SFHs from the SHMRs indicate that galaxies stay on the MS only for part of their lifetimes. Our model reproduces the evolution of the mass–metallicity relation as well.
The phase and turbulent properties of Cattail
Authors: Yuen Ka Ho , Chen Avi , Ho Ka Wai , Lazarian Alex
Published: December 2022

A recent publication discovered one of the largest filamentary neutral hydrogen features dubbed Cattail from high-resolution Five-hundred-meter Aperture Spherical radio Telescope observations that might be a new galactic arm of the Milky Way. We evaluate the turbulent and phase properties of Cattail via the newly developed Velocity Decomposition Algorithm and Force Balancing Model. We discover that if there exists a phase transition, then Cattail is unlikely in the cold neutral media phase. We also show that the Cattail is two disjoint features in caustics space, suggesting that the Cattail has two different turbulent systems. We check the spectra of the individual system separated via VDA to confirm this argument. We do not exclude the existence of smaller scale cold media being embedded within this structure.
Simulations of star-forming main-sequence galaxies in Milgromian gravity
Authors: Nagesh Srikanth T , Kroupa Pavel , Banik Indranil , Famaey Benoit , Ghafourian Neda , Roshan Mahmood , Thies Ingo , Zhao Hongsheng , Wittenburg Nils
Published: December 2022

We conduct hydrodynamical MOND simulations of isolated disc galaxies over the stellar mass range M⋆/M⊙ = 107–1011 using the adaptive mesh refinement code phantom of ramses (por), an adaptation of the ramses code with a Milgromian gravity solver. The scale lengths and gas fractions are based on observed galaxies, and the simulations are run for 5 Gyr. The main aim is to see whether the existing sub-grid physics prescriptions for star formation and stellar feedback reproduce the observed main sequence and reasonably match the Kennicutt–Schmidt relation, which captures how the local and global star formation rates relate to other properties. Star formation in the models starts soon after initialization and continues as the models evolve. The initialized galaxies indeed evolve to a state which is on the observed main sequence and the Kennicutt–Schmidt relation. The available formulation of sub-grid physics is therefore adequate and leads to galaxies that largely behave like observed galaxies, grow in radius, and have flat rotation curves – provided we use Milgromian gravitation. Furthermore, the strength of the bars tends to be inversely correlated with the stellar mass of the galaxy, whereas the bar length strongly correlates with the stellar mass. Irrespective of the mass, the bar pattern speed stays constant with time, indicating that dynamical friction does not affect the bar dynamics. The models demonstrate Renzo’s rule and form structures at large radii, much as in real galaxies. In this framework, baryonic physics is thus sufficiently understood to not pose major uncertainties in our modelling of global galaxy properties.
HubPUG: proper motions for local group dwarfs observed with HST utilizing Gaia as a reference frame
Authors: Warfield Jack T , Kallivayalil Nitya , Zivick Paul , Fritz Tobias , Richstein Hannah , Sohn Sangmo Tony , del Pino Andrés , Savino Alessandro , Weisz Daniel R
Published: December 2022

We present the method behind HubPUG, a software tool built for recovering systemic proper motions (PMs) of targets (e.g. clusters or resolved galaxies) in Hubble Space Telescope (HST) fields with two epochs of observations by utilizing stars observed by Gaia as a foreground frame of reference.HST PM experiments have typically relied on the use of distant background galaxies or quasi-stellar objects (QSOs) as stationary sources against which to measure PMs. Without consistent profiles, background galaxies are more difficult to centroid, but benefit on-aggregate from their large numbers. QSOs, though they can be fit with stellar point-spread functions, are sparse, with most fields containing none. Historically, the use of stars as references against which to measure PMs would have been difficult because they have individual PMs of their own. However, Gaia has now provided positions and PMs for over 1.4 billion stars, which are much more likely to be well-imaged in the fields around targets versus background sources, have predictable stellar profiles, and require less observing time per-image for good signal-to-noise. This technique allows us to utilize the power of Gaia to measure the PM of targets too faint for Gaia to observe itself. We have recovered PMs for the Milky Way satellites Sculptor and Draco with comparable uncertainties over HST-only and Gaia-only measurements, limited primarily by the current capabilities of the Gaia data. We also show the promise of this method for satellites of M31 with a new PM measurement for Andromeda VII.
RNA granule-clustered mitochondrial aminoacyl-tRNA synthetases form multiple complexes with the potential to fine-tune tRNA aminoacylation
Authors: Peng Gui-Xin , Mao Xue-Ling , Cao Yating , Yao Shi-Ying , Li Qing-Run , Chen Xin , Wang En-Duo , Zhou Xiao-Long
Published: December 2022

Mitochondrial RNA metabolism is suggested to occur in identified compartmentalized foci, i.e. mitochondrial RNA granules (MRGs). Mitochondrial aminoacyl-tRNA synthetases (mito aaRSs) catalyze tRNA charging and are key components in mitochondrial gene expression. Mutations of mito aaRSs are associated with various human disorders. However, the suborganelle distribution, interaction network and regulatory mechanism of mito aaRSs remain largely unknown. Here, we found that all mito aaRSs partly colocalize with MRG, and this colocalization is likely facilitated by tRNA-binding capacity. A fraction of human mitochondrial AlaRS (hmtAlaRS) and hmtSerRS formed a direct complex via interaction between catalytic domains in vivo. Aminoacylation activities of both hmtAlaRS and hmtSerRS were fine-tuned upon complex formation in vitro. We further established a full spectrum of interaction networks via immunoprecipitation and mass spectrometry for all mito aaRSs and discovered interactions between hmtSerRS and hmtAsnRS, between hmtSerRS and hmtTyrRS and between hmtThrRS and hmtArgRS. The activity of hmtTyrRS was also influenced by the presence of hmtSerRS. Notably, hmtSerRS utilized the same catalytic domain in mediating several interactions. Altogether, our results systematically analyzed the suborganelle localization and interaction network of mito aaRSs and discovered several mito aaRS-containing complexes, deepening our understanding of the functional and regulatory mechanisms of mito aaRSs.
CRISPR/Cas9-Engineered Large Fragment Deletion Mutations in Arabidopsis CEP Peptide–Encoding Genes Reveal Their Role in Primary and Lateral Root Formation
Authors: Huang Aixia , Cui Tingting , Zhang Yan , Ren Xufang , Wang Mengfang , Jia Lingyu , Zhang Yonghong , Wang Guodong
Published: December 2022

C-TERMINALLY ENCODED PEPTIDEs (CEPs) are post-translationally modified peptides that play essential roles in root and shoot development, nitrogen absorption, nodule formation and stress resilience. However, it has proven challenging to determine biological activities of CEPs because of difficulties in obtaining loss-of-function mutants for these small genes. To overcome this challenge, we thus assembled a collection of easily detectable large fragment deletion mutants of Arabidopsis CEP genes through the clustered regularly interspaced short palindromic repeat/CRISPR-associated protein 9–engineered genome editing. This collection was then evaluated for the usability by functionally analyzing the Arabidopsis growth and development with a focus on the root. Most cep mutants displayed developmental defects in primary and lateral roots showing an increased primary root length and an enhanced lateral root number, demonstrating that the genetic resource provides a useful tool for further investigations into the roles of CEPs.
The Formation of Chromite Chains and Clusters in Igneous Rocks
Authors: Holness Marian B , Vukmanovic Zoja , O’Driscoll Brian
Published: December 2022

Crystal clusters are common in both extrusive and plutonic rocks, but the mechanisms by which they form are not well-constrained. Following a consideration of the physics of nucleation, we outline the expected microstructural characteristics of clusters formed by heterogeneous nucleation and those formed by synneusis, together with the ways they might evolve during subsequent grain growth and textural equilibration. By combining analysis of the microstructures in experimental chromite-basalt charges with a detailed microstructural analysis of the UG2 chromitite of the Bushveld layered intrusion using EBSD, we argue that the UG2 chromitite formed by settling and accumulation of single grains and clusters comprising randomly oriented grains produced by the aggregation of previously isolated chromite crystals. Although there is no evidence of epitaxy, at least some of the lowermost chromite grains of the main UG2 chromitite may have nucleated heterogeneously on the silicate grains forming the floor, with subsequent accumulation and sintering of individual grains or clusters. The reduced thickness of chromitites on the steep and overhanging parts of the floor is thus due to the relative difficulty of sticking more grains to the existing layer in these orientations. The absence of any fining-upwards of grains in either the main UG2 chromitite or the associated stringer can be accounted for if both layers were formed by the settling and accumulation of clusters as well as single grains. Comparison with examples of clustered chromite grains in extrusive rocks suggests that aggregation by synneusis is a widespread magmatic process. The ‘chicken-wire’ texture formed by clustered chromite grains commonly found in olivine-rich cumulates is argued to also be formed by gravitational settling, with the possible exception of clusters of chromite grains in relatively thin seams argued to be the result of metasomatism, which may instead have formed by impingement during in situ growth.
CorrelatingCoffea canephora3D architecture to plant photosynthesis at a daily scale and vegetative biomass allocation
Authors: Rakocevic Miroslava , Baroni Danilo Força , de Souza Guilherme Augusto Rodrigues , Bernado Wallace de Paula , de Almeida Claudio Martins , Matsunaga Fabio Takeshi , Rodrigues Weverton Pereira , Ramalho José Cochicho , Campostrini Eliemar
Published: December 2022

Coffea canephora (C. canephora) has two botanical varieties, Robusta and Conilon. Intraspecific variability was hypothesized and projected for the selection of C. canephora plants able to maintain production in the context of global climate changes. For that, architectural, C-assimilation and biomass analyses were performed on 17-month-old Robusta (clones ‘A1’ and ‘3 V’) and Conilon (clones ‘14’ and ‘19’) varieties grown in non-limiting soil, water and mineral nutrient conditions. Nondestructive coffee plant architecture coding, reconstruction and plant photosynthesis estimations were performed using a functional-structural plant modeling platform OpenAlea. 3D reconstructions and inclusion of parameters calculated and estimated from light response curves, such as dark respiration (Rd), maximum rate of carboxylation of RuBisCO and photosynthetic electron transport allowed the estimation of instantaneous and daily plant photosynthesis. The virtual orchard leaf area index was low, and light was not a limiting factor in early C. canephora development stages. Under such conditions, Robusta assimilated more CO2 at the plant and orchard scale and produced higher total biomass than Conilon. Lower plant daily photosynthesis and total biomass were correlated to higher Rd in Conilon than in Robusta. Among the architectural traits, leaf inclination, size and allometry were most highly correlated with plant assimilation and biomass. Relative allocation in leaf biomass was higher in ‘19’ Conilon than in young Robusta plants, indicating intraspecific biomass partitioning. Similarly, variation in relative distribution of the root biomass and the root volume reflected clonal variation in soil occupation, indicating intraspecific variability in space occupation competitiveness. Coffea canephora denoted high root allocation in both Conilon and Robusta clones. However, relevant differences at subspecific levels were found, indicating the high potential of C. canephora to cope with drought events, which are expected to occur more frequently in the future, because of climate changes. The methodology developed here has the potential to be used for other crops and tree species.

Highlights Functional-structural plant model was used to estimate photosynthesis on a plant and daily scales in Coffea canephora (C. canephora). Among the architectural traits, leaf shape and inclination had the most impact on photosynthesis and biomass. Under non-limiting conditions, Robusta had higher plant photosynthesis and biomass than Conilon. A higher leaf biomass allocation in Conilon clone ‘19’ than in Robusta suggested variety-specific partitioning. Variation in the relative distribution of the root biomass indicated C. canephora intraspecific soil occupation variability.
Advancing considerations of context in the evaluation and implementation of evidence-based biomedical HIV prevention interventions: a review of recent research
Authors: Velloza Jennifer , Roche Stephanie , Concepcion Tessa , Ortblad Katrina F.
Published: December 2022

Purpose of review

A paradigm shift is needed in how we think about biomedical HIV prevention product effectiveness. Often, we expect randomized trial findings to be generalizable across populations and settings where products will be delivered, without consideration of key contextual drivers that could impact effectiveness. Moreover, researchers and policy-makers generally discount products with varied effect sizes across contexts, rather than explicating the drivers of these differences and using them to inform equitable product choice and delivery. We conducted a review of the recent HIV prevention research to advance considerations of context in choices of when, why, and how to implement biomedical HIV prevention products, with a particular focus on daily oral preexposure prophylaxis (PrEP) and the dapivirine vaginal ring (DPV).

Recent findings

Findings across recent studies of PrEP and DPV emphasize that products that do not work well in one context might be highly desirable in another. Key contextual drivers of PrEP and DPV effectiveness, use, and implementation include population, health system, cultural, and historical factors. We recommend conceptualization, measurement, and analysis approaches to fully understand the potential impact of context on prevention product delivery. Execution of these approaches has real-world implications for HIV prevention product choice and could prevent the field from dismissing biomedical HIV prevention products based on trial findings alone.

Ending the HIV epidemic will require tailored, person-centered, and equitable approaches to design, implement, and evaluate HIV prevention products which necessitates considerations of context in ongoing research and implementation.
Promoting patient-centered care within HIV care settings in sub-Saharan Africa
Authors: Wachira Juddy , Genberg Becky L. , Wilson Ira B.
Published: December 2022

Purpose of review

Patient centered care (PCC) in human immunodeficiency virus (HIV) care systems in sub-Saharan Africa (SSA) may improve outcomes for persons with HIV (PWH). We review the progress the region has made in promoting PCC and highlight some of the implementation challenges and potential areas of research.

Recent findings

Studies show growing interest in promoting PCC across HIV care programs in SSA. Effective implementation of PCC, however, is hampered by: (1) lack of consensus on the conceptualization of PCC, including definition, frameworks, measures, and implementation strategies; (2) limited regional studies on the adoption and sustainability of PCC interventions; and (3) healthcare structural challenges including limited capital and human resources, poor provider-patient dynamics, high provider turnover, and lack of continuity in care. Recent studies in the region have focused on identifying key PCC domains addressable in resource limited settings, understanding the PCC experiences and expectations of PWH and their providers, and testing innovative interventions. We highlight the need for additional studies to address the existing gaps.

We discuss the progress and challenges of implementing PCC in HIV care settings in SSA as well as the need for additional research to ensure that proposed PCC interventions have optimal impact.
The dysmorphic phenotype in vascular Ehlers Danlos syndrome
Authors: Lyness James R. , Morrison Patrick J.
Published: December 2022

The Ehlers Danlos syndromes are identified by their connective tissue features and are not rich in dysmorphic handles. Vascular Ehlers Danlos syndrome (vEDS) however, is characterised by a recognisable phenotypic constellation of internal and external dysmorphology. This review charts the paediatric and adult phenotypes of vEDS due primarily to COL3A1 gene variants and the potential recognition of some other EDS subtypes, including COL1A1 and COL25A1 that can present with vEDS-like features, with certain dysmorphic handles as clues to the diagnosis and the adjunct of gene testing in patients presenting with vEDS features.
Point of care diagnostics for Cryptosporidium: new and emerging technologies
Authors: Hijjawi Nawal , Zahedi Alizera , Ryan Una
Published: December 2022

Purpose of review

Although Cryptosporidium detection and typing techniques have improved dramatically in recent years, relatively little research has been conducted on point of care (POC) detection and typing tools. Therefore, the main purpose of the present review is to summarize and evaluate recent and emerging POC diagnostic methods for Cryptosporidium spp.

Recent findings

Microscopy techniques such as light-emitting diode fluorescence microscopy with auramine-phenol staining (LED-AP), still have utility for (POC) diagnostics but require fluorescent microscopes and along with immunological-based techniques, suffer from lack of specificity and sensitivity. Molecular detection and typing tools offer higher sensitivity, specificity and speciation, but are currently too expensive for routine POC diagnostics. Isothermal amplification methods such as loop-mediated isothermal amplification (LAMP) or recombinase polymerase amplification (RPA) including a commercially available LAMP kit have been developed for Cryptosporidium but are prone to false positives. Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas diagnostic technologies (CRISPRDx) have recently been combined with isothermal amplification to increase its specificity and sensitivity for detection and typing. Other emerging technologies including amplification-free CRISPR detection methods are currently being developed for Cryptosporidium using a smartphone to read the results.

Many challenges are still exist in the development of POC diagnostics for Cryptosporidium. The ideal POC tool would be able to concentrate the pathogen prior to detection and typing, which is complicated and research in this area is still very limited. In the short-term, CRISPR-powered isothermal amplification lateral flow tools offer the best opportunity for POC Cryptosporidium species and subtype detection, with a fully integrated autonomous biosensor for the long-term goal.
Hemophagocytic Lymphohistiocytosis: A Practical Review for Liver Pathologists
Authors: Xiong Yuqing , Del Portillo Armando , Fazlollahi Ladan , Remotti Helen E. , Lee Michael , Lagana Stephen M.
Published: December 2022

Hemophagocytic lymphohistiocytosis (HLH) is a rare disease with a high mortality. Liver involvement is common, with most patients demonstrating acute hepatitis. Therefore, liver biopsies are frequently obtained in the setting of suspected HLH. Several studies have described the clinicopathologic manifestations of liver involvement by HLH. The histology is highly variable, as are rates of demonstrated hemophagocytosis. This review summarizes the clinical characteristics of HLH, with particular emphasis on hepatic manifestations thereof. We then describe the histologic patterns that have been commonly and uncommonly reported. Finally, we address difficulties faced by liver pathologists when considering this entity and offer our opinions regarding the worst “pain points.”
Analysis of Body Contouring and Sustained Weight Loss in a Diverse, Urban Population: A Seven-Year Retrospective Review
Authors: Greige Nicolas , Kamel George N. , Leibl Kayla , Jacobson Joshua , Garfein Evan S. , Weichman Katie E. , Benacquista Teresa
Published: December 2022

Background:

Studies demonstrating the positive impact of body contouring on sustained weight loss in bariatric patients describe a narrow cohort. We sought to evaluate the impact of post bariatric body contouring procedures on sustained weight loss in minority race patients.

Methods:

A retrospective review of bariatric surgery patients at a single institution was performed. Patients were grouped by: (1) those that underwent body contouring, (2) those that had consultation but did not undergo body contouring, and (3) those without consultation. Body mass index (BMI) and excess body weight loss (EBWL) over 7 years were the primary outcomes.

Results:

2531 patients were analyzed, 350 in Group 1, 364 in Group 2, and 1817 in Group 3. At postoperative year 7, Groups 1 and 2 had average BMIs 4.71 and 2.31 kg/m2 lower than Group 3, respectively, while adjusting for covariates. After exclusion of 105 patients in Group 2 that were not offered body contouring due to inadequate weight loss, however, Group 2 had an average BMI 4.07 kg/m2 lower than Group 3 at postoperative year 7. During postoperative year 1, Group 1 had an average EBWL of 74.38%, which declined 1.51% yearly, and Group 2 had an average EBWL of 70.12%, which declined 1.86% yearly. After exclusion of the aforementioned patients, Group 2 had an average EBWL of 74.9% at postoperative year 1, which declined 1.88% yearly.

Conclusions:

Body contouring after bariatric surgery did not impart a clinically significant, long-term sustained weight loss benefit in our cohort. In our study population, we found that patients identifying as Black had significantly worse sustained weight loss.
Adipocyte differentiation of 3T3-L1 cells under tenofovir alafenamide, tenofovir disoproxil fumarate, and integrase strand transfer inhibitors selective challenge: an in-vitro model
Authors: Perna Angelica , Carleo Maria A. , Mascolo Silvia , Guida Alessandra , Contieri Marcella , Sellitto Carmine , Hay Eleonora , De Blasiis Paolo , Lucariello Angela , Guerra Germano , Baldi Alfonso , De Luca Antonio , Maggi Paolo , Esposito Vincenzo
Published: December 2022

Objective:

Integrase strand transfer inhibitors (INSTIs) are a class of antiretroviral therapy (ART) medications with a good tolerability profile and a high genetic barrier to HIV drug resistance. However, several studies report significant weight gain among persons receiving INSTI-based ART regimens compared with other regimens.

Design:

In-vitro model of adipogenesis.

Methods:

We used 3T3-L1 cells to investigate the effects of the nucleoside reverse transcriptase inhibitors (NRTIs) tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF), alone or in combination with INSTIs: raltegravir (RAL), elvitegravir (ELV), dolutegravir (DTG), and bictegravir (BIC) on adipose differentiation. To monitor adipocyte differentiation, expression levels of PPARɣ and C/EBPα and the intracellular lipid accumulation by Red Oil staining were used. Furthermore, we evaluated the immunohistochemical expression of ER-TR7, a fibroblastic marker, after INSTIs treatment.

Results:

Compared with control, INSTIs were able to increase adipogenesis, especially RAL and ELV. TAF and TDF inhibited adipogenesis alone and in combination with INSTIs. This ability was more evident when TAF was used in combination with DTG and BIC. Finally, INSTIs increased the expression of ER-TR7 compared with control and cells treated with TAF or TDF.

Conclusion:

Our data support the evidence that in-vitro challenge of 3T3-L1 cells with INSTIs is able to increase adipocytic differentiation and to drive a number of these cells toward the expression of fibroblastic features, with a different degree according to the various drugs used whereas TAF and TDF have an antagonistic role on this phenomenon.
A cell-and-plasma numerical model reveals hemodynamic stress and flow adaptation in zebrafish microvessels after morphological alteration
Authors: Maung Ye Swe Soe , Phng Li-Kun
Published: December 2022

The development of a functional cardiovascular system ensures successful embryonic development and a sustainable oxygen, nutrient and hormones delivery system for homeostasis in adulthood. While early vessels are formed by biochemical signaling and genetic programming, the onset of blood flow provides mechanical cues that participate in the vascular remodeling of the embryonic cardiovascular system. The zebrafish is a prolific animal model for studying the quantitative relationship between blood flow and vascular morphogenesis due to a combination of favorable factors including blood flow visualization in optically transparent larvae. While imaging techniques can be employed for measuring flow velocity and blood perfusion levels, hemodynamic forces such as the lumen wall shear stress (WSS) and lumen blood pressure cannot be measured directly. In this study, we have developed a cell and plasma blood transport model using CFD to understand how red blood cell (RBC) partitioning asymmetries affect WSS in a network. Furthermore, we employed the CFD model on rheological and morphological alterations of a wildtype network. We discuss how careful consideration of boundary conditions and acquisition of systemic parameters of blood flow are required to understand the intimate relationship between flow physiology and compensatory responses to hemorheological or morphological alterations.
Population divergence in maternal investment and embryo energy use and allocation reveals adaptive responses to cool climates
Authors: Pettersen A.K. , Ruuskanen S. , Nord Andreas , Nilsson J. F. , Miñano M.R. , Fitzpatrick L. J. , While G.M. , Uller T.
Published: December 2022

The thermal sensitivity of early life stages can play a fundamental role in constraining species distribution. For egg-laying ectotherms, cool temperatures often extend development time and exacerbate developmental energy cost. Despite these costs, egg laying is still observed at high latitudes and altitudes. How embryos overcome the developmental constraints posed by cool climates is crucial knowledge for explaining the persistence of oviparous species in such environments and for understanding thermal adaptation more broadly. Here, we studied maternal investment, and embryo energy use and allocation in wall lizards spanning altitudinal regions, as potential mechanisms of local adaptation to development in cool climates. Specifically, we compared population-level differences in (1) investment from mothers (egg mass, embryo retention and thyroid yolk hormone concentration), (2) embryo energy expenditure during development, and (3) embryo energy allocation from yolk towards tissue. We found evidence that energy expenditure was greater under cool compared with warm incubation temperatures. Females from relatively cool regions did not compensate for this energetic cost of development by producing larger eggs or increasing thyroid hormone concentration in yolk. Instead, embryos from the high-altitude region used less energy to complete development, i.e., they developed faster without a concomitant increase in metabolic rate, compared with those from the low-altitude region. Embryos from high altitudes also allocated relatively more energy towards tissue production, hatching with lower residual yolk:tissue ratios than low-altitude region embryos. These results suggest that local adaptation to cool climate in wall lizards involves mechanisms that regulate embryonic utilisation of yolk reserves and its allocation towards tissue, rather than shifts in maternal investment of yolk content or composition.
Graph neural networks learn emergent tissue properties from spatial molecular profiles
Authors: Fischer David S. , Ali Mayar , Richter Sabrina , Ertürk Ali , Theis Fabian
Published: December 2022

Tissue phenotypes such as metabolic states, inflammation, and tumor properties are functions of molecular states of cells that constitute the tissue. Recent spatial molecular profiling assays measure tissue architecture motifs in a molecular and often unbiased way and thus can explain some aspects of emergence of these phenotypes. Here, we characterize the ability of graph neural networks to model tissue-level emergent phenotypes based on spatial data by evaluating phenotype prediction across model complexities. First, we show that immune cell dispersion in colorectal tumors, which is known to be predictive of disease outcome, can be captured by graph neural networks. Second, we show that breast cancer tumor classes can be predicted from gene expression alone without spatial information and are thus too simplistic a phenotype to require a complex model of emergence. Third, we show that representation learning approaches for spatial graphs of molecular profiles are limited by overfitting in the prevalent regime of up to 100s of images per study. We address overfitting with within-graph self-supervision and illustrate its promise for tissue representation learning as a constraint for node representations.
Differential Expression Analysis for Metatranscriptomics with Sample-Paired Metagenomics Data
Authors: Yan Binghao , Wu Di
Published: December 2022

1

Motivation

Large microbial communities have contributed to essential ecosystems and multiple health and disease processes. Metatranscriptomics (MTX) is becoming increasingly important for profiling the gene expression pattern and functional activities of microbial communities. A fundamental task for analyzing the high-throughput sequencing data is the Differential Expression (DE) analysis, which aims to identify up/down-regulated genes/pathways across multiple conditions. However, DE analysis is complicated by the variation of underlying DNA copies, which is caused by the highly dynamic nature of microbial communities. The non-independent change between MTX and MGX may lead to false discoveries about which genes are biologically differentially expressed. Nevertheless, We can settle this problem by using the information from paired metagenomics (MGX) data.

Results

We proposed the MetaDePair, a statistical model for DE analysis in MTX with paired MGX data. It relied on a conditional Negative-Binomial distribution to model the count data. We showed that the adjustment of underlying DNA copies could significantly eliminate the variations of RNA data, thus improving the power of statistical inference. Also, we found that appropriate pre-filtering of zeros can also improve the sensitivity and precision of the model. Moreover, we proposed a method to simulate the paired MTX and MGX data. Using simulated data and real microbial data sets, we demonstrated that our method has a high statistical power while controlling the false discovery rate (FDR). We applied the tool to oral microbiome data and identified significant genes that are associated with Early Childhood Caries (ECC). Our tool enabled a more accurate and effective DE analysis based on MTX with paired MGX data and helped us improve the understanding of the functional characterization of microbial communities.
Single-cell profiling identifies clinically relevant interactions between tumor associated macrophages and blood endothelial cells in diffuse large B cell lymphoma
Authors: Ferrant Juliette , Le Gallou Simon , Padonou Francine , Léonard Simon , Papa Ilénia , Pangault Céline , Barthel Anne , Launay Vincent , Manson Guillaume , Hoareau Bénédicte , Deleurme Laurent , Monvoisin Céline , Albaud Benoit , Van Acker Nathalie , Laurent Camille , Llamas-Gutierrez Francisco , Michaud Henri-Alexandre , Bonnefoy Nathalie , Pécot Thierry , Tarte Karin , Roussel Mikael
Published: December 2022

Diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL) are the two most common B-cell lymphomas and are characterized by a dynamic crosstalk between tumor B cells and a heterogeneous tumor-supportive microenvironment, including immune, endothelial, and stromal components. Although their impact on the pathogenesis and prognosis of B-cell lymphoma has been acknowledged for years, tumor-associated macrophages (TAM) have not been extensively explored in DLBCL and FL. Herein, we investigate mononuclear phagocytes (MNP) heterogeneity at the single cell level and their potential co-regulation with the stromal and endothelial compartments in B-cell lymphoma lymph nodes compared to reactive secondary lymphoid organs, using a combination of mass cytometry, single cell RNA sequencing, andin silicoapproaches. We reveal a co-regulation between TAM and blood endothelial cells (BEC) in lymphoma. Moreover, we identify a specific interaction between Annexin A1 (ANXA1)-expressing BEC and formyl-peptide receptors (FPR1/2)-expressing monocytes/macrophages in DLBCL, which we confirmin situby multiplex immunofluorescence and imaging mass cytometry. This crosstalk is associated to an immunosuppressive tumor microenvironment and an adverse prognosis in DLBCL.
Genomic data suggest parallel dental vestigialization within the xenarthran radiation
Authors: Emerling Christopher A. , Gibb Gillian C. , Tilak Marie-Ka , Hughes Jonathan J. , Kuch Melanie , Duggan Ana T. , Poinar Hendrik N. , Nachman Michael W. , Delsuc Frédéric
Published: December 2022

Abstract

The recent influx of genomic data has provided greater insights into the molecular basis for regressive evolution, or vestigialization, through gene loss and pseudogenization. As such, the analysis of gene degradation patterns has the potential to provide insights into the evolutionary history of regressed anatomical traits. We specifically applied these principles to the xenarthran radiation (anteaters, sloths, armadillos), which is characterized by taxa with a gradation in regressed dental phenotypes. Whether the pattern among extant xenarthrans is due to an ancient and gradual decay of dental morphology or occurred repeatedly in parallel is unknown. We tested these competing hypotheses by examining 11 core dental genes in most living species of Xenarthra, characterizing shared inactivating mutations and patterns of relaxed selection during their radiation. Here we report evidence of independent and distinct events of dental gene loss in the major xenarthran subclades. First, we found strong evidence of complete enamel loss in the common ancestor of sloths and anteaters, suggested by the inactivation of five enamel-associated genes (AMELX, AMTN, MMP20, ENAM, ACP4). Next, whereas dental regression appears to have halted in sloths, presumably a critical event that ultimately permitted adaptation to an herbivorous lifestyle, anteaters continued losing genes on the path towards complete tooth loss. Echoes of this event are recorded in the genomes of all living anteaters, being marked by a 2-bp deletion in a gene critical for dentinogenesis (DSPP) and a putative shared 1-bp insertion in a gene linked to tooth retention (ODAPH). By contrast, in the two major armadillo clades, genes pertaining to the dento-gingival junction and amelogenesis appear to have been independently inactivated prior to losing all or some enamel. These genomic data provide evidence for multiple pathways and rates of anatomical regression, and underscore the utility of using pseudogenes to reconstruct evolutionary history when fossils are sparse.
A cosmopolitan inversion drives seasonal adaptation in overwinteringDrosophila
Authors: Nunez Joaquin C. B. , Lenhart Benedict A. , Bangerter Alyssa , Murray Connor S. , Yu Yang , Nystrom Taylor L. , Tern Courtney , Erickson Priscilla A. , Bergland Alan O.
Published: December 2022

Drosophilamelanogasterliving in temperate regions evolve as they track seasonal fluctuations. Yet, we lack an understanding of the genetic architecture of seasonal adaptive tracking. By sequencing orchard populations collected across multiple years, we characterized the genomic signal of seasonal demography and identified that the cosmopolitan inversion In(2L)t drives seasonal adaptation. In(2L)t shows footprints of selection that are inconsistent with simple explanations of genetic drift, as well as signatures of partial selective sweeps. A meta-analysis of phenotypic studies shows that seasonal loci within In(2L)t are associated with behavior, life-history, physiology, and morphology traits. Our results identify candidate regions that underlie seasonal adaptive tracking and link them to phenotype. This work supports the general hypothesis that inversions are important drivers of rapid adaptation.

One-Sentence Summary

A chromosomal inversion drives adaptive evolution between seasons in wild fruit flies.