bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hormone therapy as a possible solution for postmenopausal women with nocturia: results of a pilot trial
Authors: Pauwaert Kim , Goessaert An-Sofie , Ghijselings Lynn , Bower Wendy , Mariman An , Vogelaers Dirk , Depypere Herman , Everaert Karel 
Published: March 2021

Abstract

Objective:
To observe the impact of different hormonal treatment options on nocturia, its causative factors and bother in postmenopausal women.

Methods:
This prospective study recruited 245 postmenopausal women and divided them into four treatment groups based on patient's choice: Estrogen + Progesterone (E+P), Estrogen-only in patients with a prior hysterectomy, tissue-selective estrogen complex (TSEC) and no treatment. Nocturia and its causative factors were observed using two standardized questionnaires before and after treatment: the International Consultation on Incontinence Questionnaire Nocturia Module and the Targeting the individual's Aetiology of Nocturia to Guide Outcomes (TANGO). The results of the Targeting the individual's Aetiology of Nocturia to Guide Outcomes were divided in four influencing topics of which the sum score was calculated.

Results:
A significant reduction in prevalence of nocturia ≥ twice per night was seen after treatment, as the prevalence decreased from 27.7% (59/213) to 16.4% (35/213). Specified per therapy, a significant reduction in nocturnal voiding frequency was observed in patients treated with E+P and TSEC (P = 0.018 and P = 0.018, respectively). This improvement could be explained by a significant reduction in SLEEP sum score in patients treated with E+P and TSEC (P < 0.001, P = 0.013, respectively). Estrogen-only led to a significant change in URINARY TRACT sum score, which is the result of a reduction in urgency prevalence (P = 0.039).

Conclusions:
E+P and TSEC treatment led to a significant reduction in nocturia prevalence and bother in women with ≥ 2 nocturnal voids. This effect is mainly the result of improvement in sleep disorders, however an improvement in bladder disorders can be suggested as well. More research is necessary to confirm these findings.

Video Summary:

http://links.lww.com/MENO/A710.
A prospective controlled study of sexual function and sexually related personal distress up to 12 months after premenopausal risk-reducing bilateral salpingo-oophorectomy
Authors: Islam Rakibul M. , Davis Susan R. , Bell Robin J. , Tejada-Berges Trevor , Wrede Caspar David , Domchek Susan M. , Meiser Bettina , Kirk Judy , Krejany Efrosinia O. , Hickey Martha 
Published: March 2021

Abstract

Objective:
Premenopausal risk-reducing bilateral salpingo-oophorectomy (RRBSO) may impair sexual function, but the nature and degree of impairment and impact of estrogen therapy on sexual function and sexually related personal distress after RRBSO are uncertain.

Methods:
Prospective observational study of 73 premenopausal women at elevated risk of ovarian cancer planning RRBSO and 68 premenopausal controls at population risk of ovarian cancer. Participants completed the Female Sexual Function Index and the Female Sexual Distress Scale-Revised. Change from baseline in sexual function following RRBSO was compared with controls at 12 months according to estrogen therapy use.

Results:
Baseline sexual function domains did not differ between controls and those who underwent RRBSO and subsequently initiated (56.2%) or did not initiate (43.8%) estrogen therapy. At 12 months, sexual desire and satisfaction were unchanged in the RRBSO group compared with controls. After RRBSO, nonestrogen therapy users demonstrated significant impairment in sexual arousal (β-coefficient (95% confidence interval) −2.53 (−4.86 to −0.19), P < 0.03), lubrication (−3.40 (−5.84 to −0.96), P < 0.006), orgasm (−1.64 (−3.23 to −0.06), P < 0.04), and pain (−2.70 (−4.59 to 0.82), P < 0.005) compared with controls. Although sexually related personal distress may have been more likely after RRBSO, irrespective of estrogen therapy use, there was insufficient data to formally test this effect.

Conclusions:
The findings suggest premenopausal RRBSO adversely affects several aspects of sexual function which may be mitigated by the use of estrogen therapy. Further research is needed to understand the effects of RRBSO on sexual function and sexually related personal distress, and the potential for estrogen therapy to mitigate against any adverse effects.
Quantitative study on the efficacy of acupuncture in the treatment of menopausal hot flashes and its comparison with nonhormonal drugs
Authors: Li Ting , Zhang Yi , Cheng Qingqing , Hou Mengyuan , Zheng Xijun , Zheng Qingshan , Li Lujin 
Published: March 2021

Abstract

Objective:
This study aimed to compare the efficacy of acupuncture to that of sham acupuncture, placebo pills, and nonhormonal drugs to provide the necessary quantitative information for establishing medication guidelines for menopausal hot flashes.

Methods:
A comprehensive literature search was performed using public databases. Randomized clinical studies on acupuncture therapy for the treatment of hot flashes in menopausal women were identified. A time-course model was established to describe the efficacy characteristics of acupuncture and sham acupuncture, which were compared with the efficacy of nonhormonal drugs and placebo pills reported in the literature.

Results:
A total of 17 studies involving 1,123 participants were included. The quality of all the studies included in the analysis is medium to high, and there was no obvious risk of bias. It was found that the baseline number of hot flashes was an important factor affecting the efficacy of acupuncture and sham acupuncture. After correcting the baseline to eight hot flashes per day, the frequency of hot flashes decreased from baseline for traditional acupuncture (TA), electro-acupuncture (EA), TA&EA (merger analysis of TA and electro-acupuncture), and sham acupuncture were 3.1 (95% confidence interval [CI]: 2.8-3.4), 3.6 (95% CI: 3.2-4.0), 3.2 (95% CI: 2.9-3.5), and 2.6 (95% CI: 2.2-3.0) times/d at week 8, respectively. Compared with findings reported in the literature, we found the efficacy of electro-acupuncture was comparable to that of selective serotonin reuptake inhibitors/serotonin–norepinephrine reuptake inhibitors and neuroleptic agents such as gabapentin and escitalopram. Furthermore, the efficacy of TA&EA (merged) was significantly higher than that of placebo pills (2.3, 95% CI: 1.8-2.9).

Conclusions:
The efficacy of TA&EA (merged) was higher than that of sham acupuncture and significantly higher than that of placebo pills. The efficacy of electro-acupuncture was higher than that of traditional acupuncture, significantly higher than that of sham acupuncture, and comparable to that of selective serotonin reuptake inhibitors/serotonin–norepinephrine reuptake inhibitors and neuroleptic agents.
A combined strategy to detect plasma samples reliably with high anti-SARS-CoV-2 neutralizing antibody titers in routine laboratories
Authors: Fischer Bastian , Lichtenberg Christoph , Müller Lisa , Timm Jörg , Fischer Johannes , Knabbe Cornelius 
Published: March 2021

AbstractThe determination of anti-SARS-CoV-2 neutralizing antibodies (NAbs) is of interest in many respects. High NAb titers, for example, are the most important criterion regarding the effectiveness of convalescent plasma therapy. However, common cell culture-based NAb assays are time-consuming and feasible only in special laboratories. Our data reveal the suitability of a novel ELISA-based surrogate virus neutralization test (sVNT) to easily measure the inhibition-capability of NAbs in the plasma of COVID-19 convalescents. We propose a combined strategy to detect plasma samples with high NAb titers (≥ 1:160) reliably and to, simultaneously, reduce the risk of erroneously identifying low-titer specimens. For this approach, results of the sVNT assay are compared to and combined with those acquired from the Euroimmun anti-SARS-CoV-2 IgG assay. Both assays are appropriate for high-throughput screening in standard BSL-2 laboratories. Our measurements further show a long-lasting humoral immunity of at least 11 months after symptom onset.
Thermal modulation of Zebrafish exploratory statistics reveals constraints on individual behavioral variability
Authors: Goc Guillaume Le , Lafaye Julie , Karpenko Sophia , Bormuth Volker , Candelier Raphaël , Debrégeas Georges 
Published: March 2021

AbstractBackgroundVariability is a hallmark of animal behavior. It contributes to survival by endowing individuals and populations with the capacity to adapt to ever-changing environmental conditions. Intra-individual variability is thought to reflect both endogenous and exogenous modulations of the neural dynamics of the central nervous system. However, how variability is internally regulated and modulated by external cues remains elusive. Here we address this question by analyzing the statistics of spontaneous exploration of freely swimming zebrafish larvae, and by probing how these locomotor patterns are impacted when changing the water temperatures within an ethologically relevant range.ResultsWe show that, for this simple animal model, five short-term kinematic parameters - interbout interval, turn amplitude, travelled distance, turn probability and orientational flipping rate - together control the long-term exploratory dynamics. We establish that the bath temperature consistently impacts the means of these parameters, but leave their pairwise covariance unchanged. These results indicate that the temperature merely controls the sampling statistics within a well-defined kinematic space delineated by this robust statistical structure. At a given temperature, individual animals explore the behavioral space over a timescale of tens of minutes, suggestive of a slow internal state modulation that could be externally biased through the bath temperature. By combining these various observations into a minimal stochastic model of navigation, we show that this thermal modulation of locomotor kinematics results in a thermophobic behavior, complementing direct gradient-sensing mechanisms.ConclusionsThis study establishes the existence of a well-defined locomotor space accessible to zebrafish larvae during spontaneous exploration, and quantifies self-generated modulation of locomotor patterns. Intra-individual variability reflects a slow diffusive-like probing of this space by the animal. The bath temperature in turn restricts the sampling statistics to sub-regions, endowing the animal with basic thermophobicity. This study suggests that in Zebrafish, as well as in other ectothermic animals, ambient temperature could be used to efficiently manipulate internal states in a simple and ethological way.
The long-time orphan protistMeringosphaera mediterraneaLohmann, 1902 [1903] is a centrohelid heliozoan
Authors: Zlatogursky Vasily V. , Sh□shkin Yegor , Drachko Daria , Burki Fabien 
Published: March 2021

ABSTRACTMeringosphaerais an enigmatic marine protist without clear phylogenetic affiliation, but it has long been suggested to be a chrysophytes-related autotroph. Microscopy-based reports indicate that it has a worldwide distribution, but no sequence data exists so far. We obtained the first 18S rDNA sequence forM. mediterranea(identified using light and electron microscopy) from the West Coast of Sweden. Observations of living cells revealed granulated axopodia and up to 6 globular photosynthesizing bodies about 2 μm in diameter, the nature of which requires further investigation. The ultrastructure of barbed undulating spine scales and patternless plate scales with a central thickening is in agreement with previous reports. Molecular phylogenetic analysis placedM. mediterraneainside the NC5 environmental clade of Centroplasthelida (Haptista) along with additional environmental sequences, together closely related to Choanocystidae. This placement is supported by similar scales inMeringosphaeraand Choanocystidae. We searched the Tara Oceans 18S-V9 metabarcoding dataset which revealed four OTUs with 95.5-98.5% similarity, with oceanic distribution similar to that based on morphological observations. The current taxonomic position and species composition of the genus are discussed. The planktonic lifestyle ofM. mediterraneacontradicts the view of some authors that centrohelids enter the plankton only temporarily.
Pooled Single-Molecule transcriptomics identifies a giant gene under balancing selection in sunflower
Authors: Badouin Hélène , Boniface Marie-Claude , Pouilly Nicolas , Fuchs Anne-Laure , Vear Felicity , Langlade Nicolas B. , Gouzy Jérôme , Muños Stéphane 
Published: March 2021

SummaryGenes under balancing selection control phenotypes such as immunity, color or sex, but are difficult to identify. Self-incompatibility genes are under negative frequency-dependent selection, a special case of balancing selection, with up to 30 to 50 alleles segregating per population. We developed a method based on pooled Single-Molecule transcriptomics to identify balanced polymorphisms expressed in tissues of interest. We searched for multi-allelic, non-recombining genes causing self-incompatibility in wild sunflower (Helianthus annuus). A diversity scan in pistil identified a gene,Ha7650b,that displayed balanced polymorphism and colocalized with a quantitative trait locus for self-incompatibility. Unexpectedly,Ha7650bdisplayed gigantism (400 kb), which was caused by increase in intron size as a consequence of suppressed recombination.Ha7650bemerged after a whole-genome duplication (29 millions years ago) followed by tandem duplications and neofunctionalisation.Ha7650bshows expression, genetic location, genomic neighbourhood and predicted function that provide strong evidence that it is involved in self-incompatibility. Pooled Single-Molecule transcriptomics is an affordable and powerful new method that makes it possible to identify diversity and structural outliers simultaneously. It will allow a breakthrough in the discovery of self-incompatibility genes and other expressed genes under balancing selection.
Thermal stress triggers productive viral infection of a key coral reef symbiont
Authors: Grupstra Carsten GB , Howe-Kerr Lauren I , Veglia Alex J , Bryant Reb L , Coy Samantha R , Blackwelder Patricia L , Correa Adrienne MS 
Published: March 2021

AbstractClimate change-driven ocean warming is increasing the frequency and severity of bleaching events, in which corals appear whitened after losing their dinoflagellate endosymbionts (family Symbiodiniaceae). Viral infections of Symbiodiniaceae may contribute to some bleaching signs, but little empirical evidence exists to support this hypothesis. We present the first temporal analysis of a lineage of Symbiodiniaceae-infecting positive-sense single-stranded RNA viruses (‘dinoRNAVs’) in coral colonies, which were exposed to a 5-day heat treatment (+2.1°C). A total of 124 dinoRNAV major capsid protein gene ‘aminotypes’ (unique amino acid sequences) were detected from five colonies of two closely relatedPocillopora-Cladocopium(coral-symbiont) combinations in the experiment; most dinoRNAV aminotypes were shared between the two coral-symbiont combinations (64%) and among multiple colonies (82%). Throughout the experiment, seventeen dinoRNAV aminotypes were found only in heat-treated fragments, and 22 aminotypes were detected at higher relative abundances in heat-treated fragments. DinoRNAVs in fragments of some colonies exhibited higher alpha diversity and dispersion under heat stress. Together, these findings provide the first empirical evidence that exposure to high temperatures triggers some dinoRNAVs to switch from a persistent to a productive infection mode within heat-stressed corals. Over extended time frames, we hypothesize that cumulative dinoRNAV production in thePocillopora-Cladocopiumsystem could affect colony symbiotic status, for example, by decreasing Symbiodiniaceae densities within corals. This study sets the stage for reef-scale investigations of dinoRNAV dynamics during bleaching events.
Comprehensive patient-level classification and quantification of driver events in TCGA PanCanAtlas cohorts
Authors: Vyatkin Alexey D. , Otnyukov Danila V. , Leonov Sergey V. , Belikov Aleksey V. 
Published: March 2021

AbstractThere is a growing need to develop novel therapeutics for targeted treatment of cancer. The prerequisite to success is the knowledge about which types of molecular alterations are predominantly driving tumorigenesis. To shed light onto this subject, we have utilized the largest database of human cancer mutations – TCGA PanCanAtlas, multiple established algorithms for cancer driver prediction (2020plus, CHASMplus, CompositeDriver, dNdScv, DriverNet, HotMAPS, OncodriveCLUSTL, OncodriveFML) and developed four novel computational pipelines: SNADRIF (Single Nucleotide Alteration DRIver Finder), GECNAV (Gene Expression-based Copy Number Alteration Validator), ANDRIF (ANeuploidy DRIver Finder) and PALDRIC (PAtient-Level DRIver Classifier). A unified workflow integrating all these pipelines, algorithms and datasets at cohort and patient levels was created.We have found that there are on average 12 driver events per tumour, of which 0.6 are single nucleotide alterations (SNAs) in oncogenes, 1.5 are amplifications of oncogenes, 1.2 are SNAs in tumour suppressors, 2.1 are deletions of tumour suppressors, 1.5 are driver chromosome losses, 1 is a driver chromosome gain, 2 are driver chromosome arm losses, and 1.5 are driver chromosome arm gains. The average number of driver events per tumour increases with age (from 7 to 15) and cancer stage (from 10 to 15) and varies strongly between cancer types (from 1 to 24). Patients with 1 and 7 driver events per tumour are the most frequent, and there are very few patients with more than 40 events. In tumours having only one driver event, this event is most often an SNA in an oncogene. However, with increasing number of driver events per tumour, the contribution of SNAs decreases, whereas the contribution of copy-number alterations and aneuploidy events increases.Author SummaryBy analysing genomic and transcriptomic data from 10000 cancer patients through our custom-built computational pipelines and previously established third-party algorithms, we have found that half of all driver events in a patient’s tumour appear to be gains and losses of chromosomal arms and whole chromosomes. We therefore suggest that future therapeutics development efforts should be focused on targeting aneuploidy. We have also found that approximately a third of driver events in a patient are whole gene amplifications and deletions. Thus, therapies aimed at copy-number alterations also appear very promising. On the other hand, drugs aiming at point mutations are predicted to be less successful, as these alterations are responsible for just a couple of drivers per tumour. One notable exception are patients having only one driver event in their tumours, as this event is almost always a single nucleotide alteration in an oncogene.
Minimizing spectral overlap in multicolor flow cytometry experiments
Authors: Rønn Olsen Lars , Benso Alfredo , Politano Gianfranco , Barnkob Mike Bogetofte 
Published: March 2021

AbstractSelecting fluorochromes for polychromatic panels for flow cytometry is complex and time-consuming. Poorly designed panels can result in overlap between the emission spectra of the different fluorochromes, making their signals difficult to separate. While assessing all possible panels is simple to do programmatically, the combinatorial complexity of most real world problems renders brute force computation impractical. Here we present a novel complexity optimization algorithm for fast design of minimal spectral overlap fluorochrome combinations. To aid researchers in designing fluorochrome panels we implemented the algorithm in a web server, Spectracular, that also considers instrument laser configuration and allows users to define various constraints related to antibody-fluorochrome availability and marker co-expression.
ENCODING OF LIMB STATE BY SINGLE NEURONS IN THE CUNEATE NUCLEUS OF AWAKE MONKEYS
Authors: Versteeg Christopher , Rosenow Joshua M. , Bensmaia Sliman J. , Miller Lee E. 
Published: March 2021

AbstractThe cuneate nucleus (CN) is among the first sites along the neuraxis where proprioceptive signals can be integrated, transformed, and modulated. The objective of the study was to characterize the proprioceptive representations in CN. To this end, we recorded from single CN neurons in three monkeys during active reaching and passive limb perturbation. We found that many neurons exhibited responses that were tuned approximately sinusoidally to limb movement direction, as has been found for other sensorimotor neurons. The distribution of their preferred directions (PDs) was highly non-uniform and resembled that of muscle spindles within individual muscles, suggesting that CN neurons typically receive inputs from only a single muscle. We also found that the responses of proprioceptive CN neurons tended to be modestly amplified during active reaching movements compared to passive limb perturbations, in contrast to cutaneous CN neurons whose responses were not systematically different in the active and passive conditions. Somatosensory signals thus seem to be subject to a “spotlighting” of relevant sensory information rather than uniform suppression as has been suggested previously.
Cell cycle gene regulation dynamics revealed by RNA velocity and deep-learning
Authors: Riba Andrea , Oravecz Attila , Durik Matej , Jiménez Sara , Alunni Violaine , Cerciat Marie , Jung Matthieu , Keime Céline , Keyes William M. , Molina Nacho 
Published: March 2021

AbstractThe cell cycle is a fundamental process of life, however, a quantitative understanding of gene regulation dynamics in the context of the cell cycle is still far from complete. Single-cell RNA-sequencing (scRNA-seq) technology gives access to its dynamics without externally perturbing the cell. Here, we build a high-resolution map of the cell cycle transcriptome based on scRNA-seq and deep-learning. By generating scRNA-seq libraries with high depth, in mouse embryonic stem cells and human fibroblasts, we are able to observe cycling patterns in the unspliced-spliced RNA space for single genes. Since existing methods in scRNA-seq are not efficient to measure cycling gene dynamics, we propose a deep learning approach to fit these cycling patterns sorting single cells across the cell cycle. We characterize the cell cycle in asynchronous pluripotent and differentiated cells identifying major waves of transcription during the G1 phase and systematically study the G1-G0 transition where the cells exit the cycle. Our work presents to the scientific community a broader understanding of RNA velocity and cell cycle maps, that we applied to pluripotency and differentiation. Our approach will facilitate the study of the cell cycle in multiple cellular models and different biological contexts, such as cancer and development.