bluuebunny/crossref_metadata_2025_split huggingface dataset:
Statistical significance misuse in public health research: an investigation of the current situation and possible solutions
Authors: Rovetta Alessandro 
Published: September 2023

AbstractBackgroundDespite the efforts of leading statistical authorities and experts worldwide and the inherent dangers of interpretative errors in clinical research, misuses of statistical significance remain a common practice in the field of public health. Currently, there is a need to attempt to quantify this phenomenon.Methods97 studies were randomly selected within the PubMed database. An evaluation scale for the interpretation and presentation of statistical results (SRPS) was adopted. The maximum achievable score was 4 points. The abstracts and the full texts of the manuscripts were evaluated separately to highlight any differences in presentation. In this regard, a paired Student t-test was implemented.ResultsAll studies failed to adopt statistical significance as a continuous measure of compatibility between the model and the test result. The vast majority of them did not provide information on the validation of the model used. However, in most cases, all results were reported in full within the manuscripts. Substantial differences (a-f) between abstracts (a) and full texts (f) were highlighted when applying the SRPS (null hypothesis, P<.0001, a-f=1.2, Cohen’s D=1.7; a-f=0.5 hypothesis, P<.0001, a-f=0.7, Cohen’s D=1.0).ConclusionWhen contextualized in the current scenario, these findings provide evidence of widespread and severe shortcomings in the use and interpretation of statistical significance measures in clinical and public health research during 2023. Therefore, it is essential for academic journals to compulsorily demand higher scientific quality standards.
Views and experiences of young people on using mHealth platforms for sexual and reproductive health services in rural low- and middle-income countries: a qualitative systematic review
Authors: Laar Alexander S. , Harris Melissa L. , Khan Md N , Loxton Deborah 
Published: September 2023

AbstractIn low- and middle-income countries (LMICs), reproductive health programs use mobile health (mHealth) platforms to deliver a broad range of SRH information and services to young people in rural areas. However, young people’s experiences of using mobile phone platforms for SRH services in the rural contexts of LMICs remains unexplored. This review qualitatively explored the experiences and perceptions of young people’s use of mobile phone platforms for SRH information and services. This qualitative evidence synthesis was conducted through a systematic search of online databases: Medline, Embase, CINAHL, PsycInfo and Scopus. We included peer reviewed articles that were conducted between 2000 and 2020 and used qualitative methods. The methodological quality of papers was assessed by two authors using Grading of Recommendations, Assessment, Development and Evaluation (GRADE) and Confidence in Evidence from Reviews of Qualitative research (CERQual) approach with the identified papers synthesized using a narrative thematic analysis approach. The 26 studies included in the review were conducted in a wide range of LMIC rural settings. The studies used seven different types of mHealth platforms in providing access to SRH information and services on contraception, family planning, sexually transmitted infections (STIs) and human immunodeficiency virus (HIV) education. Participant preferences for use of SRH service platforms centred on convenience, privacy and confidentiality, as well as ease and affordability. High confidence was found in the studies preferencing text messaging, voice messaging, and interactive voice response services while moderate confidence was found in studies focused on phone calls. The overall constraint for platforms services included poor and limited network and electricity connectivity (high confidence in the study findings), limited access to mobile phones and mobile credit due to cost, influence from socio-cultural norms and beliefs and community members (moderate confidence in the study findings), language and literacy skills constraints (high confidence in the study findings). The findings provide valuable information on the preferences of mHealth platforms for accessing SRH services among young people in rural settings in LMICs and the quality of available evidence on the topic. As such, the findings have important implications for health policy makers and implementers and mHealth technology platform developers on improving services for sustainable adoption and integration in LMIC rural health systems.
Small protein mediates inhibition of ammonium transport in Methanosarcina mazei – an ancient mechanism?
Authors: Habenicht Tim , Weidenbach Katrin , Velazquez-Campoy Adrian , Buey Ruben M. , Balsera Monica , Schmitz Ruth A. 
Published: September 2023

AbstractIn the past decade, small open reading frames (sORFs) coding for proteins less than 70 amino acids (aa) in length have moved into the focus of Science. sORFs and corresponding small proteins have been recently identified in all three domains of life. However, the majority of small proteins remain functionally uncharacterized. While several bacterial small proteins have already been described, the number of identified and functionally characterized small proteins in archaea is still limited. In this study, we have discovered that the small protein 36 (sP36), which consists of only 61 aa, plays a critical role in regulating nitrogen metabolism inMethanosarcina mazei.The absence of sP36 significantly delays the growth ofM. mazeiwhen transitioning from nitrogen limitation to nitrogen sufficiency, as compared to the wild type. Through ourin vivoexperiments, we have observed that during nitrogen limitation, sP36 is dispersed throughout the cytoplasm; however, upon shifting the cells to nitrogen sufficiency, it relocates to the cytoplasmic membrane. Moreover, in vitro biochemical analysis clearly showed that sP36 interacts with high-affinity with the ammonium transporter AmtB1present in the cytoplasmic membrane during nitrogen limitation, as well as with the PII-like protein GlnK1. Based on our findings, we propose that in response to an ammonium up-shift, sP36 targets the ammonium transporter AmtB1and inhibits its activity by mediating the interaction with GlnK1.ImportanceSmall proteins containing fewer than 70 aa, which were previously disregarded due to computational prediction and biochemical detection challenges, have gained increased attention in the scientific community in recent years. However, the number of functionally characterized small proteins, especially in archaea, is still limited. Here, by using biochemical and genetic approaches, we demonstrate a crucial role for the small protein sP36 in the nitrogen metabolism ofM. mazei, regulating the ammonium transporter AmtB1according to nitrogen availability. This regulation might represent an ancient archaeal mechanism of AmtB1inhibition by GlnK, in contrast to the well-studied regulation in bacteria, which depends on covalent modification of GlnK.
The association betweenDioscorea sansibarensisandOrrella dioscoreaeas a model for hereditary leaf symbiosis
Authors: Acar Tessa , Moreau Sandra , Jardinaud Marie-Françoise , Houdinet Gabriella , Maviane-Macia Felicia , De Meyer Frédéric , Hoste Bart , Leroux Olivier , Coen Olivier , le Ru Aurélie , Peeters Nemo , Carlier Aurelien 
Published: September 2023

AbstractHereditary, or vertically-transmitted, symbioses affect a large number of animal species and some plants. The precise mechanisms underlying transmission of functions of these associations are often difficult to describe, due to the difficulty in separating the symbiotic partners. This is especially the case for plant-bacteria hereditary symbioses, which lack experimentally tractable model systems. Here, we demonstrate the potential of the leaf symbiosis between the wild yamDioscorea sansibarensisand the bacteriumOrrella dioscoreae(O. dioscoreae) as a model system for hereditary symbiosis.O. dioscoreaeis easy to grow and genetically manipulate, which is unusual for hereditary symbionts. These properties allowed us to design an effective antimicrobial treatment to rid plants of bacteria and generate whole aposymbiotic plants, which can later be re-inoculated with bacterial cultures. Aposymbiotic plants did not differ morphologically from symbiotic plants and the leaf forerunner tip containing the symbiotic glands formed normally even in the absence of bacteria, but microscopic differences between symbiotic and aposymbiotic glands highlight the influence of bacteria on the development of trichomes and secretion of mucilage. This is to our knowledge the first leaf symbiosis where both host and symbiont can be grown separately and where the symbiont can be genetically altered and reintroduced to the host.
Xenomake: a pipeline for processing and sorting xenograft reads from spatial transcriptomic experiments
Authors: Strope Benjamin S , Pendleton Katherine E , Bowie William Z , Echeverria Gloria V , Zhu Qian 
Published: September 2023

AbstractXenograft models are attractive models that mimic human tumor biology and permit one to perturb the tumor microenvironment and study its drug response. Spatially resolved transcriptomics (SRT) provide a powerful way to study the organization of xenograft models, but currently there is a lack of specialized pipeline for processing xenograft reads originated from SRT experiments. Xenomake is a standalone pipeline for the automated handling of spatial xenograft reads. Xenomake handles read processing, alignment, xenograft read sorting, quantification, and connects well with downstream spatial analysis packages. We additionally show that Xenomake can correctly assign organism specific reads, reduce sparsity of data by increasing gene counts, while maintaining biological relevance for studies.
Deprivation-induced plasticity in the early central circuits of the rodent visual, auditory, and olfactory systems: a systematic review and meta-analysis of the literature
Authors: Huang Li , Hardyman Francesca , Edwards Megan , Galliano Elisa 
Published: September 2023

AbstractActivity-dependent neuronal plasticity is crucial for animals to adapt to dynamic sensory environments. Traditionally, research on activity dependent-plasticity has used sensory deprivation approaches in animal models, and it has focused on its effects in primary sensory cortices. However, emerging evidence emphasizes the importance of activity-dependent plasticity both in the sensory organs and in sub-cortical regions where cranial nerves relay information to the brain. Additionally, a critical question arises: do different sensory modalities share common cellular mechanisms for deprivation-induced plasticity at these central entry-points? Furthermore, does the duration of deprivation correlate with specific plasticity mechanisms? This study aims to systematically review and meta-analyse research papers that investigated visual, auditory, or olfactory deprivation in rodents. Specifically, it explores the consequences of sensory deprivation in homologous regions at the first central synapse after the cranial nerve: vision—lateral geniculate nucleus and superior colliculus; audition— ventral and dorsal cochlear nucleus; olfaction—olfactory bulb. The systematic search yielded 91 research papers (39 vision, 22 audition, 30 olfaction), revealing significant heterogeneity in publication trends, experimental methods of inducing deprivation, measures of deprivation-induced plasticity, and reporting, across the three sensory modalities. Nevertheless, despite these methodological differences, commonalities emerged when correlating the plasticity mechanisms with the duration of the sensory deprivation. Following short-term deprivations (up to 1 day) all three systems showed reduced activity levels and increased disinhibition. Medium-term deprivation (1 day to a week) induced greater glial involvement and synaptic remodelling. Long-term deprivation (over a week) predominantly led to macroscopic structural changes including tissue shrinkage and apoptosis. These findings underscore the importance of standardizing methodologies and reporting practices. Additionally, they highlight the value of cross-modals synthesis for understanding how the nervous system, including peripheral, pre-cortical, and cortical areas, respond to and compensate for sensory inputs loss.
Inferring cell trajectories of spatial transcriptomics via optimal transport analysis
Authors: Shen Xunan , Huang Ke , Zuo Lulu , Ye Zhongfei , Li Zeyu , Yu Qichao , Zou Xuanxuan , Wei Xiaoyu , Xu Ping , Jin Xin , Xu Xun , Wu Liang , Zhu Hongmei , Qin Pengfei 
Published: September 2023

AbstractThe integration of cell transcriptomics and spatial coordinates to organize differentiation trajectories remains a challenge. Here we introduce spaTrack, a trajectory inference method using optimal transport to incorporate both transcriptomics and distance of spatial transcriptomics sequencing data into transition costs. spaTrack could construct fine spatial trajectories reflecting the true differentiation topology, as well as trace cell dynamics across multiple samples with temporal intervals. To capture the dynamic drivers, spaTrack models the cell fate as a function of expression profile along temporal intervals driven by transcription factors. Applying spaTrack, we successfully disentangle spatiotemporal trajectories of axolotl telencephalon regeneration and mouse midbrain development. Furthermore, we uncover diverse malignant lineages expanding in a primary tumor. One of the lineages with upregulated extracellular matrix organization implants to the metastatic site and subsequently colonizes to a secondary tumor. Overall, spaTrack greatly facilitates trajectory inference from spatial transcriptomics, providing insights in cell differentiation of broad areas.
Astrocytic uptake of posttranslationally modified amyloid-β leads to endolysosomal system disruption and induction of pro-inflammatory signaling
Authors: Wirth S , Schlößer A , Beiersdorfer A , Schweizer M , Lohr C , Grochowska KM 
Published: September 2023

AbstractThe disruption of astrocytic catabolic processes contributes to the impairment of amyloid-β (Aβ) clearance, neuroinflammatory signaling, and the loss of synaptic contacts in late-onset Alzheimer’s disease (AD). While it is known that the posttranslational modifications of Aβ have significant implications on biophysical properties of the peptides, their consequences for clearance impairment are not well understood. It was previously shown that N-terminally pyroglutamylated Aβ3(pE)-42, a significant constituent of amyloid plaques, is efficiently taken up by astrocytes, leading to the release of pro-inflammatory cytokine tumor necrosis factor α (TNFα) and synapse loss. Here we report that Aβ3(pE)-42, but not Aβ1-42, gradually accumulates within the astrocytic endolysosomal system, disrupting this catabolic pathway and inducing formation of heteromorphous vacuoles. This accumulation alters lysosomal kinetics and lysosome-dependent calcium signaling, and upregulates lysosomal stress response. These changes correlate with the upregulation of glial fibrillary acidic protein (GFAP) and increased activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NFᴋB). Treatment with a lysosomal protease inhibitor, E64, rescues GFAP upregulation, NFᴋB activation, and synapse loss, indicating that abnormal lysosomal protease activity is upstream of pro-inflammatory signaling and related synapse loss. Collectively, our data suggest that Aβ3(pE)-42-induced disruption of the astrocytic endolysosomal system leads to cytoplasmic leakage of lysosomal proteases, promoting pro-inflammatory signaling and synapse loss, hallmarks of AD-pathology.
Regulation potential of transcribed simple repeated sequences in developing neurons
Authors: Chung Tek Hong , Zhuravskaya Anna , Makeyev Eugene V. 
Published: September 2023

AbstractSimple repeated sequences (SRSs), defined as tandem iterations of microsatellite- to satellite-sized DNA units, occupy a substantial part of the human genome. Some of these elements are known to be transcribed in the context of repeat expansion disorders. Mounting evidence suggests that the transcription of SRSs may also contribute to normal cellular functions. Here, we used genome-wide bioinformatics approaches to systematically examine SRS transcriptional activity in cells undergoing neuronal differentiation. We identified thousands of long noncoding RNAs containing >200-nucleotide-long SRSs (SRS-lncRNAs), with hundreds of these transcripts significantly upregulated in the neural lineage. We show that SRS-lncRNAs often originate from telomere-proximal regions and that they have a strong potential to form multivalent contacts with a wide range of RNA-binding proteins. Our analyses also uncovered a cluster of neurally upregulated SRS-lncRNAs encoded in a centromere-proximal part of chromosome 9, which underwent an evolutionarily recent segmental duplication. Using a newly established in vitro system for rapid neuronal differentiation of induced pluripotent stem cells, we demonstrate that at least some of the bioinformatically predicted SRS-lncRNAs, including those encoded in the segmentally duplicated part of chromosome 9, indeed increase their expression in developing neurons to readily detectable levels. These data suggest that many SRSs may be expressed in a cell type and developmental stage-specific manner, providing a valuable resource for further studies focused on the functional consequences of SRS-lncRNAs in the normal development of the human brain.
Distractor-specific control adaptation in multidimensional environments
Authors: Gheza Davide , Kool Wouter 
Published: September 2023

AbstractGoal-directed behavior requires humans to constantly manage and switch between multiple, independent, and conflicting, sources of information. Conventional cognitive control tasks, however, only feature one task and one source of distraction. Therefore, it is unclear how control is allocated in multidimensional environments. To address this question, we developed a multi-dimensional task-set interference paradigm, in which people need to manage distraction from three independent dimensions. We use this task to test whether people adapt to prior conflict by enhancing task-relevant information or suppressing task-irrelevant information. Three experiments provided strong evidence for the latter hypothesis. Moreover, control adaptation was highly dimension-specific. Conflict from a given dimension only affected processing of that same dimension on subsequent trials, with no evidence for generalization. A new neural network model shows that our results can only be simulated when including multiple independent conflict-detector units. Our results call for an update to classic models of cognitive control, and their neurocomputational underpinnings.
FYN regulates aqueous humor outflow and IOP through the phosphorylation of VE-cadherin
Authors: Kizhatil Krishnakumar , Clark Graham , Sunderland Daniel , Bhandari Aakriti , Horbal Logan , Balasubramanian Revathi , John Simon 
Published: September 2023

ABSTRACTThe exact sites and molecules that determine resistance to aqueous humor drainage and control intraocular pressure (IOP) need further elaboration. Proposed sites include the inner wall of Schlemms’s canal and the juxtacanalicular trabecular meshwork ocular drainage tissues. The adherens junctions (AJs) of Schlemm’s canal endothelial cells (SECs) must both preserve the blood-aqueous humor (AQH) barrier and be conducive to AQH drainage. How homeostatic control of AJ permeability in SC occurs and how such control impacts IOP is unclear. We hypothesized that mechano-responsive phosphorylation of the junctional molecule VE-CADHERIN (VEC) by SRC family kinases (SFKs) regulates the permeability of SEC AJs. We tested this by clamping IOP at either 16 mmHg, 25 mmHg, or 45 mmHg in mice and then measuring AJ permeability and VEC phosphorylation. We found that with increasing IOP: 1) SEC AJ permeability increased, 2) VEC phosphorylation was increased at tyrosine-658, and 3) SFKs were activated at the AJ. Among the two SFKs known to phosphorylate VEC, FYN, but not SRC, localizes to the SC. Furthermore, FYN mutant mice had decreased phosphorylation of VEC at SEC AJs, dysregulated IOP, and reduced AQH outflow. Together, our data demonstrate that increased IOP activates FYN in the inner wall of SC, leading to increased phosphorylation of AJ VEC and, thus, decreased resistance to AQH outflow. These findings support a crucial role of mechanotransduction signaling in IOP homeostasis within SC in response to IOP. These data strongly suggest that the inner wall of SC partially contributes to outflow resistance.
Multi-method quantification of acetyl-CoA and further acyl-CoA species in normal and ischemic rat liver
Authors: Tokarska-Schlattner Malgorzata , Zeaiter Nour , Cunin Valérie , Attia Stéphane , Meunier Cécile , Kay Laurence , Achouri Amel , Hiriart-Bryant Edwige , Couturier Karine , Tellier Cindy , Harras Abderrafek El , Elena-Herrmann Bénédicte , Khochbin Saadi , Gouellec Audrey Le , Schlattner Uwe 
Published: September 2023

AbstractThioesters of coenzyme A (CoA) carrying different acyl chains (acyl-CoAs) are central intermediates of many metabolic pathways and donor molecules for protein lysine acylation. Acyl-CoA species largely differ in cellular concentrations and physico-chemical properties, rendering their analysis challenging. Here we compare several approaches to quantify cellular acyl-CoAs concentrations in normal and ischemic rat liver, using HPLC and LC-MS/MS for multi-acyl-CoA analysis, as well as NMR, fluorimetric and spectrophotometric techniques for quantification of acetyl-CoA. In particular, we describe a simple LC-MS/MS protocol that is suitable for the relative quantification of short and medium chain acyl-CoAs species. We show that ischemia induces specific changes in the short chain acyl-CoA relative concentrations, while mild ischemia (1-2 min), although reducing succinyl-CoA, has little effects on acetyl-CoA, and even increases some acyl-CoAs species upstream of the tricarboxylic acid cycle. In contrast, advanced ischemia (5-6 min) also reduces acetyl-CoA levels. Our approach provides the keys to accessing the acyl-CoA metabolome for a more in-depth analysis of metabolism, protein acylation and epigenetics.
UBC13-mediated template switching promotes replication stress resistance in FBH1-deficient cells
Authors: Hawks Alexandra L. , Bergmann Amy , McCraw Tyler J. , Mason Jennifer M. 
Published: September 2023

ABSTRACTThe proper resolution of DNA damage during replication is essential for genome stability. FBH1, a UvrD, helicase plays crucial roles in the DNA damage response. FBH1 promotes double strand break formation and signaling in response to prolonged replication stress to initiate apoptosis. Human FBH1 regulates RAD51 to inhibit homologous recombination. A previous study suggested that mis-regulation of RAD51 may contribute to replication stress resistance in FBH1-deficient cells, but the underlying mechanism remains unknown. Here, we provide direct evidence that RAD51 promotes replication stress resistance in FBH1-deficient cells. We demonstrate inhibition of RAD51 using the small molecule, B02, partially rescues double strand break signaling in FBH1-deficient cells. We show that inhibition of only the strand exchange activity of RAD51 rescues double strand break signaling in FBH1 knockout cells. Finally, we show that depletion of UBC13, a E2 protein that promotes RAD51-dependent template switching, rescues double strand break formation and signaling sensitizing FBH1- deficient cells to replication stress. Our results suggest FBH1 regulates template switching to promote replication stress sensitivity.