bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of calcium supplementation in people under 35 years old: A systematic review and meta-analysis of randomized controlled trials
Authors: Liu Yupeng , Le Siyu , Liu Yi , Jiang Huinan , Ruan Binye , Huang Yufeng , Ao Xuemei , Shi Xudong , Fu Xiaoyi , Wang Shuran 
Published: April 2022

ABSTRACTBackground and objectiveThe effect of calcium supplementation on bone mineral accretion in people under 35 years old is inconclusive. To comprehensively summarize the evidence for the effect of calcium supplementation on bone mineral accretion in young populations (≤35 years).DesignThis is a systematic review and meta-analysis.Data sourcesThe Pubmed, Embase, ProQuest and CENTRAL databases were systematically searched from database inception to April 25, 2021.EligibilityRandomized clinical trials assessing the effects of calcium supplementation on bone mineral density (BMD) or bone mineral content (BMC) in people under 35 years old.ResultsThis systematic review and meta-analysis identified 43 studies involving 7382 subjects. Moderate certainty of evidence showed that calcium supplementation was associated with the accretion of BMD and BMC, especially on femoral neck (SMD 0.627, 95% CI 0.338 to 0.915; SMD 0.364, 95% CI 0.134 to 0.595; respectively) and total body (SMD 0.330, 95% CI 0.163 to 0.496; SMD 0.149, 95% CI 0.006 to 0.291), also with a slight improvement effect on lumbar spine BMC (SMD 0.163, 95% CI 0.008 to 0.317), no effects on total hip BMD and BMC and lumbar spine BMD were observed. Very interestingly, subgroup analyses suggested that the improvement of bone at femoral neck was more pronounced in the peri-PBM population (20-35 years) than the pre-PBM population (<20 years).ConclusionOur findings provided novel insights and evidence in calcium supplementation, which showed that calcium supplementation significantly improves bone mass, implying that preventive calcium supplementation before or around achieving PBM may be a shift in the window of intervention for osteoporosis.FundingThis work was supported by Wenzhou Medical University grant [89219029].
Post-operative pain management practice and associated factors among nurses working at public hospitals, in Oromia region, Ethiopia
Authors: Dechasa Abebe , Kurke Abdo , Abdisa Desalegn , Gurmu Yonas 
Published: April 2022

AbstractBackgroundManagement of postoperative pain leads to positive patient progress and shortens the duration of hospital stay. Nurses, who are the majority in almost all hospitals and spend most of their time with the patients, are expected to play big role in the postoperative pain management practice. However, there is paucity of information regarding postoperative pain management practice and its associated factors among nurses.ObjectiveTo assess postoperative pain management practice and associated factors among nurses working at public hospitals, in Oromia Region, Ethiopia, 2020.MethodsInstitutional based cross sectional study was employed among randomly selected 377 nurses working at public hospitals in Oromia region, Ethiopia. Data was collected by distributing structured self-administered questionnaires that adapted from different literatures. The data were entered into Epi data version 3.1 and exported to SPSS version 22 for analysis. Variables with significant association in the bivariate analyses were entered into a multivariable regression analysis to identify the independent factors associated with nurses’ postoperative pain management practice. Significant factors were declared at P<0.05.ResultThe result showed that, 66% of nurses had good pain management practice. Nurses favorable attitude towards post-operative pain management [AOR: 4.698, 95% CI: (2.725-8.100)], having access to read pain management guideline [AOR: 3.112, 95% CI: (1.652-5.862)], adequate knowledge of post-operative pain management [AOR: 2.939, 95% CI: (1.652-5.227)], working at Operation Room [AOR: 2.934, 95% CI: (1.27-6.795)] and received training on pain management [AOR: 3.289, 95% CI: (1.461-7.403)] were significantly associated with the practices of postoperative pain management.Conclusion and recommendationSixty six percent of participants (nurses) have a good level of practice of postoperative pain management. Training on post-operative pain management (POPM), access to pain management guidelines, knowledge and attitude are significant factors in post-operative pain management practice. Governmental and other bodies concerned to post-operative care quality needs to show commitment on availing infrastructures like pain management guideline and improving nurses knowledge and attitude.
Association between breastfeeding, host genetic factors, and calicivirus gastroenteritis in a Nicaraguan birth cohort
Authors: Vielot Nadja A. , François Ruthly , González Fredman , Reyes Yaoska , Huseynova Emilya , Gutierrez Lester , Nordgren Johan , Toval-Ruiz Christian , Vilchez Samuel , Vinjé Jan , Becker-Dreps Sylvia , Bucardo Filemon 
Published: April 2022

ABSTRACTBackgroundNorovirus and sapovirus are important causes of childhood acute gastroenteritis (AGE). Breastfeeding prevents AGE generally; however, it is unknown if breastfeeding prevents AGE caused specifically by norovirus and sapovirus.MethodsWe investigated the association between breastfeeding and norovirus or sapovirus AGE episodes in a birth cohort. Weekly data on breastfeeding and AGE episodes were captured during the first year of life. Stools were collected from children with AGE and tested by RT-qPCR for norovirus and sapovirus. Time-dependent Cox models estimated associations between weekly breastfeeding and time to first norovirus or sapovirus AGE.FindingsFrom June 2017 to July 2018, 444 newborns were enrolled in the study. In the first year of life, 69 and 34 children experienced a norovirus and a sapovirus episode, respectively. Exclusive breastfeeding lasted a median of 2 weeks, and any breastfeeding lasted a median of 42 weeks. Breastfeeding in the last week did not prevent norovirus (HR: 1.09, 95% CI: 0.62, 1.92) or sapovirus (HR: 1.00, 95% CI: 0.82, 1.21) AGE in a given week, adjusting for household sanitation, consumption of high-risk foods, and mother’s and child’s histo-blood group phenotypes. Maternal secretor-positive phenotype was protective against norovirus AGE, whereas child’s secretor-positive phenotype was a risk factor for norovirus AGE.InterpretationExclusive breastfeeding in this population was short-lived, and no conclusions could be drawn about its potential to prevent norovirus or sapovirus AGE. Non-exclusive breastfeeding did not prevent norovirus or sapovirus AGE in the first year of life. However, maternal secretor-positive phenotype was associated with a reduced hazard of norovirus AGE.WHAT IS KNOWN–Breastfeeding prevents acute gastroenteritis (AGE) in nursing infants.–It is unknown if breastfeeding prevents AGE caused by norovirus or sapovirus, which are leading causes of childhood AGE worldwide.–Host genetic factors can influence AGE risk, and the mediating effects of breastfeeding are unclear.WHAT IS NEW–Exclusive breastfeeding was rare, and breastfeeding did not prevent norovirus (hazard ratio 1.09, 95% CI: 0.62, 1.92) or sapovirus (hazard ratio 1.00, 95% CI: 0.82, 1.21) AGE.–Secretor-positive phenotype of the child and the mother may be more important than breastfeeding in determining norovirus and sapovirus AGE risk in this setting.
Neural network approach to somatic SNP calling in WGS samples without a matched control
Authors: Vilov Sergey , Heinig Matthias 
Published: April 2022

AbstractSomatic variants are usually called by analysing the DNA sequences of a tumor sample in conjunction with a matched normal. However, a matched normal is not always available for instance in diagnostic settings. To unlock such data for basic research single-sample somatic variant calling is required. Previous approaches can not easily be applied in the case of typical whole genome sequencing (WGS) samples.We present a neural network-based approach for calling somatic single nucleotide polymorphism (SNP) variants in tumor WGS samples without a matched normal. The method does not require any manual tuning of filtering parameters and can be applied under the conditions of a typical WGS experiment. We demonstrate the effectiveness of the proposed approach by reporting its performance on 5 SNP datasets corresponding to 5 different cancer types.The proposed method is implemented in Python 3.6 and available as a GitHub repository at https://github.com/heiniglab/deepSNP.
Epigenetics and island-mainland divergence in an insectivorous small mammal
Authors: Cossette Marie-Laurence , Stewart Donald T. , Haghani Amin , Zoller Joseph A. , Shafer Aaron B.A. , Horvath Steve 
Published: April 2022

AbstractGeographically isolated populations, specifically island-mainland counterparts, tend to exhibit phenotypic variation in many species. The so-called island syndrome occurs when different environmental pressures lead to insular divergence from mainland populations. This phenomenon can be seen in an island population of Nova Scotia masked shrews (Sorex cinereus), which have developed a specialized feeding habit and digestive enzyme compared to their mainland counterparts. Epigenetic modifications, such as DNA methylation (DNAm), can impact phenotypes by altering gene expression without changing the DNA sequence. Here, we used ade novomasked shrew genome assembly and a mammalian methylation array profiling 37 thousand conserved CpGs to investigate morphological and DNA methylation patterns between island and mainland populations. Island shrews were morphologically and epigenetically different than their mainland counterparts, exhibiting a smaller body size. A gene ontology enrichment analyses of differentially methylated CpGs implicated developmental and digestive system related pathways. Based on our shrew epigenetic clock, island shrews might also be aging faster than their mainland counterparts. This study provides novel insight on phenotypic and epigenetic divergence in island-mainland mammal populations and suggests an underlying role of methylation in island-mainland divergence.
Effect of Chlonisol (2-[3-(2-chloroethyl)-3-nitrosoureido]-1,3-propanediol) on Overall Survival in Laboratory Rodents with Intracranial Tumors: A Meta-analysis of Preclinical Studies
Authors: Murazov Iaroslav G. , Stukov Alexander N. , Zmitrichenko Iuliia G. 
Published: April 2022

ABSTRACTBackgroundThe need for new, effective, and affordable drugs for the treatment of primary and metastatic brain tumors remains unsatisfactory. Preclinical studies of chlonisol (2-[3-(2-chloroethyl)-3-nitrosoureido]-1,3-propanediol) showed promising results in the treatment of experimental intracranial tumors.ObjectivesTo apply a meta-analytical approach to estimate the combined effect size of chlonisol on overall survival (OS) in rodents with brain tumor transplants.Search strategyData for the meta-analysis were obtained from the laboratory’s internal database from reports of preclinical studies of chlonisol.Selection criteriaEligible studies were parallel preclinical trials in rodents (mice, rats) with intracranially transplanted tumors. Chlonisol was compared with active control treatment (lomustine or temozolomide). All cytostatics were administered at the maximum tolerated dose (MTD). The duration of the studies was at least 90 days. The main outcome was OS-HR (hazard ratio).Data analysisWe applied the inverse variance technique for the meta-analysis of HRs. In HR analysis we adopted a random-effect model.ResultsThe analysis included seven trials with 132 rodents. Studies were conducted between 2016 and 2022. As a murine intracranial grafts we used Ehrlich’s carcinoma, Sarcoma 180 and the HER2-positive mammary tumor derived from a female FVB/N HER-2/neu transgenic mouse. Glioma 35 was transplanted into rats. Compared with active control, oral or intraperitoneal administration of chlonisol at MTD of 20 mg/kg, significantly reduced the risk of death by 63% (HR=0.37; 95% CI: 0.24-0.56; P<0.00001) in animals with intracranial tumors. The direction in favor of chlonisol was stable across studies despite the use of different animals and transplants, the routes of administration of chlonisol, and control treatment. No significant heterogeneity was observed between the studies (Tau2 = 0.03; Chi2 = 6.52; df = 6; P = 0.33; I2 = 8%).ConclusionCompared with lomustine and temozolomide, chlonisol treatment in MTD provides an important advantage in OS in animals with intracranial tumors. Our results may serve as a basis for further study of chlonisol as a chemotherapy agent for primary and metastatic brain tumors.
3D pose estimation enables virtual head-fixation in freely moving rats
Authors: Schneider Artur , Zimmermann Christian , Alyahyay Mansour , Steenbergen Florian , Brox Thomas , Diester Ilka 
Published: April 2022

AbstractThe impact of spontaneous movements on neuronal activity has created the need to quantify behavior. We present a versatile framework to directly capture the 3D motion of freely definable body points in a marker-free manner with high precision and reliability. Combining the tracking with neural recordings revealed multiplexing of information in the motor cortex neurons of freely moving rats. By integrating multiple behavioral variables into a model of the neural response, we derived a virtual head-fixation for which the influence of specific body movements was removed. This strategy enabled us to analyze the behavior of interest (e.g., front paw movements). Thus, we unveiled an unexpectedly large fraction of neurons in the motor cortex with tuning to the paw movements, which was previously masked by body posture tuning. Once established, our framework can be efficiently applied to large datasets while minimizing the experimental workload caused by animal training and manual labeling.
MMR Deficiency Defines Distinct Molecular Subtype of Breast Cancer with Unique Proteomic Networks and Variable Clinical Significance
Authors: Hacking Sean M. , Chou Charissa , Baykara Yigit , Wang Yihong , Uzun Alper , Uzun Ece D. Gamsiz 
Published: April 2022

AbstractMismatch repair (MMR) alterations are important prognostic and predictive biomarkers in a variety of cancer subtypes including colorectal and endometrial. However, in breast cancer (BC), the distinction and clinical significance of MMR is largely unknown. This may be due in part to the fact that genetic alterations in MMR genes are rare, and only seen to occur in around 3% of BCs. In the present study we analyzed TCGA data using a multi-sample protein-protein interactions (PPI) analysis tool, Proteinarium, and showed a distinct separation in the MMR deficient and intact specific networks. MMR deficient tumor specific networks have a highly connected cluster of histone genes, identified by unique PPI. We also found that distribution of MMR deficient breast cancer is more prevalent in HER2-enriched and triple-negative (TN) BC subtypes compared to luminal BCs. Poorer survival was seen in patients with HER2-enriched BCs with MMR deficiency, whereas an improved survival was seen in TNBCs with MMR deficiency. We recommend defining MMR deficient breast cancer by next generation sequencing (NGS) when any somatic mutation is detected in one of the 7 MMR genes found in our study. Our recommendations include labeling patients with variants of undetermined significance (VUS) as MMR deficient supported by findings from distinct clusters of patients based on our network analysis. MMR may have a role in guiding the use of immunotherapy for both TN as well as HER2-enriched BC.
Covert attention to obstacles biases zebrafish escape direction
Authors: Zwaka Hanna , McGinnis Olivia J , Pflitsch Paula , Prabha Srishti , Mansinghka Vikash , Engert Florian , Bolton Andrew D 
Published: April 2022

AbstractTo study the evolutionary origins of object perception, we investigated whether a primitive vertebrate, the larval zebrafish, is sensitive to the presence of obstacles. The zebrafish, which has become a useful model to study brain-wide circuit dynamics, executes fast escape swims when in danger of predation. We posited that collisions with solid objects during escape would be maladaptive to the zebrafish, and therefore the direction of escape swims should be informed by the locations of barriers. To answer this question, we developed a novel closed-loop high-speed imaging rig outfitted with barriers of various qualities. Using this system, we show that when larval zebrafish escape in response to a non-directional vibrational stimulus, they use visual scene information to avoid collisions with obstacles. Our study demonstrates that fish compute absolute distance to obstacles, as distant barriers outside of collision range elicit less bias than nearby collidable barriers that occupy the same visual field. The computation of barrier features is covert, as the fish’s reaction to barriers during routine swimming does not predict that they will avoid barriers when escaping. Finally, through two-photon laser ablations, we suggest the presence of an excitatory input from the visual system to Mauthner cells in the brainstem escape network that is responsible for escape direction bias. We propose that zebrafish construct “object solidity” via an integrative visual computation that is more complex than retinal occupancy alone, suggesting a primitive understanding of object features and possibly the origins of a structured model of the physical world.
Proliferative advantage of specific aneuploid cells drives evolution of tumor karyotypes
Authors: Ban Ivana , Tomašić Lucija , Trakala Marianna , Tolić Iva M. , Pavin Nenad 
Published: April 2022

ABSTRACTMost tumors have abnormal karyotypes, which arise from mistakes during mitotic division of healthy euploid cells and evolve through numerous complex mechanisms. In a recent mouse model with high levels of chromosome missegregation, chromosome gains dominate over losses both in pretumor and tumor tissues, whereas tumors are characterized by gains of chromosomes 14 and 15. However, the mechanisms driving clonal selection leading to tumor karyotype evolution remain unclear. Here we show, by introducing a mathematical model based on a concept of a macro-karyotype, that tumor karyotypes can be explained by proliferation-driven evolution of aneuploid cells. In pretumor cells, increased apoptosis and slower proliferation of cells with monosomies lead to predominant chromosome gains over losses. Tumor karyotypes with gain of one chromosome can be explained by karyotype-dependent proliferation, while for those with two chromosomes an interplay with karyotype-dependent apoptosis is an additional possible pathway. Thus, evolution of tumor-specific karyotypes requires proliferative advantage of specific aneuploid karyotypes.SignificanceMost tumors have an erroneous number of chromosomes, which arise from mistakes during division of healthy cells and evolve through numerous complex mechanisms, including chromosome missegregation, cell proliferation and cell death. However, understanding the mechanisms leading to tumor evolution from healthy cells is a hot topic. Here we show, by introducing a “macro-karyotype model”, that perturbed number of chromosomes in tumor cells arises predominantly from faster division of cells characterized by a specific combination of chromosomes, or together with irregular cell death. This finding, strengthened by comparison of our theory with experimentally observed combination of chromosomes in different stages of tumor development, gives a direction for future experiments in identifying the key processes underlying tumor development.
Evidence for a Single Rather than a Triple Dissociation in the Medial Temporal Lobe: an fMRI Recognition Memory Replication Study
Authors: Van Julie , Nielsen Sam E. , Kirwan C. Brock 
Published: April 2022

AbstractCommon research practices in neuroimaging studies using functional magnetic resonance imaging may produce outcomes that are difficult to replicate. Results that cannot be replicated have contributed to a replication crisis in psychology, neuroscience, and other disciplines over the years. Here we replicate two previous papers in which the authors present two analysis paths for a dataset in which participants underwent fMRI while performing a recognition memory test for old and new words. Both studies found activation in the medial temporal lobe including the hippocampus, with the first demonstrating a distinction in activation corresponding to true and perceived oldness of stimuli and the second demonstrating that activation reflects the subjective experience of the participant. We replicated the behavioral and MRI acquisition parameters reported in the two target articles (Daselaar, Fleck, & Cabeza, 2006; Daselaar, Fleck, Prince, et al., 2006) with N=53 participants. We focused fMRI analyses on regions of interest reported in the target articles examining fMRI activation for differences corresponding with true and perceived oldness and those associated with the subjective memory experiences of recollection, familiarity, and novelty. Comparisons between true and perceived oldness revealed main effects not only for true, but also perceived oldness along with significant interaction effects. We replicate the findings of recollection and familiarity signals in the hippocampus and medial temporal lobe cortex, respectively, but failed to replicate a novelty signal in the anterior medial temporal lobe. These results remained when we analyzed only correct trials, indicating that the effects were not due to selectively averaging correct and incorrect trials. Taken together, our findings demonstrate that activation in the hippocampus corresponds to the subjective experience associated with correct recognition memory retrieval.HighlightsWe replicated the methods of two influential papers using fMRI to examine recognition memory.The hippocampus consistently signals the subjective experience of remembering but not the objective old/new status of stimuli.Hippocampal response was consistent with recollection while the medial temporal lobe (MTL) cortex response was consistent with familiarity.We did not observe any regions in the MTL that signaled novelty, indicating recognition memory does not involve a triple dissociation of recollection, familiarity, and novelty in the MTL.
Generative power of a protein language model trained on multiple sequence alignments
Authors: Sgarbossa Damiano , Lupo Umberto , Bitbol Anne-Florence 
Published: April 2022

AbstractComputational models starting from large ensembles of evolutionarily related protein sequences capture a representation of protein families and learn constraints associated to protein structure and function. They thus open the possibility for generating novel sequences belonging to protein families. Protein language models trained on multiple sequence alignments, such as MSA Transformer, are highly attractive candidates to this end. We propose and test an iterative method that directly employs the masked language modeling objective to generate sequences using MSA Transformer. We demonstrate that the resulting sequences score as well as natural sequences, for homology, coevolution and structure-based measures. For large protein families, our synthetic sequences have similar or better properties compared to sequences generated by Potts models, including experimentally-validated ones. Moreover, for small protein families, our generation method based on MSA Transformer outperforms Potts models. Our method also more accurately reproduces the higher-order statistics and the distribution of sequences in sequence space of natural data than Potts models. MSA Transformer is thus a strong candidate for protein sequence generation and protein design.