bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thrombotic Thrombocytopenic Purpura in a Parturient Leading to Life-Threatening Thrombocytopenia and Neonatal Demise—A Case Report
Authors: Berger Amnon A. , Kowalczyk John J. , Hess Philip E. , Li Yunping 
Published: December 2022

Abstract
Thrombocytopenia is common (up to 12%) in pregnancy; thrombotic thrombocytopenia is a rare cause of thrombocytopenia; however, it is immediately life-threatening to both mother and fetus and requires immediate intervention. This is compounded by the need to act on a presumptive diagnosis with high level of suspicion given the relatively long laboratory confirmation time. A 31-year-old gravida 3, para 1 parturient at 26 weeks of gestation presented to outside hospital with recent onset of easy bruising and blurry vision. A blood count was drawn and showed a platelet count of 19,000/μL. She was transferred to our institution for management where an initial diagnosis of preeclampsia with severe features was made based on thrombocytopenia and fetal growth restriction (<1%). Platelet count nadired at 14,000/μL and a blood smear showed schistocytes, suggesting microangiopathic hemolysis, prompting discussion of urgent cesarean delivery and anesthesia consult. An urgent hematology consult led to presumptively diagnosing thrombotic thrombocytopenic purpura and cesarean delivery was deferred after discussion with the patient and team. Plasma exchange and steroid therapy were started promptly, and her platelet count improved within 12 hours. Unfortunately, the patient experienced neonatal demise. Undetectable ADAMTS13 levels confirmed diagnosis of thrombotic thrombocytopenia. She was transitioned to rituximab, platelets recovered to baseline, and she continues to do well. Thrombotic thrombocytopenia is a rare, life-threatening cause of thrombocytopenia in pregnancy. Despite grim fetal prognosis, especially in early pregnancy, low threshold of suspicion, early anesthesia involvement, and multidisciplinary approach can facilitate diagnosis and timely intervention. In our case, it was likely lifesaving.
Dose–response relationship and effect modifier of stabilisation exercises in nonspecific low back pain: a project-wide individual patient data re-analysis on 1483 intervention participants
Authors: Niederer Daniel , Pfeifer Ann-Christin , Engel Tilman , Block Andrea , Schäfer Robin , Floessel Philipp , Beck Heidrun , Platen Petra , Schiltenwolf Marcus , Schneider Christian , Wippert Pia-Maria , Vogt Lutz , Mayer Frank 
Published: December 2022

Abstract
This planned MiSpEx-Network reanalysis was designed to derive a dose–response relationship under consideration of further effect modifiers in exercises on low back pain. One thousand four hundred eighty three intervention participants with low back pain (mean age, 40.9 years [SD 14 years]) performed stabilisation exercises (3 weeks supervised, 9 weeks self-administered). Patients reported pain intensity, disability, and disability days at baseline, 3 weeks, 12 weeks, and 6 months post randomisation. Exercise characteristics and effect modifiers were prospectively monitored. Beyond the comparison to the results of the control group, linear mixed models were calculated to determine a dose–response relationship. The interventions led to small but significantly larger symptom reductions than in the control group at each measurement. Longer durations of the intervention led to larger symptom reductions. Higher exercise frequencies were associated with a decrease in pain intensity: to train once more per week led to a mean decrease of 0.93 points in pain intensity [95% CI = −1.54 to −0.32]. Disability days were also impacted (estimate = −0.07 [−0.14 to 0.00]), but disability was not (−0.09 [−0.67 to 0.48]). Adding perturbation was superior to adding stretching or a behavioural module. The relationships were robust when additional effect modifiers were considered and against the control group' effects. The odds ratio for a clinically important effect with higher exercise frequencies decreased at 3 weeks (OR = 0.71 [0.618-0.813] for >2.5*week−1) and increased at 12 weeks (1.13 [1.006-1.270], >1.5*week−1). Using longer intervention durations, adding a perturbation component to the stabilisation trainings and using higher frequencies (up to a certain point) may lead to an even more beneficial response on exercise in patients with low back pain. Developing strategies to maintain a training frequency of at least 2 times per week may be relevant in stabilisation exercises to treat low back pain.
Insights into the evolution of herbivory from a leaf-mining, drosophilid fly
Authors: Aguilar Jessica M. , Gloss Andrew D. , Suzuki Hiromu C. , Verster Kirsten I. , Singhal Malvika , Hoff Jordan , Grebenok Robert , Nabity Paul D. , Behmer Spencer T. , Whiteman Noah K. 
Published: December 2022

AbstractHerbivorous insects and their host plants comprise most known species on Earth. Illuminating how herbivory repeatedly evolved in insects from non-herbivorous lineages is critical to understanding how this biodiversity is created and maintained. We characterized the trophic niche ofScaptomyza flava, a representative of a lineage nested within theDrosophilathat transitioned to herbivory ∼15 million years ago. We used natural history studies to determine ifS. flavais a true herbivore or a cryptic microbe-feeder. Specifically, we quantified oviposition substrate choice and larval viability across food-types, trophic-related morphological traits, and nitrogen isotope and sterol profiles across putatively herbivorous and non-herbivorous drosophilids. We confirmed thatS. flavais an obligate herbivore of living plants. Paired with its genetic model host,Arabidopsis thaliana, S. flavais a novel and powerful system for exploring mechanisms underlying the evolution of herbivory, a complex trait that enabled the exceptional diversification of insects.
Parasite transmission in size-structured populations
Authors: Shaw Kelsey E , Cloud Rebecca E , Syed Raeyan , Civitello David J 
Published: December 2022

AbstractHost heterogeneity can impact parasite transmission, but determining underlying traits and incorporating them into transmission models remains challenging. Body size is easily measured and influences numerous ecological interactions, including transmission. In the snail-schistosome system, larger snails have a higher exposure to parasites but lower susceptibility to infection per parasite. We quantified the impact of size-based heterogeneity on population-level transmission by conducting transmission trials in differently size-structured snail populations and competing size-dependent transmission models. Populations with greater proportions of large snails had lower prevalence, and small snails were shielded from infection by co-occurring large conspecifics. Using the winning size-explicit model, we then estimated that schistosome transmission varies dramatically across time due to seasonal changes in snail population size structure. Thus, incorporating traits such as body size, which are impacted by and directly affect host ecology, into transmission models could yield insights for natural dynamics and disease mitigation in many systems.Open Research StatementAll experimental data and novel code used for data analysis are currently available on Figshare via this private link:https://figshare.com/s/7d70b88220b912e7eec5. Data will be made public on Figshare upon acceptance. Data set utilized for Figure 4 are from the following source: Rumi, A., D. Gutiérrez Gregoric, and A. Roche. 2009. Tendencias Del Crecimiento Individual en Poblaciones Naturales de Biomphalaria spp. (Gastropoda, Planorbidae) en la Cuenca del Plata, Argentina.Comunicaciones de la Sociedad Malacológica del Uruguay. URL:https://www.redalyc.org/articulo.oa?id=52414008002
Increased mRNA expression of CDKN2A is a transcriptomic marker of clinically aggressive meningiomas
Authors: Wang Justin Z. , Patil Vikas , Liu Jeff , Dogin Helin , Behling Felix , Skardelly Marco , Tatagiba Marcos , Hoffman Elgin , Bunda Severa , Yakubov Rebecca , Kaloti Ramneet , Brandner Sebastian , Gao Andrew , Gadol Aaron-Cohen , Barnholtz-Sloan Jennifer , Raleigh David , Sahm Felix , Boutros Paul C. , Tabatabai Ghazaleh , Aldape Kenneth , Nassiri Farshad , Zadeh Gelareh 
Published: December 2022

AbstractBackgroundHomozygous loss of CDKN2A/B is a genetic alteration found in many cancer types including meningiomas, where it is associated with poor clinical outcome. It is now also a diagnostic criterion for grade 3 meningiomas in the 2021 WHO classification for central nervous system tumors. However, as in other cancers, the relationship between copy number loss of CDKN2A/B and expression of its gene product is unclear and may be either commensurate or paradoxical in nature. Therefore, we aimed to investigate the association of CDKN2A mRNA expression with clinical prognosis, WHO grade, and other molecular biomarkers in meningiomas such as DNA methylation, molecular group, and proteomics.MethodsWe used multidimensional molecular data of 490 meningioma samples from 4 independent cohorts to examine the relationship between mRNA expression of CDKN2A and copy number status, its correlation to clinical outcome, the transcriptomic pathways altered in differential CDKN2A expression, and its relationship with DNA methylation, and proteomics using an integrated molecular approach.ResultsMeningiomas without any copy number loss were dichotomized into high (CDKN2Ahigh) and low (CDKN2Alow) CDKN2A mRNA expression groups. Patients with CDKN2Ahighmeningiomas had poorer progression free survival (PFS) compared to those with CDKN2Alowmeningiomas. CDKN2A mRNA expression was increased in more aggressive molecular groups, and in higher WHO grade meningiomas across all cohorts. CDKN2Ahighmeningiomas and meningiomas with CDKN2A copy number loss shared common up-regulated cell cycling pathways. CDK4 mRNA expression was increased in CDKN2Ahighmeningiomas and both p16 and CDK4 protein were more abundant in CDKN2Ahighmeningiomas. CDKN2Ahighmeningiomas were frequently hypermethylated at the gene body and UTR compared to CDKN2Alowmeningiomas and found be more commonly Rb-deficient.ConclusionsAn intermediate level of CDKN2A mRNA expression appears to be optimal as significantly low (CDKN2A deleted) or high expression (CDKN2Ahigh) are associated with poorer outcomes clinically. Though CDK4 is elevated in CDKN2Ahighmeningiomas, Rb-deficiency may be more common in this group, leading to lack of response to CDK inhibitors.
FACTORS IMPACTED ON WELLBEING IN ADOLESCENT WHO HAVE FAMILY MEMBER WITH MENTAL DISORDER: A LITERATURE REVIEW
Authors: Tristiana Rr Dian , Rumambo Pandin Glorino , Yusuf Ah , Moses  
Published: December 2022

ABSTRACTHaving a family member with mental disorder will affect their healthy family member life. This study to examine the factors impacted on adolescent well-being who have family member with mental disorder. This study was a literature review in two databases SCOPUS and Science which conducted by four steps: (1) identification of literature; (2) screening questions; (3) eligibility using inclusion criteria; and (4) assessment of the quality of the studies. This study found 17 article which then reviewed and analyzed. The study result found seven theme that impacted on well-being included the caregiving responsibilities; the caregiving perception; the caregiving supports; Coping; Caregiving burden; Caregiving positive effects; Psychological impact; Adaptation enhancing. This study the results show the need to explore the seven themes in relation to the conditions of well-being on adolescent who have family member with mental disorder.
Two Muscle-Specific and Direct Transcriptional Targets of DAF-16/FOXO Activated by Reduced Insulin/IGF-1 Signaling
Authors: Wu Shifei , Li Yan , Roy Charline , Wang Ying , Mulcahy Ben , Li William , Calarco John , Hung Wesley , Zhen Mei 
Published: December 2022

AbstractC. elegansinsulin/insulin-like growth factor 1 signaling (IIS) affects diverse physiological processes through the DAF-16/FOXO transcription factor. Despite its presence in all somatic cells, DAF-16’s physiological effects, such as modulation of dauer formation, synapse maturation, axon regeneration, and adult longevity, exhibit prevalent tissue-specificity as well as tissue crosstalk. This implies that tissue-specific DAF-16 transcriptional programs contribute to the functional diversity of IIS. To further examine this possibility, we sought to identify tissue-specific and direct transcriptional targets of DAF-16 in muscle cells. Following FACS-sorting to enrich mature muscle cells from young adult animals, we compared the muscle transcriptomes under high and low IIS states, with and without DAF-16. We further analyzed and compared the DAF-16 docking sites in muscle and intestine cells from published datasets. These analyses revealed 14 potential muscle-specific DAF-16 transcriptional targets, among which we validated two that are strongly and specifically activated by DAF-16 in muscles: a secreted protein C54F6.5 and a calcium-binding protein CEX-1/Calexcitin. Both genes exhibit DAF-16-independent non-muscle expression, explaining their low rank or absence from the current DAF-16 target lists generated by multiple independent whole-animal microarray or mRNA-sequencing analyses. These results support the notion of tissue-specific DAF-16 transcriptional programs and highlight the importance of verifying FOXO targets in a cell-type-specific manner.
Inhibiting POLQ-mediated alternative NHEJ enhances CRISPR/Cas9 mediated precise genome editing in CHO cells
Authors: Wang Chuanjie , Wang Ming , Zhang Mengmeng , Wang Yao , Li Xinying , Liu Chenghua , Fan Rongrong , Zheng Yuanqiang , Shen Beifen , Sun Zhaolin , Wang Jing , Feng Jiannan 
Published: December 2022

ABSTRACTCRISPR/Cas9 mediated precise gene editing requires homology-directed repair (HDR), which occurs less frequently than non-homologous end-joining (NHEJ) including the canonical NHEJ and alternative NHEJ (Alt-EJ) in mammalian cells, especially in CHO cells that inherent resist HDR. To solve the above hurdle, here we for the first time show that knockout the DNA polymerase θ (POLθ), which is essential for Alt-EJ, significantly increases the knock-in efficiency by nearly forty-fold in CHO cells via eGFP reporter system and does not affect the normal growth and proliferation of cells. Meanwhile, even when transfecting simple circular, without negative element homologous template DNA donor and CRISPR/Cas9 plasmid to two different genomic sites, the knock-in rate of 4kb donor integration can still reach a mean of over 80% (29/36) and 2.7% (1/36) of the selected cell colonies inPOLQ-/-CHO cells, however, no positive knock-in cell colonies was obtained in wild-type CHO cells which respectively selected 62 cell colonies and 36 cell colonies. Furthermore, we show thatPOLQpromotes random integration in CHO cells. Finally, RNA-sequence analysis reveals not significant altered DNA repair, metabolism, apoptosis, and cell cycle inPOLQ-/-cells. These findings open a new target genePOLQto overcome bottlenecks of the precision genome editing.
Evaluation of the Efficacy of the Hypocretin/orexin Receptor Agonists TAK-925 and ARN-776 in NarcolepticOrexin/tTA; TetO-DTAMice
Authors: Sun Yu , Ranjan Alok , Tisdale Ryan , Ma Shun-Chieh , Park Sunmee , Haire Meghan , Heu Jasmine , Morairty Stephen R. , Wang Xiaoyu , Rosenbaum Daniel M. , Williams Noelle S. , De Brabander Jef K. , Kilduff Thomas S. 
Published: December 2022

AbstractThe sleep disorder Narcolepsy, a hypocretin deficiency disorder thought to be due to degeneration of hypothalamic hypocretin/orexin neurons, is currently treated symptomatically. We evaluated the efficacy of two small molecule hypocretin/orexin receptor-2 (HCRTR2) agonists in narcoleptic maleorexin/tTA; TetO-DTAmice. TAK- 925 (1-10 mg/kg, s.c.) and ARN-776 (1-10 mg/kg, i.p.) were injected 15 min before dark onset in a repeated measures design. EEG, EMG, subcutaneous temperature (Tsc) and activity were recorded by telemetry; recordings for the first 6-h of the dark period were scored for sleep/wake and cataplexy. At all doses tested, TAK-925 and ARN-776 caused continuous wakefulness and eliminated sleep for the first hour. Both TAK-925 and ARN-776 caused dose-related delays in NREM sleep onset. All doses of TAK-925 and all but the lowest dose of ARN-776 eliminated cataplexy during the first hour after treatment; the anti-cataplectic effect of TAK-925 persisted into the 2ndhour for the highest dose. TAK-925 and ARN-776 also reduced the cumulative amount of cataplexy during the 6-h post-dosing period. The acute increase in wakefulness produced by both HCRTR2 agonists was characterized by increased spectral power in the gamma EEG band. Although neither compound provoked a NREM sleep rebound, both compounds affected NREM EEG during the 2ndhour post-dosing. TAK-925 and ARN-776 also increased gross motor activity, running wheel activity and Tsc, suggesting that the wake-promoting and sleep-suppressing activities of these compounds could be a consequence of hyperactivity. Nonetheless, the anti-cataplectic activity of TAK-925 and ARN-776 is encouraging for the development of HcrtR2 agonists.
FGF2 and BMP4 influence on FGFR2 dynamics during the segregation of epiblast and primitive endoderm cells in the pre-implantation mouse embryo
Authors: Goissis Marcelo D. , Bradshaw Brian , Posfai Eszter , Rossant Janet 
Published: December 2022

AbstractSpecification of the epiblast (EPI) and primitive endoderm (PE) in the mouse embryo involves FGF signaling through the RAS/MAP kinase pathway. FGFR1 and FGFR2 are thought to mediate this signaling in the inner cell mass (ICM) of the mouse blastocyst. In this study, we verified the dynamics of FGFR2 expression through a green fluorescent protein reporter mouse line (FGFR2-eGFP). We observed that FGFR2-eGFP is present in the late 8-cell stage; however, it is absent or reduced in the ICM of early blastocysts. We then correlated GFP expression with GATA6 and NANOG after immunostaining. We detected that GFP is weakly correlated with GATA6 in early blastocysts, but this correlation quickly increases as the blastocyst develops. The correlation between GFP and NANOG decreases throughout blastocyst development. Treatment with FGF from the morula stage onwards did not affect FGFR2-eGFP presence in the ICM of early blastocysts; however, late blastocysts presented FGFR2-eGFP in all cells of the ICM. BMP treatment positively influenced FGFR2-eGFP expression and reduced the number of NANOG-positive cells in late blastocysts. In conclusion, FGFR2 is not strongly associated with PE precursors in the early blastocyst, but it is highly correlated with PE cells as blastocyst development progresses, consistent with the proposed role for FGF in maintenance rather than initiating the PE lineage.
Observation of the dynamic changes in the urinary proteome in rats during immunization
Authors: Wang Yunlong , Gao Youhe 
Published: December 2022

AbstractObjectiveChanges in the immune system in the urine proteome were observed by injecting bovine serum albumin and aluminum hydroxide adjuvant into rats.MethodsIn this study, bovine serum albumin and aluminum hydroxide adjuvant were injected into rat thigh muscle, urine was collected, differential proteins were identified by liquid chromatography—mass spectrometry (LC—MSMS/MS), and biological pathways of differential proteins were analyzed by IPA software to observe the changes in the immune system as evidenced by rat urinary proteins.ResultsFifteen rats were intramuscularly injected with normal saline, aluminum hydroxide adjuvant, bovine serum albumin, aluminum hydroxide adjuvant, and bovine serum albumin (BSA) mixture to construct the models of the control, adjuvant, BSA, and mixed groups. Upon comparing the different proteins between different groups to obtain the relevant biological pathways, it was found that adjuvants can be observed in urine to help bovine serum albumin stimulate the immune system to respond earlier. It was also observed in urine that the mixed group successively stimulated immune-related pathways, such as the inflammatory response, T-cell activation, antigen-presenting cell-related pathways, and B-cell-related pathways.DiscussionWe can observe changes in the immune system from the urine proteome in the early stage, providing some new clues and a basis for future research on the immune system and accelerating vaccine research and development.
Genetically encoded multimeric tags for intracellular protein localisation in cryo-EM
Authors: Fung Herman KH , Hayashi Yuki , Salo Veijo T , Babenko Anastasiia , Zagoriy Ievgeniia , Brunner Andreas , Ellenberg Jan , Müller Christoph W , Cuylen-Haering Sara , Mahamid Julia 
Published: December 2022

AbstractCryo-electron tomography is a powerful label-free tool for visualizing biomolecules in their native cellular context at molecular resolution. However, the precise localisation of biomolecules of interest in the tomographic volumes is challenging. Here, we present a tagging strategy for intracellular protein localisation based on genetically encoded multimeric particles (GEMs). We show the applicability of drug-controlled GEM labelling of endogenous proteins in cryo-electron tomography and cryo-correlative fluorescence imaging in human cells.
Effects of aging on successful object encoding: Enhanced semantic representations compensate for impaired visual representations
Authors: Naspi Loris , Stensholt Charlotte , Karlsson Anna E , Monge Zachary A , Cabeza Roberto 
Published: December 2022

AbstractWhereas episodic memory and visual processing decline substantially with healthy aging, semantic knowledge is generally spared. There is evidence that older adults can take advantage of their spared semantic knowledge to support their performance in episodic memory and visual tasks. Here, we used fMRI combined with representational similarity analyses (RSA) to examine how visual and semantic representations stored during encoding predict subsequent object memory. Young and older adults encoded images of objects during fMRI scanning and recalled these images while rating the vividness of their memories. After scanning, participants discriminated between studied images and similar lures. RSA based on a deep convolutional neural network and normative concept feature data was used to link patterns of neural activity during encoding to visual and semantic representations. The quality of visual representations was reduced in older adults, consistent with dedifferentiation, whereas the quality of semantic representations was enhanced in older adults, consistent with hyperdifferentiation. Despite dedifferentiation, visual representations stored in early visual cortex predicted later recall with high vividness in both young and older adults, with no age-related differences. In contrast, semantic representations in lingual and fusiform gyrus were associated with better subsequent object picture recall in older but not in young adults. This finding is consistent with evidence that older adults rely on semantic knowledge to compensate for cognitive deficits. Taken together, the results suggest that the age-related neural dedifferentiation for visual information in posterior regions might be partly counteracted by a boost on semantic representations in more anterior areas.Significance StatementPrevious research has shown that healthy aging tends to impair memory for individual events, visual processing, and other cognitive abilities but not semantic knowledge. We investigated the effects of aging on the quality of the information stored in the brain when viewing common objects and on how this information enables subsequent memory for these objects. Using fMRI combined with modeling of the stimuli, we found that visual information was degraded in older adults, but it was sufficient to support subsequent memory. In contrast, semantic information supported subsequent memory only in older adults. This is the first direct neuroscience evidence that older adults take advantage of spared semantic representations to boost their memory for individual events.