bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ten-year mixed-method evaluation of prelicensure health professional student self-reported learning in an interfaculty pain curriculum
Authors: Dale Craig M. , Cioffi Iacopo , Murphy Laura , Langlois Sylvia , Musa Renata , Stevens Bonnie 
Published: September 2022

Abstract

See commentary: Trouvin A-P. “Ten-year mixed method evaluation of prelicensure health professional student self-reported learning in an interfaculty pain curriculum”: a view on pain education. PAIN Rep 2022;7:e1031.

Introduction:
Student perspectives on interprofessional pain education are lacking.

Objectives:
The purpose of this study was to evaluate ratings of knowledge acquisition and effective presentation methods for prelicensure health professional students attending the University of Toronto Centre for the Study of Pain Interfaculty Pain Curriculum (Canada).

Methods:
A 10-year (2009–2019) retrospective longitudinal mixed-methods approach comprising analysis and integration of quantitative and qualitative data sets was used to evaluate 5 core University of Toronto Centre for the Study of Pain Interfaculty Pain Curriculum learning sessions.

Results:
A total of 10, 693 students were enrolled (2009–2019) with a mean annual attendance of 972 students (±SD:102). The mean proportion of students rating “agree/strongly agree” for knowledge acquisition and effective presentation methods across sessions was 79.3% (±SD:3.4) and 76.7% (±SD:6.0), respectively. Knowledge acquisition or presentation effectiveness scores increased, respectively, over time for 4 core sessions: online self-study pain mechanisms module (P = 0.03/P < 0.001), online self-study opioids module (P = 0.04/P = 0.019), individually selected in-person topical pain sessions (P = 0.03/P < 0.001), and in-person patient or interprofessional panel session (P = 0.03). Qualitative data corroborated rating scores and expanded insight into student expectations for knowledge acquisition to inform real-world clinical practice and interprofessional collaboration; presentation effectiveness corresponded with smaller session size, individually selected sessions, case-based scenarios, embedded knowledge appraisal, and opportunities to meaningfully interact with presenters and peers.

Conclusion:
This study demonstrated positive and increasing prelicensure student ratings of knowledge acquisition and effective presentation methods across multifaceted learning sessions in an interfaculty pain curriculum. This study has implications for pain curriculum design aimed at promoting students' collaborative, patient-centered working skills.
Analysis of Image-Guided Superficial Radiation Therapy (IGSRT) on the Treatment of Early Stage Non-Melanoma Skin Cancer (NMSC) in the Outpatient Dermatology Setting
Authors: Tran Alison , Moloney Mairead , Kaczmarksi Peter , Zheng Songzhu , Desai Alpesh , Desai Tejas , Yu Lio 
Published: September 2022

AbstractInterest in image-guidance superficial radiation therapy (IGSRT) for the treatment of early-stage Non-Melanoma Skin Cancer (NMSC) has resurfaced given its low complication rates, superior cosmesis and local control and cure rates. Additionally, it has been recommended by the American Academy of Dermatology (AAD) for early-stage NMSC in patients who are considered poor surgical candidates.Methods1899 NMSC lesions were treated with energies ranging from 50 to 100 kilovoltage (kV), for a mean of 20.2 fractions, and treatment dose of 5364.4 centigray (cGy). Lesions were treated for a mean of 7.5 weeks and followed for 65.5 weeks. SAS studio was used to conduct Kaplan-Meier analysis to calculate local control rates and account for differences in follow-up intervals. A log-rank test was used to calculate statistical differences between histologies.ResultsAbsolute lesion control was achieved in 99.7% of the patients after an average of 7.5 weeks of treatment, with a stable control rate of 99.6% when the follow-up duration was over 12 months.ConclusionIGSRT has a high safety profile, can achieve superior cosmesis and should be considered first-line for treating early-stage NMSC tumors as cure rates have been shown to be effective in all NMSC on early follow-up.
The differential regulation of placenta trophoblast bisphosphoglycerate mutase in fetal growth restriction: preclinical study in mice and observational histological study of human placenta
Authors: Stroganov Sima , Harris Talia , Fellus-Alyagor Liat , Moyal Lital Ben , Mayo Romina Plitman , Golani Ofra , Brandis Alexander , Mehlman Tevie , Kovo Michal , Biron-Shental Tal , Dekel Nava , Neeman Michal 
Published: September 2022

AbstractBackgroundFetal growth restriction (FGR) is a pregnancy complication in which a newborn fails to achieve its growth potential, increasing the risk of perinatal morbidity and mortality. Chronic maternal gestational hypoxia, as well as placental insufficiency are associated with increased FGR incidence; however, the molecular mechanisms underlying FGR remain unknown.MethodsIn a case control study of murine and human control and FGR placentae, we implied MR imaging, IHC and metabolomics to assess the levels of BPGM and 2,3 BPG to elucidate the impact of maternal gestational hypoxia, and the molecular mechanisms underlying human FGR.ResultsWe show that murine acute and chronic gestational hypoxia recapitulates FGR phenotype and affects placental structure and morphology. Gestational hypoxia decreased labyrinth area, increased the incidence of red blood cells (RBCs) in the labyrinth while expanding the placental spiral arteries (SpA) diameter. Hypoxic placentae exhibited higher hemoglobin-oxygen affinity compared to the control. Placental abundance of bisphosphoglycerate mutase (BPGM) was upregulated in the syncytiotrophoblast and spiral artery trophoblast cells (SpA TGCs) in the murine gestational hypoxia groups compared to the control. In contrast, human FGR placentae exhibited reduced BPGM levels in the syncytiotrophoblast layer compared to placentae from healthy uncomplicated pregnancies. Levels of 2,3 BPG, the product of BPGM, were lower in cord serum of human FGR placentae compared to control. Polar expression of BPGM, was found in both human and mouse placentae syncytiotrophoblast, with higher expression facing the maternal circulation. Moreover, in the murine SpA TGCs expression of BPGM was concentrated exclusively in the apical cell side, in direct proximity to the maternal circulation.ConclusionsThis study suggests a possible involvement of placental BPGM in maternal-fetal oxygen transfer, and in the pathophysiology of FGR.FundingThis work was supported by the Weizmann - Ichilov (Tel Aviv Sourasky Medical Center) Collaborative Grant in Biomedical Research (to MN) and by the Israel Science Foundation KillCorona grant 3777/19 (to MN, MK).Graphical abstract
Relative Brain Age Is Associated with Socioeconomic Status and Anxiety/Depression Problems in Youth
Authors: Cohen Jacob W. , Ramphal Bruce , DeSerisy Mariah , Zhao Yihong , Pagliaccio David , Colcombe Stan , Milham Michael P. , Margolis Amy E. 
Published: September 2022

AbstractSocioeconomic status (SES) has been linked to differences in brain structure and psychiatric risk across the lifespan. Despite many neuropsychiatric disorders emerging in childhood, few studies have examined the influence of SES on brain aging and psychopathology in youth.We re-analyzed relative brain age (RBA) data from the Healthy Brain Network to examine the influence of SES components (parent education, occupation, household income-to-needs ratio (INR), public assistance enrollment) on RBA. RBA was previously determined using covariation patterns for cortical morphology, white, and subcortical gray matter volumes without SES in predictive models. We also examined associations between RBA and psychiatric symptoms (child behavior checklist). Full case analysis included 470 youth (5-17 years; 61.3% male), self-identifying as White (55%), African American (15%), Hispanic (9%), or multiracial (17.2%). Mean household income was 3.95±2.33 (Mean±SD) times the federal poverty threshold. Multiple linear regression examined if 1) SES components associated with RBA, and 2) RBA associated with psychiatric symptoms. Models covaried for sex, scan location, and parent psychiatric diagnoses.RBA associated with public assistance (p = 0.03), parent occupation (p = 0.01), and parent psychiatric diagnosis (p = 0.01), but not with INR and parent education. Parent occupation (p = 0.02) and RBA (p = 0.04) associated with CBCL anxiety/depression scores.Components of SES associated with brain aging, underscoring the risk of omitting these factors in developmental brain research. Further, delayed brain aging was associated with low parental occupational prestige and child anxiety/depression scores, suggesting a possible biological pathway from SES to mental health risk.
The mobilizable plasmid P3 of Salmonella enterica serovar Typhimurium SL1344 depends on the P2 plasmid for conjugative transfer into a broad range of bacteria in vitro and in vivo
Authors: Gaissmaier Marla Sofie , Laganenka Leanid , Herzog Mathias Klaus-Maria , Bakkeren Erik , Hardt Wolf-Dietrich 
Published: September 2022

ABSTRACTThe global rise of drug-resistant bacteria is of great concern. Conjugative transfer of antibiotic resistance plasmids contributes to this antibiotic resistance crisis. Despite the substantial progress in understanding the molecular basis of conjugation in vitro, the in vivo dynamics of intra- and interspecies conjugative plasmid transfer are much less understood. In this study, we focused on the streptomycin resistance-encoding mobilizable plasmid pRSF1010SL1344 (P3) of Salmonella enterica serovar Typhimurium (S. Tm) strain SL1344. We show that P3 is mobilized by interacting with the conjugation machinery of a second, conjugative plasmid pCol1B9SL1344 (P2) of SL1344. Thereby, P3 can be transferred into a broad range of relevant environmental and clinical bacterial isolates in vitro and in vivo. Our data suggests that S. Tm persisters in host tissues can serve as P3 reservoirs and foster transfer of both, P2 and P3 once they reseed the gut lumen. This adds to our understanding of resistance plasmid transfer in ecologically relevant niches including the mammalian gut.IMPORTANCES. Tm is a remarkably adaptable and globally abundant bacterial species that rapidly occupies new niches and survives unstable environmental conditions. As an enteric pathogen, it can potentially interact with a broad range of bacterial species residing in the mammalian gut. High abundance of bacteria in the gut lumen facilitate conjugation and spread of plasmid-encoded antibiotic resistance genes. By studying the transfer dynamics of the P3 plasmid in vitro and in vivo, we illustrate the impact of S. Tm-mediated antibiotic resistance spread via conjugation to a variety of relevant environmental and clinical bacterial isolates. Along with temperate phages or naked DNA, plasmids are among the most critical vehicles driving antibiotic resistance spread. Further understanding of the dynamics and drivers of antibiotic resistance transfer, along with identifying the environmental niches where this occurs, is needed to develop effective solutions for slowing down the emerging threat of multidrug-resistant bacterial pathogens.
RNAlight: a machine learning model to identify nucleotide features determining RNA subcellular localization
Authors: Yuan Guo-Hua , Wang Ying , Wang Guang-Zhong , Yang Li 
Published: September 2022

AbstractDifferent RNAs have distinct subcellular localizations. However, nucleotide features that determine these distinct distributions of lncRNAs and mRNAs have yet to be fully addressed. Here, we develop RNAlight, a machine learning model based on LightGBM, to identify nucleotide k-mers contributing to the subcellular localizations of mRNAs and lncRNAs. With the Tree SHAP algorithm, RNAlight extracts nucleotide features for cytoplasmic or nuclear localization of RNAs, indicating the sequence basis for distinct RNA subcellular localizations. By assembling k-mers to sequence features and subsequently mapping to known RBP-associated motifs, different types of sequence features and their associated RBPs were additionally uncovered for lncRNAs and mRNAs with distinct subcellular localizations. Finally, we extended RNAlight to precisely predict the subcellular localizations of other types of RNAs, including snRNAs, snoRNAs and different circular RNA transcripts, suggesting the generality of using RNAlight for RNA subcellular localization prediction.Key pointsA machine learning model, RNAlight, is developed to efficiently and sensitively predict subcellular localizations of mRNAs and lncRNAs.With embedded Tree SHAP algorithm, RNAlight further reveals distinct key sequence features and their associated RBPs for subcellular localizations of mRNAs or lncRNAs.RNAlight is successfully extended for the subcellular localization prediction of additional types of noncoding RNAs that were not used for model development, such as circular RNAs, suggesting its generality in RNA subcellular localization prediction.RNAlight is freely available at https://github.com/YangLab/RNAlight.
HuntingDrosophilaviruses from wild populations: a novel isolation approach and characterization of viruses
Authors: Bruner-Montero Gaspar , Luque Carlos , Ding Shuai Dominique , Day Jonathan P. , Jiggins Francis M. 
Published: September 2022

AbstractMetagenomic studies have demonstrated that viruses are extremely diverse and abundant in insects, but the difficulty of isolating them means little is known about the biology of these newly discovered viruses. To overcome this challenge inDrosophila, we created a cell line with increased susceptibility to infection and detected novel viruses by the presence of double-stranded RNA. We demonstrate the utility of these tools by isolating La Jolla virus (LJV) and Newfield virus (NFV) from several wildDrosophilapopulations. These viruses have different potential host ranges, with distinct abilities to replicate in fiveDrosophilaspecies. Similarly, in some species they cause high mortality and in others they are comparatively benign. In three species, NFV but not LJV caused large declines in female fecundity. This sterilization effect was associated with differences in tissue tropism, as NFV but not LJV was able to infectDrosophila melanogasterovaries. We saw a similar effect in the invasive pest of fruit cropsDrosophila suzukii, where oral infection with NFV caused reductions in the fecundity, suggesting it has potential as a biocontrol agent. In conclusion, a simple protocol allowed us to isolate new viruses and demonstrate that viruses identified by metagenomics have a large effect on the fitness of the model organismD. melanogasterand related species.
Distinct brain networks for remote episodic memory depending on content and emotional value
Authors: Auguste Anne , Fourcaud-Trocmé Nicolas , Meunier David , Gros Alexandra , Garcia Samuel , Messaoudi Belkacem , Thevenet Marc , Ravel Nadine , Veyrac Alexandra 
Published: September 2022

AbstractThe mechanisms that underlie the storage of old nontraumatic episodic memories remain enigmatic because of the difficulty in modelling this particular type of memory in humans and animals. Episodic memories combine incidental and occasional “What-Where-When/In which context” multisensory information and can be stored for long periods of time. Here, using a task in rodents that models human episodic memory, including odour/place/context components, we applied advanced behavioural and computational analyses and brain imaging of c-Fos and Zif268 to characterize remote episodic memories and their engrams for the first time. We show that the content and accuracy of memories vary across individuals and depend on the emotional relationship with odours experienced during episodes. Activated brain networks reflect the nature and content of remote episodic memories and their transformation over time, and emotional cortico-hippocampal networks play critical roles in maintaining vivid memories.
A T1R-independent mechanism for responses to hyperosmotic sugars involves a carbonic anhydrase-sensitive mechanism in Type III receptor cells
Authors: Kalyanasundar B. , Blonde Ginger D. , Spector Alan C. , Travers Susan P. 
Published: September 2022

AbstractRecent findings from our laboratory demonstrated that the rostral nucleus of solitary tract (rNST) retains some responsiveness to glutamate (MSG+amiloride-MSGa) and sugars in mice lacking the canonical T1R receptors for these tastants. Here, we recorded from the parabrachial nucleus (PBN) in mice lacking the T1R1+T1R3 heterodimer (KO1+3), using warm stimuli to optimize sugar responses and employing extended concentrations and pharmacological agents to probe mechanisms. MSGa+IMP responses were not synergized in KO1+3 mice but responses to MSGa were similar to those in B6 (WT) mice. Glutamate responses in the neurons tested were unaffected by topical application of an mGluR4 antagonist. PBN T1R-independent sugar responses, including those to concentrated glucose, were more evident than in rNST. Sugar responses were undiminished by phlorizin, an inhibitor of SGLT, a component of a hypothesized alternative glucose-sensing mechanism. There were no sugar/umami “best” neurons in KO1+3 mice, and instead, sugars activated cells that displayed acid and amiloride-insensitive NaCl responses. In WTs, concentrated sugars activated “sugar/umami” cells but also electrolyte-sensitive neurons. The efficacy of hyperosmotic sugars for driving neurons broadly responsive to electrolytes implied an origin from Type III taste bud cells. To test this, we used the carbonic anhydrase (CA) inhibitor dorzolamide (DRZ), previously shown to inhibit amiloride-insensitive sodium responses arising from Type III cells. Dorzolamide had no effect on sugarelicited responses in WT sugar/umami PBN neurons but strongly suppressed them in WT and KO electrolyte-generalist neurons. These findings suggest a novel T1R-independent mechanism for hyperosmotic sugars, involving a CA-dependent mechanism in Type-III taste bud cells.Significance StatementSince the discovery of theTas1rgene family that encodes receptors that lead to sweet and umami taste perception two decades ago, evidence has accrued that mice lacking these receptors maintain some degree of behavioral, physiological, and neural responsiveness to sugars and monosodium glutamate. But the basis for the remaining sensitivity to these nutritionally relevant compounds has remained elusive. Here we recorded from parabrachial nucleus taste neurons. Glutamate responses in mice lacking T1R1+T1R3 were unaffected by oral treatment of mGluR4 receptor antagonist suggesting that some T1R-independent glutamate responses are mediated by a different transduction pathway. Moreover, we identified a novel basis for T1R-independent responsiveness to hyperosmotic sugars that relies on carbonic anhydrase-mediated mechanism found in Type III taste bud cells.
To be and not to be: Wide-field Ca2+imaging reveals neocortical functional segmentation combines stability and flexibility
Authors: Nietz Angela K. , Streng Martha L. , Popa Laurentiu S. , Carter Russell E. , Flaherty Evelyn , Aronson Justin D. , Ebner Timothy J. 
Published: September 2022

ABSTRACTThe stability and flexibility of the functional parcellation of the cerebral cortex is fundamental to how familiar and novel information is both represented and stored. We leveraged new advances in Ca2+sensors and microscopy to understand the dynamics of functional segmentation in the dorsal cerebral cortex. We performed wide-field Ca2+imaging in head-fixed mice and used spatial Independent Component Analysis (ICA) to identify independent spatial sources of Ca2+fluorescence. The imaging data were evaluated over multiple timescales and discrete behaviors including resting, walking, and grooming. When evaluated over the entire dataset, a set of template independent components (ICs) were identified that were common across behaviors. Template ICs were present across a range of timescales, from days to 30 seconds, although with lower occurrence probability at shorter timescales, highlighting the stability of the functional segmentation. Importantly, unique ICs emerged at the shorter duration timescales that could act to transiently refine the cortical network. When data were evaluated by behavior, both common and behavior-specific ICs emerged. Each behavior is composed of unique combinations of common and behavior-specific ICs. These observations suggest that cerebral cortical functional segmentation exhibits considerable spatial stability over time and behaviors while retaining the flexibility for task-dependent reorganization.
Development of a 5-FU Modified miR-129 Mimic as a Therapeutic for Non-Small Cell Lung Cancer
Authors: Hwang Ga-Ram , Yuen John G. , Fesler Andrew , Farley Hannah , Haley John D. , Ju Jingfang 
Published: September 2022

AbstractLung cancer is the leading cause of cancer-related deaths in the United States with non-small cell lung cancer (NSCLC) accounting for most cases. Despite advances in cancer therapeutics, the 5-year survival rate has remained poor due to several contributing factors, including its resistance to therapeutics. Therefore, there is a pressing need to develop therapeutics that can overcome resistance. Non-coding RNAs, including microRNAs (miRNAs), have been found to contribute to cancer resistance and therapeutics by modulating the expression of several targets involving multiple key mechanisms. In this study, we investigated the therapeutic potential of miR-129 modified with 5-fluorouracil (5-FU) in NSCLC. Our results show that 5-FU modified miR-129 (5-FU-miR-129) inhibits proliferation, induces apoptosis, and retains function as a miRNA in NSCLC cell lines A549 and Calu-1. Notably, we observed that 5-FU-miR-129 was able to overcome resistance to tyrosine kinase inhibitors and chemotherapy in cell lines resistant to erlotinib or 5-FU. Furthermore, we observed that the inhibitory effect of 5-FU-miR-129 can also be achieved in NSCLC cells under vehicle-free conditions. Finally, 5-FU-miR-129 inhibited NSCLC tumor growth and extended survivalin vivowithout toxic side effects. Altogether, our results demonstrate the potential of 5-FU-miR-129 as a highly potent cancer therapeutic in NSCLC.
Development of the First High-Density Linkage Map in the Maize Weevil, Sitophilus zeamais
Authors: Baltzegar Jennifer Fountain , Gould Fred L. 
Published: September 2022

AbstractThe maize weevil, Sitophilus zeamais, is a worldwide pest that disproportionately affects subsistence farmers in developing countries. Damage from this pest threatens food security in these communities as widely available and effective control methods are lacking. With advances over the last decade in the development of advanced genetic pest management techniques, addressing pest issues at the ecosystem level as opposed to the farm level may be a possibility. However, pest species selected for genetic management techniques require a well-characterized genome and few genomic tools have been developed for maize weevil. Here, we have measured the genome size and developed the first genetic linkage map for this species. The genome size was determined using flow cytometry as 682 Mb and 674 Mb for females and males, respectively. The linkage map contains 11 linkage groups, which correspond to the 10 autosomes and 1 X-chromosome found in the species and it contains 1,121 SNPs. This linkage map will be useful for assembling a complete genome for maize weevil.