bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reducing Opioid-Induced Constipation Post-Cardiac Surgery
Authors: Rodrigues Miranda A. , Lofton Tochie , Tume Sebastian C. , Lemming Katherine I. 
Published: January 2022

Background:
Pain management with opioids and underutilization of prophylaxis for constipation can prolong a patient's hospital length of stay and impede pain management efforts.

Problem:
In pediatric postoperative cardiac patients, opioid therapy is a common approach to pain management but often places them at greater risk for constipation due to anatomy and age.

Methods:
A retrospective review of 50 patients' medical records for baseline data was conducted, and a survey evaluated providers' current knowledge and practice.

Interventions:
The intervention was an electronic order set that provided decision support. Additionally, prophylactic measures were supported by a validated assessment tool that created a common language to report constipation risk.

Results:
Although not statistically significant, postintervention data demonstrated a 21.5% decrease in postoperative constipation and a 57% increase in ordered bowel regimens.

Conclusion:
More focus is needed toward prophylactic bowel regimens to reduce the risk in this already high-risk population.
Induction of Cellular Senescence in Rat Vaginal Fibroblasts and Treatment With Senolytics: An in Vitro Model for the Study of Pelvic Organ Prolapse
Authors: Florian-Rodriguez Maria E. , Hare Adam M. , Gaddam Neha G. , Shi Haolin , Keller Patrick , Word Ruth Ann 
Published: January 2022

Objective
The objective of this study was to develop an in vitro model of cellular senescence using rat vaginal fibroblasts and determine the effects of treatment with senolytics.

Methods
Rat vaginal tissue biopsies were collected. Primary vaginal fibroblasts were isolated and characterized by immunofluorescence. To induce cellular senescence, fibroblasts were treated with etoposide at 3, 10, and 20 mM for 24 hours, followed by treatment with the senolytics dasatinib (1 mM) and/or quercetin (20 mM). After treatment, RNA was extracted and the expression of selected genes was quantified. Immunostaining of senescence markers was also performed.

Results
Fibroblasts were confirmed by positive immunostaining for α-smooth muscle actin and vimentin, and negative immunostaining for pan-cytokeratin. Treatment with etoposide resulted in a dose-dependent increase in expression of the senescence-associated secretory phenotype markers MMP-7, MMP-9, and IL-b1 (P < 0.05) compared with controls. Immunostaining showed increased expression of γ-H2A and p21 after treatment with etoposide. Cells treated with dasatinib and quercetin after etoposide treatment had decreased expression of p21, MMP-7, MMP-9, and IL-1b compared with cells treated only with etoposide (P < 0.05).

Conclusions
Upregulation of senescence-associated factors provided evidence that senescence can be induced in vaginal fibroblasts in vitro. Furthermore, treatment with the senolytics dasatinib and quercetin abrogated the senescence phenotype induced by etoposide in rat vaginal fibroblasts. Our findings provide a novel model for the study and development of new therapies targeting the disordered extracellular matrix associated with pelvic organ prolapse.
Comparison of Amantadine, Modafinil, and Standard of Care in the Acute Treatment of Disorders of Consciousness After Severe Traumatic Brain Injury
Authors: Hintze Trager D. , Small Clay E. , Montgomery Josephine , Reveles Kelly R. , Hafeez Shaheryar , Barthol Colleen A. 
Published: January 2022

Objective
Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Many patients who experience severe TBI have persistent disorders of consciousness. Amantadine and modafinil are used for some neurological disorders; however, a comparison of the 2 medications in TBI has not been reported. This study compared the effectiveness of amantadine, modafinil, and standard of care (SOC) on disorders of consciousness after TBI.

Methods
All adult TBI patients admitted between January 1, 2017, and September 31, 2020 who received amantadine, modafinil, or SOC treatments were screened. Data collection included: demographics, change in Glasgow Coma Scale (GCS), location of hemorrhage, medication duration, intensive care unit and hospital length of stay, adverse drug reactions, and concomitant sedative medications. Patients in the amantadine and modafinil groups were matched 1:2 with patients who received SOC therapies. The primary outcome was change in GCS ≥ 3 from baseline to discharge.

Results
A total of 142 patients met inclusion criteria. Medications were initiated a median of 8 days from admission. Patients in the SOC group experienced a greater improvement in GCS and shorter hospital length of stay compared with amantadine. A change in GCS ≥ 3 from medication initiation to hospital discharge occurred in 46.5% of amantadine patients and 53.8% of modafinil patients.

Conclusions
In this study, TBI patients did not benefit from amantadine or modafinil compared with SOC therapies, and no differences were found between medication groups. Further studies are warranted to determine whether the addition of amantadine or modafinil in the weeks after TBI provides benefit.
APOE ε4 effects on hippocampal atrophy in the healthy elderly reflect future cognitive decline
Authors: Zhang Linda , Calero Miguel , Medina Miguel , Strange Bryan A. 
Published: January 2022

AbstractThe APOE ε4 allele is the primary genetic risk factor for late onset Alzheimer’s disease (AD). A cardinal problem in determining APOE ε4’s effect on cognition and brain structure in older individuals is dissociating prodromal changes – linked to increased AD risk – from potential phenotypic differences. To address this, we used cognitive and neuroimaging data from a large cohort of cognitively normal 69-86 year-olds with up to 8 yearly follow-ups to investigate cross-sectional and longitudinal differences between APOE ε3/ε3 homozygotes and ε3/ε4 heterozygotes. Although we found a significant age-by-genotype interaction in right hippocampal volume, once our analyses were conditionalised by future diagnosis to account for prodromal mild cognitive impairment (MCI) and AD, this effect was no longer observed. Likewise, longitudinally, rate of hippocampal atrophy was determined not by genotype, but by future diagnosis. Thus, we provide direct evidence in support of the prodromal hypothesis of APOE ε4 on brain structure.
Subsequent hip fractures in patients identified by a Fracture Liaison Service (FLS) in England and Wales – linkage of the national FLS and Hip Fracture databases
Authors: Javaid MK , Mohsin Z , Johansen A , Gregson CL , Pinedo-Villanueva R 
Published: January 2022

AbstractFracture Liaison Services (FLSs) are recommended healthcare models to deliver secondary fracture prevention and reduce the risk of subsequent fractures. Several studies have demonstrated the cost and clinical effectiveness of FLSs, but there is little real-world data on the impact of FLSs on subsequent hip fracture rates.A cohort of 50,214 patients from the national FLS database with an index fracture of the hip, spine, or other in 2017 was linked to the National Hip Fracture Database from 2017 to 2020 to identify those patients who went on to have a subsequent hip fracture.One in twenty (5.1%) of the 9,888 people in whom the index fracture was at the hip went on to suffer a second hip fracture within 3-4 years, despite receiving the support of an FLS. The risk of hip fracture was similar (4.7%) if the index fracture was at the spine, but lower at other sites (2.8%, p<0.001) and the interval shortest after an index hip fracture (1.1 years (0.4,2.0) p<0.001). The proportion of patients with a subsequent hip fracture was not lower by types of anti-osteoporotic medication.This work highlights the need for alternative anti-osteoporotic management strategies to rapidly decrease the risk of subsequent hip fractures for people seen by an FLS setting with levels of risk that are even higher for patients in areas which are still not served by an FLS.
COVID-19 vaccine booster induces a strong CD8+ T cell response against Omicron variant epitopes in HLA-A*02:01+ individuals
Authors: Nguyen Andrea T. , Szeto Christopher , Chatzileontiadou Demetra S.M. , Tong Zhen Wei Marcus , Dewar-Oldis Michael J. , Cooper Lucy , Murdolo Lawton D. , Chew Keng Yih , Lineburg Katie E. , Riboldi-Tunicliffe Alan , Williamson Rachel , Gardiner Bradley J. , Jayasinghe Dhilshan , Lobos Christian A. , Ahn You Min , Grant Emma J. , Smith Corey , McMahon James , Good-Jacobson Kim L. , Barnard Peter J. , Short Kirsty R. , Gras Stephanie 
Published: January 2022

AbstractThe >30 mutated residues in the Omicron spike protein have led to its rapid classification as a new SARS-CoV-2 variant of concern. As a result, Omicron may escape from the immune system, decreasing the protection provided by COVID-19 vaccines. Preliminary data shows a weaker neutralizing antibody response to Omicron compared to the ancestral SARS-CoV-2 virus, which can be increased after a booster vaccine. Here, we report that CD8+ T cells can recognize Omicron variant epitopes presented by HLA-A*02:01 in both COVID-19 recovered and vaccinated individuals, even 6 months after infection or vaccination. Additionally, the T cell response was stronger for Omicron variant epitopes after the vaccine booster. Altogether, T cells can recognize Omicron variants, especially in vaccinated individuals after the vaccine booster.One-Sentence SummaryCD8+ T cells response against Omicron variant epitopes is stronger after the vaccine booster.
A truncated form of the p27 CDK inhibitor translated from pre-mRNA causes G2-phase arrest
Authors: Kaida Daisuke , Satoh Takayuki , Ishida Ken , Yoshimoto Rei , Komori Kanae 
Published: January 2022

AbstractPre-mRNA splicing is an indispensable mechanism for eukaryotic gene expression. Splicing inhibition causes cell cycle arrest at G1 and G2/M phases, which is thought to be one of the reasons for the potent antitumor activity of splicing inhibitors. However, the molecular mechanisms underlying the cell cycle arrest have many unknown aspects. In particular, the mechanism of G2/M-phase arrest caused by splicing inhibition is completely unknown. Here, we found that lower and higher concentrations of pladienolide B caused M-phase and G2-phase arrest, respectively. We analyzed protein levels of cell cycle regulators and found that a truncated form of the p27 CDK inhibitor, named p27*, accumulates in G2-arrested cells. Overexpression of p27* caused partial G2-phase arrest. Conversely, knockdown of p27* accelerated exit from G2/M phase after washout of splicing inhibitor. These results suggest that p27* contributes to G2/M-phase arrest caused by splicing inhibition. We also found that p27* bound to and inhibited M-phase cyclins, although it is well known that p27 regulates G1/S transition. Intriguingly, p27*, but not full-length p27, was resistant to proteasomal degradation and remained in G2/M phase. These results suggest that p27*, which is a very stable truncated protein in G2/M phase, contributes to G2-phase arrest caused by splicing inhibition.
Optineurin mediates delivery of membrane from transferrin receptor-positive endosomes to autophagosomes
Authors: Bansal Megha , Sirohi Kapil , Moharir Shivranjani C , Swarup Ghanshyam 
Published: January 2022

AbstractAutophagy is a conserved quality control mechanism that removes damaged proteins, organelles and invading bacteria through lysosome-mediated degradation. During autophagy several organelles including endoplasmic reticulum, mitochondria, plasma membrane and endosomes contribute membrane for autophagosome formation. However, the mechanisms and proteins involved in membrane delivery to autophagosomes are not clear. Optineurin (OPTN), a cytoplasmic adaptor protein, is involved in promoting maturation of phagophores into autophagosomes; it is also involved in regulating endocytic trafficking and recycling of transferrin receptor (TFRC). Here, we have examined the role of optineurin in the delivery of membrane from TFRC-positive endosomes to autophagosomes. Only a small fraction of autophagosomes was positive for TFRC, indicating that TFRC-positive endosomes could contribute membrane to a subset of autophagosomes. The percentage of TFRC-positive autophagosomes was reduced in Optineurin knockout mouse embryonic fibroblasts (Optn−/− MEFs) in comparison with normal MEFs. Upon over-expression of optineurin, the percentage of TFRC-positive autophagosomes was increased in Optn−/− MEFs. Unlike wild-type optineurin, a disease-associated mutant, E478G, defective in ubiquitin binding, was not able to enhance formation of TFRC-positive autophagosomes in Optn−/− MEFs. TFRC degradation mediated by autophagy was decreased in optineurin deficient cells. Our results suggest that optineurin mediates delivery of TFRC and perhaps associated membrane from TFRC-positive endosomes to autophagosomes, and this may contribute to autophagosome formation.
Correlations in sleeping patterns and circadian preference between spouses
Authors: Richmond Rebecca C , Howe Laurence J , Heilbron Karl , Jones Samuel , Liu Junxi ,   23andMe Research Team, Wang Xin , Weedon Michael N , Rutter Martin K , Lawlor Deborah A , Smith George Davey , Vetter Céline 
Published: January 2022

AbstractSpouses may affect each other’s sleeping behaviour. In 47,420 spouse-pairs from the UK Biobank, we found a weak positive phenotypic correlation between spouses for self-reported sleep duration (r=0.11; 95% CI=0.10, 0.12) and a weak inverse correlation for chronotype (diurnal preference) (r=-0.11; -0.12, -0.10), which replicated in up to 127,035 23andMe spouse-pairs. Using accelerometer data on 3,454 UK Biobank spouse-pairs, the correlation for derived sleep duration was similar to self-report (r=0.12; 0.09, 0.15). Timing of diurnal activity was positively correlated (r=0.24; 0.21, 0.27) in contrast to the inverse correlation for chronotype. In Mendelian randomization analysis, positive effects of sleep duration (mean difference=0.13; 0.04, 0.23 SD per SD) and diurnal activity (0.49; 0.03, 0.94) were observed, as were inverse effects of chronotype (−0.15; -0.26, -0.04) and snoring (−0.15; -0.27, -0.04). Findings support the notion that an individual’s sleep may impact that of their partner, with implications for sleep health.
Quantifying the impact of immune history and variant on SARS-CoV-2 viral kinetics and infection rebound: a retrospective cohort study
Authors: Hay James A. , Kissler Stephen M. , Fauver Joseph R. , Mack Christina , Tai Caroline G. , Samant Radhika M. , Connolly Sarah , Anderson Deverick J. , Khullar Gaurav , MacKay Matthew , Patel Miral , Kelly Shannan , Manhertz April , Eiter Isaac , Salgado Daisy , Baker Tim , Howard Ben , Dudley Joel T. , Mason Christopher E. , Nair Manoj , Huang Yaoxing , DiFiori John , Ho David D. , Grubaugh Nathan D. , Grad Yonatan H. 
Published: January 2022

AbstractBackgroundThe combined impact of immunity and SARS-CoV-2 variants on viral kinetics during infections has been unclear.MethodsWe characterized 2,875 infections from the National Basketball Association occupational health cohort identified between June 2020 and January 2022 using serial RT-qPCR testing. Logistic regression and semi-mechanistic viral RNA kinetics models were used to quantify the effect of variant, symptom status, age, infection history, vaccination and antibody titer to founder SARS-CoV-2 strain on the duration of potential infectiousness and overall viral kinetics. The frequency of viral rebounds was quantified under multiple cycle threshold (Ct) value-based definitions.ResultsAmong individuals detected partway through their infection, 51.0% (95% credible interval [CrI]: 48.2-53.6%) remained potentially infectious (Ct<30) five days post detection, with small differences across variants and vaccination history. Only seven viral rebounds (0.7%; N=999) were observed, with rebound defined as 3+ days with Ct<30 following an initial clearance of 3+ days with Ct≥30. High antibody titers against the founder SARS-CoV-2 strain predicted lower peak viral loads and shorter durations of infection. Among Omicron BA.1 infections, boosted individuals had lower pre-booster antibody titers and longer clearance times than non-boosted individuals.ConclusionsSARS-CoV-2 viral kinetics are partly determined by immunity and variant but dominated by individual-level variation. Since booster vaccination protects against infection, longer clearance times for BA.1-infected, boosted individuals may reflect a less effective immune response, more common in older individuals, that increases infection risk and reduces viral RNA clearance rate. The shifting landscape of viral kinetics underscores the need for continued monitoring to optimize isolation policies and to contextualize the health impacts of therapeutics and vaccines.FundingSupported in part by CDC contract 200-2016-91779, Emergent Ventures at the Mercatus Center, the Huffman Family Donor Advised Fund, the MorrisSinger Fund, the National Basketball Association, and the National Basketball Players Association.
Involvement of prelimbic cortex neurons and related circuits in the acquisition of cooperative learning by pairs of rats
Authors: Conde-Moro A.R. , Rocha-Almeida F. , Gebara E. , Delgado-García J.M. , Sandi C. , Gruart A. 
Published: January 2022

AbstractSocial behaviors such as cooperation are crucial for mammals. A deeper knowledge of the neuronal mechanisms underlying cooperation can be beneficial for people suffering from pathologies with impaired social behavior. Our aim was to study the brain activity when two animals synchronize their behavior to obtain a mutual reinforcement. In a previous work, we showed that the activity of the prelimbic cortex (PrL) was enhanced during cooperation in rats, especially in the ones leading most cooperative trials (leader rats). In this study, we investigated the specific cell type/s in the PrL contributing to cooperative behaviors. To this end, we collected rats’ brains at key moments of the learning process to analyze the levels of c-FOS expression in the main cellular groups of the PrL (glutamatergic cells containing D1 and D2 receptors and interneurons). Leader rats showed increased c-FOS activity in cells expressing D1 receptors during cooperation. In addition, we analyzed the levels of anxiety, dominance, and locomotor behavior, finding that leader rats are in general less anxious and less dominant than followers. We also recorded local field potentials (LFPs) from the PrL, the nucleus accumbens septi (NAc), and the basolateral amygdala (BLA). Spectral analysis showed that delta activity in PrL and NAc increased when rats cooperated, while BLA activity in delta and theta bands decreased considerably during cooperation. The PrL and NAc also increased their connectivity in the high theta band during cooperation. Thus, the present work identifies the specific PrL cell types engaged in this behavior, as well as its connectivity with subcortical brain regions (BLA, NAc) during cooperation.Significance StatementBrain mechanisms underlying cooperative behaviors remain unknown. The present study identified specific neuronal types from the PrL cortex engaged in the acquisition of a cooperative task, as well as their connectivity with subcortical projection sites, such as the NAc and the BLA during cooperation. Rats leading the cooperation trials (designated leaders) presented an increased activation of D1-containing neurons in the PrL during cooperation. The PrL and NAc electrical activity increased when rats were cooperating, while the BLA activity increased before cooperation. The PrL and NAc showed increased functional connectivity at the moment of cooperation on the platform, whereas during the individual phase the highest connectivity was found before the animals climbed individually onto the platform.
AAV11 permits efficient retrograde targeting of projection neurons
Authors: Han Zengpeng , Luo Nengsong , Kou Jiaxin , Li Lei , Ma Wenyu , Peng Siqi , Xu Zihong , Zhang Wen , Qiu Yuxiang , Wu Yang , Wang Jie , Ye Chaohui , Lin Kunzhang , Xu Fuqiang 
Published: January 2022

AbstractViral tracers that permit efficient retrograde targeting of projection neurons are powerful vehicles for structural and functional dissections of the neural circuit and for the treatment of brain diseases. Recombinant adeno-associated viruses (rAAVs) are the most potential candidates because they are low-toxic with high-level transgene expression and minimal host immune responses. Currently, some rAAVs based on capsid engineering for retrograde tracing have been widely used in the analysis and manipulation of neural circuits, but suffer from brain area selectivity and inefficient retrograde transduction in certain neural connections. Here, we discovered that the recombinant adeno-associated virus 11 (rAAV11) exhibits potent retrograde labeling of projection neurons with enhanced efficiency to rAAV2-retro in some neural connections. Combined with calcium recording technology, rAAV11 can be used to monitor neuronal activities by expressing Cre recombinase or calcium-sensitive functional probe. In addition, we further showed the suitability of rAAV11 for astrocyte targeting. These properties make rAAV11 a promising tool for the mapping and manipulation of neural circuits and gene therapy of some neurological and neurodegenerative disorders.HighlightsNaturally occurring AAV serotype capsid exhibits robust retrograde functionalityImproved distribution properties and retrograde transport efficiencyCan express Cre recombinase or calcium-sensitive functional probe for neural circuits monitoringCan specifically target astrocytes
Identifying interactions in omics data for clinical biomarker discovery using symbolic regression
Authors: Christensen Niels Johan , Demharter Samuel , Machado Meera , Pedersen Lykke , Salvatore Marco , Stentoft-Hansen Valdemar , Iglesias Miquel Triana 
Published: January 2022

ABSTRACTThe identification of predictive biomarker signatures from omics data for clinical applications is an active area of research. Recent developments in assay technologies and machine learning (ML) methods have led to significant improvements in predictive performance. However, most high-performing ML methods suffer from complex architectures and lack interpretability. Here, we present the application of a novel symbolic-regression-based algorithm, the QLattice, on a selection of clinical omics data sets. This approach generates parsimonious high-performing models that can both predict disease outcomes and reveal putative disease mechanisms. Due to their high performance, simplicity and explicit functional form, these biomarker signatures can be readily explained, thereby making them attractive tools for high-stakes applications in primary care, clinical decision making and patient stratification.