bluuebunny/crossref_metadata_2025_split huggingface dataset:
Workplace Exposures and Prescription Drug Misuse Among Nurses
Authors: Trinkoff Alison M. , Selby Victoria L. , Baek Hyang , Storr Carla L. , Steele Jenell , Han Kihye 
Published: October 2022

OBJECTIVE
This study examined the association between workplace exposure and prescription drug misuse in nurses.

BACKGROUND
Studies have found RNs and other health providers have higher rates of prescription misuse than the general population and have suggested that workplace exposures along with excessive job demands create circumstances fostering misuse.

METHODS
Survey data from 1170 RNs on workplace exposures (availability, frequency of administration, knowledge of substances, and workplace controls) were described by workplace, position, and specialty. Exposures were then related to prescription drug misuse using logistic regression.

RESULTS
Each workplace exposure was associated with past year prescription drug misuse. An index combining all exposures was significantly related to misuse (P = 0.001), and odds of misuse increased by 38% for each point increase in the exposure index.

CONCLUSIONS
Consideration of the health and well-being of nurses at higher odds of exposure to prescription drugs with misuse potential is warranted. Workplace support to help nurses maintain and restore their health should be a priority.
Use of Cephalic Vein in DIEP Breast Reconstruction Does Not Increase Risk of Lymphedema of the Ipsilateral Arm – a Cohort Study with Nine Years of Follow-up
Authors: Svee Andreas , Falk-Delgado Alberto , Folkvaljon Folke , Cederland Christoffer , Wallenius Imke , Audolfsson Thorir , Drazan Lubos , Mani Maria 
Published: October 2022

Summary:
Flap failure is a rare but devastating complication in deep inferior epigastric perforator flap (DIEP) reconstructions. Common causes of partial or complete flap failure are related to venous congestion. Although cephalic vein is usually a safe and reliable recipient vein for additional venous outflow, there is a hypothesized risk of donor-arm lymphedema secondary to lymphatic vessel damage in the vicinity of the cephalic vein or related to scarring and reduced venous backflow of the arm. The aim was to assess if the cephalic vein as an additional recipient vessel, via the superficial inferior epigastric vein in DIEP breast reconstruction, was associated with long-term volume changes of the arm and/or symptoms of lymphedema.
Arm volume was assessed preoperatively in patients scheduled to undergo unilateral delayed DIEP breast reconstruction at Uppsala University hospital, Sweden, between 2001-2007. Long-term postoperative assessments were made in 2015-2016. Water displacement and circumferential measurement were assessed preoperatively and postoperatively by the same lymphedema therapists. Patients were divided into two groups; DIEP reconstruction with cephalic vein or without. Fifty-four patients fulfilled the inclusion criteria and completed the study with a mean follow-up time of 136 months. There was no increased occurrence of lymphedema in the group undergoing DIEP with a cephalic vein as extra venous drainage, based on an analysis of change from baseline in arm volume difference.
This study shows that the cephalic vein can be used for secondary venous outflow in DIEP breast reconstruction without long-term risk of ipsilateral arm volume increase or symptoms of lymphedema.
Health Care Utilization in Systemic Lupus Erythematosus in the Community
Authors: Chevet Baptiste , Figueroa-Parra Gabriel , Valenzuela-Almada Maria O. , Hocaoglu Mehmet , Vallejo Sebastian , Osei-Onomah Shirley-Ann , Giblon Rachel E. , Dabit Jesse Y. , Chamberlain Alanna M. , Cornec Divi , Greenlund Kurt J. , Barbour Kamil E. , Crowson Cynthia S. , Duarte-García Alí 
Published: October 2022

Objective
The aim of this study was to determine inpatient health care utilization in an incident cohort of patients with systemic lupus erythematosus (SLE) compared with the general population.

Methods
This was a population-based cohort study in the upper Midwest, United States. We included patients fulfilling the European League Against Rheumatism/American College of Rheumatology SLE classification criteria between 1995 and 2018. They were 1:1 age-, sex-, county-matched with individuals without SLE. All hospital admissions and emergency department (ED) visits were electronically retrieved for 1995–2020. Rates for hospital admission, length of stay, readmission, ED visits, and discharge destination were compared between groups.

Results
Three hundred forty-one patients with SLE and 341 comparators without SLE were included (mean age, 48.6 years at diagnosis; 79.2% female). Rates of hospitalization for patients with SLE and comparators were 29.8 and 9.9 per 100 person-years, respectively. These differences were present across sexes and age groups. Hospitalization rates were higher in patients with SLE after diagnosis and remained higher than comparators for the first 15 years of the disease. Patients with SLE were more likely than comparators to visit the ED (hazard ratio, 2.71; 95% confidence interval, 2.05–3.59). Readmission rates (32% vs. 21%, p = 0.017) were higher in patients with SLE. Length of stay and discharge destination were similar between both groups.

Conclusion
Patients with SLE were more likely to be hospitalized and to visit the ED than individuals without SLE, highlighting important inpatient care needs. Increased hospitalization rates were observed in both male and female patients and all age groups.
Therapeutic strategies for pseudoaneurysm following blunt liver and spleen injuries: a multicenter cohort study in the pediatric population.
Authors: Katsura Morihiro , Kondo Yutaka , Yasuda Hideto , Fukuma Shingo , Matsushima Kazuhide , Shiraishi Atsushi , Tsuchiya Asuka , Kuriyama Akira , Gima Masafumi , Hayashida Kazuyuki , Miura Naoya , Sugiura Kenta , Toma Keiichiro , Yasumatsu Hiroshi , Kushimoto Shigeki ,   SHIPPs Study Group*
Published: October 2022

Background
Little guidance exists for the treatment of pseudoaneurysm following pediatric blunt liver and/or spleen injuries (BLSI). We aimed to describe the incidence of delayed pseudoaneurysm development and the subsequent clinical course of pseudoaneurysm in pediatric BLSI.

Methods
This multicenter retrospective cohort study from Japan included pediatric patients (≤16 years old) who sustained BLSI from 2008 to 2019. The cohort was divided into four groups based on hemostatic intervention within 48 hours of admission, namely non-operative management (NOM), NOM with interventional radiology (IR), operative management (OM), and combined IR/OM. Descriptive statistics were used to describe the incidence of delayed pseudoaneurysm among the groups and to characterize the clinical course of any pseudoaneurysms.

Results
A total of 1,407 children (median age, 9 years) from 83 institutions were included. The overall number (incidence) of cases of delayed pseudoaneurysm formation was 80 (5.7%), and the number with delayed pseudoaneurysm rupture was 16 (1.1%) cases in the entire cohort. Patients treated with NOM (1056), NOM with IR (276), OM (53), and combined IR/OM (22) developed 43 (4.1%), 32 (12%), 2 (3.8%), and 3 (14%) delayed pseudoaneurysms, respectively. Among patients who developed any pseudoaneurysms, 39% of patients underwent prophylactic IR for unruptured pseudoaneurysm, while 13% required emergency angioembolization for delayed pseudoaneurysm rupture, with one ruptured case requiring total splenectomy. At least 45% of patients experienced spontaneous resolution of pseudoaneurysm without any interventions.

Conclusion
Our results suggest that the risk of delayed pseudoaneurysm still exists even after acute phase IR as an adjunct to NOM for BLSI in children, indicating the necessity of a period of further observation. While endovascular interventions are usually successful for pseudoaneurysm management, including rupture cases, given the high incidence of spontaneous resolution, the ideal management of pseudoaneurysm remains to be investigated in future studies.

Level of evidence
Level 4; Therapeutic/Care management
Association of Maternal and Neonatal Birth Outcomes With Subsequent Pediatric Transplants
Authors: Côté-Corriveau Gabriel , Luu Thuy Mai , Bilodeau-Bertrand Marianne , Auger Nathalie 
Published: October 2022

Background.
We identified maternal and neonatal birth characteristics that were associated with organ or tissue transplants during childhood.

Methods.
We designed a retrospective cohort study of the population of children born between 2006 and 2019 in Quebec, Canada. The exposure included birth complications such as congenital anomaly, neonatal blood transfusion, and oligohydramnios. The main outcome measure was organ or tissue transplantation before 14 y of age. We categorized transplants according to type (major organs versus superficial tissues). To determine the association of birth characteristics with risk of pediatric transplant, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards models adjusted for potential confounders.

Results.
The cohort comprised 1 038 375 children with 7 712 678 person-years of follow-up, including 436 children who had transplants before 14 y of age. Birth complications were predominantly associated with major organ transplants. Congenital anomaly was associated with heart or lung (HR, 10.41; 95% CI, 5.33-20.33) and kidney transplants (HR, 13.69; 95% CI, 7.48-25.06), compared with no anomaly. Neonatal blood transfusion was associated with all major organ transplants, compared with no transfusion. Maternal complications were not as strongly associated with the risk of childhood transplant, although oligohydramnios was associated with 16.84 times (95% CI, 8.09-35.02) the risk of kidney transplant, compared with no oligohydramnios.

Conclusions.
Adverse birth outcomes such as congenital anomaly, neonatal blood transfusion, and maternal oligohydramnios are associated with a greater risk of transplantation before 14 y of age. Maternal and neonatal birth outcomes may be useful predictors of transplantation.
miR-128-3p inhibits the inflammation by targeting MAPK6 in penicillin-induced astrocytes
Authors: Pang Yuejiu , Luo Dingzhen , Wang Shuhua 
Published: October 2022

Objective
Epilepsy causes physical and mental damage to patients. As well known, microRNAs (miRNAs) provide therapeutic target potentials for patients with epilepsy. miR-128-3p was previously reported to be downregulated in temporal lobe epilepsy (TLE) patients, however, its detailed function in epilepsy is unknown.

Methods
Astrocytes function in epilepsy, penicillin-induced astrocytes can be used as a model for seizures in vitro. Currently, the expression levels of mitogen-activated protein kinase 6 (MAPK6), interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) were determined by western blot and reverse transcription-quantitative PCR analyses (RT-qPCR). The expression level of miR-128-3p was evaluated by RT-qPCR. TargetScan 7.1 and dual luciferase reporter assay were used for prediction and verification of interaction between miR-128-3p and MAPK6 3′ untranslated region (UTR). Cell viability was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay.

Results
We found that penicillin-induced decrease in cell viability, and increase of TNF-α/IL-1β in primary astrocytes. There were lower miR-128-3p and higher MAPK6 in penicillin-treated primary astrocytes. miR-128-3p overexpression rescued penicillin-induced reduction of cell viability, and upregulation of TNF-α/IL-1β, which was partially abolished by MAPK6 overexpression.

Conclusion
Altogether, miR-128-3p attenuates penicillin-induced cell injury and inflammation in astrocytes by targeting MAPK6, thus providing a protective role in epilepsy.
Alternative mammalian strategies leading towards gastrulation: losing polar trophoblast (Rauber's layer) or gaining an epiblast cavity
Authors: Pfeffer Peter L. 
Published: October 2022

Using embryological data from 14 mammalian orders, the hypothesis is presented that in placental mammals, epiblast cavitation and polar trophoblast loss are alternative developmental solutions to shield the central epiblast from extraembryonic signalling. It is argued that such reciprocal signalling between the edge of the epiblast and the adjoining polar trophoblast or edge of the mural trophoblast or with the amniotic ectoderm is necessary for the induction of gastrulation.This article is part of the theme issue ‘Extraembryonic tissues: exploring concepts, definitions and functions across the animal kingdom’.
Development of an affinity-enhanced clinical candidate TCR targeting NY-ESO-1 with optimal potency and high specificity
Authors: Ou Yusheng , Liu Min , Zhan Kai , Wu Wanli , Huang Jiao , Sun Hanli , Zheng Hongjun , Yu Xiaohong , Gong Haiping , Han Zhaosheng , Chen Aiyuan , Liao Youping , Lin Yanmei , Liu Ge , Liu Qiuping , Ma Ruijuan , Mei Yingyi , Tang Xianqing , Weng Zhiming , Wu Jieyi , Ye Yun , Zhang Tingting , Chen Jiehong , Chen Lin , Ding Qingfeng , Fan Hui , Hu Jiajia , Huang Jinhua , Huang Lihong , Li Qiaowei , Li Siyun , Liu Min , Shi Jia , Tan Xiangpeng , Wang Xiaoling , Xiang Ruirui , Yan Qingjia , Zhang Jianbin , Zheng Wenjing , Zhong Shi 
Published: October 2022

AbstractThe clinical success of T-cell receptor (TCR)-based immunotherapy depends on the efficacy and specificity of TCRs. Naturally occurring TCRs have limited anti-tumor potency due to their low affinity for tumor antigens. Affinity enhancement is a promising strategy to generate highly potent TCRs. However, it is concerned that affinity-enhanced TCRs are prone to lose specificity. We isolated low affinity TCRs specific for NY-ESO-1157-165/HLA-A*02:01 from peripheral blood mononuclear cells of healthy donors. An affinity-enhanced TCR candidate with optimal affinity and specificity was generated using phage display and an extensive set ofin vitroandin vivoassays. Alanine scanning mutagenesis showed that the TCR candidate retained specificity by making extensive contacts to the side chains of NY-ESO-1157-165peptide. Adoptive transfer of T cells engineered with this candidate (termed TAEST16001) significantly inhibited tumor growth in subcutaneous, metastatic, and patient-derived xenograft (PDX) mouse tumor models. This study demonstrates that sophisticated engineering and screening techniques can be utilized to generate a clinical candidate TCR with potent anti-tumor activity without losing specificity. TAEST16001 was approved by the Center for Drug Evaluation (CDE) as the first TCR-based immunotherapy clinical trial in China (ClinicalTrials.govIdentifier:NCT03159585).
Prioritizing prognostic-associated subpopulations and individualized recurrence risk signatures from single-cell transcriptomes of colorectal cancer
Authors: Tong Mengsha , Lin Yuxiang , Yang Wenxian , Song Jinsheng , Zhang Zheyang , Xie Jiajing , Tian Jingyi , Luo Shijie , Liang Chenyu , Huang Jialiang , Yu Rongshan 
Published: October 2022

AbstractColorectal cancer (CRC) is one of the most common gastrointestinal malignancies. There are few recurrence risk signatures for CRC patients. Single-cell RNA-sequencing (scRNA-seq) provides a high resolution platform for prognostic signature detection. However, scRNA-seq is not practical in large cohorts due to its high cost and most single-cell experiments lack clinical phenotype information. Few studies have been reported to use external bulk transcriptome with survival time to guide the detection of key cell subtypes in scRNA-seq data. We proposed a data analysis framework to prioritize prognostic-associated subpopulations based on relative expression orderings (REOs). Cell type specific gene pairs (C-GPs) were identified to evaluate prognostic value for each cell type. We found REOs-based signatures could accurately classify most cell subtypes. C-GPs achieves higher precision compared with four current methods. Moreover, we developed single-cell gene pair signatures to predict recurrence risk for patients individually. Fibro_SGK1 cells and IgA+ IGLC2+ B cells were novel prognostic-associated subpopulations. A user-friendly toolkit, scRankXMBD(https://github.com/xmuyulab/scRank-XMBD), was developed to enable implementation of this framework. Our work facilitate the application of the rank-based method in scRNA-seq data for prognostic biomarker discovery and precision oncology.
Adiponectin/leptin ratio - a marker of insulin sensitivity in pre-eclampsia and fetal growth
Authors: de Knegt Victoria Elizabeth , Hedley Paula L. , Eltvedt Anna K. , Placing Sophie , Wøjdemann Karen , Shalmi Anne-Cathrine , Rode Line , Kanters Jørgen , Sundberg Karin , Tabor Ann , Lausten-Thomsen Ulrik , Christiansen Michael 
Published: October 2022

AbstractThe serum adiponectin-leptin ratio (A/L ratio) is a surrogate marker of insulin sensitivity. Pre-eclampsia (PE) is associated with maternal metabolic syndrome and occasionally impaired fetal growth. We assessed whether the A/L ratio in first-trimester maternal serum was associated with PE and/or birth weight. Adiponectin and leptin were quantitated in first-trimester blood samples (gestational week 10+3-13+6) from 126 women who later developed PE with proteinuria, (98 mild PE; 21 severe PE; 7 HELLP syndrome), and 297 controls, recruited from the Copenhagen First-Trimester Screening Study. The A/L ratio was reduced in PE pregnancies, median 0.17 (IQR: 0.12-0.27) compared to controls, median 0.32 (IQR: 0.19-0.62), (p<0.001). A multiple logistic regression showed that PE was negatively associated with A/L ratio independent of maternal BMI (odds ratio = 0.08, 95% CI = 0.0322 to 0.214). Adiponectin (AUC = 0.632) and PAPP-A (AUC = 0.605) were negatively, and leptin (AUC = 0.712) was positively associated with PE. However, the A/L ratio was a better predictor of PE (AUC = 0.737). No significant association was found between A/L ratio and clinical severity of pre-eclampsia or preterm birth. PE was associated with significantly lower relative birth weight, (p<0.001). A significant negative correlation was found between relative birth weight and A/L ratio in controls but not in PE pregnancies, (β= −0.144, 95% CI = −9.944 to −0.093), independent of maternal BMI. After correction for maternal BMI, leptin was significantly associated with relative birth weight, (β= 0.197, 95 % CI = 2.361 to 14.353), while adiponectin was not significantly associated. Our findings suggest that an impairment of the A/L ratio (as seen in metabolic syndrome) in first-trimester is characteristic of PE, while aberrant fetal growth in PE is not dependent on insulin sensitivity but rather on leptin associated pathways.
Elucidating a locus coeruleus-hippocampal dopamine pathway for operant reinforcement
Authors: Petter Elijah A. , Fallon Isabella P. , Hughes Ryan N. , Watson Glenn D. R. , Meck Warren H. , Ulloa Severino Francesco Paolo , Yin Henry H. 
Published: October 2022

AbstractAnimals can learn to repeat behaviors to earn desired rewards, a process commonly known as reinforcement learning. While previous work has implicated the ascending dopaminergic projections to the basal ganglia in reinforcement learning, little is known about the role of the hippocampus. Here we report that a specific population of hippocampal neurons and their dopaminergic innervation contribute to operant self-stimulation. These neurons are located in the dentate gyrus, receive dopaminergic projections from the locus coeruleus, and express D1 dopamine receptors. Activation of D1+ dentate neurons is sufficient for self-stimulation: mice will press a lever to earn optogenetic activation of these neurons. A similar effect is also observed with selective activation of the locus coeruleus projections to the dentate gyrus, and blocked by D1 receptor antagonism. Calcium imaging of D1+ dentate neurons revealed significant activity at the time of action selection, but not during passive reward delivery. These results reveal the role of dopaminergic innervation of the hippocampus in supporting operant reinforcement.
Physiological Condition Dependent Changes in Ciliary GPCR Localization in the Brain
Authors: Brewer Kathryn M. , Engle Staci E. , Bansal Ruchi , Brewer Katlyn K. , Jasso Kalene R. , McIntyre Jeremy C. , Vaisse Christian , Reiter Jeremy F. , Berbari Nicolas F. 
Published: October 2022

AbstractPrimary cilia are small immotile cellular appendages which mediate diverse types of singling and are found on most mammalian cell types including throughout the central nervous system. Cilia are known to localize certain G protein-coupled receptors (GPCRs) and are critical for mediating the signaling of these receptors. Several of these neuronal GPCRs have recognized roles in feeding behavior and energy homeostasis. Heterologous cell line and model systems likeC. elegansandChlamydomonashave implicated both dynamic GPCR cilia localization and cilia length and shape changes as key for signaling. However, it is unclear if mammalian ciliary GPCRs utilize similar mechanismsin vivoand under what physiological conditions these processes may occur. Here, we use the ciliary GPCRs, melanin concentrating hormone receptor 1 (MCHR1) and neuropeptide-Y receptor 2 (NPY2R) as model ciliary receptors to determine if dynamic localization to cilia occurs. We tested physiological conditions in which these GPCRs have been implicated such as feeding behavior, obesity, and circadian rhythm. Cilia were imaged using confocal microscopy and analyzed with a computer assisted approach allowing for unbiased and high throughput analysis of cilia. We analyzed GPCR positive cilia, cilia frequency as well as cilia length and receptor occupancy. Interestingly we observed changes in ciliary length, receptor occupancy, and cilia frequency under different conditions, but no consistent theme across GPCRs or brain nuclei was observed. A better understanding of the subcellular localization dynamics of ciliary GPCRs could reveal unrecognized molecular mechanisms regulating behaviors like feeding.Significance StatementOften, primary cilia localize specific G protein-coupled receptors (GPCRs) for subcellular signaling. Cell lines and model systems have indicated that cilia deploy dynamic GPCR localization and change their shape or length to modulate signaling. We used mice to assess neuronal cilia GPCRs under physiological conditions associated with both the receptors’ known functions and ciliopathy clinical features like obesity. We show that certain cilia with specific GPCRs appear to dynamically alter their length while others appear relatively stable under these conditions. These results implicate multiple themes across cilia GPCR mediated signaling and indicate that not all cilia modulate GPCR signaling using the same mechanisms. These data will be important for potential pharmacological approaches to target cilia GPCR-mediated signaling.