bluuebunny/crossref_metadata_2025 huggingface dataset:
Role and Mechanism of MicroRNA-7a-5p in Paraventricular Nucleus on Sympathetic Overactivity in the Spontaneously Hypertensive Rats
Authors: An Mei-ling , Xu Jia-qi , Hao Yi-fan , Yuan Yue , Wang Xiu-wen , Zhang Min , Wei Xiao-wei , Li Hua , Wang Ren-jun
Published: November 2022

Background

To investigate the role and mechanism of microRNA-7a-5p (miR-7a-5p) in paraventricular nucleus on sympathetic overactivity in the spontaneously hypertensive rats (SHR).

Methods

Wistar-Kyoto (WKY) rats and SHR aged 12 weeks were randomly divided into recombinant adeno-associated virus (rAAV) overexpressing miR-7a-5p mimic, miR-7a-5p negative control (NC), antimiR-7a-5p, or NC of antimir-7a-5p treatment groups (n = 6 per group). In addition, WKY rats and SHR aged 12 weeks were randomly divided into rAAV overexpressing GABRA1, GABRA1 NC, GABRA1 shRNA, or NC of GABRA1 shRNA treatment groups (n = 6 per group). Four weeks later, hemodynamic parameters, renal sympathetic nerve activity (RSNA), and plasma norepinephrine levels were observed.

Results

Four weeks after injection of rAAV into the paraventricular nucleus, overexpression of miR-7a-5p mimic increased RSNA and mean arterial pressure (MAP) in WKY and SHR (all P < 0.05). The number of FosB positive neurons in paraventricular nucleus was significantly upregulated (all P < 0.01) while the number of GABRA1 positive neurons in paraventricular nucleus was significantly downregulated (all P < 0.01). Overexpression of GABRA1 in hypothalamic paraventricular nucleus decreased RSNA and MAP in WKY and SHR (all P < 0.05). Compared with WKY, the overexpression or knockdown of miR-7a-5p/GABRA1 had more significant effect on RSNA and MAP in SHR (all P < 0.05). The expression of miR-7a-5p in hypothalamic paraventricular nucleus in SHR was significantly upregulated (P < 0.01) while GABRA1 protein levels were significantly downregulated (P < 0.01). miR-7a-5p mimic transfection in primary brain neurons or NG108 cells resulted in significant downregulation of GABRA1 protein expression. TargetScan prediction showed that there was sequence binding at the 3′UTR end of GABRA1 mRNA by miR-7a-5p. Dual luciferase reporter assay confirmed that miR-7a-5p can target GABRA1 gene.

Conclusions

miR-7a-5p in hypothalamic paraventricular nucleus increases RSNA by inhibiting GABRA1 expression, and may contribute to the development of hypertension.
Telmisartan Reduces Atrial Fibrillation Susceptibility in Pressure Overload Rats and Its Molecular Mechanism Based on Gene Sequencing
Authors: Yao Qing-hai , Li Xi-ming , You Bing-chen
Published: November 2022

Background

To assess the effects of telmisartan on susceptibility of atrial fibrillation (AF) in pressure overload rats, and to probe the underlying molecular mechanism and signal pathways.

Methods

Forty-nine 12-week-old male SD rats were randomly divided into sham operation (n = 15), abdominal aorta coarctation (AAC, n = 17), and AAC with telmisartan treatment groups (n = 17). Telmisartan 10 mg/(kg d) was administered by gavage for 4 weeks after AAC. Four weeks after operation, the indexes of echocardiography, hemodynamics, and cardiac electrophysiology including left atrial conduction time (LACT) and interatrial conduction time (IACT) were assessed. The mRNAs were extracted from left atrial tissues and analyzed by next generation sequencing.

Results

Systolic left ventricular pressure, systolic aortic pressure, left atrial diameters, and interventricular septal thickness in AAC rats were higher than those in sham rats (all P < 0.05), all of which were lowered by telmisartan treatment (all P < 0.05). LACT and IACT were significantly increased in AAC rats and ameliorated by telmisartan treatment. In isolated perfused heart, duration of AF induced by burst electrical stimulation was longer in AAC rats, which was shortened by telmisartan treatment. A total of 897 genes were downregulated by AAC but upregulated by telmisartan treatment (down/up 897 gene set). Also, 1,542 genes were upregulated by AAC but downregulated by telmisartan treatment (up/down 1,542 gene set). Venn and GO enrichment analyses showed that 5 target genes in the down/up 897 gene set were the key rate limiting enzymes of fatty acid oxidation while 5 target genes in the up/down 1,542 gene set were involved in Wnt/β-catenin signal pathway and type I and II collagen components.

Conclusions

Telmisartan lowers AF susceptibility via suppressing the left atrial enlargement and shortening atrial conduction time. Possible molecular mechanisms may be related to the improvement of fatty acid oxidation and downregulation of the Wnt/β-catenin pathway and collagen expression.
Development of an emergency medicine pharmacy intensity score tool
Authors: Weant Kyle A , Acquisto Nicole M , Doyno Cassandra R , Gregory Haili , Rech Megan A , Schlobohm Cory J , Smith Andrew P , Won Kimberly J
Published: November 2022

Purpose

Emergency medicine pharmacists (EMPs) have been demonstrated to have a positive impact on patient outcomes in a variety of clinical scenarios in the emergency department (ED), yet their distribution across the nation is suboptimal. An emergency medicine pharmacy intensity score tool (EMPIST) would not only facilitate the quantification of EMP staffing needs and ideal resource deployment times, but would also allow practitioners to triage patient care activities. The purpose of this investigation was to develop an EMPIST and evaluate its relationship to EMP activities.

Methods

This was a multicenter, prospective, observational analysis of an EMPIST developed by practicing EMPs. EMPs prospectively documented their clinical activities during usual care for patients in their ED. Spearman’s rank-order correlation was used to determine any correlation between the EMPIST and pharmacist activities.

Results

In total, 970 EMP activities and 584 EMPIST items were documented in 352 patients by 7 EMPs across 7 different EDs. The most commonly documented EMP interventions performed were bedside monitoring (12.7%), initiation of nonantimicrobial therapy (12.6%), and antimicrobial therapy initiation and streamlining (10.6%). The total EMPIST was found to significantly correlate with EMP activities, and this correlation was consistent across both “diagnostic/presentation” and “medication” items (P < 0.001 for all comparisons).

Conclusion

The EMPIST significantly correlated with EMP activities, with consistent correlation across all subgroups. Its utilization has the potential to enhance bedside clinical practice and optimize the deployment of limited EMP services. Additional investigations are needed to examine the validity of this tool and identify any relationship it may have to patient outcomes.
Impact of long-course neoadjuvant radiation on postoperative low anterior resection syndrome and stoma status in rectal cancer: long-term functional follow-up of a randomized clinical trial
Authors: He Siqi , Zhang Jinquan , Wang Runxian , Li Li , Shi Lishuo , Ren Donglin , Wang Jianping , Deng Yanhong , Dou Ruoxu
Published: November 2022

Background

Neoadjuvant radiation has been increasingly associated with postoperative bowel dysfunction, including low anterior resection syndrome (LARS). Although permanent stoma often results from severe bowel dysfunction and significantly impacts quality of life, the presence of stoma paradoxically excludes patients from functional follow-up. Hence, stoma status is rarely reported along with LARS, while assessment of both is essential for the comprehensive evaluation of bowel dysfunction in long-term survivors of rectal cancer.

Method

Patients enrolled into the Neoadjuvant FOLFOX6 Chemotherapy with or without Radiation in Rectal Cancer (FOWARC) multicentre randomized clinical trial were randomized to receive long-course neoadjuvant chemoradiotherapy (nCRT) or chemotherapy (nCT) followed by sphincter-saving proctectomy and longitudinal follow-up. The primary outcome of the trial was disease-free survival. LARS score and stoma status were assessed secondarily for postoperative bowel function in the largest single-centre cohort of the trial.

Results

Overall, 327 patients with locally advanced rectal cancer were enrolled in the original trial and 203 responded after a median follow-up of 83.4 months, of whom 24 (11.8 per cent) had persistent stoma, and 48 patients (23.6 per cent) reported major LARS. Compared with the nCT group, the nCRT group reported more persistent stomas (16.5 per cent versus 4.9 per cent, P = 0.014), and more major LARS in patients without persistent stoma (34.7 per cent versus 16.7 per cent, P = 0.003). The combined prevalence of persistent stoma and major LARS was significantly higher in the nCRT group (45.5 per cent versus 20.7 per cent, P < 0.001). Long-course neoadjuvant radiation (OR 2.20, 95 per cent c.i. 1.10 to 4.40, P = 0.027), height of anastomosis (OR 0.74, 95 per cent c.i. 0.61 to 0.91, P = 0.004), and anastomotic leak (OR 4.97, 95 per cent c.i. 2.24 to 11.05, P < 0.001) were associated with persistent stoma and major LARS in multivariate analysis.

Conclusion

More than one-third of patients receiving sphincter-saving proctectomy reported major LARS or persistent stoma at long-term follow-up. Long-course neoadjuvant radiation, low anastomosis, and postoperative leak are independent risk factors for persistent stoma and major LARS.
Unravelling the relationship between amyloid accumulation and brain network function in normal aging and very mild cognitive decline: a longitudinal analysis
Authors: Moffat Gemma , Zhukovsky Peter , Coughlan Gillian , Voineskos Aristotle N
Published: November 2022

Pathological changes in the brain begin accumulating decades before the appearance of cognitive symptoms in Alzheimer’s disease. The deposition of amyloid beta proteins and other neurotoxic changes occur, leading to disruption in functional connections between brain networks. Discrete characterization of the changes that take place in preclinical Alzheimer’s disease has the potential to help treatment development by targeting the neuropathological mechanisms to prevent cognitive decline and dementia from occurring entirely. Previous research has focused on the cross-sectional differences in the brains of patients with mild cognitive impairment or Alzheimer’s disease and healthy controls or has concentrated on the stages immediately preceding cognitive symptoms. The present study emphasizes the early preclinical phases of neurodegeneration. We use a longitudinal approach to examine the brain changes that take place during the early stages of cognitive decline in the Open Access Series of Imaging Studies-3 data set. Among 1098 participants, 274 passed the inclusion criteria (i.e. had at least two cognitive assessments and two amyloid scans). Over 90% of participants were healthy at baseline. Over 8–10 years, some participants progressed to very mild cognitive impairment (n = 48), while others stayed healthy (n = 226). Participants with cognitive decline show faster amyloid accumulation in the lateral temporal, motor and parts of the lateral prefrontal cortex. These changes in amyloid levels were linked to longitudinal increases in the functional connectivity of select networks, including default mode, frontoparietal and motor components. Our findings advance the understanding of amyloid staging and the corresponding changes in functional organization of large-scale brain networks during the progression of early preclinical Alzheimer’s disease.
Altered controllability of white matter networks and related brain function changes in first-episode drug-naive schizophrenia
Authors: Tang Biqiu , Zhang Wenjing , Liu Jiang , Deng Shikuang , Hu Na , Li Siyi , Zhao Youjin , Liu Nian , Zeng Jiaxin , Cao Hengyi , Sweeney John A , Gong Qiyong , Gu Shi , Lui Su
Published: November 2022

Understanding how structural connectivity alterations affect aberrant dynamic function using network control theory will provide new mechanistic insights into the pathophysiology of schizophrenia. The study included 140 drug-naive schizophrenia patients and 119 healthy controls (HCs). The average controllability (AC) quantifying capacity of brain regions/networks to shift the system into easy-to-reach states was calculated based on white matter connectivity and was compared between patients and HCs as well as functional network topological and dynamic properties. The correlation analysis between AC and duration of untreated psychosis (DUP) were conducted to characterize the controllability progression pattern without treatment effects. Relative to HCs, patients exhibited reduced AC in multiple nodes, mainly distributed in default mode network (DMN), visual network (VN), and subcortical regions, and increased AC in somatomotor network. These networks also had impaired functional topology and increased temporal variability in dynamic functional connectivity analysis. Longer DUP was related to greater reductions of AC in VN and DMN. The current study highlighted potential structural substrates underlying altered functional dynamics in schizophrenia, providing a novel understanding of the relationship of anatomic and functional network alterations.
Automatic Demirci–Selçuk Meet-In-The-Middle Attack On SIMON
Authors: Lv Yin , Shi Danping , Guo Yi , Chen Qiu , Hu Lei , Guo Zihui
Published: November 2022

Demirci–Selçuk meet-in-the-middle (DS-MITM) attack is an effective method for cryptanalysis. As far as we know, the published automatic results of DS-MITM attack are all for byte-oriented ciphers. In this article, we first propose the automatic analysis method of DS-MITM attack for bit-oriented ciphers based on constraint programming, which is integrated with key-bridging technique. Based on the automatic modeling method, we propose the first result of DS-MITM attack on SIMON, which is a family of lightweight block ciphers proposed by the National Security Agency (NSA) in 2013.
Mitral intervention for anomalous left coronary artery from the pulmonary artery: midterm outcomes
Authors: Zhang Wen , Hu Renjie , Jiang Qi , Zhu Hongbin , Qiu Lisheng , Dong Wei , Zhang Haibo
Published: November 2022

OBJECTIVES

Anomalous left coronary artery from the pulmonary artery (ALCAPA) is frequently associated with significant mitral regurgitation (MR). We aim to identify surgical outcomes in patients with or without concomitant mitral intervention.

METHODS

All patients with ALCAPA who presented with >mild degree of MR at our institution between January 2008 and June 2020 were included in the retrospective study. MR recovery was defined as ≤mild MR at the last follow-up.

RESULTS

The study cohort included 101 patients. The median age at repair was 7.6 months. The concomitant mitral intervention was performed in 66 patients (65%). MR grade significantly improved at the last follow-up. The cumulative incidence of MR recovery 3 years after ALCAPA repair was 34% [95% confidence interval (CI), 19–50%) in patients with mitral intervention, compared to 59% (95% CI, 41–73%) in patients without mitral intervention (P = 0.050). MR grade on postoperative day 1 was the predictor for MR recovery in patients with mitral intervention (hazard ratio, 0.080; 95% CI, 0.018–0.366; P = 0.001), whereas preoperative mitral annulus diameter z-score was the predictor in patients without mitral intervention (hazard ratio, 0.480; 95% CI, 0.232–0.993; P = 0.048). Freedom from mitral reoperation in patients with mitral intervention was 94% and 88% at 3 and 5 years after surgery, while freedom from mitral reoperation in patients without mitral intervention was 100% at both timepoints (P = 0.177).

CONCLUSIONS

Despite significant MR improvement after ALCAPA repair, MR grade may not always return to normal regardless of the initial mitral management strategy, and reoperation for persistent MR is not rare.
Forty-year survival after Glenn procedure without Fontan procedure in patients with single ventricle
Authors: Miyake Makoto , Sakamoto Jiro , Kondo Hirokazu , Iwakura Atsushi , Doi Hiraku , Tamura Toshihiro
Published: November 2022

OBJECTIVES

There are no data on long-term outcomes beyond 30 years after the Glenn procedure without the subsequent Fontan procedure in patients with single-ventricle physiology. Hence, this study aimed to clarify the very long-term outcomes of these patients.

METHODS

This single-centre, retrospective cohort study investigated the clinical outcomes of patients with single-ventricle physiology who underwent the Glenn procedure between 1970 and 1999. Those who underwent the subsequent Fontan procedure were excluded. The primary outcome was all-cause death. The secondary outcome was a composite of all-cause death, arrhythmic events, neurological events or infective endocarditis. The prognostic factors associated with the long-term outcomes were also evaluated.

RESULTS

In total, 36 patients were enrolled (median age at Glenn procedure: 6.2 years, 56% male). During a median follow-up of 17.6 years (interquartile range: 6.1–33.4), 21 patients died and 29 experienced the composite outcome. The 20-, 30- and 40-year overall survival after the Glenn procedure was 51.2%, 44.4% and 40.3%, respectively. The 20-, 30- and 40-year event-free survival was 36.0%, 25.5% and 14.5%, respectively. Patients with dominant left ventricular morphology had better overall survival than those with dominant right ventricular morphology (hazard ratio: 0.24, 95% confidence interval: 0.08–0.76, P = 0.014). None of the patients had liver cirrhosis but 1 had protein-losing enteropathy.

CONCLUSIONS

The 40-year overall survival after the Glenn procedure without the subsequent Fontan procedure in patients with single-ventricle physiology was 40.3%. Dominant left ventricular morphology may be associated with better long-term overall survival than dominant right ventricular morphology.
Embedding telehealth for sustainable health services linking Oceania
Authors: Calyx Cobi , Weerasuriya Rona , White Sarah J
Published: November 2022

The expansion of telehealth during the COVID-19 pandemic can be further adapted and extended to align with principles of climate justice. We argue that high-emission countries with well-developed medical systems, like Australia, should support communities disproportionately impacted by climate change who request assistance, like in small island states of Oceania. Linking health services in small island states with neighbouring countries’ medical systems can support sustainability, if such reconfigurations are appropriately resourced and accessibility is prioritized. Investments in telehealth, particularly reconfiguring services through community-led linkages with larger medical systems, supports the sustainable development goal of universal access to healthcare.
Soil characteristics and redox properties of infiltrating water are determinants of microbial communities at managed aquifer recharge sites
Authors: Schrad Nicole , Pensky Jennifer , Gorski Galen , Beganskas Sarah , Fisher Andrew T , Saltikov Chad
Published: November 2022

In this study, we conducted a meta-analysis of soil microbial communities at three, pilot-scale field sites simulating shallow infiltration for managed aquifer recharge (MAR). We evaluated shifts in microbial communities after infiltration across site location, through different soils, with and without carbon-rich amendments added to test plots. Our meta-analysis aims to enable more effective MAR basin design by identifying potentially important interactions between soil physical–geochemical parameters and microbial communities across several geographically separate MAR basins. We hypothesized infiltration and carbon amendments would lead to common changes in subsurface microbial communities at multiple field sites but instead found distinct differences. Sites with coarser (mainly sandy) soil had large changes in diversity and taxa abundance, while sites with finer soils had fewer significant changes in genera, despite having the greatest increase in nitrogen cycling. Below test plots amended with a carbon-rich permeable reactive barrier, we observed more nitrate removal and a decrease in genera capable of nitrification. Multivariate statistics determined that the soil texture (a proxy for numerous soil characteristics) was the main determinant of whether the microbial community composition changed because of infiltration. These results suggest that microbial communities in sandy soil with carbon-rich amendments are most impacted by infiltration. Soil composition is a critical parameter that links between microbial communities and nutrient cycling during infiltration and could influence the citing and operation of MAR to benefit water quality and supply.
Legal and technical trade-offs in the content moderation of terrorist live-streaming
Authors: Zornetta Alessia , Pohland Ilka
Published: November 2022

Moderating terrorist live-streaming presents legal and technical trade-offs. The immediacy of live-streamed content requires a timely assessment of the content’s compliance with community guidelines and an even more expeditious action of restriction or removal in case of portrayal of illegal content. Social media companies have heavily relied on technology to moderate content. The most frequently used tools to screen and filter content and ensure compliance with community standards and regulations include hashing technology, video-fingerprinting, natural language processing and metadata analysis. Terrorist content online presents nuances that make the task of removing it particularly challenging especially when companies must rely on machine learning content moderation. We identify three trade-offs in regulating content moderation of live-streamed content: technological neutrality v specificity, explainability v adversarial machine learning, and accuracy v time-efficiency. For each trade-off, we provide an analysis of the considerations lawmakers and regulators must take into account when balancing competing interests.
Bioavailability of dissolved and crushed single tablets of bictegravir, emtricitabine, tenofovir alafenamide in healthy adults: the SOLUBIC randomized crossover study
Authors: Hocqueloux Laurent , Lefeuvre Sandrine , Bois Julie , Brucato Sylvie , Alix Antoine , Valentin Cécile , Peyro-Saint-Paul Laure , Got Laurence , Fournel François , Dargere Sylvie , Prazuck Thierry , Fournier Anna , Gregoire Nicolas , McNicholl Ian , Parienti Jean-Jacques
Published: November 2022

Background

Crushing or dissolving bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) tablets is not recommended because there are no data supporting this practice.

Methods

A crossover, randomized trial in healthy adults (NCT04244448) investigated the bioavailability of two off-label uses of BIC/TAF/FTC (50/200/25 mg), dissolved in water or crushed in apple compote, compared with the solid tablet. Pharmacokinetic (PK) parameters were estimated from sequential intensive plasma antiretroviral concentrations over a 72 h period post dose. Bioequivalence was met if the 90% CIs of the geometric least-squares means ratios comparing BIC/TAF/FTC exposures (AUC and Cmax) from the experimental phases were within 80%–125% of the reference.

Results

Eighteen subjects participated in each of the three phases. Dissolved tablet Cmax geometric mean ratio (90% CI) for BIC/TAF/FTC was 105% (93–119)/97% (87–108)/96% (74–124), respectively. Dissolved tablet AUC geometric mean ratio (90% CI) for BIC/TAF/FTC was 111% (100–122)/100% (94 to 105)/99% (81 to 120), respectively. Crushed tablet Cmax geometric mean ratio (90%) CI for BIC/TAF/FTC was 110% (97 to 124)/70% (63–78)/66% (51–85), respectively. Crushed tablet AUC geometric mean ratio (90%) CI for BIC/TAF/FTC was 107% (96–118)/86% (82–91)/84% (69–103), respectively.

Conclusions

Crushing BIC/TAF/FTC tablets may lead to suboptimal emtricitabine and tenofovir alafenamide drug exposures. Dissolving BIC/TAF/FTC in water may be acceptable if the tablet cannot be swallowed whole.
Training digital natives to transform healthcare: a 5-tiered approach for integrating clinical informatics into undergraduate medical education
Authors: Hare Allison J , Soegaard Ballester Jacqueline M , Gabriel Peter E , Adusumalli Srinath , Hanson C William
Published: November 2022

Expansive growth in the use of health information technology (HIT) has dramatically altered medicine without translating to fully realized improvements in healthcare delivery. Bridging this divide will require healthcare professionals with all levels of expertise in clinical informatics. However, due to scarce opportunities for exposure and training in informatics, medical students remain an underdeveloped source of potential informaticists. To address this gap, our institution developed and implemented a 5-tiered clinical informatics curriculum at the undergraduate medical education level: (1) a practical orientation to HIT for rising clerkship students; (2) an elective for junior students; (3) an elective for senior students; (4) a longitudinal area of concentration; and (5) a yearlong predoctoral fellowship in operational informatics at the health system level. Most students found these offerings valuable for their training and professional development. We share lessons and recommendations for medical schools and health systems looking to implement similar opportunities.
Cleaning of anthropometric data from PCORnet electronic health records using automated algorithms
Authors: Lin Pi-I D , Rifas-Shiman Sheryl L , Aris Izzuddin M , Daley Matthew F , Janicke David M , Heerman William J , Chudnov Daniel L , Freedman David S , Block Jason P
Published: November 2022

Objective

To demonstrate the utility of growthcleanr, an anthropometric data cleaning method designed for electronic health records (EHR).

Materials and Methods

We used all available pediatric and adult height and weight data from an ongoing observational study that includes EHR data from 15 healthcare systems and applied growthcleanr to identify outliers and errors and compared its performance in pediatric data with 2 other pediatric data cleaning methods: (1) conditional percentile (cp) and (2) PaEdiatric ANthropometric measurement Outlier Flagging pipeline (peanof).

Results

687 226 children (<20 years) and 3 267 293 adults contributed 71 246 369 weight and 51 525 487 height measurements. growthcleanr flagged 18% of pediatric and 12% of adult measurements for exclusion, mostly as carried-forward measures for pediatric data and duplicates for adult and pediatric data. After removing the flagged measurements, 0.5% and 0.6% of the pediatric heights and weights and 0.3% and 1.4% of the adult heights and weights, respectively, were biologically implausible according to the CDC and other established cut points. Compared with other pediatric cleaning methods, growthcleanr flagged the most measurements for exclusion; however, it did not flag some more extreme measurements. The prevalence of severe pediatric obesity was 9.0%, 9.2%, and 8.0% after cleaning by growthcleanr, cp, and peanof, respectively.

Conclusion

growthcleanr is useful for cleaning pediatric and adult height and weight data. It is the only method with the ability to clean adult data and identify carried-forward and duplicates, which are prevalent in EHR. Findings of this study can be used to improve the growthcleanr algorithm.
Reference genome of the Monkeyface Prickleback,Cebidichthys violaceus
Authors: Wright Daniel B , Escalona Merly , Marimuthu Mohan P A , Sahasrabudhe Ruta , Nguyen Oanh , Sacco Samuel , Beraut Eric , Toffelmier Erin , Miller Courtney , Shaffer H Bradley , Bernardi Giacomo , German Donovan P
Published: November 2022

Pricklebacks (Family Stichaeidae) are generally cold-temperate fishes most commonly found in the north Pacific. As part of the California Conservation Genomics Project (CCGP), we sequenced the genome of the Monkeyface Prickleback, Cebidichthys violaceus, to establish a genomic model for understanding phylogeographic patterns of marine organisms in California. These patterns, in turn, may inform the design of marine protected areas using dispersal models based on forthcoming population genomic data. The genome of C. violaceus is typical of many marine fishes at less than 1 Gb (genome size = 575.6 Mb), and our assembly is near-chromosome level (contig N50 = 1 Mb, scaffold N50 = 16.4 Mb, BUSCO completeness = 93.2%). Within the context of the CCGP, the genome will be used as a reference for future whole genome resequencing projects, enhancing our knowledge of the population structure of the species and more generally, the efficacy of marine protected areas as a primary conservation tool across California’s marine ecosystems.
Psychiatric Disorder Incidence Among Adolescents and Young Adults Aged 15-39 With Cancer: Population-Based Cohort
Authors: Rosgen Brianna K , Moss Stephana J , Fiest Kirsten M , McKillop Sarah , Diaz Ruth L , Barr Ronald D , Patten Scott B , Deleemans Julie , Fidler-Benaoudia Miranda M
Published: November 2022

Background

Adolescent and young adult (AYA) cancer survivors face physical and psychological sequelae related to having cancer decades after treatment completion. It is unclear if AYA cancer survivors are at increased risk for late psychiatric disorders.

Methods

We used the Alberta AYA Cancer Survivor Study that includes 5-year survivors of cancer diagnosed at age 15-39 years during 1991 to 2013. The primary outcome was incidence of psychiatric disorder (composite outcome) including anxiety, depressive, trauma- and stressor-related, psychotic, and substance use disorders that were identified using coding algorithms for administrative health databases. A validated coding algorithm identified people who experienced a suicide attempt or event of self-harm. Secondary outcomes were incidences of diagnoses by type of psychiatric disorder.

Results

Among 12 116 AYA 5-year cancer survivors (n = 4634 [38%] males; n = 7482 [62%] females), 7426 (61%; n = 2406 [32%] males; n = 5020 [68%] females) were diagnosed with at least 1 of 5 psychiatric disorders occurring at least 3 years after cancer diagnosis. Survivors of all cancer types were most often diagnosed with anxiety (males: 39.0%, 95% confidence interval [CI] = 37.6% to 40.4%; females: 54.5%, 95% CI = 53.3% to 55.6%), depressive (males: 32.7%, 95% CI = 31.3% to 34.0%; females: 47.0%, 95% CI = 45.8% to 48.1%), and trauma- and stressor-related disorders (males: 13.5%, 95% CI =12.5% to 14.5%; females: 22.5%, 95% CI = 21.6% to 23.5%).

Conclusions

Anxiety, depressive, and trauma- and stressor-related disorders are common among 5-year survivors of AYA cancer. Primary, secondary, or tertiary preventive strategies for AYAs diagnosed with cancer, particularly at an early age, are needed to mitigate risk of potentially severe outcomes because of psychiatric disorders.
Updates in intraoperative strategies for enhancing intra-axial brain tumor control
Authors: Wu Adela , Wu Janet Yuling , Lim Michael
Published: November 2022

To ensure excellent postoperative clinical outcomes while preserving critical neurologic function, neurosurgeons who manage patients with intra-axial brain tumors can use intraoperative technologies and tools to achieve maximal safe resection. Neurosurgical oncology revolves around safe and optimal extent of resection, which further dictates subsequent treatment regimens and patient outcomes. Various methods can be adapted for treating both primary and secondary intra-axial brain lesions. We present a review of recent advances and published research centered on different innovative tools and techniques, including fluorescence-guided surgery, new methods of drug delivery, and minimally invasive procedural options.
Ethical Issues with Artificial Ethics Assistants
Authors: O’Neill Elizabeth , Klincewicz Michal , Kemmer Michiel
Published: November 2022

This chapter examines the possibility of using artificial intelligence (AI) technologies to improve human moral reasoning and decision-making. The authors characterize such technologies as artificial ethics assistants (AEAs). The authors focus on just one part of the AI-aided moral improvement question: the case of the individual who wants to improve their morality, where what constitutes an improvement is evaluated by the individual’s own values. The authors distinguish three broad areas in which an individual might think their own moral reasoning and decision-making could be improved: one’s actions, character, or other attributes fall short of one’s values and moral beliefs; one sometimes misjudges or is uncertain about what the right thing to do is, given one’s values; or one is uncertain about some fundamental moral questions or recognizes a possibility that some of one’s core moral beliefs and values are mistaken. The authors sketch why one might think AI tools could be used to support moral improvement in those areas and distinguish two types of assistance: preparatory assistance, including advice and training supplied in advance of moral deliberation, and on-the-spot assistance, including on-the-spot advice and facilitation of moral functioning over the course of moral deliberation. Then, the authors turn to ethical issues that AEAs might raise, looking in particular at three under-appreciated problems posed by the use of AI for moral self-improvement: namely, reliance on sensitive moral data, the inescapability of outside influences on AEAs, and AEA usage prompting the user to adopt beliefs and make decisions without adequate reasons.
Combined effects of elevated CO2 and warmer temperature on limitations to photosynthesis and carbon sequestration in yellow birch
Authors: Wang Lei , Zheng Jinping , Wang Gerong , Dang Qing-Lai
Published: November 2022

Elevated CO2 and warmer temperature occur simultaneously under the current climate change. However, their combined effects on the photosynthetic traits in boreal trees are not well understood. This study investigated the morphological and photosynthetic responses of yellow birch (Betula alleghaniensis Britt.) to a combined treatment of CO2 and temperature (ambient, ACT (400 μmol mol−1 CO2 and current temperature) vs elevated, ECT (750 μmol mol−1 CO2 and current +4 °C temperature)). It was found that ECT significantly reduced leaf-area based photosynthetic rate (An), maximum Rubisco carboxylation rate (Vcmax), photosynthetic electron transport rate (Jmax), leaf nitrogen concentration, respiration and mesophyll conductance. There were two interesting findings: first, the primary mechanism of photosynthetic limitation shifted from Ribulose-1,5-bisphosphate (RuBP) carboxylation (related to Vcmax) to RuBP regeneration (related to Jmax) in response to ECT, leading to decreased transition point (Ci-t and An-t) from RuBP carboxylation to regeneration; second, the increase in total leaf area in response to ECT more than compensated for the downregulation of leaf-area based photosynthesis, leading to greater biomass in ECT than in ACT. We proposed a new protocol for evaluating photosynthetic limitations by comparing the relative relationship between the transition point (Ci-t and An-t) and the photosynthetic rate at growth CO2 (Ci-g and An-g). Furthermore, we found that Jmax (RuBP regeneration) was the primary limitation to An under ECT.
Control of Globodera pallida Using Sinapis alba or 4-Hydroxybenzyl Alcohol with the Trap Crop Solanum sisymbriifolium or the Biofumigant Brassica juncea Seed Meal Extract
Authors: Chhetri Prativa , Dandurand L. M. , Popova I.
Published: November 2022

The pale cyst nematode Globodera pallida is a highly specialized, economically important pest for potato production. The specialized hatching requirements, ability to adapt, and the loss of effective control strategies such as methyl bromide fumigation increase the challenge to eradicate G. pallida in Idaho. Without a suitable host, this nematode can remain dormant as encysted eggs in soil for up to 20 years. In this study, we first demonstrated that Sinapis alba seed meal extract (SME) or 4-hydroxybenzyl alcohol (HBA), under laboratory and greenhouse conditions, enhances G. pallida egg hatch rate when exposed to potato root diffusate (PRD). This hatch rate enhancement in the presence of PRD is speculated to be due to an increase in egg-shell permeability. We then tested the efficacy of (i) Solanum sisymbriifolium following prior treatment with S. alba SME (0 and 4.48 t/ha) or HBA (0 and 0.12 t/ha) and (ii) Brassica juncea SME (0, 0.14, 0.56, and 1.12 t/ha) following HBA treatment (0 and 4.48 t/ha) on egg viability, hatch rate, and reproduction of G. pallida encysted eggs. S. sisymbriifolium alone reduced the number of encysted eggs compared to the nontreated control by up to 67%, indicating that this trap crop triggered G. pallida eggs to hatch. When combined with S. alba SME or HBA, S. sisymbriifolium significantly reduced egg count, hatch rate, and viability more than S. sisymbriifolium alone. The combination of S. sisymbriifolium with HBA or S. alba SME eliminated G. pallida reproduction on the susceptible potato. All the tested rates of B. juncea SME alone or with HBA reduced egg hatch rate, viability, and reproduction compared to the nontreated control. Combining HBA and B. juncea SME further significantly reduced egg hatch rate, viability, and reproduction than those rates of B. juncea SME alone.
Assessing Childhood Maltreatment Exposure in Patients Without and With a Diagnosis of Substance Use Disorder
Authors: Löfberg Andreas , Gustafsson Per A. , Gauffin Emelie , Perini Irene , Heilig Markus , Capusan Andrea J.
Published: November 2022

Objectives

Childhood maltreatment (CM), widely held as a risk factor for substance use disorders (SUDs), is commonly assessed using the Childhood Trauma Questionnaire (CTQ). Retrospective self-reports are, however, potentially subject to bias. We used a unique patient sample with prospectively documented CM to examine the performance of the CTQ and how this is affected by the presence of SUD.

Methods

Analysis was based on a total of 104 individuals. Subjects with prospectively recorded CM were identified from a specialized childhood trauma unit in Linköping, Sweden (n = 55; 31 with SUD, 61% females; 24 without SUD, 71% females). Clinical controls had SUD but no CM (n = 25, 48% females). Healthy controls had neither SUD nor CM (n = 24, 54% females). We analyzed the agreement between retrospective CTQ scores and prospectively documented CM by κ analysis and assessed the performance of the CTQ to identify CM exposure using receiver operating characteristic (ROC) analysis.

Results

Agreement between prospectively and retrospectively recorded CM exposure was poor for sexual abuse (36.6%, Cohen κ = 0.32, P = 0.008) and physical abuse (67.3%, κ = 0.35, P = 0.007). Overall CTQ performance was fair (ROC: area under the ROC curve = 0.78, optimal cutoff = 36.5, sensitivity = 0.65, specificity = 0.75). However, performance was excellent in the absence of SUD (area under the ROC curve = 0.93, cutoff = 32.0, sensitivity = 0.88, specificity = 0.88), but poor in participants with lifetime SUD (area under the ROC curve = 0.62, cutoff = 42.0, sensitivity = 0.60, specificity = 0.36).

Conclusions

These data support the CTQ as a tool to assess CM exposure but suggest that it may be less useful in patients with SUD.
Autologous Serum Eye Drops in the Management of Limbal Stem Cell Deficiency Associated With Glaucoma Surgery
Authors: Niruthisard Duangratn , Bonnet Clémence , Tanasugarn Lokachet , Le Bryan , Deng Sophie X.
Published: November 2022

Purpose:

To evaluate safety and efficacy of autologous serum eye drops (AS) in the treatment of limbal stem cell deficiency (LSCD) associated with glaucoma surgery.

Methods:

Retrospective case series of eyes with glaucoma surgery-induced LSCD treated with AS. Diagnosis of LSCD was confirmed by anterior segment optical coherence tomography, in vivo confocal microscopy, and/or impression cytology. Limbal stem cell deficiency severity was staged using a clinical scoring system (2–10 points). Outcome measures were changes (≥2 points) of the LSCD score and best-corrected visual acuity (BCVA) from the baseline to the last follow-up.

Results:

Thirteen eyes of 12 consecutive patients treated with 50% AS for at least 3 months were included. The mean age was 78.9±7.5 years and the mean duration of AS use was 20.9±16.8 months. Indications of AS included LSCD progression in eight eyes (61.5%) and visual axis threatening in five eyes (38.5%). The mean LSCD score at baseline (6.7±1.6) was similar to that at last follow-up (6.5±2.2, P=0.625). Two eyes (15.4%) showed improvement, nine eyes (69.2%) were stable, and two eyes (15.4%) worsened. The mean baseline BCVA (0.89±0.64 logMAR) was similar to the mean final BCVA (1.05±0.63 logMAR, P=0.173). There were no serious adverse complications related to AS.

Conclusion:

AS appears to be well tolerated and may stabilize the progression of LSCD with limited effects. A larger study is necessary to confirm the findings.
Maneuvers to Facilitate Central Venous Catheter Advancement in the Clavicular Region
Authors: Nobre Keline Soraya Santana , Cardoso Maria Vera Lúcia Moreira Leitão , Melo Gleicia Martins de , Oliveira Débora Teles de , Silva Letícia Kelly Costa
Published: November 2022

In many situations, central venous catheters (CVCs), inserted by central or peripheral venipuncture, do not progress, even after performing some movement of the shoulder, head, and neck. This integrative review aimed to verify the scientific evidence about maneuvers to facilitate the advancement of CVCs in the clavicular region and/or shoulder in adult, pediatric, and neonatal patients. Primary studies with available electronic abstracts, independent of idiom or publication year, for which results showed aspects related to descriptions of maneuvers for CVC advancement in the clavicular region and shoulder, were included in the review. The sample included 6 studies published from 1989 to 2020 in CINAHL, Cochrane, Lilacs, Medline/PubMed, SCIELO, and Scopus databases. Maneuvers of the shoulder, arm, neck, and head facilitate CVC advancement in the shoulder and clavicular region. However, most of the studies analyzed were performed in adults. More research is needed on CVC advancement in pediatric and neonatal populations.
SOX9 Expression Is Superior to Other Stem Cell Markers K19 and EpCAM in Predicting Prognosis in Hepatocellular Carcinoma
Authors: Ruzinova Marianna B. , Ma Changqing , Brunt Elizabeth M. , Goss Charles W. , Vachharajani Neeta , Chapman William C. , Liu Ta-Chiang
Published: November 2022

Various stem cell markers (eg, epithelial cell adhesion molecule [EpCAM], cytokeratin 19 [K19]) have been reported as predictors of poor prognosis in hepatocellular carcinoma (HCC). However, the data remain limited, particularly in Western populations, and are often contradictory. In this study, the prognostic value of positive SOX9 immunohistochemistry was compared with that of more established markers EpCAM and K19 in a large cohort (n=216) of North American patients. The independent HCC cohort in The Cancer Gene Atlas (n=360) was utilized to validate our findings. Finally, molecular signatures associated with SOX9-high HCC were determined. We found that the expression of SOX9, but not EpCAM or K19, was associated with worse overall survival and disease-free survival (DFS) and was an independent prognostic factor for DFS in our North American cohort, in which hepatitis C infection was the most common underlying etiology. High SOX9 mRNA level, but not increased expression of EpCAM mRNA or K19 mRNA, was also associated with worse DFS and was an independent prognostic factor for DFS in The Cancer Gene Atlas cohort. This group had underlying causes, including an increased incidence of hepatitis B, significantly different from our initial cohort. High SOX9 mRNA level is associated with molecular pathways important in HCC pathogenesis. Increased SOX9 expression is clinically and biologically relevant for HCC arising in patients with a variety of underlying etiologies. Immunohistochemistry for SOX9 is a reliable proxy for increased SOX9 mRNA and can be used to predict prognosis in HCC cases.
The Vast Majority of Patients With Fibromyalgia Have a Straight Neck Observed on a Lateral View Radiograph of the Cervical Spine
Authors: Katz Robert S. , Leavitt Frank , Cherny Katya , Small Alexandra Katz , Small Ben J.
Published: November 2022

Objective

A straight cervical spine is an underappreciated and often overlooked finding in fibromyalgia. The aim of this medical records review study was to evaluate the cervical curvature on radiographs of patients with fibromyalgia.

Methods

A consecutive series of 270 cervical spine radiographs of patients with neck pain from 2015 to 2018 were retrospectively analyzed for cervical curvature using the Cobb angle measurement. One hundred fifty-five patients met full American College of Rheumatology criteria for fibromyalgia, whereas 115 subjects with other rheumatic diseases who were similar in age and education served as control subjects.

Results

Mean cervical curvature in fibromyalgia was 6.4 ± 5.2 degrees and 13.8 ± 7.4 degrees in control subjects. The more than 7-degree difference was significant (p < 0.001). Curvature in the magnitude of 21 degrees is at the low end of normal. At ≤10 degrees, where the cervical spine is essentially straight, there were 129 fibromyalgia patients (83.2%) and 37 control subjects (32.2%). The 51% difference was significant (p < 0.001).

Conclusion

Most patients with fibromyalgia share an abnormality in common that is verifiable by a simple radiograph. In 83.2% of the patients, the cervical spine was essentially straight (Cobb angle ≤10 degrees). In fibromyalgia patients, the loss of cervical curvature was approximately 6.5 times greater than in control subjects (50.3% vs. 7.8%). A straight neck without other radiographic abnormalities may be a major anatomical abnormality in fibromyalgia that has gone unnoticed. It may assist in the diagnosis, as well as suggest increased muscle tension/pressure as a possible etiology.
Experimental hyperoxia (O
2
supersaturation) reveals a gill diffusion limitation of maximum aerobic performance in fish
Authors: McArley T. J. , Morgenroth D. , Zena L. A. , Ekström A. T. , Sandblom E.
Published: November 2022

Several studies have demonstrated that hyperoxia increases the maximal O
2
consumption rate (ṀO
2max
) in fish, but exactly how this occurs remains to be explained. Here, we tested the hypothesis that hyperoxia improves arterial oxygenation in rainbow trout during exhaustive exercise. We demonstrate a 35% higher ṀO
2max
in hyperoxia (200% air saturation) relative to normoxia, which was achieved through a combined 15% increase in cardiac output due to elevated peak heart rate, and a 19% increase of the arterial–venous (A-V) O
2
content difference. While arterial O
2
partial pressure (PaO
2
) and O
2
saturation of haemoglobin declined post-exhaustive exercise in normoxia, this did not occur in hyperoxia. This protective effect of hyperoxia on arterial oxygenation led to a 22% higher arterial O
2
content post-exhaustive exercise, thereby allowing a higher A-V O
2
content difference. These findings indicate that ṀO
2max
is gill diffusion limited in exhaustively exercised rainbow trout. Moreover, as previous studies in salmonids have demonstrated collapsing PaO
2
in normoxia at maximal swimming speed and at acutely high temperatures, a diffusion limitation may constrain ṀO
2
in other situations eliciting peak metabolic demand. These findings, along with the fact that hyperoxia increases ṀO
2max
in several other fishes, suggest that gill diffusion limitations of ṀO
2max
may be widespread in fishes.