bluuebunny/crossref_metadata_2025 huggingface dataset:
Extinction in the Land of Its Birth
Authors: Shattuck, Jr. Gardiner H.
Published: November 2022

Concluding the book’s main narrative, this chapter examines how Charles Bridgeman and others concerned about the Middle East came to terms with the reality of a Jewish state in the Holy Land. In addition to the existential threat that Israel posed to the evangelistic aspirations of Western missionaries, the Palestinian Nakba left a humanitarian disaster similar to what had occurred in the Middle East following World War I. Responding to this new crisis Episcopalians, including Arabists such as William A. Eddy and other lay men and women knowledgeable about the region and its oil resources, were active in forming organizations that lobbied for the Palestinian cause. In this effort they sought not only to inspire churchgoers to alleviate the suffering of refugees in biblical lands, but also to demonstrate to all Americans the need to court Arab nations as allies in the budding Cold War against the Soviet Union.
Bloch and Latent Utopia
Authors: Goldman Loren
Published: November 2022

This chapter examines Ernst Bloch as a theorist of political hope. It presents Bloch in light of his respective engagements with Kant, Hegel, and Marx, and proceeds methodically through his borrowings from each thinker. It argues that Bloch’s famous notion of concrete utopia is predicated on an idiosyncratic vital materialist ontology, such that the not-yet that is central to his work is oriented toward the emergence of novel possibilities that are always already latent in the world. As such, it argues that Bloch aims to overcome what he perceives to be the shortcomings of Kant’s overly subjective account of hope, yet strays toward an equally problematic postulate of natural teleology in the process.
Brief Mindfulness-Based Cognitive Behavioral Therapy is Associated with Faster Recovery in Patients Undergoing Total Knee Arthroplasty: A Pilot Clinical Trial
Authors: Pester Bethany D , Wilson Jenna M , Yoon Jihee , Lazaridou Asimina , Schreiber Kristin L , Cornelius Marise , Campbell Claudia M , Smith Michael T , Haythornthwaite Jennifer A , Edwards Robert R , Meints Samantha M
Published: November 2022

Objective

To assess whether brief mindfulness-based cognitive behavioral therapy (MBCBT) could enhance the benefits of total knee arthroplasty (TKA) in improving pain and pain-related disability. Specifically, to determine 1) whether patients who received MBCBT differed from matched controls who received treatment-as-usual with regard to postsurgical pain outcomes and 2) whether changes in pain catastrophizing, depression, or anxiety explained the potential effects of MBCBT on pain outcomes.

Design

Pilot clinical trial.

Setting

An academic teaching hospital serving a large urban and suburban catchment area surrounding the Boston, Massachusetts metropolitan region.

Subjects

Sample of 44 patients undergoing TKA. Patients who completed a brief MBCBT intervention (n = 22) were compared with age-, race-, and sex-matched controls who received treatment-as-usual (n = 22).

Methods

The MBCBT intervention included four 60-minute sessions delivered by a pain psychologist in person and via telephone during the perioperative period. Participants were assessed at baseline and at 6 weeks, 3 months, and 6 months after surgery.

Results

Compared with matched controls, patients who received MBCBT had lower pain severity and pain interference at 6 weeks after surgery. Group differences in outcomes were mediated by changes in pain catastrophizing but not by changes in depression or anxiety. The MBCBT group had similar reductions in pain severity and interference as the control group did at 3 and 6 months after surgery.

Conclusions

This work offers evidence for a safe and flexibly delivered nonpharmacological treatment (MBCBT) to promote faster recovery from TKA and identifies change in pain catastrophizing as a mechanism by which this intervention could lead to enhanced pain-related outcomes.
Systemic lupus erythematosus phenotypes formed from machine learning with a specific focus on cognitive impairment
Authors: Barraclough Michelle , Erdman Lauren , Diaz-Martinez Juan Pablo , Knight Andrea , Bingham Kathleen , Su Jiandong , Kakvan Mahta , Grajales Carolina Muñoz , Tartaglia Maria Carmela , Ruttan Lesley , Wither Joan , Choi May Y , Bonilla Dennisse , Appenzeller Simone , Parker Ben , Goldenberg Anna , Katz Patricia , Beaton Dorcas , Green Robin , Bruce Ian N , Touma Zahi
Published: November 2022

Objective

To phenotype SLE based on symptom burden (disease damage, system involvement and patient reported outcomes), with a specific focus on objective and subjective cognitive function.

Methods

SLE patients ages 18–65 years underwent objective cognitive assessment using the ACR Neuropsychological Battery (ACR-NB) and data were collected on demographic and clinical variables, disease burden/activity, health-related quality of life (HRQoL), depression, anxiety, fatigue and perceived cognitive deficits. Similarity network fusion (SNF) was used to identify patient subtypes. Differences between the subtypes were evaluated using Kruskal–Wallis and χ2 tests.

Results

Of the 238 patients, 90% were female, with a mean age of 41 years (s.d. 12) and a disease duration of 14 years (s.d. 10) at the study visit. The SNF analysis defined two subtypes (A and B) with distinct patterns in objective and subjective cognitive function, disease burden/damage, HRQoL, anxiety and depression. Subtype A performed worst on all significantly different tests of objective cognitive function (P < 0.03) compared with subtype B. Subtype A also had greater levels of subjective cognitive function (P < 0.001), disease burden/damage (P < 0.04), HRQoL (P < 0.001) and psychiatric measures (P < 0.001) compared with subtype B.

Conclusion

This study demonstrates the complexity of cognitive impairment (CI) in SLE and that individual, multifactorial phenotypes exist. Those with greater disease burden, from SLE-specific factors or other factors associated with chronic conditions, report poorer cognitive functioning and perform worse on objective cognitive measures. By exploring different ways of phenotyping SLE we may better define CI in SLE. Ultimately this will aid our understanding of personalized CI trajectories and identification of appropriate treatments.
A Tribute to Dr. Fauci
Authors: Grady Christine
Published: November 2022

A nurse honors her husband's legacy.
Rise in Labor Action by Nurses
Authors: McSpedon Corinne
Published: November 2022

Strikes highlight common nursing challenges and concerns.
Two New Drugs Approved for Non–Small Cell Lung Cancer
Authors: Aschenbrenner Diane S.
Published: November 2022

The Food and Drug Administration (FDA) has approved capmatinib (Tabrecta) for the treatment of metastatic non–small cell lung cancer in adults whose tumors have a mutation leading to mesenchymal-epithelial transition exon 14 skipping.

Nurses should monitor patients for serious adverse effects such as interstitial lung disease/pneumonitis, hepatotoxicity, pancreatic toxicity, photosensitivity, and embryo–fetal toxicity.

The FDA has granted accelerated approval to fam-trastuzumab deruxtecan-nxki (Enhertu) for the treatment of unresectable or metastatic non–small cell lung cancer in adults whose tumors have activating human epidermal growth factor receptor 2 mutations and who have received a prior systemic therapy.

Enhertu carries a boxed warning regarding the risk of interstitial lung disease and embryo–fetal toxicity.
A Nursing School on Reservation Land
Authors: Wilson Deborah , Werk Alicia , Hemmer Brigit
Published: November 2022

An associate degree in nursing program was established six years ago at the tribal college of the Fort Belknap Indian Reservation, home of the Aaniiih and Nakoda people. As this program continues to evolve and grow, it offers a successful example of how to increase diversity in nursing and potentially improve the health outcomes of Native Americans living on and nearby reservation communities.
Oxygen Uptake Efficiency Slope as a Predictor of Mortality Risk
Authors: Peterman James E. , Novelli Dominic S. , Fleenor Bradley S. , Whaley Mitchell H. , Kaminsky Leonard A. , Harber Matthew P.
Published: November 2022

Purpose:

Oxygen uptake efficiency slope (OUES), defined as the slope of the linear relationship between oxygen uptake and the semilog transformed ventilation rate measured during an incremental exercise test, may have prognostic utility. The objective of this investigation was to examine the relationship between assessments of OUES and all-cause mortality in a cohort of apparently healthy adults.

Methods:

The sample included 2220 apparently healthy adults (48% females) with a mean age of 44.7 ± 12.9 yr who performed cardiopulmonary exercise testing. The OUES was calculated from the entire test, using data from the initial 50% (OUES50) and 75% (OUES75) of test time, and normalized to body surface area. Cox proportional hazard models assessed the relationship between measures of OUES and mortality. Prognostic peak oxygen uptake (V˙o
2peak) and OUES models were compared using the concordance index.

Results:

There were 310 deaths (29% females) over a follow-up period of 19.8 ± 11.1 yr. For males, OUES, OUES75, and normalized OUES had an inverse association with mortality, even after adjusting for traditional risk factors (P < .05). For females, only the unadjusted OUES, OUES75, and normalized OUES models were associated with mortality (P < .05). The concordance index values indicated that unadjusted OUES50 and OUES75 models had lower discrimination than the unadjusted OUES and V˙o
2peak models (P < .05). Furthermore, OUES did not complement the fully adjusted V˙o
2peak model (P≥ .32).

Conclusions:

Assessments of OUES are related to all-cause mortality in males but not in females. These findings suggest that OUES can have prognostic utility in apparently healthy males. Moreover, submaximal determinations of OUES could have value when measuring V˙o
2peak is not feasible.
LONG-TERM TREATMENT OUTCOMES AFTER BEVACIZUMAB THERAPY FOR MACULAR NEOVASCULARIZATION IN WHITE PATIENTS WITH HIGH MYOPIA
Authors: Ravenstijn Monica , Klaver Caroline C. W. , Yzer Suzanne
Published: November 2022

Purpose:

To report long-term treatment outcomes of intravitreal bevacizumab in myopic macular neovascularization (MNV).

Methods:

Retrospective analysis of longitudinal, clinical data of patients with high myopic MNV treated with intravitreal bevacizumab. One-hundred and seventeen eyes of 106 patients were followed from first injection up to 12 years. Outcome measures were best-corrected visual acuity change during follow-up and myopic MNV recurrence.

Results:

Mean (±SD) baseline best-corrected visual acuity (0.56 ± 0.46 logMAR, 20/80) significantly improved after first treatment (0.33 ± 0.33, 20/50, P < 0.001). At 4 years (n = 86), best-corrected visual acuity was no longer significantly better than at baseline (0.55 ± 0.57, P = 0.30) and continued to deteriorate to 0.84 ± 0.76 (20/125) at 10 years (n = 27). Of the 27 eyes (23%) who reached 10 years of follow-up, 53% developed MNV-related chorioretinal atrophy. The cumulative incidence of recurrent myopic MNV was 34% at 2 years and 59% at 5 years. Best-corrected visual acuity decrease in eyes with or without recurrent MNV was similar (P = 0.58). Patchy chorioretinal atrophy (hazard ratio 3.0, P = 0.02) and subfoveal MNVs (hazard ratio 2.5, P = 0.048) were significantly associated with recurrent MNV.

Conclusion:

This retrospective myopic MNV study revealed that visual improvement after intravitreal bevacizumab injections was not maintained over time. Macular neovascularization recurrences occurred frequently but did not alter the already poor visual prognosis.
Which is the best way for patients with ureteral obstruction? Percutaneous nephrostomy versus double J stenting
Authors: Zhang Kai-Ping , Zhang Yin , Chao Min
Published: November 2022

Background:

Percutaneous nephrostomy (PCN) and Double J stenting (DJS) are the 2 main treatment options of ureteral obstruction. We evaluate which of these 2 methods is superior concerning the course of procedure, postoperative complication and quality of life.

Methods:

A detailed review of electronic databases including PubMed, Embase, Cochrane Library, China Biology Medicine disc, China National Knowledge Infrastructure up to February 21st, 2021 was searched. Continuous data were evaluated using mean difference (MD) with 95% confidence interval (CI), while nominal data were analyzed by risk ratio (RR) with 95% CI. Meanwhile, we performed the subgroup analysis based on study design, disease type, sample size, sepsis, DJ diameter, nephrostomy diameter, anesthesia type and guidance under X-ray or ultrasound.

Results:

There were 18 previous studies included in current study. As a result, we found that there were significant differences in fluoroscopy time (MD = 0.31; 95% CI, 0.14–0.48, P < .001) and hospital stay (MD = 1.23; 95% CI, 0.60–1.85, P < .001). However, no statistic difference was detected in operative time (MD = 5.40; 95% CI, −1.78 to 12.58, P = .140) between the paired groups. Although DJS showed a higher rate of postoperative complications (25.19% vs 17.61%), there was no significant difference in the incidence of complications following DJS and PCN (RR = 0.92; 95% CI, 0.60–1.43; P = .720). Based on the EuroQol analysis, the 2 main treatment options had different impacts on quality of life. The pooled results showed that PCN patients reported more difficulties in self-care compared to DJS patients (RR = 3.07; 95% CI, 1.32–7.14; P = .009).

Conclusions:

DJS is a safe and better method of temporary urinary diversion than PCN for management of ureteral obstruction with shorter fluoroscopy time and hospital stay. As for quality of life, patients receiving PCN had a distinct difficulty in self-care compared to those receiving DJS. However, these 2 treatment options often depends on the individual situation.
Gastrointestinal involvement in systemic sclerosis: An updated review
Authors: Nassar Mahmoud , Ghernautan Victoria , Nso Nso , Nyabera Akwe , Castillo Francisco Cuevas , Tu Wan , Medina Luis , Ciobanu Camelia , Alfishawy Mostafa , Rizzo Vincent , Eskaros Saphwat , Mahdi Mamdouh , Khalifa Mohamed , El-Kassas Mohamed
Published: November 2022

The gastrointestinal tract (GI) is the second most affected organ system in individuals suffering from systemic/localized scleroderma (SSc) or localized scleroderma. SSc can affect any part of the GI, between the oral cavity and anorectum. The annual incidence of SSc in the United States is estimated to be 19.3 cases per million adults, with the highest incidence reported in people aged 44 to 55. Females are 5 times more likely than males to suffer from SSc. Morbidity and mortality rates associated with SSc are predominantly elevated among patients with GI manifestations. Esophageal and intestinal manifestations impact 90% and 40% to 70% of patients with systemic scleroderma, respectively. SSc patients are known to suffer from small bowel hypomotility and small intestinal bacterial overgrowth, which cause malabsorption and malnutrition, ultimately contributing to the 50% mortality rate. Fecal incontinence is a common symptom of SSc that can lead to depression. SSc patients may suffer from gastrointestinal complications that can negatively impact their quality of life on a daily basis. Multidisciplinary approaches are necessary for systematically managing gastrointestinal complications associated with SSc. A prospective study should focus on developing targeted therapies to improve recovery patterns and prognosis in cases of SSc. This article summarizes the epidemiology, commonly reported clinical manifestations, complications, and available treatments for treating GI pathology in SSc patients.
The tissue-specific autophagic response to nutrient deprivation
Authors: Yang Young Joo , Grosso Jasutkar Hilary , Griffey Christopher J. , Kim Kiryung , Melia Thomas James , Dephoure Noah , Yamamoto Ai
Published: November 2022

Macroautophagy is a highly adaptable degradative system that is essential for life. Although studies have shown the importance of this pathway across all organ systems, we have little understanding of how discrete tissues might employ autophagy and how this changes during stress. Using an approach to identify quantitatively autophagic cargoes, we sought to identify how cells from the adult liver and brain rely on autophagy under basal conditions and during nutrient deprivation. We find that in addition to the turnover of cell type specific proteins, the different organs relied on autophagy differentially for the turnover of organelles such as mitochondria, peroxisomes and ER. Moreover, in response to nutrient deprivation, although both tissues showed increased cargo capture, cell type- and tissue-specific patterns emerged. Most notably in the brain, we found an increased representation of glial and endothelial cell cargoes, whereas neuronal cargoes were relatively unchanged. In liver, we unexpectedly found a decreased representation of mitochondrial proteins, which represented a shift moving away from the whole mitochondrion turnover to piecemeal. These results indicate how the physiologic context of the different cell types significantly influence autophagy-dependence, and begins to shed insight into how the term ‘autophagy dysfunction’ might be thought of when considering different disease states.
Non-invasive real-time genomic monitoring of the critically endangered kākāpō
Authors: Urban Lara , Miller Allison K , Eason Daryl , Vercoe Deidre , Shaffer Megan , Wilkinson Shaun P , Jeunen Gert-Jan , Gemmell Neil J , Digby Andrew
Published: November 2022

We used non-invasive real-time genomic approaches to monitor one of the last surviving populations of the critically endangered kākāpō (Strigops habroptilus). We first established an environmental DNA metabarcoding protocol to identify the distribution of kākāpō and other vertebrate species in a highly localized manner using soil samples. Harnessing real-time nanopore sequencing and the high-quality kākāpō reference genome, we then extracted species-specific DNA from soil. We combined long read-based haplotype phasing with known individual genomic variation in the kākāpō population to identify the presence of individuals, and confirmed these genomically informed predictions through detailed metadata on kākāpō distributions. This study shows that individual identification is feasible through nanopore sequencing of environmental DNA, with important implications for future efforts in the application of genomics to the conservation of rare species, potentially expanding the application of real-time environmental DNA research from monitoring species distribution to inferring fitness parameters such as genomic diversity and inbreeding.
Characterization of Trajectories of Physical Activity and Cigarette Smoking from Early Adolescence to Adulthood
Authors: Shao Iris Yuefan , Suglia Shakira F. , An Weihua , Mendez David , Vaccarino Viola , Alonso Alvaro
Published: November 2022

Background

Cigarette smoking and physical inactivity are two critical risk factors for noncommunicable diseases and all-cause mortality. However, few studies have compared the long-term trajectories of both behaviors, as well as multilevel factors associated with trajectory patterns. Using the National Longitudinal Study of Adolescent to Adult Health (Add Health) Wave I through V survey data, this study characterized distinct subgroups of the population sharing similar patterns of physical activity (PA) and cigarette smoking from adolescence to adulthood, as well as predictors of subgroup membership.

Methods

Using the Add Health Wave I through V survey data, we identified the optimal number of latent classes and class-specific trajectories of PA and cigarette smoking from early adolescence to adulthood, fitting latent growth mixture models with standardized PA score and past 30-day cigarette smoking intensity as outcome measures and age as a continuous time variable. Associations of baseline sociodemographic factors, neighborhood characteristics, and sociopsychological factors with trajectory class membership were assessed using multinomial logistic regression.

Results

We identified three distinct subgroups of PA trajectories in the study population: moderately active group (N=1067, 5%), persistently inactive group (N=14257, 69%) and worsening activity group (N=5410, 26%). Similarly for cigarette smoking, we identified three distinct trajectory subgroups: persistent non-smoker (N=14939, 72%), gradual quitter (N=2357, 11%), and progressing smoker (N=3393, 16%). Sex, race/ethnicity, neighborhood environment and perceived peer support during adolescence were significant predictors of physical activity and cigarette smoking trajectory subgroup membership from early adolescence to adulthood.

Conclusion

There are three distinct subgroups of individuals sharing similar both PA and cigarette smoking behavioral profile from adolescence to adulthood in the Add Health study population. Modifiable risk factors such as neighborhood environment and relationship to peers during adolescence can be key to designing effective behavioral interventions for long-term PA promotion and cigarette smoking cessation.
Relationships of scale cortisol content suggests stress resilience in freshwater fish vulnerable to catch-and-release angling in recreational fisheries
Authors: Britton J.R. , Andreou D , Lopez-Bejar M , Carbajal A
Published: November 2022

The capture by angling of an individual fish is recognised as a short-term physiologically stressor. In fish populations exploited by catch and release angling (C&R), there is potential for some individual fishes to be captured on multiple occasions, but the longer term physiological consequences of this remain uncertain. Using scale cortisol content as a biomarker of chronic stress and scale samples from two fish populations exploited by C&R angling, we developed proxies of angling capture vulnerability before testing these proxies against scale cortisol content. In a riverine population of European barbelBarbus barbus, fish with the highest scale cortisol content were predicted as those sampled by angling rather than electric fishing, as angled fish had significantly smaller home ranges and diets based primarily on angling baits. In a population of common carpCyprinus carpioin a small pond fishery, we predicted that fish with the highest scale cortisol content would be those with higher proportions of angling bait in their diet. In both species, however, the fish predicted to be most vulnerable to angling capture had the lowest levels of scale cortisol content. We suggest that this is through fish that are captured regularly being highly stress resilient (with this independent of other traits) or fish with traits that suggest high capture vulnerability being able to minimise their recapture rates through developing hook avoidance behaviours after an initial capture. Overall, these results suggest that scale cortisol content is a useful biomarker for measuring chronic stress from C&R angling.

Highlights

In catch-and-release angling (C&R), a single capture event is a short-term stressor

The effect of multiple capture events on individual fishes in C&R is unknown

Scale cortisol content was used as a biomarker of chronic stress

Fish of high vulnerability to capture had relatively low scale cortisol content

Fish with high exposure to C&R appear to have high stress resilience.
A phylogenetically-conserved axis of thalamocortical connectivity in the human brain
Authors: Oldham Stuart , Ball Gareth
Published: November 2022

The thalamus enables key sensory, motor, emotive, and cognitive processes via connections to the cortex. These projection patterns are traditionally considered to originate from discrete thalamic nuclei, however recent work showing gradients of molecular and connectivity features in the thalamus suggests the organisation of thalamocortical connections occurs along a continuous dimension. By performing a joint decomposition of densely sampled gene expression and non-invasive diffusion tractography in the adult human thalamus, we define a principal axis of genetic and connectomic variation along a medial-lateral thalamic gradient. Projections along this axis correspond to an anterior-posterior cortical pattern and are aligned with electrophysiological properties of the cortex. The medial-lateral axis demonstrates phylogenetic conservation, reflects transitions in neuronal subtypes, and shows associations with neurodevelopment and common brain disorders. This study provides evidence for a supra-nuclear axis of thalamocortical organisation characterised by a graded transition in molecular properties and anatomical connectivity.
Interaction between habits as action sequences and goal-directed behavior under time pressure
Authors: Frölich Sascha , Esmeyer Marlon , Endrass Tanja , Smolka Michael N. , Kiebel Stefan J.
Published: November 2022

Human behaviour consists in large parts of action sequences that are often repeated in mostly the same way. Through extensive repetition, sequential responses become automatic or habitual, but our environment often confronts us with events to which we have to react flexibly and in a goal-directed manner. To assess how implicitly learned action sequences interfere with goal-directed control, we developed a novel behavioural paradigm in which we combined action sequence learning through repetition with a goal-directed task component. So-called dual-target trials require the goal-directed selection of the response with the highest reward-probability in a fast succession of trials with short response deadlines. Importantly, the response primed by the learned action sequence is sometimes different from that required by the goal-directed task. As expected, we found that participants learned the action sequence through repetition, as evidenced by reduced reaction times and error rates, while still acting in a goal-directed manner in dual target trials. Specifically, we found that the learned action sequence biased choices in the goal-directed task towards the sequential response, and this effect was more pronounced the better individuals had learned the sequence. Our novel task may help shed light on the acquisition of automatic behavioural patterns and habits through extensive repetition, allows to assess positive features of habitual behaviour (e.g. increased response speed and reduced error rates), and importantly also the interaction of habitual and goal-directed behaviours under time pressure.
MerMADE: Coupled biophysical, eco-evolutionary modelling for predicting population dynamics, movement and dispersal evolution in the marine environment
Authors: Allgayer Rebekka L , Fernandes Paul G , Wright Peter J , Travis Justin MJ
Published: November 2022

In order to understand patterns in species’ distributions, we need to understand the underlying mechanisms of dispersal, demography and evolutionary capability of these species. In the marine environment, few models combine these three key components likely due both to the computational challenges involved and the inherent challenges in data collection for parameterisation. To fill this gap, we have developed MerMADE, an individual-based, spatially explicit, eco-evolutionary coupled biophysical model for predicting population dynamics, dispersal and movement evolution in the marine environment (or aquatic environments in general). MerMADE combines dispersal in a 3D, hydrodynamically informed environment with population dynamics, demography and evolutionary functionality in order to investigate questions of connectivity, population persistence and evolution under environmental change and anthropogenic pressure. We illustrate its range of behavioural and physiological functionality using the lesser sandeel,Ammodytes marinus, as a case-study species in an invasion scenario. MerMADE’s flexibility in species-specific parameterisation makes it a widely applicable, exciting tool in future sustainable management and conservation of aquatic species under environmental change.
SLC25A51 impacts drug sensitivity in AML cells by sustaining mitochondrial oxidative flux
Authors: Lu Mu-Jie , Busquets Jonathan , Impedovo Valeria , Chang Yu-Tai , Matsui William , Tiziani Stefano , Cambronne Xiaolu A.
Published: November 2022

SLC25A51 imports oxidized NAD+into the mitochondrial matrix and is required for sustaining oxidative metabolism in human mitochondria. We observed that higher expression of SLC25A51 correlated with poorer survival in Acute Myeloid Leukemia (AML) patient data. Given AML’s dependency on oxidative cell metabolism, we sought to determine the role SLC25A51 may serve in this disease. We found that depleting SLC25A51 in AML cells led to increased apoptosis, as well as prolonged survival in a xenograft model. Metabolic flux analyses indicated that depletion of SLC25A51 shunted flux away from oxidative pathways and promoted glutamine utilization for reductive carboxylation to support aspartate production. Consequently, SLC25A51 loss sensitized AML cells to glutamine deprivation and glutaminase inhibitor CB-839. Together, the work highlights connections between SLC25A51 and oxidative mitochondrial flux in AML. We identified a rationale for targeting SLC25A51 in myeloid cancers with potential for a therapeutic window, especially when coupled with glutaminase inhibition.

Statement of significance

This investigation describes an approach to directly modulate the tricarboxylic acid cycle as a potential vulnerability in oxidative tumors. Using AML models, the work is an inaugural look into SLC25A51’s role supporting oxidative mitochondrial metabolism and identifies SLC25A51 levels as a potential marker for stratification of AML.
Consciousness is indexed by analogous cortical reorganization during sleep and anesthesia
Authors: Krause Bryan M. , Campbell Declan I. , Kovach Christopher K. , Mueller Rashmi N. , Kawasaki Hiroto , Nourski Kirill V. , Banks Matthew I.
Published: November 2022

Although sleep and anesthesia are predicted to share common neural signatures of transitions into and out of unconsciousness, supportive evidence has been elusive. We identified these signatures using intracranial electroencephalography in neurosurgical patients. We applied diffusion map embedding to map cortical location into a space where proximity indicates functional similarity using a normalized connectivity (‘diffusion’) matrix, itself a rich source of information about network properties. During reduced consciousness, diffusion matrices exhibited decreased effective dimensionality, reflecting reduced network entropy. Furthermore, functional brain regions exhibited tighter clustering in embedding space with greater distances between regions, corresponding to decreased differentiation and functional integration. These changes were not region-specific, suggesting global network reorganization. These results strongly suggest common neural substrates for loss and recovery of consciousness during anesthesia and sleep, providing a systems-level mechanistic understanding within an intuitive geometric context and laying the foundation for evaluation of cortical state transitions in clinical settings.
ETV2 upregulation marks the specification of early cardiomyocytes and endothelial cells during co-differentiation
Authors: Cao Xu , Mircea Maria , Yakala Gopala Krishna , van den Hil Francijna E. , Brescia Marcella , Mei Hailiang , Mummery Christine L. , Semrau Stefan , Orlova Valeria V.
Published: November 2022

The ability to differentiate human induced pluripotent stem cells (hiPSCs) efficiently into defined cardiac lineages, such as cardiomyocytes and cardiac endothelial cells, is crucial to study human heart development and model cardiovascular diseasesin vitro. The mechanisms underlying the specification of these cell types during human development are not well-understood which limits fine-tuning and broader application of cardiac model systems. Here, we used the expression of ETV2, a master regulator of hematoendothelial specification in mice, to identify functionally distinct subpopulations during the co-differentiation of endothelial cells and cardiomyocytes from hiPSCs. Targeted analysis of single-cell RNA sequencing data revealed differential ETV2 dynamics in the two lineages. A newly created fluorescent reporter line allowed us to identify early lineage-predisposed states and show that a transient ETV2-high state initiates the specification of endothelial cells. We further demonstrated, unexpectedly, that functional cardiomyocytes can originate from progenitors expressing ETV2 at a low level. Our study thus sheds light on thein vitrodifferentiation dynamics of two important cardiac lineages.

SIGNIFICANCE STATEMENT

In vitrodifferentiation of cardiac cell types is of great importance for understanding heart development, disease modeling and future regenerative medicine. Currently, underlying molecular mechanisms are incompletely understood, which limits the efficiency and fine-tuning of present differentiation protocols. Here, we investigated the master regulator ETV2 and showed that its upregulation marks the specification of two cardiac cell types during co-differentiation. Using single-cell RNA-seq and a new fluorescent reporter line we identified lineage-predisposed subpopulations in the ETV2+ cells. We thus resolved ETV2 dynamics at the single-cell level in the context ofin vitrohuman cardiac differentiation.
Prevalence and Burden of Chronic Hepatitis B Virus Infection in Sierra Leone, 1997-2022: Evidence from a 25-Year Systematic Review and Meta-Analysis
Authors: Yendewa George A. , Wang Gi-Ming , James Peter B. , Massaquoi Samuel P.E. , Yendewa Sahr A. , Ghazawi Manal , Babawo Lawrence S. , Ocama Ponsiano , Russell James B.W. , Deen Gibrilla F. , Sahr Foday , Kabba Mustapha , Tatsuoka Curtis , Lakoh Sulaiman , Salata Robert A.
Published: November 2022

Objective

To estimate the prevalence and burden of chronic HBV in Sierra Leone.

Methods

We used electronic databases PubMed/MEDLINE, Embase, Scopus, ScienceDirect, Web of Science, Google Scholar and African Journals Online to systematically review articles reporting hepatitis B surface antigen (HBsAg) seroprevalence estimates in Serra Leone during 1997-2022. We estimated pooled HBV seroprevalence rates and assessed sources of heterogeneity

Results

Of 406 publications screened, 22 studies of total sample size 107,186 were included in the meta-analysis. The crude pooled HBV seroprevalence was 13.0% (95% CI 10.0-16.0) (I2=99%, p-heterogeneity<0.01), translating into 1.06 million people (95% uncertainty interval 0.81-1.30) or 1 in 8 Sierra Leoneans living with chronic HBV in 2021. Sensitivity analysis yielded a pooled HBV seroprevalence of 12.0% (95% CI 10.0-14.0) (sample size 104,968) (I2=98%, p-heterogeneity<0.001). The highest HBV seroprevalence estimates were among adolescents aged 10-17 years (17.0%, 95% CI 8.8-30.5), Ebola survivors (36.8%, 95% CI 26.2-48.8), people living with HIV (15.9%, 95% CI 10.6-23.0) and in the Northern (19.0%, 95% CI 6.4-44.7) and Southern (19.7%, 95% CI 10.9-32.8) regions. HBV seroprevalence progressively declined from 17.9% during 1997-2014 to 10.7% during 2020-2022.

Conclusions

These findings necessitate the urgent implementation of national HBV prevention and control programs in Sierra Leone.
A systematically optimized awake mouse fMRI paradigm
Authors: Xu Wenjing , Pei Mengchao , Zhang Kaiwei , Tong Chuanjun , Bo Binshi , Feng Jianfeng , Zhang Xiao-Yong , Liang Zhifeng
Published: November 2022

Functional magnetic resonance imaging (fMRI) has been increasingly utilized in mice. Due to the non-negligible effects of anesthetics on mouse fMRI, it is becoming more common to perform fMRI in the awake mice. However, high stress level and head motion in awake mouse fMRI remain to be fully addressed, which limits its practical applications. Therefore, here we presented a systematically optimized awake mouse fMRI paradigm as a practical and open-source solution. First, we designed a soundproof habituation chamber in which multiple mice can be habituated simultaneously and independently. Then, combining corticosterone, body weight and behavioral measurements, we systematically evaluated the potential factors that may contribute to animals’ stress level for awake imaging. Among many factors, we found that the restraining setup allowing forelimbs freely moving and head tilted at 30-degree was optimal for minimizing stress level. Importantly, we implemented multiband simultaneous multi-slice imaging to enable ultrafast fMRI acquisition in awake mice. Compared to conventional single-band EPI, faster acquisition enabled by multiband imaging were more robust to head motion and yielded higher statistical power. Thus, more robust resting-state functional connectivity was detected using multiband acquisition in awake mouse fMRI, compared to conventional single-band acquisition. In conclusion, we presented an awake mouse fMRI paradigm that is highly optimized in both awake mice habituation and fMRI acquisition, and such paradigm minimized animals’ stress level and provided more resistance to head motion and higher statistical power.
An evolutionarily conserved olfactory receptor is required for sex differences in blood pressure
Authors: Xu Jiaojiao , Choi Rira , Gupta Kunal , Warren Helen R. , Santhanam Lakshmi , Pluznick Jennifer L.
Published: November 2022

Sex differences in blood pressure are well-established, with premenopausal women having lower blood pressure than men by ∼10mmHg; however, the underlying mechanisms are not fully understood. We report here that olfactory receptor 558 (Olfr558), which has not previously been studied in non-olfactory tissues, localizes to vascular smooth muscle cells in numerous tissues including the kidney and heart. In the kidney, Olfr558 colocalizes with renin (a hormone that plays a key role in blood pressure regulation) in the renal afferent arteriole. Based on the localization of Olfr558, we hypothesized that Olfr558 plays a role in blood pressure regulation. We find that sex differences in blood pressure are intact in Olfr558 wildtype (WT) mice, but, are absent in Olfr558 knockout (KO) mice. We find that male KO mice have lowered diastolic blood pressure, decreased renin expression and activity, and altered vascular reactivity. Female KO mice exhibit increased blood pressure and increased pulse wave velocity, indicating increased vascular stiffness. The human ortholog of Olfr558, OR51E1, was previously identified as a locus associated with diastolic blood pressure. We report here that a rare OR51E1 missense variant has a statistically significant sex interaction effect with diastolic blood pressure, increasing diastolic blood pressure in women but decreasing it in men. In addition, we characterize how two different clinically relevant OR51E1 variants influence OR51E1 signalingin vitro. In sum, our findings demonstrate an evolutionarily conserved role for Olfr558/OR51E1 to mediate sex differences in blood pressure by altering renin, vascular reactivity, and arterial stiffness.
Cold-induced loss of interaction with HSC70 triggers inflammasome activity of familial cold autoinflammatory syndrome-causing mutants of NLRP3
Authors: Raghawan Akhouri Kishore , Ramaswamy Rajashree , Swarup Ghanshyam
Published: November 2022

NLRP3 is a cytoplasmic receptor protein, which initiates caspase-1 mediated inflammatory immune response upon detection of invading pathogen or a wide array of internal distress signals. Several gain-of function mutations of NLRP3 cause hereditary disorder of cold-induced hyper-inflammation known as familial cold autoinflammatory syndrome-1 (FCAS1). Although, caspase-1 activation and downstream interleukin-1β / interleukin-18 maturation are common effectors in pathophysiology of this disorder, molecular mechanisms of how exposure to subnormal temperature triggers mutant NLRP3-inflammsome activity is not understood. Here, we show that endogenous NLRP3 is in complex with HSC70 (HSPA8), and this interaction is reduced upon exposure to cold. FCAS-causing NLRP3-L353P and NLRP3-R260W mutants show enhanced interaction with HSC70. Upon exposure to subnormal temperature, NLRP3-L353P and NLRP3-R260W show enhanced inflammasome formation, increased caspase-1 activation and reduced interaction with HSC70. Knockdown of HSC70 results in increased inflammasome formation by L353P and R260W mutants of NLRP3. Our results suggest that interaction with HSC70 suppresses inflammasome formation by FCAS-causing NLRP3 mutants at physiological temperature, and loss of this inhibitory association at subnormal temperature causes aggravated inflammasome formation and caspase-1 activation leading to interleukin-1β maturation. These results provide evidence for HSC70 being a cold-sensor and a temperature-dependent regulator of inflammatory signaling by FCAS-causing NLRP3 mutants.
GAS2 encodes a 2-oxoglutarate dependent dioxygenase involved in ABA catabolism
Authors: Lange Theo , Atiq Nadiem , Lange Maria João Pimenta
Published: November 2022

Liu et al.1recently reported the characterization ofArabidopsis thalianaGAS2 (Gain of Function in ABA-modulated Seed Germination 2), which was described as an enzyme that catalyzes the stereospecific hydration of GA12to produce GA1216, 17-dihydro-16α-ol (DHGA12). However, as previously reported2, we did not find conversion of [17-14C]-labeled or [1-,7-,12-,18-14C4]-labeled GA12by GAS2. Furthermore, the authors1state the isolation of endogenous DHGA12from dry Arabidopsis seeds, which we cannot confirm by our attempts to isolate this compound from 0.5 g dry Arabidopsis Col-0 seeds (data not shown). Instead, we present here data showing that the recombinant GAS2 enzyme is able to catabolize abscisic acid (ABA) to phaseic acid (PA) and further to a second product, putative 8’-carboxy-ABA (Fig. 1a).
Modulation of the microhomology-mediated end joining pathway suppresses large deletions and enhances homology-directed repair following CRISPR-Cas9-induced DNA breaks
Authors: Yuan Baolei , Bi Chongwei , Wang Jinchen , Jin Yiqing , Alsayegh Khaled , Tehseen Muhammad , Yi Gang , Hamdan Samir , Huang Yanyi , Li Mo
Published: November 2022

CRISPR-Cas9, an efficient genome editing tool, has been widely used in research and holds great promise in the clinic. However, large unintended rearrangements of the genome occur frequently after CRISPR-Cas9 editing and their potential risk cannot be ignored. In this study, we detected large deletions (LDs) induced by CRISPR-Cas9 in human embryonic stem cells (hESCs) and found the microhomology end joining (MMEJ) DNA repair pathway plays a predominant role in LD. We genetically targeted PARP1, RPA, POLQ and LIG3, which play critical roles in MMEJ, during CRISPR-Cas9 editing. By analyzing LD events in two independent gene loci, CD9 and PIGA, using flow cytometry and long-read individual molecule sequencing (IDMseq), we showed that knocking down PARP1 and LIG3 does not alter the frequency of Cas9-induced LD, while knocking down or inhibiting POLQ dramatically reduces LD. Knocking down RPA increases LD frequency, and overexpression of RPAs consistently reduces LD frequency. Interestingly, small-molecule inhibition of POLQ and delivery of recombinant RPA proteins also dramatically increase the efficiency of homology-directed repair (HDR). In conclusion, RPA and POLQ play opposite roles in Cas9-induced LD, modulation of POLQ and RPA can reduce LD and improve HDR, thus holding promise for safe and precise genome editing.
Rapid and Signal Crowdedness-Robust In-Situ Sequencing through Hybrid Block Coding
Authors: Chang Tianyi , Han Wuji , Jiang Mengcheng , Li Jizhou , Liao Zhizhao , Tang Mingchuan , Zhang Jianyun , Shen Jie , Chen Zitian , Fei Peng , Ren Xianwen , Pang Yuhong , Wang Guanbo , Wang Jianbin , Huang Yanyi
Published: November 2022

Spatial transcriptomics technology has revolutionized our understanding of cell types and tissue organization, opening new possibilities for researchers to explore transcript distributions at subcellular levels. However, existing methods have limitations in resolution, sensitivity, or speed. To overcome these challenges, we introduce SPRINTseq (Spatially Resolved and signal-diluted Next-generation Targeted sequencing), an innovative in situ sequencing strategy that combines hybrid block coding and molecular dilution strategies. Our method enables fast and sensitive high-resolution data acquisition, as demonstrated by recovering over 142 million transcripts using a 108 gene panel from 453,843 cells from four mouse brain coronal slices in less than two days. Using this advanced technology, we uncover the cellular and subcellular molecular architecture of Alzheimer’s disease, providing additional information into abnormal cellular behaviors and their subcellular mRNA distribution. This improved spatial transcriptomics technology holds great promise for exploring complex biological processes and disease mechanisms.
Tree growth enhancement drives a persistent biomass gain in unmanaged temperate forests
Authors: Marqués Laura , Weng Ensheng , Bugmann Harald , Forrester David I. , Rohner Brigitte , Hobi Martina L. , Trotsiuk Volodymyr , Stocker Benjamin D.
Published: November 2022

While enhanced tree growth over the last decades has been reported in forests across the globe, it remains unclear whether it drives persistent biomass increases of the stands, particularly in mature forests. Enhanced tree growth and stand-level biomass are often linked with a simultaneous increase in density-driven mortality and a reduction in tree longevity. Identifying empirical evidence regarding the balance between these processes is challenging due to the confounding effects of stand history, management, and environmental changes. Here, we investigate the link between growth and biomass via the shift in the negative relationship between average tree size and stand density (tree number). We find increasing stand density for a given tree size in unmanaged closed-canopy forests in Switzerland over the past six decades and a positive relationship between growth and stand density - qualitatively consistent with simulations by a mechanistic, cohort-resolving ecosystem model (LM3-PPA). Model simulations show that, in the absence of other disturbances, enhanced growth persistently increases biomass stocks despite simultaneous decreases in carbon residence time and tree longevity, independent of assumptions about the drivers of tree mortality. However, the magnitude of simulated changes critically depends on the shape of the mortality parameterizations. Our analyses reconcile reports of growth-induced reductions of tree longevity with model predictions of persistent biomass increases, and with our finding of a trend towards denser forests in response to growth - also in mature stands.
Comparative analysis ofGlycine BBXgene family reveals lineage-specific evolution and expansion
Authors: Deshmukh Reena , Datta Sourav
Published: November 2022

BBXgenes are associated with photomorphogenesis, hormone response and seed gemination. Although,BBXgene family is reported inG. max, little is known about its classification and expansion. Similarly, no information is available for theBBXgene family in its closest relativeGlycine soja(Siebold & Zucc.). With extensive genome diversity,G. sojacan be used as an effective genetic reservoir for introgressing important agronomic traits inG. max. In the present study, we carried out a comprehensive comparative genome-wide analysis ofBBXgene family inG. maxandG. soja, to identify their evolutionary relationship and origin in plant lineage. Our results show an ancientBBXgene family expansion through segmental duplication, further suggesting, that theGmBBXmembers are the out-paralogs. These genes show lineage-specific evolution and expansion in the ancestralGlycinegenome supported by the incidences of microsynteny betweenG. maxandG. soja. The two genomes also showed interesting evidence of conserved linkages which might be due to their common ancestor descendance, with minimum horizontal expansion inG. maxafter its split fromG. soja. Our study suggests that theBBXgene family diverged before the split ofG. maxandG. soja. As the two genomes share several regions of synteny, the paralogous members inG. maxcould have been a result of segmental duplications.