bluuebunny/crossref_metadata_2025 huggingface dataset:
Delusional intensity as a prognostic indicator among individuals with severe to extreme anorexia nervosa hospitalized at an acute medical stabilization program
Authors: De Young Kyle , Bottera Angeline , Kambanis Evelyna , Mancuso Christopher , Cass Kamila , Lohse Kristen , Benabe Jodie , Oakes Judy , Watters Ashlie , Johnson Craig , Mehler Philip
Published: November 2021

Objective

Eating disorder‐related beliefs among individuals with anorexia nervosa (AN) often approach delusional intensity. Research to date on delusional beliefs in AN has been cross sectional. Thus, it is unknown how the intensity of delusional beliefs changes over time and if such change has prognostic value.

Method

We assessed 50 individuals with severe to extreme AN (≥18 years old; M [SD] body mass index =12.7[1.3] kg/m2) at an inpatient medical stabilization facility within 96 hr of admission; 35 (70%) also completed the assessment at discharge (M[SD] = 25.53[13.21] days). Participants completed the Brown Assessment of Beliefs Scale and a battery of self‐report measures of eating disorder‐related psychopathology.

Results

The admission‐to‐discharge decrease in delusional intensity was not significant (p = .592; Hedges g = .10). Tests of predictive effects indicated that higher delusional intensity at intake predicted higher fear of fatness and restrictive eating, two hallmark features of AN, but not BMI, body checking, feared food avoidance, eating disorder‐related impairment, depression, binge eating, or purging behavior at discharge.

Discussion

Although the delusional intensity of eating disorder beliefs did not significantly improve over this relatively brief interval, delusional intensity may be associated with the severity of central eating disorder attitudes and behaviors. Delusional intensity may therefore be a negative prognostic indicator, possibly warranting further treatment. Future research should examine changes in delusional intensity over longer intervals and test whether specifically targeting delusional beliefs improves treatment outcomes among individuals with AN.
Patch size drives colonization by aquatic insects, with minor priority effects of a cohabitant
Authors: Scott Reed C. , Pintar Matthew R. , Resetarits William J.
Published: November 2021

Patch size is one of the most important factors affecting the distribution and abundance of species, and recent research has shown that patch size is an important niche dimension affecting community structure in aquatic insects. Building on this result, we examined the impact of patch size in conjunction with presence of larval anurans on colonization by aquatic insects. Hyla chrysoscelis (Cope's gray treefrog) larvae are abundant and early colonists in fishless lentic habitats, and these larvae can fill multiple ecological roles. By establishing larvae in mesocosms prior to colonization, we were able to assess whether H. chrysoscelis larvae have priority effects on aquatic insect assemblages. We conducted a series of three experiments in naturally colonized experimental landscapes to test whether (1) H. chrysoscelis larval density affects insect colonization, (2) variation in patch size affects insect colonization, and (3) the presence and larval density of H. chrysoscelis shift colonization of insects between patches of different size. Larval density independently had almost no effect on colonization, while patch size had species‐specific effects consistent with prior work. When larvae and patch size were tested in conjunction, patch size had numerous, often strong, species‐specific effects on colonization; larval density had effects largely limited to the assemblages of colonizing beetles and water bugs, with few effects on individual species. Higher larval densities in large mesocosms shifted some insect colonization to smaller patches, resulting in higher beta diversity among small patches in proximity to high density large mesocosms. This indicates establishing H. chrysoscelis larvae prior to insect colonization can likely create priority effects that slightly shape insect communities. Our results support the importance of patch size in studying species abundances and distributions and also indicate that colonization order plays an important role in determining the communities found within habitat patches.
Evidence of climate‐driven regime shifts in the Aegean Sea’s demersal resources: A study spanning six decades
Authors: Damalas Dimitrios , Sgardeli Vasiliki , Vasilakopoulos Paraskevas , Tserpes Georgios , Maravelias Christos
Published: November 2021

Climate change (CC) can alter the configuration of marine ecosystems; however, ecosystem response and resilience to change are usually case‐specific. The effect of CC on the demersal resources of the Aegean Sea (east Mediterranean Sea) was investigated during the past six decades applying a combination of multivariate analysis, non‐additive modeling and the Integrated Resilience Assessment (IRA) framework. We focused on the study of: (i) the biological “system” complex, using proxies of biomass (landings per unit of capacity) for 12 demersal taxa, and (ii) the environmental “stressor” complex, described by 12 abiotic variables. Pronounced changes have occurred in both the environmental and biological system over the studied period. The majority of the environmental stressors exhibited strikingly increasing trends (temperature, salinity, primary production indices) with values started exceeding the global historical means during late 1980s‐early 1990s. It is suggested that the biological system exhibited a discontinuous response to CC, with two apparently climate‐induced regime shifts occurring in the past 25 years. There is evidence for two‐fold bifurcations and four tipping points in the system, forming a folded stability landscape with three basins of attraction. The shape of the stability landscape for the Aegean Sea's biological system suggests that while the initial state (1966–1991) was rather resilient to CC, absorbing two environmental step‐changes, this was not the case for the two subsequent ones (intermediate: 1992–2002; recent: 2003–2016). Given the current trajectory of environmental change, it is highly unlikely that the biological system will ever return to its pre‐1990s state, as it is entering areas of unprecedented climatic conditions and there is some evidence that the system may be even shifting toward a new state. Our approach and findings may be relevant to other marine areas of the Mediterranean and beyond, undergoing climate‐driven regime shifts, and can assist to their adaptive management.
Propagule pressure and an invasion syndrome determine invasion success in a plant community model
Authors: Vedder Daniel , Leidinger Ludwig , Sarmento Cabral Juliano
Published: November 2021

The success of species invasions depends on multiple factors, including propagule pressure, disturbance, productivity, and the traits of native and non‐native species. While the importance of many of these determinants has already been investigated in relative isolation, they are rarely studied in combination. Here, we address this shortcoming by exploring the effect of the above‐listed factors on the success of invasions using an individual‐based mechanistic model. This approach enables us to explicitly control environmental factors (temperature as surrogate for productivity, disturbance, and propagule pressure) as well as to monitor whole‐community trait distributions of environmental adaptation, mass, and dispersal abilities. We simulated introductions of plant individuals to an oceanic island to assess which factors and species traits contribute to invasion success. We found that the most influential factors were higher propagule pressure and a particular set of traits. This invasion trait syndrome was characterized by a relative similarity in functional traits of invasive to native species, while invasive species had on average higher environmental adaptation, higher body mass, and increased dispersal distances, that is, had greater competitive and dispersive abilities. Our results highlight the importance in management practice of reducing the import of alien species, especially those that display this trait syndrome and come from similar habitats as those being managed.
Deuterium depletion in xylem water and soil isotopic effects complicate the assessment of riparian tree water sources in the seasonal tropics
Authors: Duvert Clément , Canham Caroline A. , Barbeta Adrià , Alvarez Cortes Diego , Chandler Lisa , Harford Andrew J. , Leggett Amie , Setterfield Samantha A. , Humphrey Chris L. , Hutley Lindsay B.
Published: November 2021

Riparian trees located in seasonally dry environments may be reliant on groundwater supplies, but the prevalence and magnitude of groundwater uptake is often unclear. Using soil water matric potential and water stable isotopes, we examined the relative contributions of soil water and groundwater to the dry season water uptake of five riparian tree species along an intermittent river of tropical northern Australia. Because xylem water was depleted in deuterium relative to source water (average offset −14.0‰), we numerically removed this offset and assessed the effect of the correction on mixing model results. We also estimated the isotopic composition of unbound soil water (i.e., the portion of soil water not tightly bound to soil particles) from bulk soil water data by using an empirical formulation from the literature and tested whether considering unbound soil water as a source would affect our results. Despite the hot and dry surface environment, we found that soil moisture was available for trees at relatively shallow (~0.7–1.5 m) depths. When unbound soil water and corrected xylem water data were considered, most tree species used a combination of this soil moisture source and groundwater from the capillary fringe. However, not correcting for isotopic effects resulted in large underestimations of the groundwater contributions to tree water uptake. Our findings suggest that ignoring soil isotopic effects and deuterium depletion in xylem water may reduce the validity of source water partitioning assessments. Further research is needed on the likely causes for deuterium depletion in xylem water.
The amount of environmental DNA increases with freshwater crayfish density and over time
Authors: Sint Daniela , Kolp Bernhard , Rennstam Rubbmark Oskar , Füreder Leopold , Traugott Michael
Published: November 2021

Over the last years, the analysis of environmental DNA (eDNA) has become an important approach to investigate species communities. Due to its non‐invasive nature and high sensitivity, this method is excellently suited to monitor the occurrence of endangered or invasive species. Native freshwater crayfish are threatened across Europe. Due to their nocturnal activity and hidden lifestyle, crayfish monitoring is difficult and time consuming with conventional methods. Thus, eDNA‐based monitoring of native, as well as invasive crayfish, would be an immense advantage in the conservation of these animals. However, although several assays for the detection of various crayfish species have been published, comparably little is known on the relationship between eDNA concentration and crayfish population densities; a pre‐requisite for estimating population sizes from eDNA measurements. In this study we, therefore, performed a set of laboratory experiments to investigate the relationship between eDNA concentrations and crayfish densities—measured as either crayfish size or biomass. We found a strong correlation between the two measurements and could also show that the amount of eDNA showed a linear increase during the first three days (at least) after crayfish were introduced to aquaria. Additionally, our experiments also suggest that crayfish activity might have a strong influence on the eDNA signal strength. Our findings will help to optimize eDNA‐based monitoring of freshwater crayfish, important for the conservation of these charismatic animals.
TLR9 signalling inhibits Plasmodium liver infection by macrophage activation
Authors: Kordes Maximilian , Ormond Louise , Rausch Sebastian , Matuschewski Kai , Hafalla Julius Clemence R.
Published: November 2021

Recognition of pathogen‐associated molecular patterns (PAMPs) through Toll‐like receptors (TLRs) plays a pivotal role in first‐line pathogen defense. TLRs are also likely triggered during a Plasmodium infection in vivo by parasite‐derived components. However, the contribution of innate responses to liver infection and to the subsequent clinical outcome of a blood infection is not well understood. To assess the potential effects of enhanced TLR‐signalling on Plasmodium infection, we systematically examined the effect of agonist‐primed immune responses to sporozoite inoculation in the P. berghei/C57Bl/6 murine malaria model. We could identify distinct stage‐specific effects on the course of infection after stimulation with two out of four TLR‐ligands tested. Priming with a TLR9 agonist induced killing of pre‐erythrocytic stages in the liver that depended on macrophages and the expression of inducible nitric oxide synthase (iNOS). These factors have previously not been recognized as antigen‐independent effector mechanisms against Plasmodium liver stages. Priming with TLR4 and ‐9 agonists also translated into blood stage‐specific protection against experimental cerebral malaria (ECM). These insights are relevant to the activation of TLR signalling pathways by adjuvant systems of antimalaria vaccine strategies. The protective role of TLR4‐activation against ECM might also explain some unexpected clinical effects observed with pre‐erythrocytic vaccine approaches.
Caught in a social crossfire: Exploring the social forces behind and experience of ambivalence about potential social change
Authors: Ton Gonneke Marina , Stroebe Katherine , van Zomeren Martijn
Published: November 2021

Social psychological research on societal debates about potential social change (e.g., abortion, racial segregation) often focuses on those who take clear positions in these debates. Yet, little is known about the often invisible yet potentially influential group that experiences ambivalence in societal debates. Extending and integrating ambivalence and social change research, we explore the relation between social forces in societal debates and the experiences of ambivalence about social change within these debates. Thematic analysis of extensive interviews with 15 Dutch students experiencing ambivalence in a heated Dutch societal debate revealed that different social forces (e.g., interpersonal relations, groups people belong to, societal systems) facilitate felt ambivalence about potential social change. Moreover, this ambivalence was often experienced as feeling caught in a social crossfire. Our work contributes to a richer psychological understanding of ambivalence about potential social change and reveals the complexity of decision‐making in the context of societal debates.
Improving the Electrochemical Performance of Pouch Cell Electric Double‐Layer Capacitors by Integrating Graphene Nanoplates into Activated Carbon
Authors: Shaker Majid , Sadeghi Ghazvini Ali Asghar , Feng Shuang , Cao Weiqi , Meng Xiaomin , Ge Qi , Riahifar Reza
Published: November 2021

Herein, activated carbon (AC) is composited with multiple weight ratios of graphene nanoplates through a facile and scalable technique, including sonicating and vacuum mixing in a slurry to fabricate pouch cell electric double‐layer capacitors (EDLCs). Among the fabricated devices, the EDLC made of 2 wt% graphene/AC composite demonstrated the best electrochemical performance by enhancing the specific capacitance of AC EDLC from 27.3 to 39.3 F g−1 at 0.05 A g−1 current density. Moreover, the addition of graphene to AC leads to a more ideal capacitive behavior, reduction of charge transfer resistance (R
ct) of the AC EDLC from 2.04 Ω to below 0.05 Ω, and the decrease of the ohmic drop at a current density of 2 A g−1 from 18.7% to 5.7%. 2 wt% graphene was considered as the optimum amount to be added to AC to increase the specific capacitance on average by 40% and improve the capacitance retention to 97% after 1000 cycles at 1 A g−1. Furthermore, the fabricated EDLC based on the optimum ratio of graphene to AC possessed satisfactory energy densities of 13.7 and 8.3 Wh kg−1 at 50 and 2000 W kg−1 power densities, respectively.
Different pharmacoresistance of focal epileptic spasms, generalized epileptic spasms, and generalized epileptic spasms combined with focal seizures
Authors: Takahashi Yukitoshi , Ota Akiko , Tohyama Jun , Kirino Tomoko , Fujiwara Yumi , Ikeda Chizuru , Tanaka Shigeki , Takahashi Jyunya , Shinoki Toshihiko , Shiraga Hiroshi , Inoue Takushi , Fujita Hiroshi , Bonno Motoki , Nagao Masayoshi , Kaneko Hideo
Published: November 2021

Objective

Among standard treatments for infantile spasms, adrenocorticotropic hormone (ACTH) is reported as the best treatment, but ACTH is ineffective in one‐half of the patients. To establish precision medicine, we examined pharmacoresistance of focal epileptic spasms (ES), generalized ES, and generalized ES combined with focal seizures, diagnosed based on the revised seizure classification of ILAE in 2017.

Methods

We conducted a retrospective nationwide study in Japan on the long‐term seizure outcome of ES. Long‐term seizure outcome was evaluated by seizure‐free rate, seizure‐free period, and Kaplan‐Meier curve. Seizure‐free was defined as seizure control for longer than 2 months.

Results

From the medical history of 501 patients, 325 patients had generalized ES only (GES group) at the start of the first treatment, 125 patients had generalized ES after focal seizure onset (FS‐GES group), seven patients had focal ES after focal seizure onset (FS‐FES group), and 24 patients had generalized ES combined with focal seizures after focal seizure onset (FS‐GES + FS group). Seizure‐free period of ES (generalized ES and focal ES) [mean (95% confidence interval)] was 2.7 (0.0‐5.4) months in GES group, 1.1 (0.1‐2.2) months in FS‐GES group, 1.0 (0.2‐1.9) months in FS‐GES + FS group, and 0.1 (−0.2‐0.5) months in FS‐FES group. Seizure‐free rate, seizure‐free period, and Kaplan‐Meier curve of generalized ES were almost the same in GES group and FS‐GES group, with characteristics of superior response to ACTH. Mean seizure‐free period of generalized ES combined with focal seizures was significantly shorter in FS‐GES + FS group than in GES group. Mean seizure‐free period of focal ES in FS‐FES group was extremely short with exceedingly early relapse.

Significance

Pharmacoresistance was different in generalized ES, focal ES, and generalized ES combined with focal seizures. ES with focal features or with focal seizures may have focal lesions, thus consider surgical options earlier in the course.
A lattice Boltzmann model for shallow water equations on the smoothed quadtree grid
Authors: Ru Zhiming , Liu Haifei , Tu Gangqin , Xing Liming , Wu Xuerong , Ding Yu , Shao Dongdong
Published: November 2021

In hydraulic simulation, the fine land‐water boundary often means more accurate result but more lattices and time cost. In this study, we developed a smoothed quadtree grid and introduced it into the lattice Boltzmann model for the shallow water equations (LABSWE) to balance this problem. The recommended grid is meticulously designed to own a minimum width of advantage over a uniform grid or multi‐block grid, and can describe the zigzag boundary via smaller size lattices with acceptable total number of lattice. As an improved multi‐block grid, the lattices are numbered in serialization for facilitating data storage and parallel computation, and a standardized process is developed to employ this grid in the LABSWE. The spatial interpolation is modified based on the water surface and fluxes instead of the water depth and velocities, in order to satisfy the necessary property (N‐property: the numerical scheme can replicate the exact solution to a stationary case in which there is a nonzero force or source term). The proposed model is verified by two benchmark tests and then applied to the long‐term simulation of unsteady flows in large aquatorium. The agreement between predictions and analytical results or other solutions are satisfactory. Three popular collision schemes, the Bhatnagar–Gross–Krook (BGK) scheme, the multiple relaxation time (MRT) scheme and the central moments (CMs) scheme, have also been tested, showing that the stability of the MRT and CMs schemes are better than the BGK scheme for the flows with higher Reynolds number, but cost only 4%–6% more computational load.
Laminin regulates oligodendrocyte development and myelination
Authors: Kang Minkyung , Yao Yao
Published: November 2021

Oligodendrocytes are the cells that myelinate axons and provide trophic support to neurons in the CNS. Their dysfunction has been associated with a group of disorders known as demyelinating diseases, such as multiple sclerosis. Oligodendrocytes are derived from oligodendrocyte precursor cells, which differentiate into premyelinating oligodendrocytes and eventually mature oligodendrocytes. The development and function of oligodendrocytes are tightly regulated by a variety of molecules, including laminin, a major protein of the extracellular matrix. Accumulating evidence suggests that laminin actively regulates every aspect of oligodendrocyte biology, including survival, migration, proliferation, differentiation, and myelination. How can laminin exert such diverse functions in oligodendrocytes? It is speculated that the distinct laminin isoforms, laminin receptors, and/or key signaling molecules expressed in oligodendrocytes at different developmental stages are the reasons. Understanding molecular targets and signaling pathways unique to each aspect of oligodendrocyte biology will enable more accurate manipulation of oligodendrocyte development and function, which may have implications in the therapies of demyelinating diseases. Here in this review, we first introduce oligodendrocyte biology, followed by the expression of laminin and laminin receptors in oligodendrocytes and other CNS cells. Next, the functions of laminin in oligodendrocyte biology, including survival, migration, proliferation, differentiation, and myelination, are discussed in detail. Last, key questions and challenges in the field are discussed. By providing a comprehensive review on laminin's roles in OL lineage cells, we hope to stimulate novel hypotheses and encourage new research in the field.
A norepinephrine‐dependent glial calcium wave travels in the spinal cord upon acoustovestibular stimuli
Authors: Orts‐Del'Immagine Adeline , Dhanasekar Mahalakshmi , Lejeune François‐Xavier , Roussel Julian , Wyart Claire
Published: November 2021

Although calcium waves have been widely observed in glial cells, their occurrence in vivo during behavior remains less understood. Here, we investigated the recruitment of glial cells in the hindbrain and spinal cord after acousto‐vestibular (AV) stimuli triggering escape responses using in vivo population calcium imaging in larval zebrafish. We observed that gap‐junction‐coupled spinal glial network exhibits large and homogenous calcium increases that rose in the rostral spinal cord and propagated bi‐directionally toward the spinal cord and toward the hindbrain. Spinal glial calcium waves were driven by the recruitment of neurons and in particular, of noradrenergic signaling acting through α‐adrenergic receptors. Noradrenergic neurons of the medulla‐oblongata (NE‐MO) were revealed in the vicinity of where the calcium wave started. NE‐MO were recruited upon AV stimulation and sent dense axonal projections in the rostro‐lateral spinal cord, suggesting these cells could trigger the glial wave to propagate down the spinal cord. Altogether, our results revealed that a simple AV stimulation is sufficient to recruit noradrenergic neurons in the brainstem that trigger in the rostral spinal cord two massive glial calcium waves, one traveling caudally in the spinal cord and another rostrally into the hindbrain.
Impact of COVID‐19 lockdowns on mental health: Evidence from a quasi‐natural experiment in England and Scotland
Authors: Serrano‐Alarcón Manuel , Kentikelenis Alexander , Mckee Martin , Stuckler David
Published: November 2021

The COVID‐19 pandemic has been associated with worsening mental health but it is unclear whether this is a direct consequence of containment measures, like “Stay at Home” orders, or due to other considerations, such as fear and uncertainty about becoming infected. It is also unclear how responsive mental health is to a changing situation. Exploiting the different policy responses to COVID‐19 in England and Scotland and using a difference‐in‐difference analysis, we show that easing lockdown measures rapidly improves mental health. The results were driven by individuals with lower socioeconomic position, in terms of education or financial situation, who benefited more from the end of the strict lockdown, whereas they suffered a larger decline in mental health where the lockdown was extended. Overall, mental health appears to be more sensitive to the imposition of containment policies than to the evolution of the pandemic itself. As lockdown measures may continue to be necessary in the future, further efforts (both financial and mental health support) are required to minimize the consequences of COVID‐19 containment policies for mental health.
Increased body mass index predicts prolonged survival in patients with head and neck squamous cell carcinoma
Authors: Wu Eric L. , Peesay Tejasvi , Randall James A. , Nelson Lacey L. , Shearer Sarah C. , Johnson Bria C. , Maxwell Jessica H.
Published: November 2021

Background

Higher body mass index (BMI) may have a protective effect on survival in patients with head and neck cancer. The aim of this study was to determine the effect of BMI on overall survival (OS) in veterans with head and neck squamous cell carcinoma (HNSCC).

Methods

A cohort of 702 patients diagnosed with HNSCC between 1995 and 2019 were identified at the Washington DC Veterans Affairs Medical Center, and 342 patients were included for analysis. Records were queried for clinical‐demographic data, BMI, and outcomes.

Results

HNSCC patients categorized as overweight or obese at time of diagnosis had a lower 3‐year risk of death (p = 0.033) and improved OS (p < 0.001) compared to patients who were underweight or normal weight. The majority of locoregional recurrences occurred in patients with low or normal pretreatment BMI.

Conclusions

Higher BMI at diagnosis may have a protective effect on OS in veterans with HNSCC.
A GLP‐1/GLP‐2 receptor dual agonist to treat NASH: Targeting the gut‐liver axis and microbiome
Authors: Kim Eun Ran , Park Jeong Su , Kim Jin Hee , Oh Ji Young , Oh In Jeong , Choi Da Hyun , Lee Yu seol , Park I. Seul , Kim SeungWon , Lee Da Hyun , Cheon Jae Hee , Bae Jin‐Woo , Lee Minyoung , Cho Jin Won , An In Bok , Nam Eun Joo , Yang Sang‐In , Lee Myung‐Shik , Bae Soo Han , Lee Yong‐ho
Published: November 2021

Background and Aims

Currently there is no Food and Drug Administration–approved drug to treat NAFLD and NASH, the rates of which are increasing worldwide. Although NAFLD/NASH are highly complex and heterogeneous conditions, most pharmacotherapy pipelines focus on a single mechanistic target. Considering the importance of the gut‐liver axis in their pathogenesis, we investigated the therapeutic effect of a long‐acting dual agonist of glucagon‐like peptide (GLP)‐1 and GLP‐2 receptors in mice with NAFLD/NASH.

Approach and Results

C57BL/6J mice were fed a choline‐deficient high‐fat diet/high fructose and sucrose solution. After 16 weeks, mice were randomly allocated to receive vehicle, GLP1‐Fc, GLP2‐Fc, or GLP1/2‐Fc fusion (GLP1/2‐Fc) subcutaneously every 2 days for 4 weeks. Body weight was monitored, insulin/glucose tolerance tests were performed, feces were collected, and microbiome profiles were analyzed. Immobilized cell systems were used to evaluate direct peptide effect. Immunohistochemistry, quantitative PCR, immunoblot analysis, tunnel assay, and biochemical assays were performed to assess drug effects on inflammation, hepatic fibrosis, cell death, and intestinal structures. The mice had well‐developed NASH phenotypes. GLP1/2‐Fc reduced body weight, glucose levels, hepatic triglyceride levels, and cellular apoptosis. It improved liver fibrosis, insulin sensitivity, and intestinal tight junctions, and increased microvillus height, crypt depth, and goblet cells of intestine compared with a vehicle group. Similar effects of GLP1/2‐Fc were found in in vitro cell systems. GLP1/2‐Fc also changed microbiome profiles. We applied fecal microbiota transplantation (FMT) gain further insight into the mechanism of GLP1/2‐Fc–mediated protection. We confirmed that FMT exerted an additive effect on GLP1‐Fc group, including the body weight change, liver weight, hepatic fat accumulation, inflammation, and hepatic fibrosis.

Conclusions

A long‐acting dual agonist of GLP‐1 and GLP‐2 receptors is a promising therapeutic strategy to treat NAFLD/NASH.
Favorable impact in hepatitis C–related mortality following free access to direct‐acting antivirals in Spain
Authors: Politi Julieta , Guerras Juan‐Miguel , Donat Marta , Belza María J. , Ronda Elena , Barrio Gregorio , Regidor Enrique
Published: November 2021

Background and Aims

Free treatments for HCV infection with direct‐acting antivirals became widespread in Spain in April 2015. We aimed to test whether, after this intervention, there was a more favorable change in population mortality from HCV‐related than from non‐HCV‐related causes.

Approach and Results

Postintervention changes in mortality were assessed using uncontrolled before–after and single‐group interrupted time series designs. All residents in Spain during 2001–2018 were included. Various underlying death causes were analyzed: HCV infection; other HCV‐related outcomes (HCC, liver cirrhosis, and HIV disease); and non‐C hepatitis, other liver diseases, and nonhepatic causes as control outcomes. Changes in mortality after the intervention were first assessed by rate ratios (RRs) between the postintervention and preintervention age‐standardized mortality rates. Subsequently, using quasi‐Poisson segmented regression models, we estimated the annual percent change (APC) in mortality rate in the postintervention and preintervention periods. All mortality rates were lower during the postintervention period, although RRs were much lower for HCV (0.53; 95% CI, 0.51–0.56) and HIV disease than other causes. After the intervention, there was a great acceleration of the downward mortality trend from HCV, whose APC went from −3.2% (95% CI, −3.6% to −2.8%) to −18.4% (95% CI, −20.6% to −16.3%). There were also significant accelerations in the downward trends in mortality from HCC and HIV disease, while they remained unchanged for cirrhosis and slowed or reversed for other causes.

Conclusions

These results suggest that the favorable changes in HCV‐related mortality observed for Spain after April 2015 are attributable to scaling up free treatment with direct‐acting antivirals and reinforce that HCV eradication is on the horizon.
Risk of HBV reactivation during therapies for HCC: A systematic review
Authors: Papatheodoridi Margarita , Tampaki Maria , Lok Anna S. , Papatheodoridis George V.
Published: November 2021

Background and Aims

Treatment for HCC has evolved rapidly, but the risk of HBV reactivation to new therapies is unclear. We systematically reviewed data on HBV reactivation in patients receiving HCC therapy in relation to use of HBV antiviral prophylaxis.

Approach and Results

A literature search was performed to identify all published studies including HBsAg‐positive patients with HCC providing data on HBV reactivation. Forty‐one studies with 10,223 patients, all from Asia, were included. The pooled HBV reactivation rate was 5% in patients receiving no specific HCC therapy and was higher in patients undergoing surgical resection (16%), transarterial chemoembolization (19%), or radiotherapy (14%) and intermediate in patients treated with local ablation therapy (7%) or systemic agents (7%). HBV reactivation rates were higher in those without compared to those with HBV prophylaxis (ablation, 9% versus 0%; resection, 20% versus 3%; chemoembolization, 23% versus 1%; external radiotherapy alone, 18% versus 0%; systemic therapy, 9% versus 3%). HBV‐related biochemical reactivation rates varied between 6%–11% and 2% in patients receiving HCC therapies with high and intermediate HBV reactivation risk, respectively. Liver decompensation and death were rarely reported (0%–3%) and only in patients receiving HCC treatment with high HBV reactivation risk.

Conclusions

HBsAg‐positive patients with HCC are at high or intermediate risk of HBV reactivation depending on the type of HCC therapy. Nucleos(t)ide analogue prophylaxis reduces the risk of HBV reactivation, practically eliminates the risk of hepatitis flare, and should be administered regardless of HCC treatment.
Multifunctional manipulation of red blood cells using optical tweezers
Authors: Xie Yanzheng , Liu Xiaoshuai
Published: November 2021

Serving as natural vehicles to deliver oxygen throughout the whole body, red blood cells (RBCs) have been regarded as important indicators for biomedical analysis and clinical diagnosis. Various diseases can be induced due to the dysfunction of RBCs. Hence, a flexible tool is required to perform precise manipulation and quantitative characterization of their physiological mechanisms and viscoelastic properties. Optical tweezers have emerged as potential candidates due to their noncontact manipulation and femtonewton‐precision measurements. This review aimed to highlight the recent advances in the multifunctional manipulation of RBCs using optical tweezers, including controllable deformation, dynamic stretching, RBC aggregation, blood separation and Raman characterization. Further, great attentions have been focused on the precise assembly of functional biophotonics devices with trapped RBCs, and a brief overview was offered for the growing interests to manipulate RBCs in vivo.
Drug metabolism‐related eight‐gene signature can predict the prognosis of gastric adenocarcinoma
Authors: Yin Hong‐mei , He Qiong , Chen Jia , Li Zhen , Yang Wanli , Hu Xiaobo
Published: November 2021

Background

Metabolic abnormalities in patients with gastric adenocarcinoma lead to drug resistance and poor prognosis. Therefore, this study aimed to explore biomarkers that can predict the prognostic risk of gastric adenocarcinoma by analyzing drug metabolism‐related genes.

Methods

The RNA‐seq and clinical information on gastric adenocarcinoma were downloaded from the UCSC and gene expression omnibus databases. Univariate and least absolute shrinkage and selection operator regression analyses were used to identify the prognostic gene signature of gastric adenocarcinoma. The relationships between gastric adenocarcinoma prognostic risk and tumor microenvironment were assessed using CIBERSORT, EPIC, QUANTISEQ, MCPCounter, xCell, and TIMER algorithms. The potential drugs that could target the gene signatures were predicted in WebGestalt, and molecular docking analysis verified their binding stabilities.

Results

Combined with clinical information, an eight‐gene signature, includingGPX3,ABCA1,NNMT,NOS3,SLCO4A1,ADH4,DHRS7, andTAP1, was identified from the drug metabolism‐related gene set. Based on their expressions, risk scores were calculated, and patients were divided into high‐ and low‐risk groups, which had significant differences in survival status and immune infiltrations. Risk group was also identified as an independent prognostic factor of gastric adenocarcinoma, and the established prognostic and nomogram models exhibited excellent capacities for predicting prognosis. Finally, miconazole and niacin were predicted as potential therapeutic drugs for gastric adenocarcinoma that bond stably withNOS3andNNMTthrough hydrogen interactions.

Conclusions

This study proposed a drug metabolism‐related eight‐gene signature as a potential biomarker to predict the gastric adenocarcinoma prognosis risks.
Effectiveness of remote simulation‐based learning for periodontal instrumentation: A non‐inferiority study
Authors: Oh Se‐Lim , Mishler Oksana , Yang Ji Seung , Barnes Christine
Published: November 2021

Objectives

While numerous virtual/remote simulation‐based learning (SBL) modules were implemented due to the COVID‐19 pandemic, limited data on their effectiveness are available. This study aimed to investigate the effectiveness of a remote SBL module for periodontal instrumentation compared to traditional onsite SBL modules.

Methods

Calibrated faculty members have instructed in all modules. Synchronous remote SBL activities using a secure videoconferencing application, which replaced onsite practices, were conducted in a small group setting in the remote SBL module for the class of 2023. After the class took the onsite second‐year practical examination, a set of multiple and logistic regression analyses (N = 389) were conducted to test if the second‐year practical examination scores and the passing rates were significantly different between the remote SBL (class of 2023) and onsite SBL I and II (class of 2019 and 2022) groups.

Results

Both mean practical examination score and passing rate from the remote SBL group (class of 2023) were significantly higher than those from the onsite SBL II group (class of 2022) when their first‐year practical examination scores were not considered (p < 0.05). Once the first‐year practical examination scores were considered, the remote SBL group was not significantly different from the onsite SBL I and II groups with respect to the mean second‐year practical examination score and the passing rate.

Conclusion

The proposed remote SBL module achieved the comparable student learning outcomes compared to the onsite SBL modules while it utilized less staff, time, and material expenditure.
Balloon‐occluded retrograde transvenous obliteration for gastric varices improves hepatic functional reserve in long‐term follow‐up
Authors: Waguri Nobuo , Osaki Akihiko , Watanabe Yusuke , Matsubara Tsuyoshi , Yamazaki Shun , Yokoyama Hanako , Kimura Kiwamu , Wakabayashi Takuya , Mito Masaki , Yakubo Shunta , Azumi Rie , Kohisa Junji , Takaku Kennichi , Sato Munehiro , Furukawa Kouichi
Published: November 2021

Background and Aim

Balloon‐occluded retrograde transvenous obliteration (BRTO) has been widely adopted for the management of gastric fundal varices (GVs). There are a few reports that BRTO leads to the improvement of mid‐term and long‐term hepatic functional reserve (HFR). We retrospectively investigated the long‐term effect on HFR and prognosis among patients who had undergone BRTO for GVs.

Methods

This single‐center, retrospective study included 57successful patients out of 60 patients who underwent BRTO for GVs from December 2005 to September 2018. We examined the indicators of HFR (e.g., encephalopathy and ascites statuses, serum total bilirubin and albumin levels, % prothrombin time, and Child–Pugh and albumin–bilirubin [ALBI] scores) during 3 years of follow‐up after BRTO. We analyzed survival using the Kaplan–Meier method and identified the independent prognostic factors via multivariate analyses.

Results

GVs disappeared in all patients who were successfully treated by BRTO. At 3 years after BRTO, serum albumin levels were significantly elevated (from 3.3 to 4.0 g/dL, P = 0.008), while Child–Pugh and ALBI scores were significantly decreased (from 7.0 to 5.7, P = 0.043, and from −1.94 to −2.60, P = 0.006, respectively). The median survival time among all patients was 2207 days; the survival rates after BRTO were 87.0% at 1 year, 81.8% at 3 years, 67.3% at 5 years, and 44.1% at 10 years. Multivariate analyses revealed that ascites, hepatic encephalopathy, and malignant neoplasms were independently associated with poor prognosis.

Conclusion

BRTO for GVs has a favorable effect on long‐term HFR.
Synthesis and characterization of 4(R)‐epimer impurities of zanamivir and laninamivir octanoate
Authors: Duan Chuanqi , Liu Weiyuan , Bi Siju , Chen Liang , Pan Jing , Zhou Ting , Lin Kuaile , Zhou Weicheng
Published: November 2021

The synthesis and characterization of compounds 7c and 8d, the 4(R)‐epimer impurities of zanamivir and laninamivir octanoate, were reported for the first time. Their structures were confirmed by NMR and MS and distinguished from their corresponding active pharmaceutical ingredient (API) by coupling constant in 1H NMR and HPLC spectra. This work is of great significance for the drug‐related substances analysis in zanamivir and laninamivir octanoate.
Radiomic Analysis of Pharmacokinetic Heterogeneity Within Tumor Based on the Unsupervised Decomposition of Dynamic Contrast‐Enhanced MRI for Predicting Histological Characteristics of Breast Cancer
Authors: Zhang Liangliang , Fan Ming , Wang Shiwei , Xu Maosheng , Li Lihua
Published: November 2021

Background

Breast tumor heterogeneity is associated with histological characteristics. However, pharmacokinetic (PK) heterogeneity within tumor might merit further exploration.

Purpose

To enhance the predictive power of molecular subtypes, Ki‐67, and tumor grade by analyzing PK heterogeneity within tumor based on dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI).

Study Type

Retrospective.

Population

Two hundred and eight biopsy‐proven breast cancer patients, randomly divided into a training cohort (N = 144) and a testing cohort (N = 64).

Field Strength/Sequence

T1‐weighted DCE‐MRI at 3.0 T.

Assessment

A convex analysis of mixtures‐compartmental modeling decomposition method was used to estimate the PK parameter (i.e., the volume transfer constant Ktrans) in tumor subregions with distinct physiological kinetic patterns, including fast‐flow kinetics, slow‐flow kinetics, and plasma input. Radiomic features based on the PK parameter were calculated from each tumor subregion.

Statistical Tests

The training cohort was used to build random forest classifiers based on the optimal features determined by the 5‐fold cross‐validation method. The performance was assessed on the testing cohort using the area under the receiver operating characteristic curve (AUC). The AUCs derived from the tumor subregion‐based PK parameter were compared with those of the original images of the entire tumor using the DeLong test. A P‐value of <0.05 was considered statistically significant.

Results

The tumor subregion‐based PK parameter, which yielded the highest AUCs of 0.8782, 0.7568, 0.7019, 0.7963, 0.8080, and 0.7375 for luminal A, luminal B, basal‐like, human epidermal growth factor receptor 2, Ki‐67, and tumor grade, respectively, obtained better diagnostic performance than the original images in the entire tumor (highest AUCs = 0.8612, 0.6191, 0.5593, 0.7704, 0.7494, and 0.6261, respectively). In particular, statistically significant improvement in the diagnostic performance was obtained for luminal B.

Data Conclusion

Radiomic analysis of PK heterogeneity within tumor can enhance the predictive performance of radiomic models compared with that of the entire tumor.

Level of Evidence

4

Technical Efficacy Stage

3
Gas‐phase fragmentation of protonated 3‐phenoxy imidazo[1,2‐a] pyridines using tandem mass spectrometry and computational chemistry
Authors: Guo Yanchun , Li Shigai , Chen Hong , Wang Yuexiu , Cao Shuxia , Zhao Yufen
Published: November 2021

Imidazo[1,2‐a] pyridine is one of the pharmaceutically important scaffolds and has been widely studied due to its extensive biological activities. In this work, electrospray ionization tandem mass spectrometry (ESI‐MS/MS) in positive mode was used to study the gas‐phase fragmentation behavior of a series of 3‐phenoxy imidazo[1,2‐a] pyridines. Proposed fragmentation pathways were supported by ESI‐MS/MS data and computational thermochemistry. Homolytic cleavage of the 3‐phenoxy C‐O bond was the characteristic fragmentation of 3‐phenoxy imidazo [1,2‐a] pyridines. The eliminations of the one substituted phenoxy radical and CO produced other diagnostic ions for 3‐phenoxy imidazo [1,2‐a] pyridines, which were useful to identify the 3‐phenoxy group and imidazo [1,2‐a] pyridine scaffold. The results contribute to the further understanding of the gas‐phase fragmentation of 3‐phenoxy imidazo [1,2‐a] pyridines and the identification of other analogs using tandem mass spectrometry techniques.
Metabolism of Du Zhong Formula in rats using UPLC‐Q‐TOF/MS
Authors: Song Lili , Yin Hongqing , Han Rui , Li Jingfang , Ma Ningning , Wang Yan , Guo Hong
Published: November 2021

Du Zhong Formula (DZF), a traditional Chinese medicine formula derived from BeiJiQianJinYaoFang, is used to treat kidney deficiency and lumbago. In this study, ultra‐high‐performance liquid chromatography quadrupole time‐of‐flight mass spectrometer (UPLC‐Q‐TOF/MS) technique combined with pattern recognition analysis was applied for analysis of metabolic profiles of the bioactive components of the DZF in rat biological samples. In this experiment, a total of 73 compounds, including 53 prototype components and 20 metabolites, were identified tentatively in vivo compared with blank urine, plasma, feces, and cerebrospinal fluid (CSF). The prototype ingredients in DZF include terpenoids, gingerols, phenylpropanoids, alkaloids, phenanthrenes, bibenzyls, organic acids, and other ingredients. The metabolic pathways of DZF involved reduction, demethylation, hydroxylation, desugarization, deoxygenation, glucuronidation, sulfation, and methylation. The proposed method could develop an integrated template approach to analyze screening and identification of the bioactive components in plasma, urine, feces, and CSF after oral administration of herb medicines. Additionally, this investigation might provide helpful chemical information for further pharmacology and activity mechanism of DZF.
Reconstructed precipitation in the Lohit River basin, southern Tibetan Plateau since 1720 CE and its weak linkages with monsoon‐season Brahmaputra discharge
Authors: Yue Weipeng , Zhao Xiaoen , Chen Feng , Khan Adam , Gao Zhihong
Published: November 2021

High Asian glaciers and precipitation have directly or indirectly influenced the freshwater supply of billions of people and natural ecosystems in surrounding areas. To better understand the hydroclimatic changes in the High Asian transboundary river basins in the context of global warming, more precipitation‐sensitive proxy data are needed. In this paper, we used the tree‐ring cores of Pinus densata and Picea brachytyla from the southern Tibetan Plateau (TP) to establish a tree‐ring‐width composite chronology and estimate hydrological annual (September–August) precipitation (r2 = 47.0%, p <  0.01) for the Lohit River basin from 1720 to 2019. Our reconstructed precipitation was closely linked with the glacier mass balance of Shishapangma peak, which may provide us with some evidence for glacier fluctuations in the southern TP. Our precipitation reconstruction successfully captured recent dry trends and generally agreed with other tree‐ring‐based precipitation reconstructions from nearby regions. In addition, reconstructed precipitation variations were inconsistent with recorded monsoon‐season Brahmaputra discharge.