bluuebunny/crossref_metadata_2025 huggingface dataset:
Multicenter real‐world data of patients harboring rare mutations other than EGFR or ALK in advanced or metastatic non‐small cell lung cancer
Authors: Lee Su Yeon , Kim Young Chul , Lee Kye Young , Lee Sung Yong , Lee Shin Yup , Lee Min Ki , Lee Jeong Eun , Jang Seung Hun , Jang Tae‐Won , Choi Chang Min
Published: December 2021

Background

Studies on the application of targeted therapies for patients with non‐small cell lung cancer (NSCLC) who harbor rare genetic mutations are ongoing. In the present study, we investigated the real‐world data of NSCLC patients who harbor rare mutations.

Methods

We retrospectively analyzed patients with advanced or metastatic nonsquamous NSCLC aged >20 years with confirmed rare mutations (BRAF, ROS1, MET, RET, HER2, FGFR, and NTRK) from January 2015 to September 2020 at nine tertiary hospitals. In addition, we validated the lung cancer PCR panel kit in patients with confirmed mutations by NGS.

Results

Among 118 patients included, 88 received platinum‐based chemotherapy as first‐line chemotherapy. The progression‐free survival of patients with BRAF, ERBB2, MET, RET, and ROS1 mutations was 10.9 months (95% confidence interval [CI]: 1.3–20.5), 5.3 months (95% CI: 3.0–7.5), 7.2 months (95% CI: 3.6–10.9), 11.4 months (95% CI: 9.2–13.6), and 10.0 months (95% CI: 3.7–16.4) respectively (p = 0.041). The median overall survival (OS) was not reached in patients with ROS1 mutations; however, in BRAF, ERBB2, MET, and RET mutant patients, median OS was 14.1 months (95% CI: 10.1–14.1), 34.5 months (95% CI: 13.2–36.9), 22.7 months (95% CI: 1.7–24.0), and 29.8 months (95% CI: 28.9–61.3), respectively (p = 0.006). Of the 27 tissue samples, 26 (96.3%) showed the same PCR panel kit result with NGS.

Conclusions

First‐line platinum‐based chemotherapy showed durable benefit in patients with advanced or metastatic nonsquamous NSCLC harboring rare genetic mutation other than EGFR or ALK.
Efficacy and utilization of an acceptance and commitment therapy‐based smartphone application for smoking cessation among Black adults: secondary analysis of the iCanQuit randomized trial
Authors: Santiago‐Torres Margarita , Mull Kristin E. , Sullivan Brianna M. , Kwon Diana , Nollen Nicolle L. , Zvolensky Michael J. , Bricker Jonathan B.
Published: December 2021

Background and aims

Black adults who smoke are less likely to seek treatment and to succeed in quitting compared with other racial groups. The lack of efficacious and engaging trials for smoking cessation further contributes to this disparity. This study explored whether an acceptance and commitment therapy (ACT)‐based smartphone application (iCanQuit) was more efficacious for smoking cessation than a United States Clinical Practice Guidelines (USCPG)‐based smartphone application (QuitGuide) among Black adults.

Design

Secondary analysis of a two‐arm randomized trial with 12‐month follow‐up.

Setting

United States (US).

Participants

A total of 554 Black adults who smoke daily were recruited from 34 US states and enrolled between May 2017 and September 2018.

Interventions

Participants were randomized to receive iCanQuit (n = 274) or QuitGuide (n = 280) for 12 months.

Measurements

Smoking cessation outcomes were measured at 3, 6, and 12 months. The primary outcome was self‐reported complete‐case 30‐day point prevalence abstinence (PPA) at 12 months. Secondary outcomes were 7‐day PPA, missing‐as‐smoking imputation, multiple imputation, prolonged abstinence, and cessation of all tobacco products at 12 months. Study retention, treatment engagement, and change in ACT‐based processes were also compared between arms.

Findings

Study retention was 89% at 12 months and did not differ by arm (P > 0.05). The complete‐case 30‐day PPA was 28% for iCanQuit versus 20% for QuitGuide at 12 months (odds ratio [OR] = 1.60; 95% confidence interval [CI] = 1.03, 2.46). Similar associations were observed for the missing‐as‐smoking imputation, although non‐significant (25% iCanQuit vs 18% QuitGuide; OR = 1.50; 95% CI = 0.98, 2.30). iCanQuit vs QuitGuide participants were significantly more engaged with iCanQuit application as measured by the number of logins from baseline to 6 months (incidence rate ratio = 3.26; 95% CI = 2.58, 4.13). Increased acceptance of cues to smoke mediated the effect of treatment on cessation (indirect effect: OR = 0.20; 95% CI = 0.05, 0.29).

Conclusions

Among Black adults, an acceptance and commitment therapy‐based smartphone application appeared to be more efficacious and engaging for smoking cessation than the United States Clinical Practice Guidelines‐based QuitGuide application.
Effect of hyperoxia and hypoxia on retinal vascular parameters assessed with optical coherence tomography angiography
Authors: Hommer Nikolaus , Kallab Martin , Sim Yin Ci , Lee Ashe XY , Chua Jacqueline , Tan Bingyao , Schlatter Andreas , Werkmeister René M. , Schmidl Doreen , Schmetterer Leopold , Garhöfer Gerhard
Published: December 2021

Purpose

To investigate the response of the superficial and deep capillary plexuses to hyperoxia and hypoxia using optical coherence tomography angiography (OCT‐A) and retinal vessel analyzer.

Methods

Twenty‐four healthy volunteers participated in this randomized, double‐masked, cross‐over study. For each subject, two study days were scheduled: on one study day, hyperoxia was induced by breathing 100% oxygen whereas on the other study day, hypoxia was induced by breathing a mixture of 88% nitrogen and 12% oxygen. Perfusion density was calculated in the superficial vascular plexus (SVP) and the deep capillary plexus (DCP), using OCT‐A before (normal breathing) and during breathing of the gas mixtures. Retinal vessel calibres in major retinal vessels were measured using a dynamic vessel analyzer.

Results

During 100% oxygen breathing, a significant decrease in DCP perfusion density from 41.7 ± 2.4 a.u to 35.6 ± 3.1 a.u. (p < 0.001) was observed, which was accompanied by a significant decrease in vessel diameters in major retinal arteries and veins (p < 0.001 each). No significant change in perfusion density in the SVP occurred (p = 0.33). In contrast, during hypoxia, perfusion density in the SVP significantly increased from 34.4 ± 3.0 a.u. to 37.1 ± 2.2 a.u. (p < 0.001), while it remained stable in the DCP (p = 0.25). A significant increase in retinal vessel diameters was found (p < 0.01). Systemic oxygen saturation correlated negatively with perfusion density in the SVP and the DCP and retinal vessel diameters (p < 0.005 each).

Conclusion

Our results show that systemic hyperoxia induces a significant decrease in vessel density in the DCP, while hypoxia leads to increased vessel density limited to the SVP. These results indicate that the retinal circulation shows the ability to adapt its blood flow to metabolic changes with high local resolution dependent on the capillary plexus.
Alcohol consumption and risk of inflammatory bowel disease among three prospective US cohorts
Authors: Casey Kevin , Lopes Emily W. , Niccum Blake , Burke Kristin , Ananthakrishnan Ashwin N. , Lochhead Paul , Richter James M. , Chan Andrew T. , Khalili Hamed
Published: December 2021

Background and aims

There are limited data on alcohol dose and types and risk of Crohn's Disease (CD) and Ulcerative Colitis (UC). We therefore sought to comprehensively examine the association between alcohol consumption and risk of CD and UC.

Methods

We conducted a prospective cohort study of 237,835 participants from the Nurses’ Health Study, Nurses’ Health Study II, and Health Professional Follow‐Up Study. Alcohol consumption was obtained through questionnaires submitted every four years; additional covariates were obtained at two or four‐year intervals. Cases were confirmed independently by two physicians through medical record review. We used Cox proportional hazards regression to estimate age and multivariable‐adjusted hazards ratios and 95% confidence intervals.

Results

Across 5,170,474 person‐years of follow‐up, 370 cases of CD and 486 cases of UC were documented. Increased consumption of alcohol intake was not associated with CD (Ptrend = 0.455) or UC (Ptrend = 0.745). Compared to non‐users, the MV‐adjusted HRs for 15.0 + g/day of alcohol intake group were 0.84 (95% CI 0.56, 1.24) for CD and 1.08 (95% CI 0.77, 1.51) for UC. In analyses of alcohol subtypes, we observed that only moderate consumption of beer (>1‐4 servings/week) was marginally associated with reduced risk of CD, while consumption of >4 servings/week of liquor was associated with an increased risk of UC.

Conclusion

This prospective study did not identify a relationship between overall alcohol consumption and risk of CD or UC. Our suggestive associations between alcohol types and risk of CD and UC deserve additional investigation.
The smell of cooperativeness: Do human body odours advertise cooperative behaviours?
Authors: Tognetti Arnaud , Durand Valerie , Dubois Dimitri , Barkat‐Defradas Melissa , Hopfensitz Astrid , Ferdenzi Camille
Published: December 2021

Several physical features influence the perception of how cooperative a potential partner is. While previous work focused on face and voice, it remains unknown whether body odours influence judgements of cooperativeness and if odour‐based judgements are accurate. Here, we first collected axillary odours of cooperative and uncooperative male donors through a public good game and used them as olfactory stimuli in a series of tasks examining whether and how they influence cooperative decision‐making in an incentivized economic game and ratings of cooperativeness. Our results show that having access to the donor's body odours provided a strategic advantage to women during economic decisions (but not to men): with age, women were more likely to cooperate with cooperative men and to avoid interacting with uncooperative men. Ratings of cooperativeness were nonetheless unrelated to the donors’ actual cooperativeness. Finally, while men with masculine and intense body odours were judged less cooperative, we found no evidence that donors’ actual cooperativeness was associated with less masculine or less intense body odour. Overall, our findings suggest that, as faces and voices, body odours influence perceived cooperativeness and might be used accurately and in a non‐aware manner as olfactory cues of cooperativeness, at least by women.
Financial cycle, business cycle, and policy uncertainty in India: An empirical investigation
Authors: Paramanik Rajendra N. , Bhandari Avishek , Kamaiah Bandi
Published: December 2021

This paper is an empirical attempt to assess the relations among business cycles, financial cycles, and economic uncertainty for India during the period January 2003 to January 2020. Empirical findings from the vector autoregression model suggest a bidirectional causal relationship between the real and financial markets. Further, the aforementioned markets are found to influence the uncertainty index in India. We employ the Granger causality test in the frequency domain which exhibits the dynamic nature of causal relations, while our novel fractal connectivity approach reveals the long‐run correlation structure among all three variables.
Effects of maternal adverse child experiences on parental maltreatment of children: An empirical study of mediating factors among Japanese mothers
Authors: Mitani Haruyo
Published: December 2021

Despite increasing research into connections between adverse childhood experiences (ACEs) and health problems, the impact of parental ACEs on parenting practices has not been sufficiently clear. The objective of the study was to consider whether the association between maternal ACEs and child maltreatment is affected by three mediating factors: socio‐economic status (SES), social support and maternal psychological distress in adulthood. The Kochi Child Health Impact of Living Difficulty (K‐CHILD) study (2016) provided the data for this study. Mothers who had children in the first, fifth, eighth and eleventh grade and who lived in the Kochi Prefecture of Japan participated. A pool of 11,954 completed child and caregiver questionnaires was used for analysis. We found that a large number of maternal ACEs was connected to higher risk of physical abuse, psychological abuse and neglect. Maternal psychological distress had the greatest mediating effect. Maternal ACEs can be a risk factor for maltreatment of children. This study suggests that care for mothers with psychological distress will be a key intervention to break the cycle of childhood adversity.
Predicting the influence of river network configuration, biological traits and habitat quality interactions on riverine fish invasions
Authors: Dominguez Almela Victoria , Palmer Stephen C. F. , Andreou Demetra , Gillingham Phillipa K. , Travis Justin M. J. , Britton J. Robert
Published: December 2021

Aim

The relationships between species and their landscape are important for understanding migration patterns. In fluvial systems, the complexity of the river network can strongly influence the dispersal and colonization rates of invading alien fishes, but habitat quality, species’ biological traits and their location of introduction are also potentially important. However, understandings of how these factors interact in the wild to influence the spatial distribution of invasive species over time are limited from empirical studies.

Location

“Virtual” and “real‐world” rivers from England and Wales.

Method

We developed an individual‐based model (IBM) to predict how these different factors influenced the invasion dynamics and population growth rates (as abundances) of nine “virtual” alien fishes over two timeframes (10 and 30 years). The alien fishes differed in their demographic (r‐ to K‐selected) and dispersal (fast to slow) characteristics and the rivers in their network complexity.

Results

Irrespective of river type, species and timeframe, the main drivers of both dispersal and population growth were the location of the introduction and the mean habitat quality of the patch into which the species were released. The introduction location determined whether dispersal was mainly passive in a downstream direction (faster) or active in an upstream direction (slower), with higher habitat quality then enabling faster population growth rates. Over 30 years, invasion rates were predicted to increase as the complexity of the river network increased, as this opened multiple invasion fronts where the invader traits favoured faster dispersal.

Main conclusions

This novel IBM revealed how the complexity of the physical environment interacts with the biological traits of alien species to influence invasion outcomes, with the location of the introduction and its habitat quality being the most important factors. These results thus substantially increase understanding of the factors that influence the dispersal and colonization rates of alien freshwater fishes.
Fire affects galling insect communities through vegetation changes in a subtropical seasonally semiarid forest
Authors: Kuzmanich Nicolás , Giorgis Melisa A. , Salvo Adriana
Published: December 2021

Fire is one of the main factors shaping vegetation characteristics around the world, with deep and complex effects on higher levels of the food web and ecosystem functioning. Specialist insects tend to be more vulnerable to fire than generalists due to their higher dependency on host plants; however, fire effects on specialist insects are still not clearly known.

Our aim was to understand how fire‐induced changes in plant richness and floristic composition modulate community features of galling insects under different fire scenarios. Specifically, we address the following questions: Are changes in galling insect richness and herbivory explained by the variation in plant richness and floristic composition under different fire scenarios? Are species composition of vegetation and galling insect communities coupled under different fire scenarios?

Species richness of plant and galling insect communities was higher in burned than in unburned plots, but the highest species richness was observed under different fire scenarios in both communities. Galling insect richness was better predicted by floristic composition than plant richness. Herbivory was similar under different fire scenarios and weakly related to plant richness and composition. Species composition of vegetation and galling insect communities was strongly coupled across different fire scenarios.

The characteristics of galling insect communities were strongly affected by fire through vegetation changes, and were better explained by floristic composition than by plant richness. Our results highlight the importance of selecting areas under different fire scenarios to maximise biodiversity conservation.
Impact of COVID‐19 on dental education in Europe: The students' perspective
Authors: Coughlan James , Timuş Daniela , Crnic Tin , Srdoč Dora , Halton Ciara , Dragan Irina F.
Published: December 2021

Introduction

COVID‐19 pandemic impacted dental students and postgraduate residents world‐wide, forcing them to rapidly adapt to new forms of teaching and learning. Dental school leaderships needed to ensure the academic continuity, therefore the majority of the in‐person actives were transitioned into a virtual setting. The aim of this study was to identify students' perception regarding the measures taken to adapt during the pandemic by different dental schools in the European Region.

Materials and Methods

This cross‐sectional study utilised a validated 37 questions survey. Ethical approval was obtained from the Trinity College Dublin, Ireland. Using this instrument, the perceptions of the European dental students regarding the impact of COVID‐19 on their education and mental health were identified. The questions were divided into categories: standard demographic information; models of education during the COVID‐19 pandemic (types of teaching, examination and other educational activities) and support received. The survey was administered through electronic online tools, and all responses remained confidential. The data were processed through quantitative and qualitative analysis.

Results

A total of 879 student responses to the survey from 34 countries in the European Region were included in this study. When asked about the time spent on their education, 50% of the participants (n = 435) reported spending less time on their education and 30% (n = 265) reported spending more time. The types of teaching included showed a heterogeneous approach, varying from online simulations to problem solving for the didactic setting, or a hybrid model with group activities for the clinical setting. There were broad splits in satisfaction with the education delivered, with 44% (n = 382) being either satisfied or very satisfied and 31% (n = 279) being either unsatisfied or very unsatisfied. Students were most concerned with their clinical experience and skills.

Conclusions

The qualitative and quantitative data compiled in this cross‐sectional study enable a direct comparison between different approaches to adapt dental education during the COVID‐19 in the European Region. Future studies are recommended that will include compiling perceptions from the staff, faculty and administrators on the transition as well.
Chronotopes of urban centralities: Looking for prominent urban times and places
Authors: Lískovec Radim , Lichter Marek , Mulíček Ondřej
Published: December 2021

The aim of the paper is to discuss an issue of urban centralities not only in spatial but also in temporal terms. We seek to overcome the traditional view of urban centralities as materialised places. We argue that prominence of place is closely tied to a certain time regime or rhythm and that some prominent times tend to be spatialised through certain urban places. We emphasise the hybrid spatiotemporal nature of urban centrality that emerges from the inseparable coupling of the spatial and temporal dimensions of urban everydayness. The paper seeks to introduce timing, synchronisation and rhythms as important constituents of the urban tissue. The methodology links together Lefebvre‐inspired rhythmanalysis and the concept of chronotope. A complex dataset that depicts the aggregated rhythms of people's presence in selected locales is employed to demonstrate multiplicity of prominent times present in the contemporary city. The chronotopes are narrated as recurrent situations in which specific urban locales and specific times are animated and linked together through the presence of interacting individuals. The elusive spatiotemporal centrality is reflected in the story of the chronotope, describing its rhythm, scale, pacemakers, and actors.
Contrasting genetic responses to habitat fragmentation for two Lycaenid butterfly species
Authors: Trense Daronja , Habel Jan Christian , Finger Aline , Fischer Klaus
Published: December 2021

Biodiversity is currently declining at the global scale. Apart from species declines and lowered abundances, the loss of genetic diversity is equally concerning as it may undermine fitness and the potential to adapt to future environmental change. We compared genetic diversity of historical and recent Alpine populations of two butterfly species, Lycaena helle and L. hippothoe, over a period of about 10 years. Using microsatellite markers, we found no changes over time in L. helle, while genetic diversity decreased, and differentiation increased in L. hippothoe. Lycaena helle inhabits peat bogs and wetland fallows with populations being strongly isolated, while L. hippothoe used to occur in population networks on hay meadows, with the latter being strongly exposed to agricultural intensification. We conclude that currently L. hippothoe populations are strongly declining due to changes in land use, resulting in genetic erosion potentially due to the collapse of population networks.
Storytelling as a tool: A family‐based intervention for newly resettled Syrian refugee children
Authors: Abi Zeid Daou Kim Roger , Abi Zeid Daou Léa Roger , Cousineau‐Pérusse Maxime
Published: December 2021

The conflict in Syria has resulted in a humanitarian emergency and one of the largest refugee crises in history. The Canadian government has welcomed over 40,000 Syrian refugees. Stressors caused by instability, conflict, and the resettlement process put refugee children at high risk for mental health problems. Anxiety is a common problem experienced by refugee children. Thus, early intervention is crucial to promote their adequate adaptation and development. This study explores the impact and value of a culturally specific family‐based storybook intervention for newly resettled Syrian refugee children. Six refugee families participated. Anxiety symptoms were measured before and after the intervention, and families shared their experiences, thoughts, and feedback regarding the intervention. The results showed a significant decrease in children's anxiety symptoms. Furthermore, qualitative analyses demonstrated that the intervention was culturally relevant to Syrian refugee families and that it was effective in promoting children's overall well‐being, agency, and family connectedness.
Changes in active ageing in a Nordic regional context: Results based on the GERDA study in 2005 and 2016
Authors: Nyqvist Fredrica , Nygård Mikael , Snellman Fredrik
Published: December 2021

The study examined changes in active ageing among 65/66‐ and 75/76‐year‐olds in northern Sweden and western Finland. Data were retrieved from a repeated cross‐sectional survey conducted in 2005 and 2016. Logistic regression was used to estimate the probability of ageing actively in terms of employment, social and political participation, confidence in healthcare, economic situation, self‐rated health and social contacts. The results showed no significant changes in employment, social participation or economic situation. However, the level of political participation and self‐rated good health was significantly higher in 2016 compared with 2005, whereas confidence in healthcare and social contacts was lower. Considering that the implementation of active ageing policies relies heavily on municipal and/or regional level in our study region, our results could be used as a framework for regional policymaking.
Rabaptin5 acts as a key regulator for Rab7l1‐mediated phagosome maturation process
Authors: Shrivastava Rohini , Pradhan Gourango , Ghosh Sudip , Mukhopadhyay Sangita
Published: December 2021

Phagosome maturation is an important innate defence mechanism of macrophages against pathogen infections. Phagosome–lysosome (P‐L) fusion is a highly regulated process. Different RabGTPases are involved in P‐L fusion. Rab7l1 is shown to regulate P‐L fusion process. In this study, we demonstrate that Rabaptin5 is a guanine nucleotide exchange factor (GEF) for Rab7l1. We reveal that Rabaptin5 interacts with Rab7l1‐GTP form and promotes its recruitment to phagosome. In the absence of Rabaptin5, localization of P‐L markers like EEA1, Rab7, LAMP1 and LAMP2 was found to be poorer. Thus, our data suggest that Rabaptin5 works upstream to Rab7l1 and triggers Rab7l1 activation for further recruitment of P‐L markers and downstream regulation of phagosomal maturation process.
Why metacognition matters more than ever before: Real lessons of 2020
Authors: Riney Robert
Published: December 2021

As we study, this pivotal time in our history and the ongoing implications, one thing that has become abundantly clear is the incredible need for strong critical thinking skills across our population. Based on several years of prior research four metacognitive skills appear to be pivotal to deftly manage the coming years. These include the breadth of approach, information management, proactive thinking, and integrative strategy. This article provides insights and examples of the implications of these four skills.
Real‐world implications of high‐performance competencies and strategic management simulation technology
Authors: Cockerill Anthony Peter , Satish Usha
Published: December 2021

The construct and criterion‐related validity of 11 High‐Performance Competencies (H‐PC) are explored through data collected by three highly reliable methods: work shadowing, assessment centres, and Strategic Management Simulation Technology. A large international managerial sample indicates that some H‐PC are more highly developed than others. This suggests that managers may have a restricted capacity to co‐operatively address the multidimensional issues that loom large today. Strategic Management Simulation Technology is discussed as a way of developing a more balanced leadership capability profile and enhancing desirable real‐world outcomes.
The impact of connections between the CEO and top executives on appointment, turnover and firm value
Authors: Balsam Steven , Kwack So Yean
Published: December 2021

We find that network connections with the CEO established outside the current firm positively impact the focal executive's career trajectory and job security, that is, are associated with increases in the likelihood of being appointed to the top management team and the board of directors, and reductions in the likelihood of turnover. We then show that there is a positive impact of these connections on firm value as measured by proxies for Tobin's Q. This latter finding contrasts with prior literature, that is, Fracassi and Tate (2012), which suggests connections between the CEO and directors reduce firm value. We believe our differential finding is driven by the distinct roles ascribed to directors and executives. That is, directors monitor CEOs, and consequently connections that are perceived to adversely impact their independence adversely impact the market value of the firm. In contrast, the executive team is expected to run the firm as a group. While the CEO is the leader of the group, she/he needs to work with the others in the group to run the firm efficiently. To the extent that connections within the group facilitate collaboration and communication, connections between the CEO and executives positively impact firm value.
LOXL1‐AS1 communicating with TIAR modulates vasculogenic mimicry in glioma via regulation of the miR‐374b‐5p/MMP14 axis
Authors: Yi Bolong , Li Hao , Cai Heng , Lou Xin , Yu Mingjun , Li Zhen
Published: December 2021

At present, growing evidence indicates that long non‐coding RNAs (lncRNAs) participate in the progression of glioma. The function of LOXL1‐AS1 in vasculogenic mimicry (VM) in glioma remains unclear. First, the expressions of TIAR, the lncRNA LOXL1‐AS1, miR‐374b‐5p and MMP14 were examined by qRT‐PCR and Western blot in both, glioma tissues and glioma cell lines. Proliferation, migration, invasion and tube formation assays were conducted to evaluate the roles of TIAR, LOXL1‐AS1, miR‐374b‐5p and MMP14 in malignant cellular behaviours in glioma cells. A nude mouse xenograft model and dual staining for CD34 and PAS were used to assess whether VM was affected by TIAR, LOXL1‐AS1 or miR‐374b‐5p in vivo. In this study, low levels of TIAR and high levels of LOXL1‐AS1 were found in glioma cells and tissues. TIAR downregulated the expression of LOXL1‐AS1 by destabilizing it. LOXL1‐AS1 acted like a miRNA sponge towards miR‐374b‐5p so that downregulation of the former greatly inhibited cell proliferation, migration, invasion and VM. Additionally, miR‐374b‐5p overexpression repressed malignant biological behaviours and VM in glioma by modifying MMP14. In summary, we demonstrated that TIAR combined with LOXL1‐AS1 modulates VM in glioma via the miR‐374b‐5p/MMP14 axis, revealing novel targets for glioma therapy.
Tacrolimus alleviates LPS‐induced AKI by inhibiting TLR4/MyD88/NF‐κB signalling in mice
Authors: Hu Xueqing , Zhou Wenqian , Wu Shun , Wang Rui , Luan Zhiyong , Geng Xin , Xu Na , Zhang Zhaoyong , Ruan Zhenmin , Wang Zenghui , Li Furong , Yu Chen , Ren Hongqi
Published: December 2021

Lipopolysaccharide (LPS)‐induced sepsis‐associated acute kidney injury (SA‐AKI) is a model of clinical serious care syndrome, with high morbidity and mortality. Tacrolimus (TAC), a novel immunosuppressant that inhibits inflammatory response, plays a pivotal role in kidney diseases. In this study, LPS treated mice and cultured podocytes were used as the models of SA‐AKI in vivo and in vitro, respectively. Medium‐ and high‐dose TAC administration significantly attenuated renal function and renal pathological manifestations at 12, 24 and 48 h after LPS treatment in mice. Moreover, the Toll‐like receptor 4 (TLR4)/myeloid differential protein‐88 (MyD88)/nuclear factor‐kappa (NF‐κB) signalling pathway was also dramatically inhibited by medium‐ and high‐dose TAC administration at 12, 24 and 48 h of LPS treatment mice. In addition, TAC reversed LPS‐induced podocyte cytoskeletal injury and podocyte migratory capability. Our findings indicate that TAC has protective effects against LPS‐induced AKI by inhibiting TLR4/MyD88/NF‐κB signalling pathway and podocyte dysfunction, providing another potential therapeutic effects for the LPS‐induced SA‐AKI.
Reconstruction of evolutionary changes in fat and toxin consumption reveals associations with gene losses in mammals: A case study for the lipase inhibitor PNLIPRP1 and the xenobiotic receptor NR1I3
Authors: Wagner Franziska , Ruf Irina , Lehmann Thomas , Hofmann Rebecca , Ortmann Sylvia , Schiffmann Christian , Hiller Michael , Stefen Clara , Stuckas Heiko
Published: December 2021

The inactivation of ancestral protein‐coding genes (gene loss) can be associated with phenotypic modifications. Within placental mammals, repeated losses of PNLIPRP1 (gene inhibiting fat digestion) occurred preferentially in strictly herbivorous species, whereas repeated NR1I3 losses (gene involved in detoxification) occurred preferentially in strictly carnivorous species. It was hypothesized that lower fat contents of herbivorous diets and lower toxin contents of carnivorous diets cause relaxed selection pressure on these genes, resulting in the accumulation of mutations and ultimately to convergent gene losses. However, because herbivorous and carnivorous diets differ vastly in their composition, a fine‐grained analysis is required for hypothesis testing. We generated a trait matrix recording diet and semi‐quantitative estimates of fat and toxin consumption for 52 placental species. By including data from 31 fossil taxa, we reconstructed the ancestral diets in major lineages (grundplan reconstruction). We found support that PNLIPRP1 loss is primarily associated with low levels of fat intake and not simply with herbivory/carnivory. In particular, PNLIPRP1 loss also occurred in carnivorous lineages feeding on a fat‐poor diet, suggesting that the loss of this gene may be beneficial for occupying ecological niches characterized by fat‐poor food resources. Similarly, we demonstrated that carnivorous species are indeed less exposed to diet‐related toxins, suggesting that the loss of NR1I3 and related genes (NR1I2 and UGT1A6) resulted from relaxed selection pressure. This study illustrates the need of detailed phenotype studies to obtain a deeper understanding of factors underlying gene losses and to progress in understanding genomic causes of phenotypic variation in mammals.
Morphological discreteness of the estuarine croaker Pseudotolithus elongatus (Teleostei: Sciaenidae)
Authors: Asuquo Philomena E. , Ifon Honor T.
Published: December 2021

The estuarine croaker (Pseudotolithus elongatus, Sciaenidae) has long‐term socio‐economic and ecological significance in tropical and subtropical regions of the world, but little has been reported on the population demographics of this species. In this study, a traditional morphometric approach was used to test the hypothesis that island samples are morphologically distinctive from adjoining estuarine waters. The study involved a total number of 612 specimens from four islands (Alligator, Tobacco, Parrot and James) of the lower Cross River, Nigeria as well as from the mouth of the Cross River estuary, sampled from January to July 2020. Each specimen was subjected to morphometric measurements consisting of 14 allometrically modified characters. Results of principal component analysis explained 85.6% of the total variance. The pooled between‐groups discriminant function analysis correctly classified 66.0% of individuals into two distinct stocks (Island and Estuary mouth). The present finding demonstrates that the Cross River Islands hold a unit stock of P. elongatus that is morphologically separable from the adjoining estuarine waters. We therefore recommend that the croaker population in Cross River should be managed as separate stocks.
On the invalid resurrection of the lamprey genus Exomegas Gill, 1883
Authors: Riva‐Rossi Carla , Renaud Claude B. , Neira Francisco J. , Baigún Claudio , Baker Cindy F. , Quiroga Pamela , Potter Ian
Published: December 2021

The lamprey genus Exomegas Gill, 1883, was erected on the assumption that it was distinguishable from Geotria Gray, 1851, by possessing three rather than two cusps on the transverse lingual lamina (TLL). Based on literature review and examination of holotypes and new data, the authors reaffirm that the TLL of Geotria possesses two or three cusps in the adult stage. The reduction or disappearance of the middle cusp at the beginning or during the spawning run constitutes a key feature of Geotria. The resurrection of Exomegas by Firpo Lacoste, Fernández and Scioscia, Journal of Fish Biology, 2021, 1–6, 1507–1512, is therefore unjustified and not supported.
Testing the equilibrium model: An example from the Caledonian Kalak Nappe Complex (Finnmark, Arctic Norway)
Authors: Gaidies Fred , Heldwein Olivier K. A. , Yogi Maria Thereza A. G. , Cutts Jamie A. , Smit Matthijs A. , Rice A. Hugh N.
Published: December 2021

The equilibrium model has been tested using Barrovian garnet‐zone micaschists of the Kalak Nappe Complex. In our model, equilibrium in the MnNCKFMASHT system was established across the entire rock volume during prograde metamorphism except for garnet, which developed growth zoning preserved at levels controlled by the kinetics of intracrystalline diffusion. The preservation potential of the disequilibrium fluctuations required for nucleation of garnet has been considered in our simulations, using a moving boundary multicomponent diffusion and growth model. Results indicate that the core of garnet that crystallizes during regional metamorphism does not retain the major element composition of the nucleus but reflects the compositional signature of the immediate overgrowth. The differences between the metamorphic conditions of successive garnet growth steps of the samples indicate characteristic trends in their pressure‐temperature evolutions that can be predicted with the equilibrium model. There is some latitude with regard to the absolute metamorphic conditions due to the inherent uncertainty of the thermodynamic data and the approximation of the reactive volume composition. However, the slopes of the pressure‐temperature paths together with systematic trends in the lithological, geochemical, and Lu–Hf garnet whole‐rock isotopic properties of the rocks, as well as their garnet crystal size frequency distributions, enable the identification of the Veidnes, Bekkarfjord, and Kolvik Nappes involved in the Caledonian Orogeny and provide new insight into their metamorphic evolutions. According to our findings, the base of the Kalak Nappe Complex experienced wide‐spread Barrovian‐type metamorphism at c. 420 Ma with a gradient of ∼40 bar/°C and peak conditions of ∼560°C and 6.7 kbar in the Bekkarfjord and Veidnes Nappes, whereas the hinterland‐placed Kolvik Nappe was metamorphosed at peak conditions of ∼590°C and 7.5 kbar. This event was preceded by moderate‐pressure metamorphism at c. 423 Ma resulting in garnet crystallization exclusively in the Bekkarfjord Nappe, along a gradient of ∼20 bar/°C and peak conditions of ∼570°C and 6.0 kbar. We consider both of these metamorphic and deformational episodes to be different stages of the Scandian phase during the Caledonian Orogeny. An additional orogenic event at c. 464 Ma is preserved in the Veidnes Nappe, which was juxtaposed with the Scandian Nappes by repeated out‐of‐sequence thrusting associated with the final continent–continent collision. This nappe provides a unique insight into an earlier stage of the Caledonian Orogeny, indicating a low‐pressure Barrovian‐type metamorphic history with a gradient of ∼15 bar/°C and peak conditions of ∼560°C and 4.5 kbar.
Structural amyloid plaque polymorphism is associated with distinct lipid accumulations revealed by trapped ion mobility mass spectrometry imaging
Authors: Michno Wojciech , Wehrli Patrick M. , Koutarapu Srinivas , Marsching Christian , Minta Karolina , Ge Junyue , Meyer Sven W. , Zetterberg Henrik , Blennow Kaj , Henkel Corinna , Oetjen Janina , Hopf Carsten , Hanrieder Jörg
Published: December 2021

Understanding of Alzheimer's disease (AD) pathophysiology requires molecular assessment of how key pathological factors, specifically amyloid β (Aβ) plaques, influence the surrounding microenvironment. Here, neuronal lipids have been implicated in Aβ plaque pathology, though the lipid microenvironment in direct proximity to Aβ plaques is still not fully resolved. A further challenge is the microenvironmental molecular heterogeneity, across structurally polymorphic Aβ features, such as diffuse, immature, and mature, fibrillary aggregates, whose resolution requires the integration of advanced, multimodal chemical imaging tools. Herein, we used matrix‐assisted laser desorption/ionization trapped ion mobility spectrometry time‐of‐flight based mass spectrometry imaging (MALDI TIMS TOF MSI) in combination with hyperspectral confocal microscopy to probe the lipidomic microenvironment associated with structural polymorphism of Aβ plaques in transgenic Alzheimer's disease mice (tgAPPSWE). Using on tissue and ex situ validation, TIMS MS/MS facilitated unambiguous identification of isobaric lipid species that showed plaque pathology‐associated localizations. Integrated multivariate imaging data analysis revealed multiple, Aβ plaque‐enriched lipid patterns for gangliosides (GM), phosphoinositols (PI), phosphoethanolamines (PE), and phosphatidic acids (PA). Conversely, sulfatides (ST), cardiolipins (CL), and polyunsaturated fatty acid (PUFA)‐conjugated phosphoserines (PS), and PE were depleted at plaques. Hyperspectral amyloid imaging further delineated the unique distribution of PA and PE species to mature plaque core regions, while PI, LPI, GM2 and GM3 lipids localized to immature Aβ aggregates present within the periphery of Aβ plaques. Finally, we followed AD pathology‐associated lipid changes over time, identifying plaque‐ growth and maturation to be characterized by peripheral accumulation of PI (18:0/22:6). Together, these data demonstrate the potential of multimodal imaging approaches to overcome limitations associated with conventional advanced MS imaging applications. This allowed for the differentiation of both distinct lipid components in a complex micro‐environment as well as their correlation to disease‐relevant amyloid plaque polymorphs.

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https://doi.org/10.1111/jnc.15390
Combined oral contraceptive use in rheumatoid arthritis for the purpose of pregnancy prevention and additional benefits: A narrative review
Authors: Lopane Cassandra M. , Comstock Brianne , Nagel Angela K. , Gandhi Mona A.
Published: December 2021

Combined oral contraceptives are a common method of contraception and many females prefer them regardless of their medical history. The use in patients with rheumatoid and autoimmune disorders has not been extensively studied with previous reviews focusing on the safety component. This review seeks to address the effectiveness and benefits of utilizing combined oral contraceptives in females with rheumatoid arthritis (RA). Current literature regarding combined oral contraceptives was surveyed for its use in RA and two PubMed searches were conducted, yielding 202 and 142 results, respectively. Results were screened and analyzed for relevance to this review topic. Eighteen results, consisting of clinical trials, observational studies, patient cases, and meta‐analyses were used in this narrative review. Historically, it was thought that females with an autoimmune disorder such as RA need to be on contraception due to the teratogenicity potential with disease‐modifying therapy but no evidence exists about which type of contraception is the most effective and least interacting. Current evidence available shows no preference for types of contraception in this population, but it has been demonstrated that combination oral contraceptives may provide contraceptive benefits and have a potential for other benefits such as less disability and the prevention of disease progression. Although current evidence provides reasoning to believe combination oral contraceptives are safe and efficacious in patients with RA and may even offer additional benefits, further studies and clinical trials are needed to completely understand the role combination oral contraceptives play in this patient population.
Minority language maintenance and the production‐prescription interface: Number agreement in New York Yiddish
Authors: Bleaman Isaac L.
Published: December 2021

Standardization is a focus of language maintenance efforts in many, but not all, minority language communities. What is the impact of this choice on interspeaker variation in maintained languages? This study investigates variable number agreement in Yiddish, a minority language spoken by two distinct communities in the New York area: (1) Hasidic Jews, who maintain the language without standardization, and (2) Yiddishists, who are overtly committed to maintaining a “correct” Yiddish. An analysis of data from 40 sociolinguistic interviews shows that Yiddishists have significantly higher rates of normative agreement than Hasidim do. The Yiddishists’ standard language ideology has also contributed to a leveling of the differences across grammatical constructions, a predictor that is more robust among the Hasidic speakers. These community‐based differences in speech reflect differences in speakers’ prescriptive judgments, which were elicited through a novel postinterview text editing task.
Attachment to God and Psychological Distress: Evidence of a Curvilinear Relationship
Authors: Henderson W. Matthew , Kent Blake Victor
Published: December 2021

Previous religion/spirituality (R/S) research on attachment to God and mental well‐being has relied entirely on linear models. Scholars, however, have called for more nuanced analysis of religious beliefs and dispositions relative to mental health, and several studies using a nonlinear approach have yielded fruitful results with a handful of R/S predictors. Relying on national data from the 2010 Baylor Religion Survey, this study investigates potential nonlinear associations between attachment to God and psychological distress by fitting curvilinear models of avoidant attachment to God and multiple measures of general and psychological distress. For conceptual reasons, linear models of anxious attachment are also employed. Results reveal a nonlinear relationship between avoidant/secure attachment and distress and a deleterious linear relationship between anxious attachment to God and distress. This supports the overall hypothesis that anxiety or a lack of certainty about one's relationship with the divine represents a threat to psychological well‐being.
A lizard with two tales: What diversification within Sceloporus occidentalis teaches us about species formation
Authors: Pereira Ricardo J. , Singhal Sonal
Published: December 2021

In 1859, Charles Darwin proposed that species are not fundamentally different from subspecies or the varieties from which they evolve. A century later, Dobzhansky (1958) suggested that many such lineages are ephemeral and are likely to reverse differentiation through introgression (Figure 1a); only a few evolve complete reproductive isolation and persist in sympatry. In this issue of Molecular Ecology, Bouzid et al. (2021) showed how new analytical methods, when applied to genomic data, allow us to more precisely determine whether or not species formation follows the paths outlined by Darwin and Dobzhansky (Figure 1b). The authors studied the diversification of the lizard Sceloporus occidentalis, finding a continuum of genetic interactions between the preservation of genetic identity to genetic merger, analogous to what is exemplified by ring species. In doing so, they teach us two tales about species formation: that lineages are fractal byproducts of evolutionary processes such as genetic drift and selection, and that lineages are often ephemeral and do not always progress into fully reproductively isolated taxa. Studying ephemeral lineages like those in S. occidentalis allows us to capture divergence at its earliest stages, and potentially to determine the factors that allow lineages to remain distinct despite pervasive gene flow. These lineages thus serve as a natural laboratory to address long standing hypotheses about species formation.