bluuebunny/crossref_metadata_2025 huggingface dataset:
The actin depolymerizing factor StADF2 alters StREM1.3 plasma membrane nanodomains to inhibit thePotato Virus X
Authors: Jolivet Marie-Dominique , Gouguet Paul , Legrand Anthony , Xhelilaj Kaltra , Faiss Natalie , Massoni-Laporte Aurélie , Robbe Terezinha , Sagot Isabelle , Boudsocq Marie , German-Retana Sylvie , Üstün Suayib , Loquet Antoine , Habenstein Birgit , Germain Véronique , Mongrand Sébastien , Gronnier Julien
Published: January 2023

The dynamic regulation of the plasma membrane (PM) organization at the nanoscale emerged as a key element shaping the outcome of host-microbe interactions. Protein organization into nanodomains (ND) is often assumed to be linked to the activation of cellular processes. In contrast, we have previously shown that the phosphorylation of theSolanum tuberosumREM1.3 (StREM1.3) N-terminal domain disperses its native ND organization and promotes its inhibitory effect onPotato Virus X(PVX) cell-to-cell movement. Here, we show that the phosphorylation of StREM1.3 modify the chemical environment of numerous residues in its intrinsically-disordered N-terminal domain. We leveraged exploratory screens to identify potential phosphorylation-dependent interactors of StREM1.3. Herewith, we uncovered uncharacterized regulators of PVX cell-to-cell movement, linking StREM1.3 to autophagy, water channels and the actin cytoskeleton. We show that theSolanum tuberosumactin depolymerizing factors 2 (StADF2) alters StREM1.3 NDs and limits PVX cell-to-cell movement in a REMORIN-dependent manner. Mutating a conserved single residue reported to affect ADFs affinity to actin inhibits StADF2 effect on StREM1.3 ND organization and PVX cell-to-cell movement. These observations provide functional links between the organization of plant PM and the actin cytoskeleton and suggests that the alteration of StREM1.3 ND organization promotes plant anti-viral responses. We envision that analogous PM re-organization applies for additional signaling pathways in plants and in other organisms.
Development of a conceptual framework to guide description and evaluation of social interventions for people with serious mental health conditions
Authors: Appleton Rebecca , Barnett Phoebe , Chipp Beverley , Clark Michael , Goldblatt Peter , Jeffreys Stephen , Machin Karen , Needle Justin J , Shah Prisha , Thompson Georgina , Trevillion Kylee , Webber Martin , Worden Minnie , Johnson Sonia , Lloyd-Evans Brynmor
Published: January 2023

People with serious mental health conditions face social exclusion and have poorer social outcomes compared to the general population in several areas of life. Social exclusion also negatively impacts mental health. Promising models of support to improve social outcomes for people with serious mental health conditions have been described in the literature and proliferate in practice, but typologies of support are not clearly established and a robust evidence base for effective approaches is lacking in many areas. We conducted a scoping review of relevant literature and consulted with experts in the field to identify models to improve social circumstances across eight life domains, with the aim of developing a conceptual framework to distinguish the main broad approaches to improving the social circumstances of people with serious mental health conditions. We also sought to explore which approaches have been used in models within each life domain, and to detect any preliminary indications of which approaches are most promising, based on evaluations of identified models of support. This work was conducted in collaboration with a group of expert stakeholders, including people with lived experience of accessing mental health services. We developed a conceptual framework which distinguishes sources and types of support, allowing description of complex interventions to improve the social circumstances of people with serious mental health problems, and providing a framework to guide future service development and evaluation.
Rate of tuberculosis screening and isoniazid prophylaxis treatment among human immunodeficiency virus patients in Obio/Akpor Local Government Area: A retrospective study
Authors: Edoja Precious Ruth , Apugo Uchechukwu Ifeanyichukwu , Anekwe Ekenedilichukwu Chukwudubem
Published: January 2023

Background

The co-occurrence of Tuberculosis (TB) and Human Immunodeficiency Virus (HIV) has been recognised as a global public health problem with considerable mutual interaction and a leading cause of death worldwide.

Aim

To determine the rate of TB screening among People Living with HIV (PLWH) and treatment with isoniazid (INH) prophylaxis in directly observed treatment short course (DOTS) clinics in Primary Healthcare centres (PHCs) in Obio/Akpor Local Government Area of Rivers state.

Materials and Method

This clinic-based, two-year retrospective cross-sectional study involved a complete review and abstraction of all records for HIV patients (18 years and above) who have been receiving HIV care and treatment for at least 6 months prior to the study in DOTS clinics in five selected PHCs in OBALGA. The data were extracted using a checklist while the statistical analysis of the study was carried out using SPSS version 23.

Results

The proportion of HIV-positive patients screened for TB was 79.8% while those who had TB diagnostic evaluation among them was 38.6%, and 38.7% of the HIV/TB co-infected patients were placed on INH prophylaxis.

Conclusion

Insufficient attention is being paid to TB diagnostic evaluation and IPT. Hence, it is recommended that the PHCs in the LGA should be equipped with appropriate devices for TB diagnosis as well as engage the Healthcare Workers in sensitization workshops on the need for continuous screening of PLWH for TB.
Histone-organized chromatin in bacteria
Authors: Hocher Antoine , Laursen Shawn P. , Radford Paul , Tyson Jess , Lambert Carey , Stevens Kathryn M , Picardeau Mathieu , Sockett R. Elizabeth , Luger Karolin , Warnecke Tobias
Published: January 2023

Histones are the principal constituents of chromatin in eukaryotes and most archaea, while bacteria generally rely on an orthogonal set of proteins to organize their chromosomes. However, several bacterial genomes encode proteins with putative histone fold domains. Whether these proteins are structurally and functionally equivalent to archaeal and eukaryotic histones is unknown. Here, we demonstrate that histones are essential and are major components of chromatin in the bacteriaBdellovibrio bacteriovorusandLeptospira interrogans. Patterns of sequence evolution suggest important roles in several additional bacterial clades. Structural analysis of theB. bacteriovorushistone (Bd0055) dimer shows that histone fold topology is conserved between bacteria, archaea, and eukaryotes. Yet, unexpectedly, Bd0055 binds DNA end-on and forms a sheath of tightly packed histone dimers to encase straight DNA. This binding mode is in stark contrast to archaeal, eukaryotic, and viral histones, which invariably bend and wrap DNA around their outer surface. Our results demonstrate that histones are integral chromatin components across the tree of life and highlight organizational innovation in the domain Bacteria.
Insights into polyprotein processing and RNA-protein interactions in foot-and-mouth disease virus genome replication
Authors: Pierce Danielle M. , Rowlands David J. , Stonehouse Nicola J. , Herod Morgan R.
Published: January 2023

Foot-and-mouth disease affects cloven hoofed animals and is caused by foot-and-mouth disease virus (FMDV), a picornavirus with a positive-sense RNA genome. The FMDV genome contains a single open reading frame, which is translated to produce a polyprotein that is cleaved by viral proteases to produce the viral structural and non-structural proteins. Initial processing of the polyprotein occurs at three main junctions to generate four primary products; Lproand the P1, P2 and P3 precursors (also termed 1ABCD, 2BC and 3AB1,2,3CD). The 2BC and 3AB1,2,3CD precursors undergo subsequent proteolysis to generate non-structural proteins that are required for viral replication, including the enzymes 2C, 3Cproand 3Dpol. These precursors can be processed through bothcisandtrans(i.e., intra- and inter-molecular proteolysis) pathways, which are thought to be important for controlling virus replication. Our previous studies suggested that a single residue in the 3B3-3C junction had an important role in controlling 3AB1,2,3CD processing. Here, we usein vitrobased assays to show that a single point mutation at the 3B3-3C boundary increases the rate of proteolysis to generate a novel 2C-containing precursor. Complementation assays showed that while this point mutation permitted production of some non-enzymatic non-structural proteins, those with enzymatic functions were inhibited. Interestingly, replication could only be supported by complementation with mutations incisacting RNA elements, providing genetic evidence for a functional interaction between replication enzymes and RNA elements.

Importance

Foot-and-mouth disease virus (FMDV) is an economically important pathogen of animals that is responsible for foot-and-mouth disease (FMD). FMD is endemic in many parts of the world and can results in major economic losses. Replication of the virus is a highly coordinated event that occurs within membrane-associated compartments in infected cells and requires the viral non-structural proteins. These are all initially produced as a polyprotein that undergoes proteolysis likely through bothcisandtranspathways (i.e., intra- and inter-molecular proteolysis). Alternative processing pathways can provide a mechanism to help coordinate viral replication by providing temporal control to protein production. Here, we analyse the consequences of mutations that change temporal control of FMDV polyprotein processing. Our data suggests that correct processing is required to produce key enzymes for replication in an environment in which they can interact with essential viral RNA elements. These data further the understanding of FMDV genome replication.
Assembly properties ofSpiroplasmaMreB involved in swimming motility
Authors: Takahashi Daichi , Miyata Makoto , Fujiwara Ikuko
Published: January 2023

Bacterial actin MreB forms filaments in which the unit of the structure is an antiparallel double strand. The wall-less helical bacteriumSpiroplasmahas five MreB homologs (MreB1–5), a part of which is composed of an intra-cellular ribbon for driving its swimming motility. The interaction modes of each ribbon component are unclear, although these are clues for understandingSpiroplasmaswimming. Here, we examined the assembly properties ofSpiroplasma eriocheirisMreB5 (SpeMreB5), which forms sheets and is a component protein of the ribbon. Electron microscopy (EM) revealed that sheet formation was inhibited under acidic conditions and paracrystal structures were formed under acidic and neutral conditions with low ionic strength. Solution assays found four properties of paracrystals as follows: (I) their formation followed sheet formation, (II) electrostatic interactions were required for their formation, (III) the positively charged and unstructured C-terminal region contributed to the nucleation of their formation, and (IV) their formation required Mg2+at neutral pH but was inhibited by divalent cations under acidic conditions. During these studies, we found two aggregation modes of SpeMreB5, with distinct responses to ATP. These properties will shed light on SpeMreB5 assembly dynamics at the molecular level.
Host cell cAMP-Epac pathway inhibition by hawthorn extract as a potential treatment for Chagas disease
Authors: Ferri Gabriel , Fernández Lucía R. , Di Mario Guillermo , Palermo Jorge A. , Edreira Martin M.
Published: January 2023

Benznidazole (BNZ) and nifurtimox (NFX), drugs used in the treatment of Chagas disease (CD), are effective in acute and congenital cases. However, due to the high toxicity of both drugs, the long duration of the treatment, the high doses, and the low effectiveness during the chronic phase, new therapies are needed. Recently, there has been an increase in alternative medicine and natural products popularity. Medicinal herbs emerge as a promising alternative for the development of new therapies against CD. The development of new active drugs requires the identification of new molecular targets. Host cell cAMP-Epac pathway plays a key role duringTrypanosoma cruziinvasion. We have previously shown that Epac1 is required during the cAMP-mediated invasion of this parasite. Moreover, vitexin, a natural flavone that protects against ischemia-reperfusion damage, acts by inhibiting the expression of Epac and Rap1 proteins. Vitexin can be found in plants of the genusCrataegus spp., traditionally known as hawthorn, that are of great interest considering their highly documented use as cardio-protectors. In this work, using HPLC-HRMS and MS2, we could confirm the presence of vitexin in an extract ofC. oxyacantha(CO-EE). Interenstingly, treating cells with CO-EE, similar results forT. cruziinvasion than the ones observed for Epac1 specific inhibitor ESI-09 were observed. In addition, treated cells have a diminished activated Rap1b, suggesting that the extract could act through the cAMP-Epac signalling pathway. Most significantly, when using CO-EE in conjunction with NFX we observed an addition of the negative effects on the invasion, opening the possibility of decreasing the dosage/time currently used and thus alleviating the secondary side effects of available drugs, as well as theper capitatreatment cost of CD.
New tools to study the interaction between integrins and latent TGFβ1
Authors: Bachmann Michael , Kessler Jérémy , Burri Elisa , Wehrle-Haller Bernhard
Published: January 2023

Transforming growth factor beta (TGFβ) 1 regulates cell differentiation and proliferation in different physiological settings, but is also involved in fibrotic progression and protects tumors from the immune system. Integrin αVβ6 has been shown to activate latent TGFβ1 by applying mechanical forces onto the latency-associated peptide (LAP). While the extracellular binding between αVβ6 and LAP1 is well characterized, less is known about the cytoplasmic adaptations that enable αVβ6 to apply such forces. Here, we generated new tools to facilitate the analysis of this interaction. We combined the integrin-binding part of LAP1 with a GFP and the Fc chain of human IgG. This chimeric protein, sLAP1, revealed a mechanical rearrangement of immobilized sLAP1 by αVβ6 integrin. This unique interaction was not observed between sLAP1 and other integrins. We also analyzed αVβ6 integrin binding to LAP2 and LAP3 by creating respective sLAPs. Compared to sLAP1, integrin αVβ6 showed less binding to sLAP3 and no rearrangement. These observations indicate differences in the binding of αVβ6 to LAP1 and LAP3 that have not been appreciated so far. Finally, αVβ6-sLAP1 interaction was maintained even at strongly reduced cellular contractility, highlighting the special mechanical connection between αVβ6 integrin and latent TGFβ1.
Adolescent length growth spurts in bonobos and other primates: Mind the scale
Authors: Berghänel Andreas , Stevens Jeroen M.G. , Hohmann Gottfried , Deschner Tobias , Behringer Verena
Published: January 2023

Adolescent growth spurts (GS) in body length seem to be absent in non-human primates and are considered a distinct human trait. However, this distinction between present and absent length-GSs may reflect a mathematical artefact that makes it arbitrary. We first outline how scaling issues and inappropriate comparisons between length (linear) and weight (volume) growth rates result in misleading interpretations like the absence of length-GSs in non-human primates despite pronounced weight-GSs, or temporal delays between length- and weight-GSs. We then apply a scale-corrected approach to a comprehensive dataset on 258 zoo-housed bonobos that includes weight and length growth as well as several physiological markers related to growth and adolescence. We found pronounced GSs in body weight and length in both sexes. Weight and length growth trajectories corresponded with each other and with patterns of testosterone and IGFBP-3 levels, resembling adolescent GSs in humans. We further re-interpreted published data of non-human primates, which showed that aligned GSs in weight and length exist not only in bonobos. Altogether, our results emphasize the importance of considering scaling laws when interpreting growth curves in general, and further show that pronounced, human-like adolescent length-GSs exist in bonobos and probably also many other non-human primates.
The effects of online restaurant menus on consumer purchase intention: evidence from an emerging economy
Authors: Le Thanh Tiep , Bui Thi Tuyet Nhu , Le Anh Thu , Dang Thi Kim Ngan , Trinh Thi Thai Ninh , Nguyen Lan Anh
Published: January 2023

Purpose

This study evaluates the impact of online menus and perceived convenience of online food ordering on consumer purchase intention and shows how a desire for food creates a relationship between an online menu and a customer's purchase intention. Suggestions for management are proposed to design an effective menu to improve business performance in the competitive market in Vietnam.

Design/methodology/approach

The paper follows a quantitative method. Quantitative research aims to analyze and critically evaluate the research question(s) to discover new factors.

Findings

Findings indicate a positive relationship between menu visual appeal (MV), menu informativeness (MI), desire for food (DF), the perceived convenience (PC) of ordering food online and intention to purchase (PI). The attractiveness of images and information is a significant factor affecting diners’ desire to eat, while the demand for food and the convenience of ordering food online are also factors affecting purchase intention.

Practical implications

The study confirms the importance of online menus to purchase intention. Economically, when supply and demand are reasonable, the market is stable and technology develops. In terms of social, hygiene, attractiveness and price factors, it is helpful to have an overview. Research is the premise for further studies with factors from menu to customer trust.

Originality/value

The study provides a solid foundation for further studies on restaurant menu elements as well as a new perspective on how restaurants improve their dishes.
Research on the bifurcation approach for turbulent flows with rotation and curvature: effect of the base models
Authors: Pang Kaiwen , Huang Xianbei , Liu Zhuqing , Li Yaojun , Yang Wei , Lu Jiaxing
Published: January 2023

Purpose

This study aims to research the prediction performance of the bifurcation approach with different base models in different kinds of turbulent flows with rotation and curvature.

Design/methodology/approach

The k−ω and Shear-Stress Transport (SST) k−ω models are modified by using the complete eddy viscosity coefficient expression, and the latter is modified by using two sets of model coefficients. The two bifurcation models were tested in three cases: rotating channel flow with system rotation, Taylor–Couette flow with wall rotation and curvature effect and swirling flow through an abrupt axisymmetric expansion with inlet swirling flow.

Findings

In these flows, the bifurcation approach can significantly improve the prediction performance of the base model in the fluctuation velocity. The deviation of the BSkO model is slightly superior to the BkO model by about 2% in the Taylor–Couette flow. The prediction effect of the root-mean-square (RMS) velocity of the BSkO model increases by about 4–5% as the number of grids increases about 2.37 times, and the best is the Large Eddy Simulation (LES) grid used. Finally, compared with the SST k−ω model, the average iteration time of the SST with curvature correction (SST-CC), bifurcation k−ω (BkO) and bifurcation SST k−ω (BSkO) models increased by 27.7%, 86.9% and 62.3%, respectively.

Originality/value

This study is helpful to understand further the application of the bifurcation method in the turbulence model.
Is customer participation always good in service recovery? The moderating role of customers' positive psychological capital
Authors: Alotaibi Meteb Naif , Chaouali Walid , Mjahed Hammami Samiha , Schoefer Klaus , Aloui Narjess , Abdulhamid Saleh Mahmoud
Published: January 2023

Purpose

So far, whether customers' involvement strengthens or weakens the process of service recovery has remained unclear. Filling this gap, this study aims to investigate the effect of customers' participation on customers' post-recovery outcomes in the context of the banking industry. More specifically, this study delineates how and when customer participation (CP) proves effective in creating and enhancing favourable post-recovery outcomes.

Design/methodology/approach

With the help of an online survey, this study collects responses from 314 bank customers and analyses them using SmartPLS.

Findings

The results show that customers' participation in service recovery positively affects customers' perceived utilitarian and hedonic values. Customers' perceived utilitarian and hedonic values positively influence customers' recovery satisfaction which, in turn, positively relates to their continuance intention and positive word-of-mouth (PWOM). Furthermore, customers' positive psychological capital (CPPC) positively moderates the relationship of CP in service recovery with perceived utilitarian value and hedonic value.

Originality/value

This study unveils the negative facet of co-created service recovery, which has rarely been addressed in the service recovery literature, especially in the context of the banking industry. This study demonstrates that the effectiveness of customers' participation in creating favourable post-recovery outcomes is contingent on CPPC. Moreover, this study confirms that not all customers may value customers' participation in the service recovery process.
The moderating effect of fan engagement on the relationship between fan knowledge and fan co-creation in social media
Authors: Behnam Mohsen , Dickson Geoff , Delshab Vahid , Gerke Anna , Savari Nikou Parvaneh
Published: January 2023

Purpose

Social media has enhanced the ability of fans to interact with each other. Whilst previous research investigates fan co-creation, few studies focus on the interactive effects within the co-creation process. The authors develop a model for synthesizing the interactive concepts related to fan co-creation in social media, which leads to team identification.

Design/methodology/approach

Participants (N = 483) were recruited from fans of clubs in the Persian Gulf Pro League of Iran. Structural equation modelling was applied to test the research model.

Findings

The results showed that fan knowledge facilitates fan co-creation, which in turn leads to team identification. Additionally, fan engagement had a moderating effect on the mediating role of fan co-creation in the association between fan knowledge and team identification.

Research limitations/implications

The findings suggest that fan knowledge is an important antecedent of fan co-creation and highlight the significance of fan co-creation in promoting team identification in highly engaged fans at football clubs.

Originality/value

The current study contributes to the field of fan co-creation and provides significant implications for sport fan marketers.
Soil microbial legacies influence freeze–thaw responses of soil
Authors: Pastore Melissa A. , Classen Aimée T. , English Marie E. , Frey Serita D. , Knorr Melissa A. , Rand Karin , Adair E. Carol
Published: January 2023

Warmer winters with less snowfall are increasing the frequency of soil freeze–thaw cycles across temperate regions. Soil microbial responses to freeze–thaw cycles vary and some of this variation may be explained by microbial conditioning to prior winter conditions, yet such linkages remain largely unexplored. We investigated how differences in temperature history influenced microbial community composition and activity in response to freeze–thaw cycles.

We collected soil microbial communities that developed under colder (high elevation) and warmer (low elevation) temperature regimes in spruce‐fir forests, then added each of these soil microbial communities to a sterile bulk‐soil in a laboratory microcosm experiment. The inoculated high‐elevation cold and low‐elevation warm microcosms were subjected to diurnal freeze–thaw cycles or constant above‐freezing temperature for 9 days. Then, all microcosms were subjected to a 7‐day above‐freezing recovery period.

Overall, we found that the high‐elevation cold community had, relative to the low‐elevation warm community, a smaller reduction in microbial respiration (CO2 flux) during freeze–thaw cycles. Further, the high‐elevation cold community, on average, experienced lower freeze–thaw‐induced bacterial mortality than the warm community and may have partly acclimated to freeze–thaw cycles via increased lipid membrane fluidity. Respiration of both microbial communities quickly recovered following the end of the freeze–thaw treatment period and there were no changes in soil extractable carbon or nitrogen.

Our results provide evidence that past soil temperature conditions may influence the responses of soil microbial communities to freeze–thaw cycles. The microbial community that developed under a colder temperature regime was more tolerant of freeze–thaw cycles than the community that developed under a warmer temperature regime, although both communities displayed some level of resilience. Taken together, our data suggest that microbial communities conditioned to less extreme winter soil temperatures may be most vulnerable to rapid changes in freeze–thaw regimes as winters warm, but they also may be able to quickly recover if mortality is low.

Read the free Plain Language Summary for this article on the Journal blog.
The non‐random assembly of network motifs in plant–pollinator networks
Authors: Lanuza Jose B. , Allen‐Perkins Alfonso , Bartomeus Ignasi
Published: January 2023

Ecological processes leave distinct structural imprints on the species interactions that shape the topology of animal–plant mutualistic networks. Detecting how direct and indirect interactions between animals and plants are organised is not trivial since they go beyond pairwise interactions, but may get blurred when considering global network descriptors.

Recent work has shown that the meso‐scale, the intermediate level of network complexity between the species and the global network, can capture this important information. The meso‐scale describes network subgraphs representing patterns of direct and indirect interactions between a small number of species, and when these network subgraphs differ statistically from a benchmark, they are often referred to as ‘network motifs’. Although motifs can capture relevant ecological information of species interactions, they remain overlooked in natural plant–pollinator networks.

By exploring 60 empirical plant–pollinator networks from 18 different studies with wide geographical coverage, we show that some network subgraphs are consistently under‐ or over‐represented, suggesting the presence of worldwide network motifs in plant–pollinator networks. In addition, we found a higher proportion of densely connected network subgraphs that, based on previous findings, could reflect that species relative abundances are the main driver shaping the structure of the meso‐scale on plant–pollinator communities. Moreover, we found that distinct subgraph positions describing species ecological roles (e.g. generalisation and number of indirect interactions) are occupied by different groups of animal and plant species representing their main life‐history strategies (i.e. functional groups). For instance, we found that the functional group of ‘bees’ was over‐represented in subgraph positions with a lower number of indirect interactions in contrast to the rest of floral visitors groups. Finally, we show that the observed functional group combinations within a subgraph cannot be retrieved from their expected probabilities (i.e. joint probability distributions), indicating that plant and floral visitor associations within subgraphs are not random either.

Our results highlight the presence of common network motifs in plant–pollinator communities that are formed by a non‐random association of plants and floral visitors functional groups.
A 21st‐Century perspective on snow drought in the Upper Colorado River Basin
Authors: Heldmyer Aaron J. , Bjarke Nels R. , Livneh Ben
Published: January 2023

In the Upper Colorado River Basin (UCRB), there is a deep reliance on seasonal snowpack for maintenance of water resources. The term “snow drought” has recently emerged to describe periods of anomalously low snowpack. Unique seasonal patterns in precipitation and temperature that drive snow drought can have distinct hydrologic signatures, and these relationships have not been carefully studied in the UCRB. Here we examine snow drought with a new classification scheme using peak snow water equivalent (SWE) and the ratio of basin‐wide modeled peak SWE to accumulated (onset to peak) precipitation (SWE/P) that clusters snow drought years into three distinct groups—“warm,” “dry,” and “warm & dry”—that minimize within‐group variance. Over the period 1916–2018, we identify 14 warm years ( = 160 mm;  = 0.24), 24 dry years ( = 117 mm;  = 0.35), and 21 warm & dry years ( = 94 mm;  = 0.23). An elevation‐based analysis reveals two distinct patterns: warm snow droughts see severe SWE reductions primarily at lower (<2600 m) elevations (65% at lower elevations, 37% overall), whereas “dry” scenarios exhibit a consistent reduction across all elevations (39% overall). Using naturalized streamflow data, we also differentiate snow droughts by their earlier streamflow timing and decreased peakedness (warm: 7 days, 2%; dry: 7 days, 2%; warm & dry: 13 days, 5%). This research provides new insights into snow drought patterns relevant for regional water management.
Efficacy and safety of carboplatin and etoposide in older extensive‐stage small‐cell lung cancer patients with a poor performance status
Authors: Mamesaya Nobuaki , Kodama Hiroaki , Iida Yuko , Kobayashi Haruki , Ko Ryo , Wakuda Kazushige , Ono Akira , Kenmotsu Hirotsugu , Naito Tateaki , Murakami Haruyasu , Shimizu Tetsuo , Gon Yasuhiro , Takahashi Toshiaki
Published: January 2023

Carboplatin plus etoposide is a standard treatment for older extensive‐stage small‐cell lung cancer (ES‐SCLC) patients with performance status (PS) 2. However, older patients often exhibit poor PS (3, 4), and the treatment effect in them is poorly understood. To determine the therapeutic efficacy and safety of carboplatin plus etoposide therapy for this population, we retrospectively analyzed 63 patients with ES‐SCLC with PS ≥2, aged ≥71 years, who had received first‐line carboplatin plus etoposide therapy. We compared the treatment efficacy and safety in patients with baseline PS 2 versus those with PS 3–4. In the PS 2 (38 patients) and PS ≥3 (25 patients) groups, the overall response rate was 71.1% and 72.0%, median progression‐free survival was 4.6 and 3.1 months, and overall survival was 7.7 and 5.1 months, respectively. PS improved to 0–1 post‐treatment in 65.8% and 48.0% of the patients in the PS 2 and PS ≥3 groups, respectively. Patients with PS ≥3 showing improved PS had a progression‐free survival of 6.1 months. A higher incidence of grade ≥3 decreased neutrophil counts, febrile neutropenia, and treatment‐related death was observed in the PS ≥3 group. The progression‐free survival of patients administered prophylactic granulocyte colony‐stimulating factor (G‐CSF) was 5.2 and 6.1 months in the PS2 and PS ≥3 groups. Overall, carboplatin plus etoposide therapy provided comparable tumor shrinkage, but shorter progression‐free and overall survival in older ES‐SCLC patients with PS ≥3 than in those with PS 2. Thus, supportive care, such as prophylactic G‐CSF administration, may be necessary to ensure safety and survival.
Community fashioning
Authors: Landry Jean‐Michel
Published: January 2023

In the shari‘a seminaries (hawza) of South Beirut, young Shi‘i Muslims articulate a notion of ethics that is realized in and through collective life. Classes on ethics (akhlaq) help them reweave the moral fabric of their neighborhoods by addressing volatile public situations, correcting improper conduct, and emulating virtuous figures. The concerns that animate these classes, and the practices of caretaking shaped therein, illuminate the political work that ethical action can achieve. Understanding how future clerics learn to fashion their community (and themselves) requires a theorization of subject formation that moves beyond conventional views of the self and that enables us to approach the public atmosphere as an ethical force. For this, a powerful starting point is offered by the tradition of political ethics as elaborated in the writings of Antonio Gramsci, Simone Weil, and others.
Platelets and endothelial dysfunction in gestational diabetes mellitus
Authors: Valero Paola , Cornejo Marcelo , Fuentes Gonzalo , Wehinger Sergio , Toledo Fernando , van der Beek Eline M. , Sobrevia Luis , Moore‐Carrasco Rodrigo
Published: January 2023

The prevalence of gestational diabetes mellitus (GDM) has increased in recent years, along with the higher prevalence of obesity in women of reproductive age. GDM is a pathology associated with vascular dysfunction in the fetoplacental unit. GDM‐associated endothelial dysfunction alters the transfer of nutrients to the foetus affecting newborns and pregnant women. Various mechanisms for this vascular dysfunction have been proposed, of which the most studied are metabolic alterations of the vascular endothelium. However, different cell types are involved in GDM‐associated endothelial dysfunction, including platelets. Platelets are small, enucleated cell fragments that actively take part in blood haemostasis and thrombus formation. Thus, they play crucial roles in pathologies coursing with endothelial dysfunction, such as atherosclerosis, cardiovascular diseases, and diabetes mellitus. Nevertheless, platelet function in GDM is understudied. Several reports show a potential relationship between platelet volume and mass with GDM; however, platelet roles and signaling mechanisms in GDM‐associated endothelial dysfunction are unclear. This review summarizes the reported findings and proposes a link among altered amount, volume, mass, reactivity, and function of platelets and placenta development, resulting in fetoplacental vascular dysfunction in GDM.
Inflammatory cytokine‐enriched microenvironment plays key roles in the development of breast cancers
Authors: Takeuchi Yasuto , Gotoh Noriko
Published: January 2023

As the incidence of breast cancer continues to increase, it is critical to develop prevention strategies for this disease. Inflammation underlies the onset of the disease, and NF‐κB is a master transcription factor for inflammation. Nuclear factor‐κB (NF‐κB) is activated in a variety of cell types, including normal epithelial cells, cancer cells, cancer‐associated fibroblasts (CAFs), and immune cells. Ductal carcinoma in situ (DCIS) is the earliest stage of breast cancer, and not all DCIS lesions develop into invasive breast cancers (IBC). Currently, most patients with DCIS undergo surgery with postoperative therapy, although there is a risk of overtreatment. In BRCA mutants, receptor activator of NF‐κB (RANK)‐positive progenitors serve as the cell of origin, and treatment using the RANK monoclonal antibody reduces the risk of IBC. There is still an unmet need to diagnose malignant DCIS, which has the potential to progress to IBC, and to establish appropriate prevention strategies. We recently demonstrated novel molecular mechanisms for NF‐κB activation in premalignant mammary tissues, which include DCIS, and the resultant cytokine‐enriched microenvironment is essential for breast cancer development. On the early endosomes in a few epithelial cells, the adaptor protein FRS2β, forming a complex with ErbB2, carries the IκB kinase (IKK) complex and leads to the activation of NF‐κB, thereby inducing a variety of cytokines. Therefore, the FRS2β‐NFκB axis in the inflammatory premalignant environment could be targetable to prevent IBC. Further analysis of the molecular mechanisms of inflammation in the premalignant microenvironment is necessary to prevent the risk of IBC.
Anthocyanin oligomer (grape skin extract) administration improves dry eye disease: A randomised, double‐blind, placebo‐controlled study
Authors: Fan Meiqi , Kim Su Ah. , Choi Young‐Jin , Tang Yujiao , Yang Hyun Pil , Kim Eun‐Kyung
Published: January 2023

Background

Dry eye disease is a chronic, progressive ocular disease characterised by ocular discomfort and is one of the most common ophthalmological disorders that affects people's lives.

Methods

This study investigated the clinical efficacy of anthocyanin oligomers (grape skin extract) for the treatment of dry eye. One hundred and eight patients with dry eye were randomly divided into placebo and treatment groups, each with 54 cases. The placebo group received maltodextrin (800 mg/day) and the treatment group received anthocyanin oligomers (800 mg/day). Clinical efficacy, clinical indices, and occurrence of adverse reactions were compared between the two groups.

Results

Anthocyanin oligomers were safe and effective in mild‐to‐moderate dry eye disease, improving the tear break‐up time, intraocular pressure, ocular surface disease, and patient symptomatology.

Conclusions

The use of oral anthocyanin oligomers in the treatment of dry eye patients can enhance the therapeutic effect and improve the quality of life of patients while ensuring the safety of treatment, making this therapeutic option suitable for wider application.
Impact of baseline kidney function on the effects of sodium‐glucose co‐transporter‐2 inhibitors on kidney and heart failure outcomes: A systematic review and meta‐analysis of randomized controlled trials
Authors: Maddaloni Ernesto , Cavallari Ilaria , La Porta Ylenia , Appetecchia Alessandro , D'Onofrio Luca , Grigioni Francesco , Buzzetti Raffaella , Holman Rury R.
Published: January 2023

Aim

To determine whether the magnitude of the cardiorenal benefits of sodium‐glucose co‐transporter‐2 inhibitors (SGLT2is) varies with baseline kidney function.

Methods

We searched randomized, placebo‐controlled trials testing the effects of SGLT2is on renal and cardiovascular outcomes. Efficacy outcomes, stratified by baseline estimated glomerular filtration rate (eGFR) categories, included renal disease progression, a composite heart failure (HF) outcome and mortality.

Results

Thirteen trials testing SGLT2is in 90 402 participants with available eGFR data were included. The risk of bias was judged as low for all trials. SGLT2is reduced the relative risks of renal disease progression by 27% to 57% and of HF outcomes by 13% to 32% across different eGFR categories, with an overall low heterogeneity. Meta‐regression analyses showed a significant direct relationship between baseline eGFR and the magnitude of SGLT2is’ renal protection (P = .003). The greatest risk reduction was in participants with an eGFR of 90 ml/min/1.73m2 or higher (HR 0.43, 95% CI: 0.32‐0.58) and the smallest was in those with an eGFR of less than 30 ml/min/1.73m2 (HR 0.73, 95% CI: 0.62‐0.86, P < .001). Conversely, for HF, the greatest risk reduction was in those with an eGFR of less than 30 ml/min/1.73m2 (HR 0.68, 95% CI: 0.48‐0.96) and the smallest was in those with an eGFR of 90 ml/min/1.73m2 or higher (HR 0.87, 95% CI: 0.56‐1.34).

Conclusions

SGLT2is reduce the risk of renal and HF outcomes for all eGFR categories. The greatest benefits in terms of kidney protection may be achieved by early initiation of SGLT2is in people with preserved eGFR. The greatest risk reduction for HF outcomes is observed in people with lower eGFR values.
Meta‐analysis of head‐to‐head clinical trials comparing incretin‐based glucose‐lowering medications and basal insulin: An update including recently developed glucagon‐like peptide‐1 (GLP‐1) receptor agonists and the glucose‐dependent insulinotropic polypeptide/GLP‐1 receptor co‐agonist tirzepatide
Authors: Nauck Michael A. , Mirna Abd El Aziz , Quast Daniel R.
Published: January 2023

Objective

To assess comparative efficacy, safety and tolerability of injectable incretin‐based glucose‐lowering medications (IBGLMs) versus basal insulin treatment in patients with type 2 diabetes.

Research Design and Methods

We performed an updated meta‐analysis of randomized clinical trials of head‐to‐head comparisons of IBGLMs (short‐ and long‐acting glucagon‐like peptide‐1 [GLP‐1] receptor agonists [GLP‐1RAs] and glucose‐dependent insulinotropic polypeptide [GIP]/GLP‐1 receptor co‐agonist tirzepatide) versus basal insulin using a PubMed database search (April 2022). The primary endpoint was difference in reduction of glycated haemoglobin (HbA1c) versus baseline between pooled IBGLMs (fixed‐effects meta‐analysis) and their subgroups (random‐effects meta‐analysis) versus basal insulin treatment (mean differences). Secondary endpoints were fasting plasma glucose, body weight, HbA1c target achievement, hypoglycaemia, blood pressure and lipids. Risk of bias assessment was performed using Jadad scores and the Risk of Bias tool 2.0.

Results

In all, 20 studies, representing 47 study arms and 11 843 patients, were eligible. Compared with basal insulin, IGBLMs lowered HbA1c by 0.48 (0.45‐0.52)% more than did basal insulin treatment. This effect was driven by pooled long‐acting GLP‐1RAs (ΔHbA1c −0.25 [−0.38; −0.11]%) and the only GIP/GLP‐1 receptor co‐agonist, tirzepatide (pooled doses; ΔHbA1c −0.90 [−1.06; −0.75]%), while short‐acting GLP‐1RAs were equally effective compared with basal insulin (P = 0.90). All IBGLM subgroups achieved significantly lower body weight versus insulin treatment (−4.6 [−4.7; −4.4] kg), in particular tirzepatide (−12.0 [−13.8; −10.1] kg). IBGLMs significantly reduced hypoglycaemia and blood pressure and improved lipid variables. Risk of bias was low. IBGLM treatment was associated with more nausea, vomiting and diarrhoea and study medication discontinuation.

Conclusions

Recently introduced, highly effective IBGLMs were superior to basal insulin treatment, reinforcing the recommendation that IBGLMs should be considered as the first injectable treatment for most patients with type 2 diabetes.
Long‐term impact of weight loss for people with overweight but not obesity, and with type 2 diabetes: 10‐year outcomes of a randomized trial of gastric band surgery
Authors: Qi Qi Yang Damien , Playfair Julie , Brown Wendy A. , Burton Paul , O'Brien Paul E. , Wentworth John M.
Published: January 2023

Aim

Randomized trials reporting 5‐year outcomes have shown bariatric surgery  to induce diabetes remission and improve cardiovascular risk. However, the longer‐term effects of surgery are uncertain, with only one randomized trial reporting 10‐year diabetes outcomes in people with obesity. We aimed to compare 10‐year diabetes outcomes of people who are overweight but not obese, randomly assigned to receive either multidisciplinary diabetes care, or multidisciplinary diabetes care combined with gastric band (GB) surgery.

Methods

Between 2009 and 2011, 51 adults were randomized. After 5 years, they were discharged to receive community care and reassessed after 10 years. The primary outcome was diabetes remission, defined as glycated haemoglobin (HbA1c) <6.5% (48 mmol/mol) without glucose‐lowering medication.

Results

Forty‐one participants (20 medical and 21 GB) completed the 10‐year assessment. The median (Q1, Q3) weight loss in the GB group was 9.8 (6.7, 16.3)% at 10 years compared with 5.6 (3.4, 7.6)% in the medical group (median difference 4.2%; p = .008). Diabetes remission occurred in five GB participants and no medical participants (relative risk 0.76, 95% CI: 0.55‐0.93, p = .048). GB participants used fewer glucose‐lowering medications at 10 years but HbA1c, fasting glucose, calculated cardiovascular risk, quality‐of‐life and incident diabetes complications did not differ significantly between the groups.

Conclusion

When compared with medical care, GB surgery achieved greater weight loss and modestly increased the likelihood of diabetes remission. However, it did not improve HbA1c, cardiovascular risk or quality of life.
Status and mortality: Is there a Whitehall effect in the United States?
Authors: Nicholas Tom
Published: January 2023

The influential Whitehall studies found that top‐ranking civil servants in Britain experienced lower mortality than civil servants below them in the organizational hierarchy due to differential exposure to workplace stress. I test for a Whitehall effect in the United States using a 1930 cohort of white‐collar employees at a leading firm – General Electric (GE). All had access to a corporate health and welfare program during a critical period associated with the health transition. I measure status using position in the managerial hierarchy, attendance at prestigious management training camps and promotions, none of which is associated with a Whitehall‐like rank‐mortality gradient. Instead, senior managers and executives experienced a 3–5‐year decrease in lifespan relative to those in lower levels, with the largest mortality penalty experienced by individuals in the second level of the hierarchy. I discuss generalizability and potential explanations for this reversal of the Whitehall phenomenon using additional data on the status and lifespan of top business executives and US senators.
Beyond mean fitness: Demographic stochasticity and resilience matter at tree species climatic edges
Authors: Guyennon Arnaud , Reineking Björn , Salguero‐Gomez Roberto , Dahlgren Jonas , Lehtonen Aleksi , Ratcliffe Sophia , Ruiz‐Benito Paloma , Zavala Miguel A. , Kunstler Georges
Published: January 2023

Aim

Linking local population dynamics and species distributions is crucial to predicting the impacts of climate change. Although many studies focus on the mean fitness of populations, theory shows that species distributions can be shaped by demographic stochasticity or population resilience. Here, we examine how mean fitness (measured by invasion rate), demographic stochasticity and resilience (measured by the ability to recover from disturbance) constrain populations at the edges compared with the climatic centre.

Location

Europe: Spain, France, Germany, Finland and Sweden.

Period

Forest inventory data used for fitting the models cover the period from 1985 to 2013.

Major taxa

Dominant European tree species; angiosperms and gymnosperms.

Methods

We developed dynamic population models covering the entire life cycle of 25 European tree species with climatically dependent recruitment models fitted to forest inventory data. We then ran simulations using integral projection and individual‐based models to test how invasion rates, risk of stochastic extinction and ability to recover from stochastic disturbances differ between the centre and edges of the climatic niches of species.

Results

Results varied among species, but in general, demographic constraints were stronger at warm edges and for species in harsher climates. Conversely, recovery was more limiting at cold edges. In addition, we found that for several species, constraints at the edges were attributable to demographic stochasticity and capacity for recovery rather than mean fitness.

Main conclusions

Our results highlight that mean fitness is not the only mechanism at play at the edges; demographic stochasticity and population capacity to recover also matter for European tree species. To understand how climate change will drive species range shifts, future studies will need to analyse the interplay between population mean growth rate and stochastic demographic processes in addition to disturbances.