bluuebunny/crossref_metadata_2025 huggingface dataset:
OSBP-mediated PI(4)P-cholesterol exchange at endoplasmic reticulum-secretory granule contact sites controls insulin secretion
Authors: Panagiotou Styliani , Tan Kia Wee , Nguyen Phuoc My , Müller Andreas , Oqua Affiong Ika , Tomas Alejandra , Wendt Anna , Eliasson Lena , Tengholm Anders , Solimena Michele , Idevall-Hagren Olof
Published: February 2023

Insulin secretion is the process whereby insulin-containing granules fuse with the plasma membrane of pancreatic β-cells. Exocytosis is preceded by cargo loading and granule biogenesis at the Golgi, followed by maturation and transport of the secretory granules; processes that require modification of both the protein and lipid composition of the granules. Here, we show that insulin-containing secretory granules form physical contacts with the endoplasmic reticulum. The lipid exchange protein OSBP dynamically redistributes to ER-SG contacts in a process regulated by Ca2+and cytosolic pH, and contributes to cholesterol loading of the granules. This process depends on granular PI(4)P and ER-localized VAPs, and is positively regulated by granular PI4-kinases and negatively regulated by granule-localized Sac2. Loss of Sac2 results in excess accumulation of cholesterol on insulin granules that is normalized when OSBP expression is reduced, and both acute inhibition and siRNA-mediated knockdown of OSBP suppresses glucose-stimulated insulin secretion without affecting insulin production or intracellular Ca2+ signaling. In conclusion, we show that lipid exchange at ER-granule contact sites is involved in the exocytic process, and propose that these contacts act as reaction centers with multimodal functions during insulin granule maturation.
Incommensurate structures and radiation damage in Rb2V3O8 and K2V3O8 mixed-valence vanadate fresnoites
Authors: Grzechnik Andrzej , Petříček Vaclav , Chernyshov Dmitry , McMonagle Charles , Geise Tobias , Shahed Hend , Friese Karen
Published: February 2023

The structures and phase transitions to incommensurate structures in Rb2V3O8 and K2V3O8 mixed-valence vanadate fresnoites are studied with synchrotron single-crystal diffraction at low temperatures and ambient pressure. Although mixed satellite reflections are absent, the modulated structure of K2V3O8 below 115 K is better described in (3 + 2)- than in (3 + 1)-dimensional space. The geometries of the VO4 and VO5 building units are rigid and it is mainly slight rotations of these polyhedra and small variation of the intermediate K—O distances that are modulated. Prolonged exposure to the high-brilliance synchrotron beam suppresses the incommensurate phase. The previously postulated phase transition to the incommensurate phase in Rb2V3O8 at 270 K was not observed. One of the reasons could be that the intense radiation also affects the modulation in this material. Strategies to collect and analyse single-crystal diffraction data measured with very intense synchrotron radiation using modern low-noise pixel area detectors are discussed.
Synthesis, structure, in vitro pharmacology, and in vivo activity of trans‐3,4‐dichloro‐N‐[[1‐(dimethylamino)‐4‐phenylcyclohexyl]methyl]‐benzamide (AP01; 4‐phenyl‐AH‐7921), a novel mixed μ‐/κ‐opioid
Authors: Krstenansky John L. , Bacsa John , Zambon Alexander
Published: February 2023

Analogs of non‐fentanyl novel synthetic opioids (NSO) with modifications that fall outside of established structure–activity relationships (SARs) for that class of drugs create the question whether or not it should be considered an analog, as defined by 21 U.S.C. §802(32)(A), which is important for its inclusion in the US system of drug scheduling. AH‐7921 is a US Schedule I drug and an example of the 1‐benzamidomethyl‐1‐cyclohexyldialkylamine class of NSO. The SARs regarding substitution of the central cyclohexyl ring have not been well characterized in the literature. Therefore, in order to expand the SAR surrounding AH‐7921 analogs, trans‐3,4‐dichloro‐N‐[[1‐(dimethylamino)‐4‐phenylcyclohexyl]methyl]‐benzamide (AP01; 4‐phenyl‐AH‐7921) has been synthesized, analytically characterized, and tested in vitro and in vivo pharmacologically. Using methods described in the original patents for this class of NSO, it was found that the single trans geometric isomer was obtained. The proton nuclear magnetic resonance, mass spectrum, infrared spectrum, and Raman spectrum are reported along with the melting point of the hydrochloride salt. In vitro binding to a battery of 43 central nervous system receptors showed it to be a high‐affinity μ‐opioid receptor (MOR) and κ‐opioid receptor (KOR) ligand (60 nM and 34 nM, respectively). AP01 also had a 4 nM affinity for the serotonin transporter (SERT), which is a higher level of potency at this receptor than most other opioids. In rats, it exhibited antinociception in the acetic acid writhing test. Therefore, the 4‐phenyl modification results in an active NSO, but carries with it potential toxicities beyond those expected for currently approved opioid drugs.
Myopericytomatosis: A rare entity mimicking other vascular tumours and malformations
Authors: Zhang Lois , Kang Mina , Kossard Steven , Parsi Kurosh
Published: February 2023

Myopericytoma is a rare tumour which typically presents as a benign lesion that mimics features of other more common vascular tumours and malformations. We present a case of a symptomatic diffuse myopericytomatosis of the left abdomen presenting as multiple subcutaneous vascular tumours detected on ultrasound and treated with ultrasound‐guided sclerotherapy.
Spatial mismatch between wild bee diversity hotspots and protected areas
Authors: Casanelles‐Abella Joan , Fontana Simone , Meier Eliane , Moretti Marco , Fournier Betrand
Published: February 2023

Wild bees are critical for multiple ecosystem functions but are currently threatened. Understanding the determinants of the spatial distribution of wild bee diversity is a major research gap for their conservation. We modeled wild bee α and β taxonomic and functional diversity in Switzerland to uncover countrywide diversity patterns and determine the extent to which they provide complementary information, assess the importance of the different drivers structuring wild bee diversity, identify hotspots of wild bee diversity, and determine the overlap between diversity hotspots and the network of protected areas. We used site‐level occurrence and trait data from 547 wild bee species across 3343 plots and calculated community attributes, including taxonomic diversity metrics, community mean trait values, and functional diversity metrics. We modeled their distribution with predictors describing gradients of climate, resource availability (vegetation), and anthropogenic influence (i.e., land‐use types and beekeeping intensity). Wild bee diversity changed along gradients of climate and resource availability; high‐elevation areas had lower functional and taxonomic α diversity, and xeric areas harbored more diverse bee communities. Functional and taxonomic β diversities diverged from this pattern, with high elevations hosting unique species and trait combinations. The proportion of diversity hotspots included in protected areas depended on the biodiversity facet, but most diversity hotspots occurred in unprotected land. Climate and resource availability gradients drove spatial patterns of wild bee diversity, resulting in lower overall diversity at higher elevations, but simultaneously greater taxonomic and functional uniqueness. This spatial mismatch among distinct biodiversity facets and the degree of overlap with protected areas is a challenge to wild bee conservation, especially in the face of global change, and calls for better integrating unprotected land. The application of spatial predictive models represents a valuable tool to aid the future development of protected areas and achieve wild bee conservation goals.
Use of the FreeStyle Libre system and diabetes treatment progression in T2DM: Results from a retrospective cohort study using a Canadian private payer claims database
Authors: Harris Stewart B. , Levrat‐Guillen Fleur
Published: February 2023

Background

Up to one‐third of Canadians are estimated to be living with prediabetes or diabetes. A retrospective study using Canadian private drug claims data was conducted to investigate whether flash glucose monitoring using the FreeStyle Libre system (FSL) among people with type 2 diabetes mellitus (T2DM) in Canada can be associated with changes in treatment intensification when compared with blood glucose monitoring (BGM) alone.

Materials and Methods

Using a Canadian national private drug claims database comprising approximately 50% coverage of insured individuals in Canada, cohorts of people with T2DM using FSL or BGM were identified algorithmically based on treatment history and followed over a 24‐month study period, tracking their progression in diabetes treatment therapy. The Andersen‐Gill model for recurrent time‐to‐event data was used to evaluate whether the rate of treatment progression differs between the FSL and BGM treatment cohorts. The survival function was used to calculate comparative treatment progression probabilities between the cohorts.

Results

In total, 373 871 people with T2DM met the inclusion criteria. Across treatment (FSL) and control (BGM) groups, people using FSL had a higher probability of treatment progression compared with BGM alone, with a relative risk ranging between 1.86 and 2.81 (p < .001). A higher probability of treatment progression was independent of the diabetes treatment at the enrolment date (index date) or the patient status, and independent of whether patients were treatment naïve or on established diabetes therapy. Assessment of the ending treatment relative to the starting therapy indicated that dynamic treatment changes were most evident for patients in the FSL cohort and that the FSL cohort had a much greater portion of patients who ended with insulin treatment (when they started with non‐insulin treatment) compared with the BGM cohort.

Conclusions

People with T2DM using FSL had a greater probability for treatment progression compared with BGM alone, irrespective of the starting therapy, which may suggest that FSL can be used to support escalation of diabetes therapy to improve therapeutic inertia in T2DM.
Rosmarinic acid alleviates ultraviolet‐mediated skin aging via attenuation of mitochondrial and ER stress responses
Authors: Gupta Divya , Sharma Raghu Rai , Rashid Haroon , Bhat Aalim Maqsood , Tanveer Malik Ahmad , Abdullah Sheikh Tasduq
Published: February 2023

Chronic exposure to Ultraviolet B radiation (UV‐B) evokes a myriad of toxic signalling events in the irradiated skin. One of such response is ER stress, which is known to exacerbate photodamage responses. Also, recent literature has highlighted the adverse impact of environmental toxicants on mitochondrial dynamics and mitophagy. Impaired mitochondrial dynamics escalates oxidative damage and causes apoptosis. There have been evidences that support crosstalk between ER stress and mitochondrial dysfunction. However, mechanistic clarification is still needed to verify the interactions between UPR responses and mitochondrial dynamics impairment in UV‐B‐induced photodamage models. Lastly, plant‐based natural agents have garnered attention as therapeutic agents against skin photodamage. Thus, gaining mechanistic insights of plant‐based natural agents is required for their application and feasibility in clinical settings. With this aim in view, this study was performed in primary human dermal fibroblasts (HDFs) and Balb/C mice. Different parameters regarding mitochondrial dynamics, ER stress, intracellular damage and histological damage were analyzed using western blot, rt‐PCR and microscopy. We demonstrated that UV‐B exposure leads to induction of UPR responses, upregulation of Drp‐1 and inhibition of mitophagy. Further, 4‐PBA treatment leads to reversal of these noxious stimuli in irradiated HDF cells, thereby, indicating an upstream role of UPR induction in mitophagy inhibition. Also, we explored the therapeutic effect of Rosmarinic acid (RA) against ER stress and impaired mitophagy in photodamage models. RA prevents intracellular damage via alleviation of ER stress and mitophagic responses in HDFs and irradiated Balb/C mice skin. The current study summarizes the mechanistic insights into UVB‐mediated intracellular damage and role of natural plant‐based agent (RA) in ameliorating these toxic responses.
Effects of litter placement, soil moisture and temperature on soil carbon dioxide emissions in a sandy grassland soil
Authors: Hosseiniaghdam Elnazsadat , Yang Haishun , Mamo Martha , Kaiser Michael , Schacht Walter H. , Eskridge Kent M. , Abagandura Gandura O.
Published: February 2023

Semiarid grasslands contribute significantly to global soil carbon (C) storage. Carbon loss from these systems via microbial decomposition is controlled by abiotic and biotic factors such as soil moisture and temperature and C input. Plant litter in these systems can be present above the soil surface or mixed with surface soil by trampling, especially in intensively grazed areas. A quantitative understanding of abiotic factors' interactive effect is critical for predicting soil C dynamics in response to grassland management and environmental conditions changes. Therefore, we conducted a 3‐month laboratory incubation experiment to quantify the impact of litter placement and soil moisture on soil carbon dioxide (CO2) emissions under three controlled temperatures. The treatments including three litter placements (no litter, litter on top and litter mixed with surface soil) and three soil moisture levels (23%, 37% and 50% water‐filled pore space [WFPS]) were incubated at three temperatures (10°C, 20°C and 30°C). Carbon dioxide fluxes were measured every 2 weeks. Soil CO2 fluxes were higher for all moisture and litter treatments initially and declined overtime at 20°C and 30°C. Mixing litter with soil increased the cumulative CO2 emissions by 24% and 19.5% at 20°C and 30°C, respectively, compared to no litter. Also, soil‐litter mixing compared with litter on top showed a 14.3% and 21.6% increase in cumulative CO2 emissions at temperatures of 20°C and 30°C, respectively. At all temperatures, 37% and 50% WFPS resulted in similar cumulative CO2 emissions. The results from this study indicate that rising temperatures from 10°C to 30°C accelerate the effect of soil litter mixing on increasing CO2 emissions compared to litter on top and no litter.
Effects of sodium heparin on δ13C, δ15N and δ34S values in avian whole blood
Authors: Lato Kimberly A. , Thorne Lesley H.
Published: February 2023

Anticoagulants are often added to avian blood samples immediately after collection to allow plasma to be extracted at a later time, but the effects of anticoagulants on stable isotope studies are not well understood. We use a Bayesian approach to assess the effects of sodium heparin, one of the most commonly used anticoagulants, on δ13C, δ15N and δ34S values in avian whole blood using Herring Gulls Larus argentatus and Great Black‐backed Gulls Larus marinus as study species. We found that the addition of sodium heparin only had a significant effect on δ34S values (−0.4‰) and that this effect did not meaningfully impact the estimated diet proportions of broad‐scale stable isotope mixing models, and only slightly affected the output of finer‐scale stable isotope mixing models. Our results highlight that researchers should be aware of the possible impacts of sodium heparin on measured stable isotope values in avian blood, particularly for δ34S, and that this effect should be carefully considered relative to the scale and particulars of the study (e.g. generalist versus specialist species and broad‐scale versus fine‐scale analyses).
High survival promotes persistence in a reintroduced population of Common Crane (Grus grus)
Authors: Donaldson Lynda , Bridge Damon J. , Hilton Geoff M.
Published: February 2023

Reintroductions are increasingly used for re‐establishing populations, though the documented success rates are variable. Success is typically measured by the survival and breeding success of released individuals and subsequent establishment and growth of the population. However, few studies quantify demographic rates of reintroduced populations of long‐lived species, with slower dynamics and lower reproductive rates, and the demographic rates of subsequent generations, which determine population growth and persistence, are often unknown. We document the success of the reintroduction of the Common Crane Grus grus to south‐west England in the UK, using survival analysis and population modelling to determine whether the overarching aim of establishing a self‐sustaining population is likely to be achieved. Between 2010 and 2014, 93 Common Cranes were hatched from wild eggs, custom‐reared and soft‐released into suitable habitat. Survival of all age‐classes was apparently higher than survival of healthy wild individuals, particularly in juvenile age‐classes, and was higher in females than in males. Productivity was relatively low, but increased with age. Assuming that the demographic rates of subsequent generations are at the levels estimated for the captive‐reared population, slow positive population growth is predicted over the next 30 years. Sensitivity analyses showed that the persistence of this population is sensitive to even a slight decrease in values of adult survival, and growth is impacted to a lesser extent by juvenile survival and levels of productivity. This study highlights the ability to achieve persistence in a reintroduced population despite low levels of productivity when survival is exceptionally high. It also illustrates the need for long‐term monitoring to establish reintroduction success in animals that have slow life histories: 9 years after initial releases, the Common Crane population remains dominated by first‐generation birds and productivity is skewed by transient age‐structure and the late onset of reproductive success.
Ion migration study in acid‐leached soda–lime–silica glass by thermally stimulated depolarization current analysis
Authors: Nieves Cesar A. , Ogrinc Andrew L. , Kim Seong H. , Furman Eugene , Lanagan Michael T.
Published: February 2023

Ionic conductivity in silicate glasses is a major issue in the energy sector due to its detrimental effect on electric energy generation and storage and has received increasing attention over the past years. In this study, surface modification of soda–lime–silica (SLS) float glass via acid‐leaching treatment (pH 1) was implemented to understand the impact on ionic transport. The acid‐leaching treatment created a sodium‐depleted “silica‐like” structure in the near‐surface region with depths of 110 ± 20 nm for the air‐side and 93 ± 2 nm for the tin‐side of the SLS glass. Using the thermally stimulated depolarization current technique, two thermally activated relaxation peaks were found to be associated with different ion migration mechanisms. The first peak (P1) with activation energy of ∼0.85 eV was attributed to dc conduction of Na+ ions through the glass bulk. A second overlapping peak (P2) at a higher temperature was found to be related to a more limited Na+ ion migration through the acid‐leached structure, due to H+ conduction, or a coupled contribution of both mechanisms.
How does government policy influence the employment and training of nurse practitioners and physician assistants? A realist analysis using qualitative interviews
Authors: Dankers‐de Mari Ellen J. C. M. , Thijssen Marjolein C. E. , Van Hees Suzanne G. M. , Albertus Job , Batenburg Ronald , Jeurissen Patrick P. T. , Van Vught Anneke J. A. H.
Published: February 2023

Aims

The aim of this study was to develop insights into how and why Dutch government policies on deployment and training of nurse practitioners and physician assistants have effect and under what circumstances.

Design

A realist analysis using qualitative interviews.

Methods

Data analysis of 50 semi‐structured interviews conducted in 2019 with healthcare providers, sectoral and professional associations, and training coordinators. Stratified purposive and snowball sampling were used.

Results

Policies stimulated employment and training of nurse practitioners and physician assistants by: (1) contributing to the familiarity of participants in the decision‐making process in healthcare providers with and medical doctors' trust in these professions; (2) contributing to participants' motivation in employment and training; and (3) eliminating barriers perceived by medical doctors, managers and directors. The extent to which policies affected employment and training was largely determined by sectoral and organizational circumstances, such as healthcare demand and complexity, and decision‐makers in healthcare providers (medical doctors or managers/directors).

Conclusion

Effectuating familiarity and trust among participants in the decision‐making process is a crucial first step. Next, policymakers can motivate participants and lower their perceived barriers by extending the scope of practice, creating reimbursement opportunities and contributing to training costs. Theoretical insights into nurse practitioner and physician assistant employment and training have been refined.

Impact

The findings highlight how governments, health insurers, sectoral and professional associations, departments, councils, healthcare providers and professionals can facilitate and support nurse practitioner and physician assistant employment and training by contributing to familiarity, trust and motivation, and by clearing perceived barriers.
Habitat and not topographic heterogeneity constrains the range sizes of African mammals
Authors: Lauer Daniel A. , Shipley Benjamin R. , McGuire Jenny L.
Published: February 2023

Aim

The extinction risks of species are influenced by their geographical range sizes, as species with smaller ranges are more likely to go extinct following disturbance events. Theoretically, heterogeneous landscapes can maintain small‐ranged species, because they facilitate the coexistence of taxa that are each constrained to distinct abiotic conditions. However, we do not fully understand whether this process is more attributable to variation in habitat types (habitat heterogeneity) or physical elevations (topographic heterogeneity) across landscapes. Here, we compare the influences of habitat versus topographic heterogeneity on mammalian range sizes in Africa.

Location

Africa.

Taxon

Mammalia.

Methods

We built a phylogenetic generalized least squares model to predict the range sizes of 1033 mammalian species from their functional traits and abiotic conditions. We assessed how the performance of the model changed when we incorporated measures of the local habitat and, separately, topographic heterogeneity that species experience.

Results

Habitat and topographic heterogeneity are weakly correlated across Africa (ρ = 0.14). Habitat heterogeneity is inversely related to range size (model coefficient = −0.88). Incorporating habitat heterogeneity significantly decreased the model's AICc, increased its likelihood and increased the proportion of variance that is explained in the range sizes of species. Conversely, topographic heterogeneity is not significantly related to range size and had no impact on the model's AICc, likelihood or predictive performance. This contrast between habitat and topographic heterogeneity is particularly prevalent in carnivorous mammalian clades. Results at multiple spatial resolutions differed minimally.

Main Conclusions

Our findings advance ecological theory by demonstrating that a landscape's variation in habitats, and not in elevations, relates inversely with mammalian range size and therefore facilitates the coexistence of small‐ranged mammals. Conservation efforts in regions of high habitat heterogeneity will be critical to prevent extinctions in Africa's biodiverse mammalian species.
DNA methylation and miR‐92a‐3p‐mediated repression of HIP1R promotes pancreatic cancer progression by activating the PI3K/AKT pathway
Authors: Zhu Sixian , Xu Huiting , Chen Runzhi , Shen Qian , Yang Dongmei , Peng Hui , Tong Jin , Fu Qiang
Published: February 2023

Pancreatic cancer (PAAD) is a highly malignant tumour characterized of high mortality and poor prognosis. Huntingtin‐interacting protein 1‐related (HIP1R) has been recognized as a tumour suppressor in gastric cancer, while its biological function in PAAD remains to be elucidated. In this study, we reported the downregulation of HIP1R in PAAD tissues and cell lines, and the overexpression of HIP1R suppressed the proliferation, migration and invasion of PAAD cells, while silencing HIP1R showed the opposite effects. DNA methylation analysis revealed that the promoter region of HIP1R was heavily methylated in PAAD cell lines when compared to the normal pancreatic duct epithelial cells. A DNA methylation inhibitor 5‐AZA increased the expression of HIP1R in PAAD cells. 5‐AZA treatment also inhibited the proliferation, migration and invasion, and induced apoptosis in PAAD cell lines, which could be attenuated by HIP1R silencing. We further demonstrated that HIP1R was negatively regulated by miR‐92a‐3p, which modulates the malignant phenotype of PAAD cells in vitro and the tumorigenesis in vivo. The miR‐92a‐3p/HIP1R axis could regulate PI3K/AKT pathway in PAAD cells. Taken together, our data suggest that targeting DNA methylation and miR‐92a‐3p‐mediated repression of HIP1R could serve as novel therapeutic strategies for PAAD treatment.
Proportion of subsequent clinic visits among persons without regular clinic visits who were screened as having hyperglycemia: A retrospective cohort study
Authors: Matsumura Hiroshi , Sugiyama Takahiro , Sakata Nobuo , Ihana‐Sugiyama Noriko , Imai Kenjiro , Ohsugi Mitsuru , Ueki Kohjiro , Tamiya Nanako , Iso Hiroyasu
Published: February 2023

Aims/Introduction

We aimed to examine the proportion of subsequent clinic visits for persons screened as having hyperglycemia based on glycated hemoglobin (HbA1c) levels at screening and the presence/absence of hyperglycemia at health checkups before 1 year of the screening among those without previous diabetes‐related medical care and attending regular clinic visits.

Materials and methods

This retrospective cohort study used the 2016–2020 data of Japanese health checkups and claims. The study analyzed 8,834 adult beneficiaries aged 20–59 years without regular clinic visits who had never received diabetes‐related medical care and whose recent health checkups showed hyperglycemia. The rates of 6‐month subsequent clinic visits after health checkups were evaluated according to HbA1c levels and the presence/absence of hyperglycemia at checkups a year before.

Results

The overall clinic visit rate was 21.0%. The HbA1c‐specific rates were 17.0, 26.7, 25.4 and 28.4% for <7.0, 7.0–7.4, 7.5–7.9 and ≥8.0% (64 mmol/mol), respectively. Persons with hyperglycemia at a previous screening had lower clinic visit rates than those without hyperglycemia, particularly in the HbA1c category of <7.0% (14.4% vs 18.5%; P < 0.001) and 7.0–7.4% (23.6% vs 35.1%; P < 0.001).

Conclusions

The overall rate of subsequent clinic visits among those without previous regular clinic visits was <30%, including for participants with HbA1c ≥8.0%. Persons with previously detected hyperglycemia had lower clinic visit rates, despite requiring more health counseling. Our findings might be useful for designing a tailored approach to encourage high‐risk individuals to seek diabetes care through clinic visits.
Crafting Personal territory in a political world: A human agency approach to organizational politics
Authors: Liang Jian , Chen Hui , Du Danyang , He Xiao (CiCi)
Published: February 2023

To examine human agency in organizational politics, this study investigates how employees take action to craft their working environments in response to their perception of organizational politics (POP). In Study 1, we manipulated POP using video materials in an experiment. Results from 209 participants show that POP triggered the intention to engage in both relational crafting and task crafting behaviours. In Study 2, we collected survey data from 176 supervisor–subordinate dyads. Our results replicate the findings of Study 1. Furthermore, we found significant indirect relationships between POP and two outcome variables (i.e., task performance and opportunistic behaviour) through relational crafting. The two indirect relationships were stronger for employees with lower emotional intelligence. Meanwhile, significant indirect relationships existed between POP and two outcome variables (i.e., opportunistic behaviour and turnover intention) through task crafting and these indirect relationships were stronger for employees with higher emotional intelligence. Both theoretical and managerial implications are discussed.
Duration of bite force reduction following a single injection of botulinum toxin in the masseter muscle bilaterally: A one‐year non‐randomized trial
Authors: Ågren Martin , Nanchaipruek Yanisorn , Phumariyapong Phumithep , Apinuntham Chalermkwan , Rakchart Sarawalai , Pettersson Mattias , Wanitphakdeedecha Rungsima
Published: February 2023

Background

Previous studies concerning the effect of botulinum toxin in masseter muscle have mainly reported effects observed through inspection of facial features or differences in pain levels. One systematic review of studies utilizing objective measurements reported that long‐term muscular effect of botulinum neurotoxin injections into masseter muscle was inconclusive.

Objective

To evaluate the duration of reduced maximal voluntary bite force (MVBF) after botulinum toxin intervention.

Methods

The intervention group was comprised of individuals seeking aesthetic treatment for masseter reduction (n = 20), the reference group (n = 12) comprised of individuals with no intervention. Intervention through 25 units of Xeomin® (Merz Pharma GmbH & Co KGaA, Frankfurt am Main, Germany) botulinum neurotoxin type A injected into the masseter muscles bilaterally (totalling 50 units). A reference group did not receive any intervention. MVBF was measured in Newtons using a strain gauge meter at the incisors and first molars. MVBF was measured at baseline, at 4 weeks, 3 months, 6 months, and after 1 year.

Results

Both groups were similar in terms of bite force, sex and age at baseline. MVBF remained similar compared to baseline in the reference group. At 3 months, a significant reduction at all measurement points was observed in the intervention group; at 6 months, this reduction was no longer significant.

Conclusion

A single intervention of 50 units of botulinum neurotoxin results in a reversible MVBF reduction of at least 3 months, although a visually discernable reduction may be more long‐lasting.
To err is divine?
Authors: Swails Jennifer L. , Bernstam Elmer V.
Published: February 2023

Swails and Bernstam highlight the advantages and disadvantages of being given space to fail, highlighting the importance of preparation for failure and psychological safety.
Laser ablation tomography (LATscan) as a new tool for anatomical studies of woody plants
Authors: Cunha Neto Israel L. , Hall Benjamin T. , Lanba Asheesh R. , Blosenski Joshua D. , Onyenedum Joyce G.
Published: February 2023

Traditionally, botanists study plant anatomy by carefully sectioning samples, histological staining to highlight tissues of interests, then imaging slides under light microscopy. This approach generates significant details; however, this workflow is laborious, particularly in woody vines (lianas) with heterogeneous anatomies, and ultimately yields two‐dimensional (2D) images. Laser ablation tomography (LATscan) is a high‐throughput imaging system that yields hundreds of images per minute. This method has proven useful for studying the structure of delicate plant tissues; however, its utility in understanding the structure of woody tissues is underexplored.

We report LATscan‐derived anatomical data from several stems of lianas (c. 20 mm) of seven species and compare these results with those obtained through traditional anatomical techniques.

LATscan successfully allows the description of tissue composition by differentiating cell type, size, and shape, but also permits the recognition of distinct cell wall composition (e.g. lignin, suberin, cellulose) based on differential fluorescent signals on unstained samples.

LATscan generate high‐quality 2D images and 3D reconstructions of woody plant samples; therefore, this new technology is useful for both qualitative and quantitative analyses. This high‐throughput imaging technology has the potential to bolster phenotyping of vegetative and reproductive anatomy, wood anatomy, and other biological systems.
Metabolism of periodontal pathobionts: Their regulatory roles in the dysbiotic microbiota
Authors: Ding Jing , Zhao Chuanjiang , Gao Li
Published: February 2023

The onset and development of periodontitis centers around microbiota dysbiosis and disrupted host responses. Dynamic metabolic activities of the subgingival microbiota modify the polymicrobial community, shape the microenvironment, and modulate the host response. A complicated metabolic network exists in interspecies interactions between periodontal pathobionts and commensals, which can lead to the development of dysbiotic plaque. Dysbiotic subgingival microbiota undergo metabolic interactions with the host and disrupt host–microbe equilibrium. In this review, we discuss the metabolic profiles of the subgingival microbiota, the metabolic crosstalk in polymicrobial communities, including pathobionts and commensals, and the metabolic interactions between microbes and the host.
EvaluatingEEGcomplexity metrics as biomarkers for depression
Authors: Lord Brian , Allen John J. B.
Published: February 2023

Nonlinear EEG analysis offers the potential for both increased diagnostic accuracy and deeper mechanistic understanding of psychopathology. EEG complexity measures have previously been shown to positively correlate with clinical depression. In this study, resting state EEG recordings were taken across multiple sessions and days with both eyes open and eyes closed conditions from a total of 306 subjects, 62 of which were in a current depressive episode, and 81 of which had a history of diagnosed depression but were not currently depressed. Three different EEG montages (mastoids, average, and Laplacian) were also computed. Higuchi fractal dimension (HFD) and sample entropy (SampEn) were calculated for each unique condition. The complexity metrics showed high internal consistency within session and high stability across days. Higher complexity was found in open‐eye recordings compared to closed eyes. The predicted correlation between complexity and depression was not found. However, an unexpected sex effect was observed, in which males and females exhibited different topographic patterns of complexity.
Is FeNOtyping in COPD the path to precision medicine?
Authors: Flynn Cara , Brightling Chris
Published: February 2023

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Who contributes to disaster preparedness? Predicting decision making in social dilemmas pertaining to community resilience
Authors: Johnson Paul M. , Baroud Hiba , Brady Corey E. , Abkowitz Mark
Published: February 2023

Planning for community resilience through public infrastructure projects often engenders problems associated with social dilemmas, but little work has been done to understand how individuals respond when presented with opportunities to invest in such developments. Using statistical learning techniques trained on the results of a web‐based common pool resource game, we analyze participants' decisions to invest in hypothetical public infrastructure projects that bolster their community's resilience to disasters. Given participants' dispositions and in‐game circumstances, Bayesian additive regression tree (BART) models are able to accurately predict deviations from players' decisions that would reasonably lead to Pareto‐efficient outcomes for their communities. Participants tend to overcontribute relative to these Pareto‐efficient strategies, indicating general risk aversion that is analogous to individuals purchasing disaster insurance even though it exceeds expected actuarial costs. However, higher trait Openness scores reflect an individual's tendency to follow a risk‐neutral strategy, and fewer available resources predict lower perceived utilities derived from the infrastructure developments. In addition, several input variables have nonlinear effects on decisions, suggesting that it may be warranted to use more sophisticated statistical learning methods to reexamine results from previous studies that assume linear relationships between individuals' dispositions and responses in applications of game theory or decision theory.
Running speed changes the distribution of excitation within the biceps femoris muscle in 80 m sprints
Authors: Cerone Giacinto L. , Nicola Riccardo , Caruso Marco , Rossanigo Rachele , Cereatti Andrea , Vieira Taian Martins
Published: February 2023

Predictors and mitigators of strain injuries have been studied in sprint‐related sports. While the rate of axial strain, and thus running speed, may determine the site of muscle failure, muscle excitation seemingly offers protection against failure. It seems therefore plausible to ask whether running at different speeds changes the distribution of excitation within muscles. Technical limitations undermine, however, the possibility of addressing this issue in high‐speed, ecological conditions. Here, we circumvent these limitations with a miniaturized, wireless, multi‐channel amplifier, suited for collecting spatio‐temporal data and high‐density surface electromyograms (EMGs) during overground running. We segmented running cycles while 8 experienced sprinters ran at speeds close to (70% and 85%) and at (100%) their maximum, over an 80 m running track. Then, we assessed the effect of running speed on the distribution of excitation within biceps femoris (BF) and gastrocnemius medialis (GM). Statistical parametric mapping (SPM) revealed a significant effect of running speed on the amplitude of EMGs for both muscles, during late swing and early stance. Paired SPM revealed greater EMG amplitude when comparing 100% with 70% running speed for BF and GM. Regional differences in excitation were observed only for BF, however. As running speed increased from 70% to 100% of the maximum, a greater degree of excitation was observed at more proximal BF regions (from 2% to 10% of the thigh length) during late swing. We discuss how these results, in the context of the literature, support the protective role of pre‐excitation against muscle failure, suggesting the site of BF muscle failure may depend on running speed.
Beyond path dependency: Analysing Indonesia's social policy responses to two crises
Authors: Yuda Tauchid Komara
Published: February 2023

This article sets out a coherent framework for debates and discussions on social policy changes during crisis periods. Using Indonesia as a case, this article compares its social policy responses to the 1997–1998 economic crisis and the current COVID‐19 pandemic crisis. Both two crises and their responses, once analysed, lead to an argument that path dependence does not always dominate policy processes, as most literature claims, but rather it operates alongside other path‐creation‐related processes, such as path‐clearing policy accelerators and path‐creation policy accelerators. This article also presents that ‘old player’ penetration in policy processes does not necessarily preclude alternatives and, in some examined cases, it, instead, strengthens impulses toward substantial reforms. Therefore, revised policies must be viewed as political vehicles for seeking popular support and power reconsolidation as democracy allows. Furthermore, this current analysis contributes to enhancing our understanding of crises, often seen as issues in public policy literature, yet less explored in terms of their importance as unique critical junctures and their implications for social policy changes in multiple paths.
Disruption of day‐to‐night changes in circadian gene expression with chronic tendinopathy
Authors: Yeung Ching‐Yan Chloé , Svensson René B. , Yurchenko Kateryna , Malmgaard‐Clausen Nikolaj M. , Tryggedsson Ida , Lendal Marius , Jokipii‐Utzon Anja , Olesen Jens L. , Lu Yinhui , Kadler Karl E. , Schjerling Peter , Kjær Michael
Published: February 2023

Overuse injury in tendon tissue (tendinopathy) is a frequent and costly musculoskeletal disorder and represents a major clinical problem with unsolved pathogenesis. Studies in mice have demonstrated that circadian clock‐controlled genes are vital for protein homeostasis and important in the development of tendinopathy. We performed RNA sequencing, collagen content and ultrastructural analyses on human tendon biopsies obtained 12 h apart in healthy individuals to establish whether human tendon is a peripheral clock tissue and we performed RNA sequencing on patients with chronic tendinopathy to examine the expression of circadian clock genes in tendinopathic tissues. We found time‐dependent expression of 280 RNAs including 11 conserved circadian clock genes in healthy tendons and markedly fewer (23) differential RNAs with chronic tendinopathy. Further, the expression of COL1A1 and COL1A2 was reduced at night but was not circadian rhythmic in synchronised human tenocyte cultures. In conclusion, day‐to‐night changes in gene expression in healthy human patellar tendons indicate a conserved circadian clock as well as the existence of a night reduction in collagen I expression.

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Key points

Tendinopathy is a major clinical problem with unsolved pathogenesis.

Previous work in mice has shown that a robust circadian rhythm is required for collagen homeostasis in tendons.

The use of circadian medicine in the diagnosis and treatment of tendinopathy has been stifled by the lack of studies on human tissue.

Here, we establish that the expression of circadian clock genes in human tendons is time dependent, and now we have data to corroborate that circadian output is reduced in diseased tendon tissues.

We consider our findings to be of significance in advancing the use of the tendon circadian clock as a therapeutic target or preclinical biomarker for tendinopathy.
Acute Mechanical and Metabolic Responses to Different Resistance Training Protocols With Equated Volume Load
Authors: Sánchez-Moreno Miguel , Rodiles-Guerrero Luis , Rendeiro-Pinho Gonçalo , Prieto-Veloso António , Pareja-Blanco Fernando
Published: February 2023

Purpose: To investigate the effect of different resistance training protocols with equated volume load on acute mechanical and metabolic responses. Methods: In a randomized order, 18 men performed 8 different training protocols in the bench press exercise consisting of (sets, repetitions, intensity, and interset recoveries) 3 × 16, 40% 1-repetition maximum (1RM), 2 and 5 minutes; 6 × 8, 40% 1RM, 2 and 5 minutes; 3 × 8, 80% 1RM, 2 and 5 minutes; and 6 × 4, 80% 1RM, 2 and 5 minutes. Volume load was equalized between protocols (1920 arbitrary units). Velocity loss and effort index were calculated during the session. Movement velocity against the 60% 1RM and blood lactate concentration pre–post exercise were used to assess the mechanical and metabolic responses, respectively. Results: Resistance training protocols performed with heavy load (80% 1RM) resulted in a lower (P < .05) total number of repetitions (effect size = −2.44) and volume load (effect size = −1.79) than the scheduled ones when longer set configurations and shorter rest periods were used in the same protocol (ie, higher-training-density protocols). Protocols including a higher number of repetitions per set and shorter rest times induced higher velocity loss, effort index, and lactate concentrations than the rest of the protocols. Conclusions: Our results suggest that resistance training protocols with similar volume load but different training variables (ie, intensity, number of sets and repetitions, rest between sets) produce different responses. Implementing a lower number of repetitions per set and longer rest intervals is recommended to reduce the intrasession and postsession fatigue.
Kilohertz Frequency Alternating Current Induces Less Evoked Torque and Less Neuromuscular Efficiency Than Pulsed Current in Healthy People: A Randomized Crossover Trial
Authors: Paz Isabel de Almeida , Sonda Francesca Chaida , Fröhlich Matias , Durigan João Luiz Quagliotti , Vaz Marco Aurélio
Published: February 2023

Context: Pulsed current and kilohertz frequency alternating current are 2 types of neuromuscular electrical stimulation (NMES) currents often used by clinicians during rehabilitation. However, the low methodological quality and the different NMES parameters and protocols used in several studies might explain their inconclusive results in terms of their effects in the evoked torque and the discomfort level. In addition, the neuromuscular efficiency (ie, the NMES current type that evokes the highest torque with the lowest current intensity) has not been established yet. Therefore, our objective was to compare the evoked torque, current intensity, neuromuscular efficiency (evoked torque/current intensity ratio), and discomfort between pulsed current and kilohertz frequency alternating current in healthy people. Design: A double-blind, randomized crossover trial. Methods: Thirty healthy men (23.2 [4.5] y) participated in the study. Each participant was randomized to 4 current settings: 2 kilohertz frequency alternating currents with 2.5 kHz of carrier frequency and similar pulse duration (0.4 ms) and burst frequency (100 Hz) but with different burst duty cycles (20% and 50%) and burst durations (2 and 5 ms); and 2 pulsed currents with similar pulse frequency (100 Hz) and different pulse duration (2 and 0.4 ms). The evoked torque, current intensity at the maximal tolerated intensity, neuromuscular efficiency, and discomfort level were evaluated. Results: Both pulsed currents generated higher evoked torque than the kilohertz frequency alternating currents, despite the similar between-currents discomfort levels. The 2 ms pulsed current showed lower current intensity and higher neuromuscular efficiency compared with both alternated currents and with the 0.4 ms pulsed current. Conclusions: The higher evoked torque, higher neuromuscular efficiency, and similar discomfort of the 2 ms pulsed current compared with 2.5-kHz frequency alternating current suggests this current as the best choice for clinicians to use in NMES-based protocols.
Structure-informed microbial population genetics elucidate selective pressures that shape protein evolution
Authors: Kiefl Evan , Esen Ozcan C. , Miller Samuel E. , Kroll Kourtney L. , Willis Amy D. , Rappé Michael S. , Pan Tao , Eren A. Murat
Published: February 2023

Comprehensive sampling of natural genetic diversity with metagenomics enables highly resolved insights into the interplay between ecology and evolution. However, resolving adaptive, neutral, or purifying processes of evolution from intrapopulation genomic variation remains a challenge, partly due to the sole reliance on gene sequences to interpret variants. Here, we describe an approach to analyze genetic variation in the context of predicted protein structures and apply it to a marine microbial population within the SAR11 subclade 1a.3.V, which dominates low-latitude surface oceans. Our analyses reveal a tight association between genetic variation and protein structure. In a central gene in nitrogen metabolism, we observe decreased occurrence of nonsynonymous variants from ligand-binding sites as a function of nitrate concentrations, revealing genetic targets of distinct evolutionary pressures maintained by nutrient availability. Our work yields insights into the governing principles of evolution and enables structure-aware investigations of microbial population genetics.