bluuebunny/crossref_metadata_2025 huggingface dataset:
Time‐in‐range derived from self‐measured blood glucose in people with type 2 diabetes advancing to iGlarLixi: A participant‐level pooled analysis of three phase 3 LixiLan randomized controlled trials
Authors: Haluzík Martin , Al‐Sofiani Mohammed E. , Cheng Alice Y. Y. , Lauand Felipe , Melas‐Melt Lydie , Rosenstock Julio
Published: September 2024

Aim

To evaluate the efficacy of a fixed‐ratio combination of insulin glargine 100 U/mL plus lixisenatide (iGlarLixi) in people with type 2 diabetes (T2D) using derived time‐in‐range (dTIR).

Methods

Participant‐level data from LixiLan‐L, LixiLan‐O and LixiLan‐G were pooled and dTIR (70‐180 mg/dL), derived time‐above‐range (> 180 mg/dL) and derived time‐below‐range (dTBR; < 70 mg/dL) were calculated from participant seven‐point self‐monitored blood glucose profiles.

Results

This pooled analysis included data from 2420 participants receiving iGlarLixi (n = 1093), iGlar (n = 836), Lixi (n = 234) or a glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA) (n = 257). Numerically greater improvements in least square (LS) means dTIR were seen from baseline to end of treatment (EOT) with iGlarLixi (25.7%) versus iGlar (15.8%), Lixi (11.7%) or GLP‐1 RA (16.2%). At EOT, the mean (standard deviation) dTBR was 0.71% ± 3.4%, 0.61% ± 3.2%, 0.08% ± 1.0% and 0.0% ± 0.0% for iGlarLixi, iGlar, Lixi and GLP‐1 RA, respectively. In a subgroup analysis, participants aged younger than 65 years (n = 1690) and 65 years or older (n = 713) showed numerically greater improvements in LS means dTIR from baseline to EOT with iGlarLixi versus iGlar, Lixi or GLP‐1 RA.

Conclusions

iGlarLixi achieved improvements in dTIR, with low dTBR values, providing further evidence to inform clinical outcomes with the use of iGlarLixi.
Semaglutide use in people with obesity and type 2 diabetes from real‐world utilization data: An analysis of the All of US Program
Authors: Mayer Craig S. , Fontelo Paul
Published: September 2024

Aim

To analyse data from the All of Us Research Program to evaluate the real‐world application and long‐term effectiveness of semaglutide in treating type 2 diabetes and obesity patients in a large population.

Materials and Methods

We identified patients prescribed semaglutide and analysed differences in route of administration and the time on semaglutide. For individuals diagnosed with obesity, we measured changes in body mass index (BMI) and weight from baseline, while measured changes in HbA1c for those patients with type 2 diabetes. We also examined the occurrence of newly diagnosed common adverse events from taking semaglutide.

Results

For 3739 semaglutide patients, those on injectable semaglutide (3364 patients) averaged 301.54 days on the medication, with 20.36% having no end date, while those on oral semaglutide (435 patients) averaged 172.48 days, with 24.60% having no end date. We found average decreases of 1.54 kg/m2 in BMI, 4.65 kg in weight and 0.75% in HbA1c for semaglutide users. The decreases were larger in participants taking injectable formulation, probably because of higher starting values. Over time, improvements in these outcomes diminished, but the values remained significantly lower than baseline levels. Approximately only 1.0% of patients reported newly diagnosed common adverse events.

Conclusions

Consistent with clinical trial findings, this real‐world data analysis showed that semaglutide was well tolerated and that, for a large population, it effectively reduced BMI, body weight and HbA1c, albeit to smaller magnitudes than observed in clinical trials. These findings provide valuable insights into real‐world experience and the long‐term effectiveness of semaglutide.
Glyburide use is associated with a greater likelihood of mortality or rehospitalization after acute coronary syndrome compared to gliclazide use in adults with type 2 diabetes: A cohort study
Authors: Long Wentong , Light Peter E. , Simpson Scot H.
Published: September 2024

Aim

To examine the likelihood of mortality or rehospitalization following acute coronary syndrome with glyburide versus gliclazide use in adults with type 2 diabetes undergoing cardiac catheterization.

Research Design and Methods

This retrospective cohort study used clinical data linked with administrative health data from Alberta, Canada between April 2008 and March 2021. Three methods were used to define exposure to glyburide and gliclazide in the year before catheterization. Multivariable logistic regression was used to compare the likelihood of a composite outcome of 1‐year mortality or rehospitalization with use of glyburide versus use of gliclazide.

Results

A total of 11 140 individuals with type 2 diabetes had a cardiac catheterization for acute coronary syndrome. Their mean age was 66 years and 31% were female. In the year before catheterization, 5% used glyburide and 19% used gliclazide. Any glyburide or gliclazide exposure in the year before catheterization was associated with a similar likelihood of all‐cause mortality or rehospitalization (adjusted odds ratio [aOR] 1.14, 95% confidence interval [CI] 0.93–1.41; p = 0.20). However, current glyburide exposure (aOR 1.37, 95% CI 1.06–1.79; p = 0.018) and long exposure to glyburide (aOR 1.37, 95% CI 1.03–1.83; p = 0.030) were associated with a higher likelihood of the composite outcome compared to current and long exposure to gliclazide, respectively.

Conclusions

Current and long exposure to glyburide was associated with a greater likelihood of mortality or rehospitalization following cardiac catheterization for acute coronary syndrome, when compared to similar gliclazide exposure definitions. This study adds further evidence of the need to avoid using glyburide if a sulphonylurea is required for type 2 diabetes management.
Spatial and Ontogenetic Patterns in the Trophic Ecology of Two Predatory Fishes in a Large River
Authors: Valentine Shaley A. , Whitledge Gregory W.
Published: September 2024

Fishes use a variety of physical and biological resources that shift ontogenetically, seasonally and spatially. Quantifying what resources such as prey are required for persistence can improve understanding of ecological needs of fishes and riverine macrosystem functioning. Bowfin (Amia ocellicauda) and largemouth bass (Micropterus nigricans) cohabitate in their native range and potentially compete with one another. Yet, there have been no direct comparisons of their diets across spatial gradients to assess whether they partition resources or shift in prey use. We used multiple univariate and multivariate analyses to compare diet composition, diet overlap, feeding strategy, prey importance and diet partitioning between largemouth bass and bowfin across three reaches of the Upper Mississippi River. Largemouth bass ontogenetically shifted their diet from aquatic invertebrates to fishes and a more diverse assemblage of aquatic invertebrates. Bowfin and adult largemouth bass were top predators which consumed mostly crayfish and fish and overlapped in their diets. Despite overlapping diets, predators partitioned resources by consuming different lengths and abundances of prey, and largemouth bass had greater trophic plasticity. Within a predator group, few differences in diets existed spatially, underscoring the relative homogeneity in resource use potentially from similarities in the river's physical structure. Combined, prey use likely differed sufficiently to reduce potential competition between largemouth bass and bowfin, allowing long‐term coexistence in this system. Our results also highlighted the importance of crayfishes to riverine food webs and underscored the use of multiple prey and habitat types that sustain these predators.
Starting the pill during adolescence: Age of onset and duration of use influence morphology of the hippocampus and ventromedial prefrontal cortex
Authors: Brouillard Alexandra , Davignon Lisa‐Marie , Vachon‐Presseau Étienne , Roy Mathieu , Marin Marie‐France
Published: September 2024

From adolescence, women become more likely to experience fear dysregulation. Oral contraceptives (OCs) can modulate the brain regions involved in fear processes. OCs are generally used for years and often initiated during adolescence, a sensitive period where certain brain regions involved in the fear circuitry are still undergoing important reorganization. It remains unknown whether OC use during adolescence may induce long‐lasting changes in the fear circuitry. This study aimed to examine whether age of onset moderated the relationship between duration of use and fear‐related brain structures. We collected structural MRI data in 98 healthy adult women (61 current users, 37 past users) and extracted grey matter volumes (GMV) and cortical thickness (CT) of key regions of the fear circuitry. Non‐linear multiple regressions revealed interaction effects between age of onset and quadratic duration of use on GMV of the right hippocampus and right ventromedial prefrontal cortex (vmPFC). Among women who initiated OCs earlier in adolescence, a short duration of use was associated with smaller hippocampal GMV and thicker vmPFC compared to a longer duration of use. For both GMV and CT of the right vmPFC, women with an early OC onset had more grey matter at a short duration of use than those with a later onset. Our results suggest that OC use earlier in adolescence may induce lasting effects on structural correlates of fear learning and its regulation. These findings support further investigation into the timing of OC use to better comprehend how OCs could disrupt normal brain development processes.
Temperature controls the relation between soil organic carbon and microbial carbon use efficiency
Authors: Luo Zhaoyang , Ren Jianning , Manzoni Stefano , Fatichi Simone
Published: September 2024

Microbial carbon use efficiency (CUE) is an important variable mediating microbial effects on soil organic carbon (SOC) since it summarizes how much carbon is used for microbial growth or is respired. Yet, the role of CUE in regulating SOC storage remains debated, with evidence for both positive and negative SOC‐CUE relations. Here, we use a combination of measured data around the world and numerical simulations to explore SOC‐CUE relations accounting for temperature (T) effects on CUE. Results reveal that the sign of the CUE‐T relation controls the direction of the SOC‐CUE relations. A negative CUE‐T relation leads to a positive SOC‐CUE relation and vice versa, highlighting that CUE‐T patterns significantly affect how organic carbon is used by microbes and hence SOC‐CUE relations. Numerical results also confirm the observed negative SOC‐T relation, regardless of the CUE‐T patterns, implying that temperature plays a more dominant role than CUE in controlling SOC storage. The SOC‐CUE relation is usually negative when temperature effects are isolated, even though it can become positive when nonlinear microbial turnover is considered. These results indicate a dominant role of CUE‐T patterns in controlling the SOC‐CUE relation. Our findings help to better understand SOC and microbial responses to a warming climate.
Changes in use of acute and preventive medications for migraine after erenumab initiation over 12 months: A United States retrospective cohort study
Authors: Multani Jasjit K. , Urman Robert , Park Andrew S. , Gill Karminder , Vuvu Fiston , Sun Kainan , Patel Leah B. , Stockl Karen M. , Hawkins Kevin , Rhyne Christopher , Bensink Mark E.
Published: September 2024

Objective

To assess changes in real‐world use of acute and preventive medications for migraine over a 12‐month follow‐up period in the United States following initiation of the anti‐calcitonin gene‐related peptide (CGRP) pathway monoclonal antibody (mAb) erenumab.

Background

Early assessments of real‐world use of acute and preventive medications for migraine after initiation of erenumab have been limited to 6 months of follow‐up.

Methods

This retrospective cohort study used data from the IQVIA open‐source longitudinal prescription (LRx) and medical (Dx) claims databases. Adult patients with an initial claim (index date) for erenumab between May 2018 and April 2020 were identified.

Results

Among 201,176 patients who met inclusion criteria, the mean (standard deviation [SD]) age was 47.5 (13.8) years and 85.6% (n = 172,153) were female. Most patients used one or more acute (88.4%; n = 177,795) and one or more traditional preventive (86.1%; n = 173,225) medications during the 12‐month pre‐index period. Adherence to erenumab (proportion of days covered [PDC] ≥0.80) was 40.2% (n = 80,927) with an overall mean (SD) PDC of 0.60 (0.34). Among all patients, 70.0% (n = 140,809) discontinued erenumab. After accounting for 24.7% (n = 49,720) of patients who restarted erenumab, discontinuation without reinitiation was observed in 45.3% (n = 91,089) of total patients. Switching to a different anti‐CGRP pathway mAb was observed in 13.1% (n = 26,446) of total patients. Among 177,795 patients with pre‐index use of one or more acute migraine medication class, 86.5% (n = 153,788) had post‐index use of the same class, and 56.7% (87,134/153,788) of them discontinued one or more class of acute medication in the 12‐month follow‐up period. Similarly, among 173,225 patients with pre‐index use of one or more traditional migraine preventive medication class, 67.7% (n = 117,274) had post‐index use of the same class, and 46.7% (54,790/117,274) of them discontinued one or more class of traditional preventive medication in the 12‐month follow‐up period.

Conclusions

In this long‐term study, we observed the discontinuation of both acute and preventive medications for migraine post‐erenumab initiation.
Impact of consumer familiarity on acceptability and purchase intent of a novel amaranth‐based coffee creamer
Authors: Sánchez‐Arellano Lucía , Ramírez‐Rivera Emmanuel de Jesús , López‐Espindola Mirna , Argumedo‐Macías Adrián , Cabal‐Prieto Adán , Juárez‐Barrientos José Manuel , Herrera‐Corredor José Andrés
Published: September 2024

The objective of the study was to identify the impact of consumer familiarity on liking, acceptability, purchase intention and textual description of a novel cream substitute formulated with popped amaranth flour. Four formulations were evaluated in different proportions of amaranth vs. a control. A total of 400 consumers from two regions participated (Veracruz: familiar with coffee and Tlaxcala: familiar with amaranth). Consumers from both regions had significant differences in liking the attributes of the different formulations. Liking across regions was mainly a function of product aroma. Regarding the acceptance of the product, it was found that the attributes flavour, colour and overall liking were significant (P < 0.05) for consumers from Veracruz, whereas appearance and mouthfeel were significant (P < 0.05) for consumers from Tlaxcala. In purchase intent, overall liking was significant for both regions (P < 0.05). In relation to the impact of amaranth on purchase intention, Tlaxcala showed higher purchase willingness. The words used for sensory characterisation and that are important for both regions were the amaranth aroma, and the creamy flavour in the formulation with the highest amaranth content. The findings of this study allowed for understanding the potential of amaranth to formulate new creamers in a cross‐cultural context, considering consumers from two different levels of familiarity with specific crops.
Clinical perspectives: Takotsubo cardiomyopathy
Authors: Ravindran Jayant , Brieger David
Published: September 2024

Takotsubo syndrome is a condition characterised by temporary acute left ventricular dysfunction with regional wall abnormalities extending beyond a single coronary artery territory. Initially thought to be benign, this condition, which is challenging to distinguish from acute coronary syndrome, has substantial morbidity and mortality. The mechanism behind this condition remains elusive, but multiple theories have been proposed. Although beta blockers and angiotensin‐converting enzyme inhibitors are used as treatments for left ventricular dysfunction, currently, there are no randomised controlled trials to support their use. In this paper, we review the latest evidence regarding aetiologies, pathophysiology, diagnostic criteria, prognosis, complications and management of Takotsubo syndrome.
Skills Development in Hydrologic Sciences for Cohorts of Graduate Students from Morocco, Egypt, Türkiye, and Indonesia
Authors: Fryar Alan E. , Milewski Adam M. , Agouridis Carmen T. , Hanley Carol D. , Schroeder Paul A. , Sultan Mohamed , Ward James W. , Laftouhi Nour‐Eddine , Pandjaitan Nora H. , El Kadiri Racha , Benaabidate Lahcen , Fekri Ahmed , Suharyanto Agus , Yilmaz Koray K.
Published: September 2024

In developing countries in Africa and Asia, meeting challenges of water scarcity and pollution has often been hampered by shortcomings in higher education, including insufficient research productivity and funding, lack of opportunity for university graduates, and a mismatch between university activities and societal needs. To address these issues, we developed novel programs integrating technical instruction and preparation for professional practice in hydrology for cohorts of graduate students from Morocco and Egypt (2012–2013) and from Türkiye and Indonesia (2013–2014). Students participated in an initial online course and a follow‐up workshop featuring geographic information systems (GIS), remote sensing, and hydrologic modeling with internet‐based data sets. Field activities in the USA (first cohort) and in the students’ home countries (second cohort) included stream gauging, measurement of water levels in wells, water sampling, and measurement of hydrochemical parameters. A subsequent online course focused on research ethics, preparing proposals and publications, and presenting findings to technical audiences and the public, culminating in presentations at conferences in the USA. Participants mentored other students at their home institutions and at K‐12 schools in Türkiye and Indonesia. Participant feedback during and after the programs tended to be strongly positive, and participants have continued to engage with project leaders and mentor students in their home countries and the USA. Our modular, hybrid approach offers a template for students in hydrology and related fields to develop relevant skills and engage internationally.
Involvement of heparanase in the pathogenesis of acute pancreatitis: Implication of novel therapeutic approaches
Authors: Hamo‐Giladi Dalit B. , Fokra Ahmad , Sabo Edmond , Kabala Aviva , Minkov Irena , Hamoud Shadi , Hadad Salim , Abassi Zaid , Khamaysi Iyad
Published: September 2024

Acute pancreatitis (AP) is a common gastrointestinal disease with high morbidity and mortality rate. Unfortunately, neither the etiology nor the pathophysiology of AP are fully understood and causal treatment options are not available. Recently we demonstrated that heparanase (Hpa) is adversely involved in the pathogenesis of AP and inhibition of this enzyme ameliorates the manifestation of the disease. Moreover, a pioneer study demonstrated that Aspirin has partial inhibitory effect on Hpa. Another compound, which possesses a mild pancreato‐protective effect against AP, is Trehalose, a common disaccharide. We hypothesized that combination of Aspirin, Trehalose, PG545 (Pixatimod) and SST0001 (Roneparstat), specific inhibitors of Hpa, may exert pancreato‐protective effect better than each drug alone. Thus, the current study examines the pancreato‐protective effects of Aspirin, Trehalose, PG545 and SST0001 in experimental model of AP induced by cerulein in wild‐type (WT) and Hpa over‐expressing (Hpa‐Tg) mice. Cerulein‐induced AP in WT mice was associated with significant rises in the serum levels of lipase (X4) and amylase (X3) with enhancement of pancreatic edema index, inflammatory response, and autophagy. Responses to cerulein were all more profound in Hpa‐Tg mice versus WT mice, evident by X7 and X5 folds increase in lipase and amylase levels, respectively. Treatment with Aspirin or Trehalose alone and even more so in combination with PG545 or SST0001 were highly effective, restoring the serum level of lipase back to the basal level. Importantly, a novel newly synthesized compound termed Aspirlose effectively ameliorated the pathogenesis of AP as a single agent. Collectively, the results strongly indicate that targeting Hpa by using anti‐Hpa drug combinations constitute a novel therapy for this common orphan disease.
A common variant in PIK3CG gene associated with the prognosis of heart failure
Authors: Hu Dong , Xiao Lei , Li Shiyang
Published: September 2024

Phosphoinositide 3‐kinase γ (PI3Kγ) is G‐protein‐coupled receptor‐activated lipid kinase with both kinase‐dependent and kinase‐independent activity. Plenty of evidence have demonstrated that PI3Kγ participated in TAC and I/R‐induced myocardial remodelling and heart failure (HF). In this study, we tested the hypothesis that common variants in the PI3Kγ gene (PIK3CG) were associated with the prognosis of HF in the Chinese Han population. Through re‐sequencing and genotyping, we finally identified a common variant in the 3′UTR of PIK3CG strongly associated with the prognosis of HF in two‐stage population: adjusted p = 0.007, hazard ratio = 0.56 (0.36–0.85) in the first cohort and adjusted p = 0.024, hazard ratio = 0.39 (0.17–0.88) in the replicated cohort. A series of functional assays revealed that rs10215499‐A allele suppressed PIK3CG translation by facilitating has‐miR‐133a‐3p binding, but not the G allele. Subjects carrying the GG genotype showed higher mRNA and protein level than those with AA and AG genotype. Furthermore, overexpression of PIK3CG could protect AC16 from hypoxia/reoxygenation (H/R)‐induced apoptosis, while the case was opposite for PIK3CG silencing. In conclusion, common variant rs10215499 in the 3′‐UTR of PIK3CG might affect the prognosis of HF by interfering with miR‐133a‐3p binding and PIK3CG is a promising target for HF treatment in the future.
Increased forebrain EAAT3 expression confers resilience to chronic stress
Authors: Ardiles Nicolás M. , Tapia‐Cuevas Vissente , Estay Sebastián F. , Alcaino Alejandro , Velásquez Victoria B. , Sotomayor‐Zárate Ramón , Chávez Andrés E. , Moya Pablo R.
Published: September 2024

Depression is a disabling and highly prevalent psychiatric illness. Multiple studies have linked glutamatergic dysfunction with the pathophysiology of depression, but the exact alterations in the glutamatergic system that contribute to depressive‐like behaviors are not fully understood. Recent evidence suggests that a decreased level in neuronal glutamate transporter (EAAT3), known to control glutamate levels and limit the activation of glutamate receptors at synaptic sites, may contribute to the manifestation of a depressive phenotype. Here, we tested the possibility that increased EAAT3 expression at excitatory synapses could reduce the susceptibility of mice to develop depressive‐like behaviors when challenged to a 5‐week unpredictable chronic mild stress (UCMS) protocol. Mice overexpressing EAAT3 in the forebrain (EAAT3glo/CMKII) and control littermates (EAAT3glo) were assessed for depressive‐like behaviors and long‐term memory performance after being subjected to UCMS conditions. We found that, after UCMS, EAAT3glo/CMKII mice did not exhibit depressive‐like behaviors or memory alterations observed in control mice. Moreover, we found that EAAT3glo/CMKII mice did not show alterations in phasic dopamine release in the nucleus accumbens neither in long‐term synaptic plasticity in the CA1 region of the hippocampus after UCMS, as observed in control littermates. Altogether these results suggest that forebrain EAAT3 overexpression may be related to a resilient phenotype, both at behavioral and functional level, to the deleterious effect of chronic stress, highlighting the importance of neuronal EAAT3 in the pathophysiology of depressive‐like behaviors.

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Clinical and genetic features of CMT2T in Italian patients confirm the importance of MME pathogenic variants in idiopathic, late‐onset axonal neuropathies
Authors: Geroldi Alessandro , La Barbera Andrea , Mammi Alessia , Origone Paola , Gaudio Andrea , Ponti Clarissa , Sanguineri Francesca , Matà Sabrina , Sperti Martina , Carboni Ilaria , Bellone Emilia , Gotta Fabio , Gemelli Chiara , Massucco Sara , Valeria Guglielmino , Marinelli Lucio , Grandis Marina , Bisogni Giulia , Sabatelli Mario , Piscosquito Giuseppe , Esposito Gabriella , Schenone Angelo , Manganelli Fiore , Mandich Paola , Tozza Stefano , Luigetti Marco
Published: September 2024

Background and Aims

Since 2016, biallelic mutations in the membrane metalloendopeptidase (MME) gene have been associated with late‐onset recessive CMT2 (CMT2T). More recently, heterozygous mutations have also been identified in familial and sporadic patients with late‐onset axonal neuropathy, ranging from subclinical to severe. This indicates that the heterozygous MME variants may not be fully penetrant, or alternatively, that they may be a potential risk factor for neuropathy. Here, we describe the clinical, neurophysiological, and genetic findings of 32 CM2T Italian patients.

Methods

The patients were recruited from four different Italian referral centers. Following a comprehensive battery of neurological, electrophysiological, and laboratory examinations, the patients' DNA was subjected to sequencing in order to identify any variants in the gene. Bioinformatic and modeling analyses were performed to evaluate the identified variants' effects.

Results

We observe a relatively mild axonal sensory‐motor neuropathy with a greater impairment of the lower extremities. Biallelic and monoallelic patients exhibit comparable disease severity, with an earlier onset observed in those with biallelic variants. When considering a subgroup with more than 10 years of disease, it becomes evident that biallelic patients exhibit a more severe form of neuropathy. This suggests that they are more prone to quick progression.

Interpretation

CM2T has been definitively defined as a late‐onset neuropathy, with a typical onset in the fifth to sixth decades of life and a more rapidly progressing worsening for biallelic patients. CMT2T can be included in the neuropathies of the elderly, particularly if MME variants heterozygous patients are included.
Comparative electron microscopic visualization of the lung alveolar epithelial glycocalyx with different staining and labeling methods
Authors: Gluhovic Vladimir , Timm Sara , Kuebler Wolfgang M. , Lopez‐Rodriguez Elena , Ochs Matthias
Published: September 2024

The alveolar surface of the lung is lined by an epithelium consisting of type I (AECI) and type II alveolar epithelial cells (AECII). This epithelium is covered by a liquid alveolar lining layer (ALL). Besides intra‐alveolar surfactant, ALL also contains the alveolar epithelial glycocalyx on the apical side of AECI and AECII. To better understand the alveolar epithelial glycocalyx, its ultrastructural visualization by transmission electron microscopy is required. The aim of this study was to systematically re‐evaluate routine cytochemical methods for visualization of the alveolar epithelial glycocalyx and specifically its glycan components. For this purpose, we used chemical fixation by vascular perfusion with aldehydes as a common routine approach in mice. After fixation, staining is needed for glycocalyx visualization. Cytochemical staining agents such as alcian blue, ruthenium red, and lanthanum nitrate were compared. In addition, SNL (Sambucus nigra lectin) and UEA1 (Ulex europaeus agglutinin I) were used for sialic acid and fucose‐specific labeling. Alcian blue showed the strongest staining, with cloud‐like structures, whereas ruthenium red appeared as thread‐like structures. On the other hand, lanthanum nitrate did not stain the alveolar epithelial glycocalyx. For specific sialic acid and fucose labeling, both lectins presented a specific signal. In conclusion, these methods can be used routinely for assessing ultrastructural changes of the alveolar epithelial glycocalyx in experimental in vivo models under different physiological and pathological conditions. In addition, cytochemical staining by tissue massage and post‐embedding lectin labeling after vascular perfusion support 3R (reduction, refinement, replacement) principles of animal welfare.
Poly‐d,l‐Lactic Acid Via Transdermal Microjet Drug Delivery for Treating Rosacea in Asian Patients
Authors: Seo Suk Bae , Wan Jovian , Thulesen Jesper , Jalali Arash , Vitale Massimo , Kim Soo‐Bin , Yi Kyu‐Ho
Published: September 2024

Background

Rosacea, a chronic inflammatory skin condition, is marked by enduring redness, visible blood vessels, and inflammatory eruptions in facial areas. Managing rosacea remains a persistent challenge for dermatologists, especially in cases unresponsive to conventional treatments. Injectable poly‐d,l‐lactic acid (PDLLA) has shown promise in treating erythema and telangiectasia associated with rosacea in addition to age‐related concerns. Employing Mirajet, a laser‐induced microjet system, for administering PDLLA is a novel and promising treatment for rosacea.

Aims

We aimed to evaluate the efficacy and safety of injectable PDLLA delivered via a needle‐free microjet system for managing rosacea.

Methods

Four Korean women with persistent and refractory rosacea received five monthly sessions of PDLLA needle‐free injections. Clinical assessments were conducted using the Clinician's Erythema Assessment and Patient's Self‐Assessment (PSA) at baseline, 4 weeks post‐treatment, and 22 weeks post‐final treatment. Adverse events were monitored throughout the study period.

Results

At 4 weeks post‐treatment, both Clinician's Erythema Assessment and PSA scores indicated significant improvements in erythema that were sustained up to the 22‐week follow‐up. Patients reported high satisfaction with resolution of redness and improved skin texture. Mild swelling, redness, and petechiae were observed post‐treatment but resolved spontaneously. No product‐related adverse events were noted during the study period.

Conclusion

Injectable PDLLA delivered via laser‐induced microjet injection demonstrated promising efficacy in improving rosacea symptoms and skin quality for up to 22 weeks without significant adverse effects. Larger randomized controlled trials are needed to confirm these findings and evaluate long‐term safety and sustainability of outcomes.
Portal vein thrombosis and hepatic infarction due to hepatic mobilization after primary debulking surgery for advanced ovarian cancer: A case report
Authors: Onishi Junki , Odajima Suguru , Koike Yuki , Takenaka Shin , Tanabe Hiroshi
Published: September 2024

Hepatic mobilization is essential in debulking surgery for resecting diaphragmatic lesions in advanced ovarian cancer. However, hepatic mobilization potentially induces postoperative portal vein thrombosis and hepatic infarction. No reports exist regarding these postoperative complications of gynecological surgeries. Thus, we reported a case of portal vein thrombosis and hepatic infarction after ovarian cancer surgery with upper abdominal surgery. The 51‐year‐old female patient who had been diagnosed with advanced ovarian and early endometrial cancer underwent primary debulking surgery. Ultimately, she underwent the following surgical procedures: a hysterectomy, bilateral salpingo‐oophorectomy, total parietal peritonectomy, low anterior resection, ileostomy, and appendicectomy. The hepatic enzymatic and D‐dimer levels were elevated, postoperatively. Contrast‐enhanced computed tomography revealed portal vein thrombosis and an infarction of the hepatic S3 region. The portal vein thrombosis resolved post‐administration of unfractionated heparin. The hepatic infarction improved. Meticulous intra‐ and postoperative management should encompass the deliberation of the potential risk of these postoperative complications.
Getting Down to Business: Governing the Hybridization of UK Charities
Authors: Curran Kevin , Ozcan Pinar
Published: September 2024

Charity organizations are important to solving complex social and environmental issues that are beyond the reach of government and commercial organizations. However, these organizations are under increasing pressure for survival due to a sharp decrease in their traditional sources of funding. This study examines how leaders of charity organizations can improve the financial security and impact of their organization by adopting commercial structures into their organization, and therefore undergoing a process of hybridization. We conducted a multiple comparative case study of 18 UK charities comparing how they engaged with emerging social finance funding opportunities that required them to adopt commercial structures which lay outside their dominant logic of action. We identified several aspects that influenced the likelihood of a charity organization to engage with this opportunity and, therefore, strategically hybridize. These included whether a charity executive had sufficient socialization in both the social and commercial logics to view social finance as a strategic opportunity and whether the organization could alter the role expectations of trustees with a commercial background to enable them to actively use both logics rather than compartmentalizing them in their decision‐making. Our findings have important implications for research streams on hybridization and hybrid governance.
Vertical marginal gap and internal fit of virgilite‐based lithium disilicate glass ceramic veneers with different preparation designs
Authors: Rizk Amr , Abdou Ahmed , Samy Amira Mohammad , Mahmoud Nouran , Omar Sarah
Published: September 2024

Purpose

To evaluate and compare internal fit and marginal adaptation of conventional lithium disilicate (LDS) glass ceramics and LDS containing virgilite computer‐aided design and manufacturing (CAD‐CAM) blocks before and after aging.

Materials and Methods

Seventy‐two epoxy replicated dies from two prepared maxillary right central incisors acrylic typodont were divided into two groups of different preparation designs (n = 36): Group I, incisal butt‐joint, and Group P, incisal overlap. Each group was further subdivided into two equal groups according to ceramic material (n = 18): Group E, IPS e.max CAD, and Group T, Tessera advanced lithium disilicate (ALD) CAD‐CAM blocks. The replica technique was used to assess the internal fit using a stereomicroscope at 45× magnification. Laminate veneers were cemented to their corresponding epoxy dies, then the vertical marginal gap was evaluated before and after thermal cycling. Repeated measures analysis of variance (ANOVA) were used for marginal fit data and 2‐way ANOVA for internal fit measurements (α = 0.05).

Results

For internal fit, there were no significant differences between tested groups. For vertical marginal gap results, two‐way ANOVA showed that only aging had a significant effect on the vertical marginal gap (p < 0.001), while different CAD‐CAM materials and preparation designs did not affect the vertical marginal gap.

Conclusions

The vertical marginal gap and internal fits of IPS e.max CAD and CEREC Tessera CAD for both preparation designs were comparable. Aging significantly affected the vertical marginal gap of the laminate veneers of both materials and both preparation designs; however, all were within clinically acceptable ranges before and after aging.
Cytosolic Factors Controlling PASTA Kinase‐Dependent ReoM Phosphorylation
Authors: Rothe Patricia , Wamp Sabrina , Rosemeyer Lisa , Rismondo Jeanine , Doellinger Joerg , Gründling Angelika , Halbedel Sven
Published: September 2024

Bacteria adapt the biosynthesis of their envelopes to specific growth conditions and prevailing stress factors. Peptidoglycan (PG) is the major component of the cell wall in Gram‐positive bacteria, where PASTA kinases play a central role in PG biosynthesis regulation. Despite their importance for growth, cell division and antibiotic resistance, the mechanisms of PASTA kinase activation are not fully understood. ReoM, a recently discovered cytosolic phosphoprotein, is one of the main substrates of the PASTA kinase PrkA in the Gram‐positive human pathogen Listeria monocytogenes. Depending on its phosphorylation, ReoM controls proteolytic stability of MurA, the first enzyme in the PG biosynthesis pathway. The late cell division protein GpsB has been implicated in PASTA kinase signalling. Consistently, we show that L. monocytogenes prkA and gpsB mutants phenocopied each other. Analysis of in vivo ReoM phosphorylation confirmed GpsB as an activator of PrkA leading to the description of structural features in GpsB that are important for kinase activation. We further show that ReoM phosphorylation is growth phase‐dependent and that this kinetic is reliant on the protein phosphatase PrpC. ReoM phosphorylation was inhibited in mutants with defects in MurA degradation, leading to the discovery that MurA overexpression prevented ReoM phosphorylation. Overexpressed MurA must be able to bind its substrates and interact with ReoM to exert this effect, but the extracellular PASTA domains of PrkA or MurJ flippases were not required. Our results indicate that intracellular signals control ReoM phosphorylation and extend current models describing the mechanisms of PASTA kinase activation.
Association between obesity paradox in the all‐cause mortality among patients with cardiac resynchronization therapy device
Authors: Wattanachayakul Phuuwadith , Yanpiset Panat , Wannaphut Chalothorn , Suenghataiphorn Thanathip , Rujirachun Pongprueth , Danpanichkul Pojsakorn , Polpichai Natchaya , Saowapa Sakditad , Kewcharoen Jakrin , Charoenngam Nipith , Ungprasert Patompong
Published: September 2024

Background

Recent studies have demonstrated an obesity paradox, where obese patients with cardiovascular disease have a better outcome compared to those with normal weight. However, the effect of obesity and body mass index (BMI) on the outcome of patients with cardiac resynchronization therapy (CRT) devices remains unclear. The current study aims to investigate this relationship using all available published data.

Methods

We systematically reviewed studies from Medline and EMBASE databases from inception to January 2024. Eligible studies must investigate the association between BMI status and all‐cause mortality in individuals with CRT devices. Relative risk (RR) or hazard ratio (HR) and 95% CIs were retrieved from each study and combined using the generic inverse variance method.

Results

A total of 12 cohort studies were included in the meta‐analysis. Pooled analysis showed that overweight and obesity patients had lower all‐cause mortality compared to those with normal body weight with the pooled risk ratios (RR) for overweight of 0.77 (95% CI 0.69–0.87, I2 47%) and for obesity of 0.81 (95% CI 0.67–0.97, I2 59%). Conversely, the underweight exhibited higher all‐cause mortality than the group with normal weight, with a pooled RR of 1.37 (95% CI 1.14–1.64, I2 0%). Additionally, higher BMI as continuous data was associated with decreased all‐cause mortality, with a pooled HR of 0.94 (95% CI 0.89–0.98, I2 72%).

Conclusions

The pooled analyses observed an obesity paradox in patients with CRT, where overweight and obesity were associated with reduced all‐cause mortality, while underweight individuals exhibited higher all‐cause mortality. Further research is necessary to investigate the underlying mechanisms and their implications for clinical practice.
Spontaneous fluctuation in atrial fibrillation burden and duration in patients with implantable loop monitors
Authors: Mekary Wissam , Campbell Martin , Bhatia Neal K. , Westerman Stacy , Shah Anand , Leal Miguel , Delurgio David , Patel Anshul M. , Tompkins Christine , El‐Chami Mikhael F. , Merchant Faisal M.
Published: September 2024

Background

Most studies of device‐detected atrial fibrillation (AF) have recommended indefinite anticoagulation once a patient crosses a particular threshold for AF duration or burden. However, durations and burdens are known to fluctuate over time, but little is known about the magnitude of spontaneous fluctuations and the potential impact on anticoagulation decisions.

Objective

To quantify spontaneous fluctuations in AF duration and burden in patients with implantable loop recorders (ILRs)

Methods

We reviewed all ILR interrogations for patients with non‐permanent AF at our institution from 2018 to 2023. We excluded patients treated with rhythm control. The duration of longest AF episode at each interrogation was classified as < 6, 6–24, and > 24 h, and the AF burden reported at each interrogation was classified as < 2%, 2%–11.4%, and > 11.4%.

Results

Out of 156 patients, the mean age at ILR implant was 70.9 ± 12.5 years, CHA2DS2‐VASc score was 4.2 ± 1.8, duration of ILR follow‐up was 23.4 ± 11.2 months, and number of ILR interrogations per patient was 18.0 ± 8.9. The duration of longest AF episode at any point during follow‐up was < 6 , 6–24 , and > 24 h in 110, 30, and 16 patients, respectively. Among the 30 patients with a longest AF episode of 6–24 h at some point during follow‐up, out of 594 total ILR interrogations, only 75 (12%) showed a longest episode of 6–24 h. In the remaining 519 interrogations, the longest episode was < 6 h. In patients with a longest episode of > 24 h at any point during follow‐up (n = 16), only 47 out of 320 total ILR interrogations (15%) showed an episode of > 24 h. When evaluating AF burden, 96, 38, and 22 patients had maximum reported AF burdens of < 2%, 2%–11.4%, and > 11.4% at any point during ILR follow‐up. Among those with a maximum burden of 2%–11.4% at some point during follow‐up (n = 38), out of 707 ILR interrogations, only 76 (11%) showed a burden of 2%–11.4%. In the remaining 631 interrogations, the burden was < 2%. In the 22 patients with a burden > 11.4% at some point during follow‐up, only 80 out of 480 interrogations (17%) showed a burden of > 11.4%. In 65% of interrogations, the burden was < 2%.

Conclusion

Significant, spontaneous fluctuations in AF burden and duration are common in patients with ILRs. Even in patients with AF episodes of 6–24 h or > 24 h at some point during follow‐up, the vast majority of interrogations show episodes of < 6 h. Similarly, in patients with burdens of 2%–11.4% or > 11.4% at some point during follow‐up, the vast majority of interrogations show burdens of < 2%. More data are needed to determine whether crossing an AF burden or duration threshold once is sufficient to merit lifelong anticoagulation or whether spontaneous fluctuations in AF burden and duration should impact anticoagulation decisions.
Loss of OsMATE6 Function Enhances Drought Resistance Without Yield Penalty by Regulating Stomatal Closure in Rice
Authors: Chen Si‐Yan , Zhang Zi‐Sheng , Zhang Zheng‐Yi , Sun Liang‐Qi , Fan Shi‐Jun , Zhang Guo‐Hua , Wu Jie , Xia Jin‐Qiu , Yu Jing , Hou Sui‐Wen , Qin Peng , Li Shi‐Gui , Xiang Cheng‐Bin
Published: September 2024

Drought is one of the most severe environmental factors limiting plant growth and crop yield, necessitating the identification of genes that enhance drought resistance for crop improvement. Through screening an ethyl methyl sulfonate‐mutagenized rice mutant library, we isolated the PEG tolerance mutant 97‐1 (ptm97‐1), which displays enhanced resistance to osmotic and drought stress, and increased yield under drought conditions. A point mutation in OsMATE6 was identified as being associated with the drought‐resistant phenotype of ptm97‐1. The role of OsMATE6 in conferring drought resistance was confirmed by additional OsMATE6 knockout mutants. OsMATE6 is expressed in guard cells, shoots and roots and the OsMATE6‐GFP fusion protein predominantly localizes to the plasma membrane. Our ABA efflux assays suggest that OsMATE6 functions as an ABA efflux transporter; mutant protoplasts exhibited a slower ABA release rate compared to the wild type. We hypothesize that OsMATE6 regulates ABA levels in guard cells, influencing stomatal closure and enhancing drought resistance. Notably, OsMATE6 knockout mutants demonstrated greater yields under field drought conditions compared to wild‐type plants, highlighting OsMATE6 as a promising candidate for improving crop drought resistance.
The effects of the COVID‐19 pandemic on the activities of Initial‐phase Intensive Support Team for Dementia in Kobe City
Authors: Ibi Kyoko , Kubota Mami , Matsuzaki Yoko , Hasegawa Noriko
Published: September 2024

Background

This study aimed to review the activities of the Kobe City Initial‐phase Intensive Support Team for Dementia pre‐ and during the coronavirus disease 2019 (COVID‐19) pandemic, to compare the characteristics of the target population and the performance of the team's activities, and determine the impact of the pandemic on the team's project.

Methods

The summary data obtained at the time of consultation, team activities, and participants' characteristics were extracted from 662 participants who started to receive support between April 2018 and March 2022. Statistical analysis was performed by dividing the participants into the following two groups: pre‐ and during COVID‐19 pandemic groups.

Results

There was no significant difference in the number of new cases or cases that led to a dementia diagnosis between the pre‐ and during COVID‐19 pandemic groups. However, there were significant differences in the number of home visits and rate of introduction of medical care between the two groups. In our study population, the number of participants with financial management difficulties and delusions increased and the number of participants who refused visitations slightly decreased.

Conclusion

The Kobe City Initial‐phase Intensive Support Team was able to continue its activities during the pandemic partly because the team is an independent, dedicated team. During the pandemic, there was an increase in the number of participants who were isolated because they were deprived of opportunities to interact with others, and who developed delusions and other psychiatric symptoms. Despite this situation, the professional team responded quickly through individual assessment of the individual needs by continuous outreach, taking into account the infection situation, and thus this outreach team functioned well even under the COVID‐19 pandemic.
Using demographic modeling to develop post‐fire restoration strategies for a native shrub in a sage scrub community
Authors: Thomson Diane M.
Published: September 2024

Mediterranean‐climate shrublands are key biodiversity hotspots and carbon storage pools, but are increasingly threatened by climate change, non‐native species, and altered fire regimes. Fires are important to historic shrubland disturbance cycles but can also promote non‐native plants, which may limit post‐fire native shrub recovery. Increasing drought with climate change could also reduce post‐fire shrub regeneration. I developed a stochastic, individual‐based demographic model (IBM) for the native shrub Artemisia californica, parameterized from an experimental removal of non‐native annuals after a 2013 fire in southern California. The IBM simulated A. californica recovery for 7 years after fire under different rainfall conditions (drought or pre‐drought) and non‐native removal strategies (from no years to all 7 years). Drought lowered A. californica canopy volume 7 years after fire by 90% or more. Rainfall in the second year after fire, when most A. californica germination occurred, had particularly strong effects on final canopy cover. Non‐native removal in all 7 years increased canopy volume by three times under drought conditions and 3.5 times under pre‐drought conditions. Targeting non‐native removal in the first 2 years proved nearly as effective, achieving from 88% (drought) to 95% (pre‐drought) the benefits of removal in all 7 years. In sum, low rainfall may be the most important limitation on post‐fire shrub recovery, but removal of non‐natives in years of pulsed shrub recruitment can be an effective restoration strategy even under drought conditions. More generally, this study illustrates how demographic models can help optimize the targeting of scarce management and restoration resources.