bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction of Th17 differentiations‐related gene polymorphisms and environmental factors contributing to the disease classification, complications, and surgical risks of Crohn's disease in the Chinese Han population
Authors: Zhou Ru Ning , Ruan Ge Chong , Wu Mei Xu , Guo Ming Yue , Liang Hao Zheng , Bai Xiao Yin , Yang Hong
Published: July 2024

Objectives

Few studies have been conducted on gene–environment interactions in the Chinese population with Crohn's disease (CD). We aimed to investigate the association between single nucleotide polymorphisms (SNPs) on the T helper 17 (Th17) cell and CD susceptibility/performance in Chinese individuals.

Methods

We conducted a case–control and case‐only study at the Peking Union Medical College Hospital. Four SNPs related to the Th17 cell pathway genes were prioritized, including rs2284553 (interferon gamma receptor 2), rs7517847 (interleukin 23 receptor), rs7773324 (interferon regulatory factor 4), and rs4263839 (tumor necrosis factor superfamily 15). SNP frequency was calculated, and gene–environment interaction was assessed by multifactor dimensionality reduction analysis.

Results

Altogether 159 CD patients and 316 healthy controls were included. All analyzed SNPs were found in Hardy–Weinberg equilibrium (P > 0.05). The frequency of rs2284553‐A allele and rs4263839‐A allele were lower in CD patients compared with controls (P < 0.05). While the rs4263839‐A allele was more prevalent in ileocolonic CD patients than in those with isolated small intestinal or colonic disease (P = 0.035). Gene–environment interactions revealed associations between rs2284553 and breastfeeding, sunshine exposure, and fridge‐stored food, affecting age at diagnosis, intestinal involvement, and intestinal stricture. Interaction of rs4263839 and breastfeeding influenced small intestinal lesions and intestinal stricture in CD.

Conclusions

This study provided information on the genetic background in Chinese CD patients. Incorporating these SNPs into predictive models may improve risk assessment and outcome prediction. Gene–environment interaction contributes to the understanding of CD pathogenesis.
The circadian rhythm: A key variable in aging?
Authors: Winterhalter Patrick R. , Georgevici Adrian‐Iustin , Gharpure Nitin J. , Szabó Gábor , Simm Andreas
Published: July 2024

The determination of age‐related transcriptional changes may contribute to the understanding of health and life expectancy. The broad application of results from age cohorts may have limitations. Altering sample sizes per time point or sex, using a single mouse strain or tissue, a limited number of replicates, or omitting the middle of life can bias the surveys. To achieve higher general validity and to identify less distinctive players, bulk RNA sequencing of a mouse cohort, including seven organs of two strains from both sexes of 5 ages, was performed. Machine learning by bootstrapped variable importance and selection methodology (Boruta) was used to identify common aging features where the circadian rhythms (CiR) transcripts appear as promising age markers in an unsupervised analysis. Pathways of 11 numerically analyzed local network clusters were affected and classified into four major gene expression profiles, whereby CiR and proteostasis candidates were particularly conspicuous with partially opposing changes. In a data‐based interaction association network, the CiR‐proteostasis axis occupies an exposed central position, highlighting its relevance. The computation of 11,830 individual transcript associations provides potential superordinate contributors, such as hormones, to age‐related changes, as in CiR. In hormone‐sensitive LNCaP cells, short‐term supraphysiologic levels of the sex hormones dihydrotestosterone or estradiol increase the expression of the CiR transcript Bhlhe40 and the associated senescence regulator Cdkn2b (p15). According to these findings, the bilateral dysregulation of CiR appears as a fundamental protagonist of aging, whose transcripts could serve as a biological marker and its restoration as a therapeutic opportunity.
Histone β‐hydroxybutyrylation is critical in reversal of sarcopenia
Authors: Wang Qiquan , Lan Xinqiang , Ke Hao , Xu Siman , Huang Chunping , Wang Jiali , Wang Xiang , Huang Tiane , Wu Xia , Chen Mengxin , Guo Yingqi , Zeng Lin , Tian Xiao‐Li , Xiang Yang
Published: July 2024

Sarcopenia, a leading cause for global disability and mortality, is an age‐related muscular disorder, characterized by accelerated muscle mass loss and functional decline. It is known that caloric restriction (CR), ketogenic diet or endurance exercise lessen sarcopenia and elevate circulating β‐hydroxybutyrate (β‐HB) levels. Whether the elevated β‐HB is essential to the reversal of sarcopenia, however, remains unclear. Here we show in both Caenorhabditis elegans and mouse models that an increase of β‐HB reverse myofiber atrophy and improves motor functions at advanced ages. β‐HB‐induced histone lysine β‐hydroxybutyrylation (Kbhb) is indispensable for the reversal of sarcopenia. Histone Kbhb enhances transcription of genes associated with mitochondrial pathways, including oxidative phosphorylation, ATP metabolic process and aerobic respiration. This ultimately leads to improve mitochondrial integrity and enhance mitochondrial respiration. The histone Kbhb are validated in mouse model with CR. Thus, we demonstrate that β‐HB induces histone Kbhb, increases mitochondrial function, and reverses sarcopenia.
Disentangling drivers of vertebrate roadkill in a protected area in the Amazon rainforest
Authors: Coeli Gomes de Lucena Costa Andréa , Campos Gomides Samuel
Published: July 2024

Vertebrates' roadkill impacts many species in natural areas. However, data on this topic in the Amazon domain are still scarce, especially within protected areas. In this study, we analysed data from 2 years of monitoring amphibians, reptiles, mammals and birds' roadkill on five types of terrestrial transport infrastructure in a protected area in the Brazilian Amazon. We tested which vertebrate classes and feeding guilds were most recorded, the influence of seasonality and the spatial pattern of roadkill. In the studied area, 2795 roadkills were recorded, with amphibians suffering the most casualties. Most of the roadkills occurred during the rainy season (57%). Correcting the roadkill data using observer efficiency and carcass persistence time data, we concluded that mortality rates might be underestimated by up to 40 times when compared to raw data. There was no significant difference between feeding guilds concerning the number of fatalities, and rainfall and temperature significantly affected the roadkill pattern of all vertebrate classes. The spatial pattern of roadkill varied between traffic routes and vertebrate class types. The results indicate that amphibians are the most common victims of roadkill, although they are neglected in many roadkill monitoring. Consequently, mitigation strategies should prioritize periods with the highest mortality rates, as rainfall and temperature influence the frequency of these accidents. In addition, different classes of vertebrates have different patterns of impact concentration along traffic routes, which makes mitigation planning more complex. Therefore, planning to reduce vertebrate deaths from roadkill must consider each taxon's particularity and seasonality.
Male contraception: Focus on behavioral and barrier methods
Authors: Kopa Zsolt , Scafa Raffaele , Graziani Andrea , Goulis Dimitrios G. , Ferlin Alberto
Published: July 2024

Introduction

Male contraception includes various methods designed to prevent pregnancy by focusing on the male's role in reproduction.

Results

Behavioral methods, such as withdrawal and periodic abstinence, offer non‐invasive alternatives that require self‐control and precise timing to avoid depositing sperm in the female reproductive tract during fertile periods. However, these methods generally have low effectiveness and rely heavily on user adherence and experience. The male condom, a barrier method, provides both contraception and protection against sexually transmitted infections. Its effectiveness relies on correct and consistent use.

Discussion

Access to comprehensive sexual education and medical counseling is essential to dispel the stigma surrounding contraceptive use and correct misconceptions, ensuring proper usage and ultimately contributing to better reproductive health outcomes.
Mitochondria can substitute for parvalbumin to lower cytosolic calcium levels in the murine fast skeletal muscle
Authors: Marcucci Lorenzo , Nogara Leonardo , Canato Marta , Germinario Elena , Raffaello Anna , Carraro Michela , Bernardi Paolo , Pietrangelo Laura , Boncompagni Simona , Protasi Feliciano , Paolocci Nazareno , Reggiani Carlo
Published: July 2024

Aim

Parvalbumin (PV) is a primary calcium buffer in mouse fast skeletal muscle fibers. Previous work showed that PV ablation has a limited impact on cytosolic Ca2+ ([Ca2+]cyto) transients and contractile response, while it enhances mitochondrial density and mitochondrial matrix‐free calcium concentration ([Ca2+]mito). Here, we aimed to quantitatively test the hypothesis that mitochondria act to compensate for PV deficiency.

Methods

We determined the free Ca2+ redistribution during a 2 s 60 Hz tetanic stimulation in the sarcoplasmic reticulum, cytosol, and mitochondria. Via a reaction–diffusion Ca2+ model, we quantitatively evaluated mitochondrial uptake and storage capacity requirements to compensate for PV lack and analyzed possible extracellular export.

Results

[Ca2+]mito during tetanic stimulation is greater in knock‐out (KO) (1362 ± 392 nM) than in wild‐type (WT) (855 ± 392 nM), p < 0.05. Under the assumption of a non‐linear intramitochondrial buffering, the model predicts an accumulation of 725 μmoles/L
fiber (buffering ratio 1:11 000) in KO, much higher than in WT (137 μmoles/L
fiber, ratio 1:4500). The required transport rate via mitochondrial calcium uniporter (MCU) reaches 3 mM/s, compatible with available literature. TEM images of calcium entry units and Mn2+ quenching showed a greater capacity of store‐operated calcium entry in KO compared to WT. However, levels of [Ca2+]cyto during tetanic stimulation were not modulated to variations of extracellular calcium.

Conclusions

The model‐based analysis of experimentally determined calcium distribution during tetanic stimulation showed that mitochondria can act as a buffer to compensate for the lack of PV. This result contributes to a better understanding of mitochondria's role in modulating [Ca2+]cyto in skeletal muscle fibers.
Letter: Role of Helicobacter pylori and metabolic syndrome‐related insulin resistance and lipotoxicity in the pathogenesis of MAFLD and MASH
Authors: Kountouras Jannis , Polyzos Stergios A. , Kazakos Evangelos , Zavos Christos , Grigoriadis Nikolaos , Papanikolaou Ioannis S. , Vardaka Elisabeth , Tzilves Dimitrios , Chatzopoulos Dimitrios , Tzitiridou‐Chatzopoulou Maria , Touloumtzi Maria , Doulberis Michael , Papaefthymiou Apostolis
Published: July 2024

LINKED CONTENT

This article is linked to Lin et al papers. To view these articles, visit https://doi.org/10.1111/apt.17930 and https://doi.org/10.1111/apt.18182.
Letter: Role of Helicobacter pylori and metabolic syndrome‐related insulin resistance and lipotoxicity in the pathogenesis of MAFLD and MASH—Authors’ reply
Authors: Bansal S. K. , Bansal M. B.
Published: July 2024

LINKED CONTENT

This article is linked to Bansal et al. papers. To view these articles, visit https://doi.org/10.1111/apt.17930 and https://doi.org/10.1111/apt.18124.
Studying and stimulating a sense of community through co‐productive zine‐making in public libraries
Authors: van Melik Rianne , Kofi Jamea , Landau‐Donnelly Friederike
Published: July 2024

This paper reports on our ongoing experiences of using co‐productive zine‐making as a creative and participatory method in a research project on public libraries as social infrastructures. Engaging different audiences, including library management and staff, patrons and urban government authorities, the project aims to simultaneously study and stimulate a sense of community in public libraries. While many libraries already deploy zine‐making programmes as a low‐cost visitor activity, we use it as both a data collection and community‐building tool. Co‐productive zine‐making offers opportunities for reflection and mutual understanding to foster education, exchange and encounter between different stakeholders. It challenges the traditional power dynamics of knowledge production in academia and beyond. Zine‐making can act as a creative tool that pushes researchers to be more (self‐)reflexive. Yet, despite these benefits, zine‐making does not come without challenges, and therefore requires a specific researchers' skillset. This paper provides insight into both practical and ethical issues we encountered before, during and after the organisation of the first out of five zine‐making workshops in our project, held with community librarians in Rotterdam.
Friend influence and susceptibility to influence on emotions towards math: The role of adolescent temperament
Authors: Kiuru Noona , DeLay Dawn , Tervahartiala Katja , Polet Juho , Hirvonen Riikka
Published: July 2024

Background and Aims

Peer relationships during adolescence play an important role in shaping academic outcomes. The present study examined friend influences on emotions towards math, as well as the role of temperament in these influences.

Sample

The sample consisted of 350 Finnish students (mean age 13.29 years; 64% girls) who were involved in stable friendship dyads from fall to spring of Grade 7.

Methods

In this two‐wave study, information on adolescents' temperament (i.e., negative emotionality, extraversion, effortful control) and on seven emotions towards math (i.e., enjoyment, hope, pride, anger, anxiety, shame, hopelessness, and boredom) was collected during grade 7. The data were analysed using longitudinal actor‐partner interdependence models.

Results

The results showed that friends resembled each other in all the investigated math‐related emotions. Furthermore, over and above these initial similarities, friends mutually influenced each other's math‐related enjoyment and anger towards math. Students characterized by higher negative emotionality also influenced their friends with lower levels of negative emotionality towards an increase in math‐related anger and a lack of effortful control made adolescents more susceptible to friend influence over math‐related shame and anxiety.

Conclusion

Our findings demonstrate that friends influence each other over time in math‐related enjoyment and frustration. Furthermore, high negative emotionality may make adolescents more influential over their friends' math‐related anger and a lack of effortful control may make adolescents more susceptible to friend influence over math‐related shame and anxiety. Thus, the current findings have implications for how peer relations may impact individual outcomes in mathematics, for better or worse.
Seasonal plasticity in sympatric Bicyclus butterflies in a tropical forest where temperature does not predict rainfall
Authors: Mallick Soumen , Granados‐Tello Jorge , van Bergen Erik , Kodandaramaiah Ullasa , Brattström Oskar , Brakefield Paul M. , Molleman Freerk
Published: July 2024

While variation in temperature appears to be the main environmental cue for plasticity in adult traits in many species of Mycalesina, relying on temperature would result in a mismatch between adult phenotype and environment in some regions. We measured phenotypes of six species of Bicyclus butterflies (Nymphalidae: Satyrinae: Mycalesina) in a humid tropical forest with two rainy seasons per year and modest unimodal seasonal temperature variation, such that temperature does not predict rainfall and butterflies can reproduce year‐round. The butterflies showed subtle temporal variation in body size and relative eyespot size, while relative androconia length was robust to temporal environmental variation. After higher temperatures, body size tended be smaller, and relative eyespot size was larger for some species‐eyespot combinations. This indicates that these butterflies follow the “hotter is smaller” rule, and show developmental plasticity in eyespot size that is typical in this clade. Eyespot sizes tended to be correlated with each other, except Cu1 in B. auricruda and some eyespots that always remained very small. Androconia length was not related to eyespot size. This pattern of correlations suggests conserved cue‐use and shared mechanisms for eyespot size using both temperature and rainfall‐related cues, with some exceptions.
Diversity and dominance in bird assemblages across habitats in the Ñeembucú wetlands complex
Authors: Ortiz Fátima , Salinas Patricia , Mendoza Medes , Zárate Griselda , da Motta Fátima Piris , Esquivel Alberto , Núñez Karina , Silla Fernando
Published: July 2024

Understanding how diversity responds to habitat heterogeneity in a landscape is a central issue for implementing effective conservation plans. In this study, we analyzed how the composition and abundance of neotropical bird assemblages vary among habitats in the Ñeembucú Wetlands Complex, the largest wetland system in Paraguay. Bird surveys were conducted during 1 year within dominant habitats in the landscape: riparian forests, natural grasslands, savannas, and anthropized sites. The Ñeembucú Wetlands Complex showed a high bird richness (209 species) that contrasted with a pattern of dominance by a small set of 16 species that comprised half of the abundance. This set of oligarchic species consists of generalist species that exploited a wide variety of habitats and were well adapted to human disturbance, contributing to an important overlap in the composition of assemblages. However, despite this overall similarity, there is still significant differentiation in bird assemblages, especially between habitats with the most contrasting vegetation physiognomy. Riparian forests and savannas showed higher diversity values than the more structurally homogeneous grasslands. Also, all natural habitats showed, in general, higher diversity values than anthropized sites. Oligarchic species had higher importance in anthropized environments, which also had the most uneven distribution of abundance between species, indicating the dominance by a smaller number of species and the loss of ecological diversity as farmland and urban development increase.

Abstract in Spanish is available with online material.
Advancements in dental implantology: The alveolar ridge split technique for enhanced osseointegration
Authors: Luo Feng , Mo Yafei , Jiang Jiapei , Wen Jing , Ji Yixuan , Li Lei , Wan Qianbing
Published: July 2024

The alveolar ridge split (ARS) technique is a pivotal advancement in dental implantology, addressing the limitation of insufficient bone width for implant placement. This review traces the historical development of ARS from its initial conceptualization to current practices and future directions. Emphasizing the technique's development, indications, procedural overview, and osteotomy variations, we highlight its minimally invasive nature, which reduces patient morbidity and treatment time. This article reviews various osteotomy methods within ARS, examining their applications, benefits, and limitations. Furthermore, it discusses the technique's role in expanding treatment options for patients with compromised alveolar structures, underpinned by a high implant survival rate and the potential for immediate implant placement. We also cover the necessity of meticulous surgical technique, the importance of patient‐specific factors, and the promising future of ARS facilitated by advancements in biomaterials and regenerative medicine. In summary, this review provides a comprehensive overview of ARS, offering valuable insights for dental professionals and informing future clinical practices and research in implantology.
Patch tests in non‐immediate cutaneous adverse drug reactions: Late readings on Day 4 is more sensitive than on Day 3
Authors: Matei Ilaria , Bettuzzi Thomas , Weill Amandine , Gener Gwendeline , Hareth Kamar Bel , Margaux Fleck , Verlinde‐Carvalho Muriel , Paul Muriel , Ingen‐Housz‐Oro Saskia , Assier Haudrey
Published: July 2024

Background

Patch tests (PTs) are recommended to identify the culprit drug in non‐immediate cutaneous adverse drug reactions (NICADRs). We recently reported that, in patients with NICADRs, a unique reading of PTs at day (D)2 compared with an additional second late reading at D4 missed almost half (45.3%) of the positive PTs.

Objectives

To assess the change in sensitivity of the PT reading on D4 compared with the reading on D3.

Methods

We performed a retrospective (July 2020–June 2023) monocentric study of patients who had PTs with two readings for a NICADR. We compared reading on D3 and the second reading on D4 for the suspected drug (primary outcome) and for the related drugs tested simultaneously (secondary outcome).

Results

During the study period, 249 patients underwent patch testing with D3 and D4 readings. Regarding the primary outcome, the first reading at D3 was positive for 13.7% of patients, and the reading at D4 for 24.9% of patients (p < 0.0001). Regarding the secondary outcome, only 9.6% of patients had all their positive PT at D3 compared with 24.9% of patients at D4 (p < 0.0001). Considering the evaluated drug classes, no statistical difference was observed. However, we highlight that D3 reading detected all positive carbamazepine PTs (n = 3) while positive clindamycin PTs (n = 4) were identified only with the help of the second reading on D4.

Conclusion

This study showed that, an additional D4 reading compared with a single D3 reading enhanced the sensitivity of PTs to identify culprit drugs and related. Further studies should replicate these findings and evaluate the medico‐economic balance and safety of a single reading of PTs on D4.
Drug–drug interactions between pemafibrate and statins on pharmacokinetics in healthy male volunteers: Open‐label, randomized, 6‐sequence, 3‐period crossover studies
Authors: Kamimura Tomohiro , Hounslow Neil , Suganami Hideki , Tanigawa Ryohei
Published: July 2024

Elevated triglyceride levels are associated with an increased risk of cardiovascular events despite guideline‐based statin treatment of low‐density lipoprotein cholesterol. Peroxisome proliferator‐activated receptor α (PPARα) agonists exert a significant triglyceride‐lowering effect. However, combination therapy of PPARα agonists with statins poses an increased risk of rhabdomyolysis, which is rare but a major concern of the combination therapy. Pharmacokinetic interaction is suspected to be a contributing factor to the risk. To examine the potential for combination therapy with the selective PPARα modulator (SPPARMα) pemafibrate and statins, drug–drug interaction studies were conducted with open‐label, randomized, 6‐sequence, 3‐period crossover designs for the combination of pemafibrate 0.2 mg twice daily and each of 6 statins once daily: pitavastatin 4 mg/day (n = 18), atorvastatin 20 mg/day (n = 18), rosuvastatin 20 mg/day (n = 29), pravastatin 20 mg/day (n = 18), simvastatin 20 mg/day (n = 20), and fluvastatin 60 mg/day (n = 19), involving healthy male volunteers. The pharmacokinetic parameters of pemafibrate and each of the statins were similar regardless of coadministration. There was neither an effect on the systemic exposure of pemafibrate nor a clinically important increase in the systemic exposure of any of the statins on the coadministration although the systemic exposure of simvastatin was reduced by about 15% and its open acid form by about 60%. The HMG‐CoA reductase inhibitory activity in plasma samples from the simvastatin and pemafibrate combination group was about 70% of that in the simvastatin alone group. In conclusion, pemafibrate did not increase the systemic exposure of statins, and vice versa, in healthy male volunteers.
Bariatric arterial embolization slows gastric emptying and improves postprandial glycaemia in obese dogs with impaired glucose tolerance
Authors: Wang Zhi , Cao Qing‐Yue , Xiang Chunjie , Yu Chao , Xie Cong , Luo Biao , Zhu Dan‐Qi , Xu Yi , Chen Ya‐Jing , Wu Tongzhi , Teng Gao‐Jun
Published: July 2024

Aim

To evaluate the effects of bariatric arterial embolization (BAE) on gastric emptying of, and the glycaemic response to, an oral glucose load in an obese canine model with impaired glucose tolerance.

Methods

Eleven male dogs were fed a high‐fat, high‐fructose diet for 7 weeks before receiving BAE, which involved selective embolization of the left gastric artery (n = 5; 14.9 ± 0.8 kg), or the sham (n = 6; 12.6 ± 0.8 kg) procedure. Postprocedural body weight was measured weekly for 4 weeks. Prior to and at 4 weeks postprocedure, a glucose solution containing 13C‐acetate was administered orally for evaluation of the gastric half‐emptying time (T50) and the glycaemic response. The relationship between the changes in the blood glucose area under the curve over the first 60 minutes (AUC0‐60min) and the T50 was also assessed.

Results

At 4 weeks postprocedure, BAE reduced body weight (BAE vs. the sham procedure: −5.7% ± 0.9% vs. 3.5% ± 0.9%, P < .001), slowed gastric emptying (T50 at baseline vs. postprocedure: 75.5 ± 2.0 vs. 82.5 ± 1.8 minutes, P = .021 in the BAE group; 73.8 ± 1.8 vs. 74.3 ± 1.9 minutes in the sham group) and lowered the glycaemic response to oral glucose (AUC0‐60min at baseline vs. postprocedure: 99.2 ± 13.7 vs. 67.6 ± 9.8 mmol·min/L, P = .043 in the BAE group; 100.2 ± 13.4 vs. 103.9 ± 14.6 mmol·min/L in the sham group). The change in the glucose AUC0‐60min correlated inversely with that of the T50 (r = −0.711; P = .014).

Conclusions

In a canine model with impaired glucose tolerance, BAE, while reducing body weight, slowed gastric emptying and attenuated the glycaemic response to an oral glucose load.
Efficacy and safety of insulin glargine 300 U/mL in people with type 2 diabetes in China: The INITIATION study
Authors: Chen Liming , Wen Binhong , Liu Haixia , Wu Hongmei , Duan Binhong , Shu Hongyan , Zhang Qiu , Wu Xiaohong , Li Min , Han Yanfang , Kang Lei , Zhang Minlu
Published: July 2024

Aim

To evaluate the efficacy and safety of insulin glargine 300 U/mL (Gla‐300) in people with suboptimally controlled type 2 diabetes (T2D) in China.

Methods

INITIATION (NCT05002933) was a prospective, interventional, multicentre, single‐arm, phase IV study conducted in China. Individuals with suboptimally controlled T2D who were insulin naïve or switching from another basal insulin (insulin experienced) were included. The primary endpoint was the change in HbA1c from baseline to week 24. Safety assessments included hypoglycaemia and adverse events (AEs).

Results

In total, 568 participants were enrolled and 562 initiated Gla‐300 treatment (189 in the insulin‐naïve subgroup; 373 in the insulin‐experienced subgroup). At week 24, the mean ± standard error (SE) change in HbA1c from baseline was −0.91% ± 0.05% (−9.9 ± 0.5 mmol/mol; P < .0001). Significant HbA1c reductions were also observed in the insulin‐naïve (mean ± SE change: −1.38% ± 0.09% [−15.1 ± 1.0 mmol/mol]) and insulin‐experienced (−0.68% ± 0.05% [−7.4 ± 0.5 mmol/mol]) subgroups (both P < .0001). During the 24‐week treatment period, the incidence of confirmed hypoglycaemia (plasma glucose ≤ 3.9 mmol/L) was 39.7% for all hypoglycaemia and 13.3% for nocturnal hypoglycaemia; the incidence of severe hypoglycaemia was low (0.5%). Overall, treatment‐emergent AEs (TEAEs) were reported in 126 participants (22.4%), with no serious treatment‐related TEAEs.

Conclusions

Gla‐300 was effective in improving glycaemic control and had a relatively low risk of hypoglycaemia in people with suboptimally controlled T2D who were insulin naïve or switching from another basal insulin in China.
Cardiac magnetic resonance imaging in the evaluation and management of mitral valve prolapse – a comprehensive review
Authors: Mangini Francesco , Scarcia Maria , Biederman Robert W. W. , Calbi Roberto , Spinelli Francesco , Casavecchia Grazia , Brunetti Natale Daniele , Gravina Matteo , Fiore Corrado , Suma Sergio , Milo Maria , Turchetti Cristiano , Pesce Ernesto , Caramia Remo , Lombardi Francesca , Grimaldi Massimo
Published: July 2024

Mitral valve prolapse is a common valve disorder that usually has a benign prognosis unless there is significant regurgitation or LV impairment. However, a subset of patients are at an increased risk of ventricular arrhythmias and sudden cardiac death, which has led to the recognition of “arrhythmic mitral valve prolapse” as a clinical entity. Emerging risk factors include mitral annular disjunction and myocardial fibrosis. While echocardiography remains the primary method of evaluation, cardiac magnetic resonance has become crucial in managing this condition. Cine magnetic resonance sequences provide accurate characterization of prolapse and annular disjunction, assessment of ventricular volumes and function, identification of early dysfunction and remodeling, and quantitative assessment of mitral regurgitation when integrated with flow imaging. However, the unique strength of magnetic resonance lies in its ability to identify tissue changes. T1 mapping sequences identify diffuse fibrosis, in turn related to early ventricular dysfunction and remodeling. Late gadolinium enhancement sequences detect replacement fibrosis, an independent risk factor for ventricular arrhythmias and sudden cardiac death. There are consensus documents and reviews on the use of cardiac magnetic resonance specifically in arrhythmic mitral valve prolapse. However, in this article, we propose an algorithm for the broader use of cardiac magnetic resonance in managing this condition in various scenarios. Future advancements may involve implementing techniques for tissue characterization and flow analysis, such as 4D flow imaging, to identify patients with ventricular dysfunction and remodeling, increased arrhythmic risk, and more accurate grading of mitral regurgitation, ultimately benefiting patient selection for surgical therapy.
Inflation targeting, output stabilization, and real indeterminacy in monetary models with an interest rate rule
Authors: Platonov Konstantin
Published: July 2024

Central banks set the nominal interest rate to target inflation and stabilize output. In monetary models, monetary policy affects output directly via the wealth effect. I show that in these models, the response of the central bank to fluctuations in output may induce real indeterminacy even if the Taylor principle is satisfied. I find that the determinacy conditions depend on the interest elasticity of output and generally, the Taylor principle is neither necessary nor sufficient for determinacy. This is in stark contrast with the New Keynesian model where a sufficiently strong policy response to inflation or output usually ensures determinacy.
Antiemetic prophylaxis regimens in haematologic malignancies patients undergoing a hematopoietic stem cell transplantation. Which is the best standard of care? A systematic review
Authors: Báez‐Gutiérrez Nerea , Suárez‐Casillas Paloma , Pérez‐Moreno Maria Antonia , Blázquez‐Goñi Cristina , Abdelkader‐Martín Laila
Published: July 2024

Introduction

This systematic review, adhering to PRISMA guidelines, aimed to evaluate the efficacy and safety of antiemetic prophylaxis in haematological patients undergoing high‐dose chemotherapy as part of their hematopoietic stem cell transplantation (HSCT) conditioning regimens.

Methods

We performed a comprehensive search in PubMed, EMBASE, ClinicalTrials.gov and the Cochrane database to identify randomised controlled trials (RCTs) and systematic reviews of antiemetic prophylaxis. Studies in English, French, Italian or Spanish were included. This review is registered with PROSPERO, ID CRD42023406380.

Results

Eight RCTs were analysed. The antiemetic regimens evaluated ranged from monotherapy with 5‐Hydroxytryptamine Receptor 3 antagonists (5‐HT3RAs) to complex combinations including olanzapine, neurokinin‐1 receptor antagonists, 5‐HT3RAs and corticosteroids. Complete response rates for triplet or quadruple regimens varied between 23.5% and 81.9%. Although no significant adverse effects were observed, minor symptoms such as diarrhoea, constipation, sedation and headaches were reported.

Conclusion

Existing evidence on HSCT antiemetic therapy highlights its benefits but fails to provide clear clinical directions. The choice between triplet and quadruplet therapies for different patient scenarios is still uncertain. Until more detailed research is available, healthcare providers must rely on the latest guidelines and their judgement to customise antiemetic care for each patient's specific needs and risks.
Epigenetic mechanisms and oral mucositis in children with acute lymphoblastic leukaemia
Authors: Guimarães Juliana Ramalho , de Souza Beatriz Fernandes , Filho José Maria Chagas Viana , Damascena Lecidamia Cristina Leite , Valença Ana Maria Gondim , Persuhn Darlene Camati , de Oliveira Naila Francis Paulo
Published: July 2024

This study aimed to investigate the relationship between epigenetic mechanisms and oral mucositis (OM) in paediatric patients with acute lymphoblastic leukaemia. Oral cells were collected from 76 participants, including 15 healthy individuals, 10 patients with acute lymphoblastic leukaemia but without a history of OM and 51 acute lymphoblastic leukaemia patients with a history of OM (35 with active OM and 16 who had recovered from OM). Global DNA methylation in the miR‐9‐1 and miR‐9‐3 genes was performed. Seven polymorphisms rs1801131, rs1801133 (MTHFR), rs2228611 (DNMT1), rs7590760, rs1550117 (DNMT3A), rs6087990, rs2424913 (DNMT3B) were genotyped and an analysis of association with global DNA methylation was performed. The global methylation levels were lower in cancer patients recovered from OM than in the other groups. A higher frequency of unmethylated profile for miR‐9‐1 and partially methylated profile for miR‐9‐3 was observed in cancer patients regardless of OM history compared to healthy patients. The GG genotype of the rs2228611 (DNMT1) polymorphism was associated with higher levels of global methylation in cancer patients irrespective of OM. It was concluded that global methylation is associated with mucosal recovery. The effect of DNMT1 genotype on the global DNA methylation profile, as well as the methylation profile of miR‐9‐1 and miR‐9‐3 in cancer patients is independent of OM.
Unveiling the value of C‐reactive protein as a severity biomarker and the IL4/IL13 pathway as a therapeutic target in recessive dystrophic epidermolysis bullosa: A multiparametric cross‐sectional study
Authors: Quintana‐Castanedo Lucía , Sánchez‐Ramón Silvia , Maseda Rocío , Illera Nuria , Pérez‐Conde Isabel , Molero‐Luis Marta , Butta Nora , Arias‐Salgado Elena G. , Monzón‐Manzano Elena , Zuluaga Pilar , Martínez‐Santamaría Lucía , Fernández‐Arquero Miguel , Llames Sara G. , Meana Álvaro , de Lucas Raúl , del Río Marcela , Vicente Ángeles , Escámez María José , Sacedón Rosa
Published: July 2024

Patients with recessive dystrophic epidermolysis bullosa (RDEB) experience numerous complications, which are exacerbated by inflammatory dysregulation and infection. Understanding the immunological mechanisms is crucial for selecting medications that balance inflammation control and immunocompetence. In this cross‐sectional study, aiming to identify potential immunotherapeutic targets and inflammatory biomarkers, we delved into the interrelationship between clinical severity and systemic inflammatory parameters in a representative RDEB cohort. Encompassing 84 patients aged 1–67 and spanning all three Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) severity categories, we analysed the interrelationship of infection history, standard inflammatory markers, systemic cytokines and Ig levels to elucidate their roles in RDEB pathophysiology. Our findings identify C‐reactive protein as an excellent biomarker for disease severity in RDEB. A type 2 inflammatory profile prevails among moderate and severe RDEB patients, correlating with dysregulated circulating IgA and IgG. These results underscore the IL4/IL13 pathways as potential evidence‐based therapeutic targets. Moreover, the complete inflammatory scenario aligns with Staphylococcus aureus virulence mechanisms. Concurrently, abnormalities in IgG, IgE and IgM levels suggest an immunodeficiency state in a substantial number of the cohort's patients. Our results provide new insights into the interplay of infection and immunological factors in the pathogenesis of RDEB.
Did the entry of the corn ethanol industry in Brazil affect the relationship between domestic and international corn prices?
Authors: Justus Marcelo , Bachion Luciane Chiodi , Arantes Sofia Marques , Moreira Marcelo Melo Ramalho , Rodrigues Luciano
Published: July 2024

This study investigates the relationship between corn prices in Brazil and the international market, considering a rise in corn ethanol production in Brazil's Midwest region since 2017. Did the entry of the corn ethanol industry in Brazil affect the relationship between domestic and international corn prices? A cointegration analysis was made with a monthly time series from May 2005 to August 2023 controlling for different exogenous events or shocks that may have affected global agricultural markets. The study's findings indicate a stable long‐term relationship between the international and Brazilian corn prices, with changes in international prices being predictors of variations in Brazilian domestic prices, while the opposite was not statistically supported. The study also found no evidence to support the claim that the entry of the corn ethanol industry into Mato Grosso state in 2017 impacted the prices paid to local producers. Therefore, the increase in Brazilian corn prices cannot be attributed to additional demand for corn by local mills, an important result that contributes to discussions such as food versus fuel and indirect land use change.
Misrecognition and labor market inclusion of refugee mothers
Authors: Maj Jolanta , Hamza‐Orlinska Aneta , Sytnik Inessa , Stopochkin Artem , Özbilgin Mustafa
Published: July 2024

185,000 refugees from Ukraine have started working in Poland since the Russian war began. Drawing on Bourdieusian concepts of capitals, misrecognition, habitus, and the field, the paper theorizes the subjective and objective terms of inclusion across intersectional interplay of motherhood, ethnicity, and refugee status. In particular, we explore how intersectional marginalized identities of individuals shape their negotiation power over terms of their labor market inclusion. Using qualitative interview data from 10 Ukrainian working mothers in Poland who became refugees following the Russian war in Ukraine in 2022, we demonstrate that misrecognition leads to uneven relations of power curtailing working refugee mothers' agency to negotiate the terms of their inclusion.
Retained PAX2 expression associated with DNA mismatch repair deficiency in endometrial endometrioid adenocarcinoma
Authors: X. Zhang Gloria , Yang Bin
Published: July 2024

Aims

Loss of expression of tumour suppressor PAX2 and MMR deficiency (dMMR) has been frequently seen in endometrial endometrioid adenocarcinoma (EEC). However, the relationship between PAX2 expression and MMR status is unknown.

Methods and Results

We studied the PAX2 expression and examined its association with MMR status at the protein and genetic levels in 180 cases of EEC. Overall, total loss of PAX2 expression was found in about 70%, while retained PAX2 expression was seen in 30% of EEC. Among 125 cases with loss of PAX2, 68.8% were found in EECs with pMMR, while 31.2% were seen in those with dMMR. Among 55 cases of EECs with retained PAX2 expression, 92.7% were EECs with dMMR and 7.3% were those with pMMR (P < 0.001). While dMMR cases with MLH1 hypermethylation show almost equal retained or loss of PAX2 expression (52% versus 48%), dMMR with genetic alterations had significantly more retained PAX2 expression than loss of PAX2 (92.3% versus 7.7%), regardless of somatic or germline mutations. Loss of PAX2 was observed in 97.3% of dMMR with MLH1 hypermethylation compared to 2.7% of dMMR with genetic alterations (P < 0.001). Aggressive features such as higher tumour grades (FIGO 2–3) and advanced clinical stage (T2–T4) were significantly more frequently seen in dMMR with retained PAX2 expression, compared those to pMMR with loss of PAX2 expression.

Conclusion

Our study demonstrates a close correlation between retained PAX2 expression and dMMR in EEC. The molecular mechanism and clinical significance linking these two pathways in EEC remains to be unravelled.
Spatio‐temporal differences in the diet and trophic ecology of Kelp Gulls (Larus dominicanus) in South Africa
Authors: Reusch Katharina , Connan Maëlle , Ryan Peter G. , Butler Mike , Pichegru Lorien
Published: July 2024

Opportunistic species, including some gulls (Laridae), can benefit from urbanization and increased anthropogenic food resources. Knowledge of the level of exploitation of anthropogenic resources by gulls is crucial to understand how changes in food availability might affect their populations, which in turn may impact other species. The Kelp Gull Larus dominicanus is widely distributed in the southern hemisphere and consumes a wide variety of resources, from waste in landfills to seabirds. We assessed if proximity to landfills influenced the diet and trophic ecology of Kelp Gull incubating adults and chicks using a combination of conventional diet sampling (stomach contents, regurgitated pellets), and carbon and nitrogen stable isotope analysis of blood plasma in seven colonies over two consecutive years in South Africa. Kelp Gulls consumed a variety of resources, including marine (e.g. fish), coastal (e.g. molluscs), terrestrial natural (e.g. insects, mammals), or terrestrial anthropogenic (e.g. chicken, bread) items. Inter‐annual differences were most apparent among gulls breeding next to a seabird colony, whereas gulls breeding at other colonies were more consistent in diet and trophic ecology. At most colonies, chicks were fed more natural and higher trophic level food items than were consumed by incubating adults. Overall, distance to landfill did not strongly affect the diet and trophic ecology and our results suggest that the Kelp Gull's broad feeding ecology allows it to buffer changes in food availability by switching among food resources. However, such dietary changes triggered by human actions may impact other species, including threatened seabirds.
Artificial intelligence in endodontics: Data preparation, clinical applications, ethical considerations, limitations, and future directions
Authors: Mohammad‐Rahimi Hossein , Sohrabniya Fatemeh , Ourang Seyed AmirHossein , Dianat Omid , Aminoshariae Anita , Nagendrababu Venkateshbabu , Dummer Paul Michael Howell , Duncan Henry F. , Nosrat Ali
Published: July 2024

Artificial intelligence (AI) is emerging as a transformative technology in healthcare, including endodontics. A gap in knowledge exists in understanding AI's applications and limitations among endodontic experts. This comprehensive review aims to (A) elaborate on technical and ethical aspects of using data to implement AI models in endodontics; (B) elaborate on evaluation metrics; (C) review the current applications of AI in endodontics; and (D) review the limitations and barriers to real‐world implementation of AI in the field of endodontics and its future potentials/directions. The article shows that AI techniques have been applied in endodontics for critical tasks such as detection of radiolucent lesions, analysis of root canal morphology, prediction of treatment outcome and post‐operative pain and more. Deep learning models like convolutional neural networks demonstrate high accuracy in these applications. However, challenges remain regarding model interpretability, generalizability, and adoption into clinical practice. When thoughtfully implemented, AI has great potential to aid with diagnostics, treatment planning, clinical interventions, and education in the field of endodontics. However, concerted efforts are still needed to address limitations and to facilitate integration into clinical workflows.
Effect of silicon carbide content on microstructure, physical and mechanical properties in vat photopolymerization of alumina
Authors: Zhao Zhengyu , Wu Hailong , Guo Anfu , Kong Dekun , Wang Lu , Liu Chang , Yin Lvfa , Xia Guojun , Su Xiaofei
Published: July 2024

Vat photopolymerization (VPP) printing of ceramic parts offers advantages such as low cost, simple operation, and short fabrication cycles. However, drawbacks include low toughness and brittleness in the printed parts. This study explores enhancing the toughness and strength of alumina (Al2O3) ceramics by incorporating silicon carbide (SiC) particles as additives. The impact of varying SiC contents on the quality of VPP‐printed Al2O3 parts is examined, encompassing microstructure, physical properties, and mechanical properties. Results indicate that optimal SiC addition reduces Al2O3 ceramics' porosity, enhances crystalline quality, and boosts mechanical properties. Excessive SiC, however, diminishes these benefits. The most significant strengthening of Al2O3 parts occurred with a 1.5 wt.% SiC content, increasing bending strength and fracture toughness by 239.7% and 564.7%, respectively. This underscore SiC's positive role in enhancing the quality of VPP‐printed Al2O3 parts.
Antioxidant capacity, antitumor activity and metabolomic profile of tamarillo (Solanum betaceum)
Authors: Silva Luciana de Oliveira , Rosado Carolyne Pimentel , Samary Manuela , Cruz Marta Angela de Almeida Sousa , Montenegro Júlia , Silva Giovana Ramalho Patrizi da , Antonio Ananda da Silva , Pereira Henrique Marcelo Gualberto , Veiga‐Junior Valdir Florêncio da , Palumbo Antonio , Teodoro Anderson Junger , Nunes Juliana Cortes
Published: July 2024

Tamarillo (Solanum betaceum), native to the Andes and a PANC in Brazil, contains bioactive compounds with potential anticancer properties in vitro. This study aimed to assess the influence of tamarillo extracts for their antioxidant activity, chemical composition and antiproliferative effects on human prostate cells. Aqueous (AE) and ethanolic extracts (EE) were tested, revealing higher phenolic content and superior antioxidant activity in EE (TPC: 1191.78 ± 28.16 mg GAE/100 g, DPPH: 514.90 μmol TE g−1; FRAP: 150.35 ± 4.42 μmol Fe2SO4 g−1). UPLC‐MS analysis identified twenty‐two compound classes, mainly flavonoids (eleven), carboxylic acids and derivatives (eight), organooxygen compounds (eight) and fatty acyls (seven). Tamarillo extracts significantly reduced cell viability in DU‐145 and PC‐3 cells by almost 60% in 48 h, with PC‐3 cells showing greater resilience and a 30% reduction with EE. Additionally, tamarillo extracts induced cell cycle arrest (G2/M phase) and apoptosis, suggesting their potential as natural antioxidants with protective effects against prostate cancer.