bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between glycemic status and the risk of acute pancreatitis: a nationwide population-based study
Authors: Cho In Rae , Han Kyung-Do , Lee Sang Hyub , Choi Young Hoon , Chung Kwang Hyun , Choi Jin Ho , Park Namyoung , Lee Min Woo , Paik Woo Hyun , Ryu Ji Kon , Kim Yong-Tae
Published: May 2023

Background

Although diabetes is reportedly associated with the occurrence of acute pancreatitis (AP), the risk of AP according to the duration and severity of diabetes is not yet clear. We aimed to investigate the risk of AP based on glycemic status and the presence of comorbidities using a nationwide population-based study.

Methods

We enrolled 3,912,496 adults who underwent health examinations under the National Health Insurance Service in 2009. All participants were categorized by glycemic status as normoglycemic, impaired fasting glucose (IFG), or diabetes. Baseline characteristics and the presence of comorbidities at the time of health check-up were investigated, and the occurrence of AP was followed up until 31 December 2018. We estimated the adjusted hazard ratios (aHRs) for AP occurrence according to the glycemic status, duration of diabetes (new-onset, duration < 5 years, or ≥ 5 years), type and number of anti-diabetic medications, and presence of comorbidities.

Results

During the observation period of 32,116,716.93 person-years, 8,933 cases of AP occurred. Compared with normoglycemia, the aHRs (95% confidence interval) were 1.153 (1.097–1.212) in IFG, 1.389 (1.260–1.531) in new-onset diabetes, 1.634 (1.496–1.785) in known diabetes < 5 years, and 1.656 (1.513–1.813) in patients with known diabetes aged ≥ 5 years. The presence of comorbidities associated with diabetes severity had a synergistic effect on the relationship between diabetes and AP occurrence.

Conclusion

As glycemic status worsens, the risk of AP increases, and there is a synergistic effect when comorbidities coexist. To reduce the risk of AP, active control of factors that can cause AP should be considered in patients with long-standing diabetes and comorbidities.
Comparative developmental genomics of sex-biased gene expression in early embryogenesis across mammals
Authors: Richardson Victorya , Engel Nora , Kulathinal Rob J.
Published: May 2023

Background

Mammalian gonadal sex is determined by the presence or absence of a Y chromosome and the subsequent production of sex hormones contributes to secondary sexual differentiation. However, sex chromosome-linked genes encoding dosage-sensitive transcription and epigenetic factors are expressed well before gonad formation and have the potential to establish sex-biased expression that persists beyond the appearance of gonadal hormones. Here, we apply a comparative bioinformatics analysis on a pair of published single-cell datasets from mouse and human during very early embryogenesis—from two-cell to pre-implantation stages—to characterize sex-specific signals and to assess the degree of conservation among early acting sex-specific genes and pathways.

Results

Clustering and regression analyses of gene expression across samples reveal that sex initially plays a significant role in overall gene expression patterns at the earliest stages of embryogenesis which potentially may be the byproduct of signals from male and female gametes during fertilization. Although these transcriptional sex effects rapidly diminish, sex-biased genes appear to form sex-specific protein–protein interaction networks across pre-implantation stages in both mammals providing evidence that sex-biased expression of epigenetic enzymes may establish sex-specific patterns that persist beyond pre-implantation. Non-negative matrix factorization (NMF) on male and female transcriptomes generated clusters of genes with similar expression patterns across sex and developmental stages, including post-fertilization, epigenetic, and pre-implantation ontologies conserved between mouse and human. While the fraction of sex-differentially expressed genes (sexDEGs) in early embryonic stages is similar and functional ontologies are conserved, the genes involved are generally different in mouse and human.

Conclusions

This comparative study uncovers much earlier than expected sex-specific signals in mouse and human embryos that pre-date hormonal signaling from the gonads. These early signals are diverged with respect to orthologs yet conserved in terms of function with important implications in the use of genetic models for sex-specific disease.
Sustaining medical research – the role of trust and control
Authors: John Michael , Kloyer Martin , Fleßa Steffen
Published: May 2023

Background

Medical research is increasingly interdisciplinary. However, not all projects are successful and cooperation is not always sustained beyond the end of funding. This study empirically assesses the effect of control and trust on the sustainability of interdisciplinary medical research in terms of its performance and satisfaction.

Methods

The sample consists of 100 German publicly funded medical research collaborations with scientists from medicine, natural and social sciences (N = 364). We develop a system model to analyze the influence of trust and control on performance and satisfaction of the cooperation.

Findings

Both control and trust are important prerequisites for sustainability, control mainly for the performance of the collaboration, and trust primarily for its satisfaction. While the level of interdisciplinarity is a positive moderator for performance, expectation of continuity is a negative intervening variable for the effect of trust and control on satisfaction. Moreover, trust principally adds to the positive impact of control on sustainability.

Conclusions

Interdisciplinary medical research requires a participative but systematic management of the respective consortium.
Bacterial pathogens and in-hospital mortality in revision surgery for periprosthetic joint infection of the hip and knee: analysis of 346 patients
Authors: Migliorini Filippo , Weber Christian David , Bell Andreas , Betsch Marcel , Maffulli Nicola , Poth Vanessa , Hofmann Ulf Krister , Hildebrand Frank , Driessen Arne
Published: May 2023

Introduction

The management of periprosthetic joint infections (PJI) of the lower limb is challenging, and evidence-based recommendations are lacking. The present clinical investigation characterized the pathogens diagnosed in patients who underwent revision surgery for  PJI of total hip arthroplasty (THA) and total knee arthroplasty (TKA).

Methods

The present study follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). The institutional databases of the RWTH University Medical Centre of Aachen, Germany, were accessed. The OPS (operation and procedure codes) 5–823 and 5–821 and the ICD (International Statistical Classification of Diseases and Related Health Problems) codes T84.5, T84.7 or T84.8 were used. All patients with PJI of a previous THA and TKA who underwent revision surgery were retrieved and included for analysis.

Results

Data from 346 patients were collected (181 THAs and 165 TKAs). 44% (152 of 346 patients) were women. Overall, the mean age at operation was 67.8 years, and the mean BMI was 29.2 kg/m2. The mean hospitalization length was 23.5 days. 38% (132 of 346) of patients presented a recurrent infection.

Conclusion

PJI remain a frequent cause for revisions after total hip and knee arthroplasty. Preoperative synovial fluid aspiration was positive in 37%, intraoperative microbiology was positive in 85%, and bacteraemia was present in 17% of patients. Septic shock was the major cause of in-hospital mortality. The most common cultured pathogens were Staph. epidermidis, Staph. aureus, Enterococcus faecalis, and Methicillin-resistant Staph aureus (MRSA). An improved understanding of PJI pathogens is important to plan treatment strategies and guide the choice of empirical antibiotic regimens in patients presenting with septic THAs and TKAs.

Level of Evidence: Level III, retrospective cohort study.
Individuation of the best agronomic practices for organic durum wheat cultivation in the Mediterranean environment: a multivariate approach
Authors: Carucci Federica , Gatta Giuseppe , Gagliardi Anna , Bregaglio Simone , Giuliani Marcella Michela
Published: May 2023

Background

The main challenge of organic cereal systems is ensuring high yields and grain quality while maintaining pedo-environmental sustainability. Despite the potential benefits of organic farming systems, a debated limitation is their actual contribution to food security. Durum wheat [Triticum turgidumL. subsp.durum(Desf.) Husn.], one of the most important staple food crops, is mainly grown in the Mediterranean environments, where farmers have to face profound inter-annual fluctuations in productions, expecially under organic system, due to prolonged drought and heat spells. With the overarching objective of deriving practical indications to support organic wheat production in the Mediterranean region, we tested the effect of nitrogen and sulphur-based organic foliar fertilizers on two ancient and two modern durum wheat varieties grown in two seasons (2018–2019) characterized by different weather conditions. Moreover, we evaluated the effect of a foliar application of Selenium at booting on grain yield and quality.

Results

Results from the Principal Component analysis revealed that seasonal weather and the varietal choice determined most of the variability of yield and quality traits, while Selenium application markedly affected the performance of organic durum wheat, especially in the milder season. The Cluster Analysis computed on the Principal Components revealed three groups, representative of (i) the modern variety, Marco Aurelio, grown in the dryest season (average yield, low protein content), (ii) all varieties grown in 2018, with the addition of sodium selenate (high yield, high protein content), and (iii) the ancient variety, Cappelli, grown in both seasons (low yield, average protein content).

Conclusions

This study evidenced that tailored agronomic practices are needed to sustain the organic durum wheat systems in the Mediterranean area. The promising beneficial effect of Selenium would deserve a dedicated research program, where additional experiments should further investigate its impact on organic durum wheat yield and quality. The multivariate approach permitted us to identify the most effective agronomic practices in relation to different environmental conditions; the outputs from this study are ready to be transferred to organic farmers aiming at improving the performance of durum wheat systems and at providing an effective contribution to food security.
Views and experiences of migrants and stakeholders involved in social and health care for migrants in Italy during the COVID-19 pandemic: a qualitative study
Authors: Lotito Claudia , Turrini Giulia , Purgato Marianna , Bryant Richard A. , Felez-Nobrega Mireia , Haro Josep Maria , Lorant Vincent , McDaid David , Mediavilla Roberto , Melchior Maria , Nicaise Pablo , Nosè Michela , Park A-La , McGreevy Kerry R. , Roos Rinske , Tortelli Andrea , Underhill James , Martinez Julian Vadell , Witteveen Anke , Sijbrandij Marit , Barbui Corrado
Published: May 2023

Background

The COVID-19 pandemic has had major and potentially long-lasting effects on mental health and wellbeing across populations worldwide. However, these impacts were not felt equally, leading to an exacerbation of health inequalities, especially affecting vulnerable populations such as migrants, refugees and asylum seekers. Aiming to inform the adaptation and implementation of psychological intervention programmes, the present study investigated priority mental health needs in this population group.

Methods

Participants were adult asylum seekers, refugees and migrants (ARMs) and stakeholders with experience in the field of migration living in Verona, Italy, and fluent in Italian and English. A two-stage process was carried out to examine their needs using qualitative methods including free listing interviews and focus group discussions, according to Module One of the DIME (Design, Implementation, Monitoring, and Evaluation) manual. Data were analyzed using an inductive thematic analyses approach.

Results

A total of 19 participants (12 stakeholders, 7 ARMs) completed the free listing interviews and 20 participants (12 stakeholders and 8 ARMs) attended focus group discussions. Salient problems and functions that emerged during free listing interviews were discussed during the focus group discussions. During the COVID-19 pandemic, ARMs struggled with many everyday living difficulties in their resettlement country due to social and economic issues, revealing a strong influence of contextual factors in determining mental health. Both ARMs and stakeholders highlighted a mismatch between needs, expectations and interventions as factors that may hamper proper implementation of health and social programmes.

Conclusions

The present findings could help in the adaptation and implementation of psychological interventions targeting the needs of asylum seekers, refugees and migrants aiming to find a match between needs, expectations, and the corresponding interventions.

Trial registration

Registration number 2021-UNVRCLE-0106707, February 11 2021.
Engagement over telehealth: comparing attendance between dialectical behaviour therapy delivered face-to-face and via telehealth for programs in Australia and New Zealand during the Covid-19 pandemic
Authors: Walton Carla J. , Gonzalez Sharleen , Cooney Emily B. , Leigh Lucy , Szwec Stuart
Published: May 2023

Background

While the COVID-19 crisis has had numerous global negative impacts, it has also presented an imperative for mental health care systems to make digital mental health interventions a part of routine care. Accordingly, through necessity, many Dialectical Behaviour Therapy (DBT) programs transitioned to telehealth, despite little information on clinical outcomes compared with face-to-face treatment delivery. This study examined differences in client engagement (i.e. attendance) of DBT: delivered face-to-face prior to the first COVID-19 lockdown in Australia and New Zealand; delivered via telehealth during the lockdown; and delivered post-lockdown. Our primary outcomes were to compare: [1] client attendance rates of DBT individual therapy delivered face-to-face with delivery via telehealth, and [2] client attendance rates of DBT skills training delivered face-to-face compared with delivery via telehealth.

Methods

DBT programs across Australia and New Zealand provided de-identified data for a total of 143 individuals who received DBT treatment provided via telehealth or face-to-face over a six-month period in 2020. Data included attendance rates of DBT individual therapy sessions; attendance rates of DBT skills training sessions as well as drop-out rates and First Nations status of clients.

Results

A mixed effects logistic regression model revealed no significant differences between attendance rates for clients attending face-to-face sessions or telehealth sessions for either group therapy or individual therapy. This result was found for clients who identified as First Nations persons and those who didn’t identify as First Nations persons.

Conclusions

Clients were as likely to attend their DBT sessions over telehealth as they were face-to-face during the first year of the Covid-19 pandemic. These findings provide preliminary evidence that providing DBT over telehealth may be a viable option to increase access for clients, particularly in areas where face-to-face treatment is not available. Further, based on the data collected in this study, we can be less concerned that offering telehealth treatment will compromise attendance rates compared to face-to-face treatment. Further research is needed comparing clinical outcomes between treatments delivered face-to-face compared delivery via telehealth.
Eco-friendly cellulose-based hydrogels derived from wastepapers as a controlled-release fertilizer
Authors: Ahmad Dayang Fazirah Binyi Abg , Wasli Mohd Effendi , Tan Cindy Soo Yun , Musa Zaki , Chin Suk-Fun
Published: May 2023

In this study, an eco-friendly controlled release fertilizer cellulose-based hydrogel was prepared from cellulose fibers derived from wastepaper, epichlorohydrin (ECH) as a crosslinker and carboxy methyl cellulose (CMC) as a gelling agent. A maximum swelling capacity of 2000% was achieved for cellulose hydrogel with optimum composition. The soil moisture contents in the presence of optimized cellulose hydrogels were determined using the digital moisture meter. Maximum soil moisture of 36.5% was obtained in topsoil, followed by 30.1% in wet clayey soil and 23.4% in sandy soil after 7 days. Urea as a model fertilizer was loaded onto the cellulose hydrogels to control the release of fertilizer. The maximum loading capacity of urea in cellulose hydrogel is 0.51 g/g. The urea-controlled release profiles of the cellulose hydrogel in distilled water and various types of soils were investigated. The formulation of cellulose hydrogels was observed to facilitate the gradual release of urea, with about 74.71% release in topsoil, 73.37% release in wet clayey soil and 71.84% release in sandy soil within 42 days when compared to the free urea which was about 97.32%, 95.09% and 98.47% release in topsoil, wet clayey soils and sandy soils, respectively within 7 days. The result of this study shows that the urea-loaded cellulose hydrogel could be a promising controlled-release fertilizer.

Graphical Abstract
Effectiveness of digital educational game and game design in STEM learning: a meta-analytic review
Authors: Gui Yang , Cai Zhihui , Yang Yajiao , Kong Lingyuan , Fan Xitao , Tai Robert H.
Published: May 2023

Digital educational games exhibit substantial promise in advancing STEM education. Nevertheless, the empirical evidence on both the efficacy of digital game-based learning and its designs in STEM education is characterized by notable inconsistencies. Therefore, the current study aimed to investigate (1) the general effect of digital game-based STEM learning over STEM learning without digital game, and (2) the enhancement effect of added game-design elements against base game versions in STEM learning. Two meta-analyses were conducted in this study. Based on the 136 effect sizes extracted from 86 studies, the first meta-analysis revealed a medium to large general effect of digital game-based STEM learning over conventional STEM learning (g = 0.624, 95% CI [0.457, 0.790]). In addition, digital game-based STEM learning appeared to be differentially effective for different learning outcome, different types of game, and different subject. A total of 44 primary studies and 81 effect sizes were identified in the second meta-analysis. The results revealed a small to medium enhancement effect of added game-design elements over base game versions (g = 0.301, 95% CI [0.163, 0.438]). Furthermore, our results indicated that the game-design elements added for content learning were more effective than those added for gaming experience. Possible explanations for these findings, as well as the limitations and directions for future research were discussed.
Time–frequency multiresolution of fault-generated transient signals in transmission lines using a morphological filter
Authors: Quispe Juan Carlos , Morales John , Orduna Eduardo , Liebermann Carlo , Bruhns Michael , Schegner Peter
Published: May 2023

The ongoing transformation of electrical power systems highlights the weaknesses of the protection schemes of traditional devices because they are designed and configured according to traditional characteristics of the system. Therefore, this work proposes a new methodology to study the fault-generated high frequency transient signals in transmission lines through multiresolution analysis. The high frequency components are determined by a new digital filtering technique based on mathematical morphology theory and a spectral energy index. Consequently, wide spectra of signals in the time–frequency domain are obtained. The performance of this method is verified on an electrical power system modeled in ATP-Draw, where simulation and test signals are developed for different locations, fault resistances, inception angles, high frequency noises, sampling frequencies, types of faults, and shapes of the structuring element. The results show the characteristics of the fault such as the traveling wave frequency, location, and starting time.
Drug release kinetics of capsule shells from seaweed carrageenan extract (Eucheuma cottonii) and potato starch as a gelling agent
Authors: Erawati Emi , Hamid Hamid , Musthofa Malik , Fatoni Rois , Nurwaini Setyo , Rahmah Anisa Ur , Setiawan Panji Rasma
Published: May 2023

Background

Capsules are created to put a drug or active pharmaceutical ingredient in an elegant, odorless, tasteless, easy-to-swallow and to-fill shell commonly produced from gelatin. Therefore, carrageenan is one of the other natural ingredients that can replace gelatin. This study aims to make capsule shells from carrageenan seaweed (Eucheuma cottonii) with variations in carrageenan composition and temperature using potato starch as a gelling agent with the addition of PEG as a plasticizer and to determine the kinetics model of the drug release system from the capsules that have been made.

Results

In the research there are two variations namely composition and temperature. The capsule shell dissolution test results were calculated using kinetic models of order 0, order 1, Higuchi, and Korsmeyer-Peppas. The result on zero order is that at the C composition and temperature 55 ºC variations obtained the reaction rate constant (k) are 1.05 and 1.27 min respectively. While in first order obtained the reaction rate constant of 4.59 × 10–2 and 2.06 × 10−2 min−1 respectively at variations in capsule D composition and temperature of 60ºC. In the Higuchi model, the correlation coefficient for composition variation is better than temperature variation of 0.92. In the Korsmeyyer-Peppas model, the value of reaction rate constant (k) at composition C and temperature of 55 ºC variations are 1.41 × 10–2 and 9.49 × 10−3 min−n.

Conclusions

The Korsmeyyer–Peppas kinetic model is suitable for illustrating the drug release kinetics of capsule shells from seaweed carrageenan extract (Eucheuma cottonii) and potato starch as a gelling agent.
Concrete–filled steel tube truss girders—a state-of-the-art review
Authors: Joseph Jane Regita , Henderson Jane Helena
Published: May 2023

Steel–concrete composite construction is practised worldwide due to the strength and stiffness achieved with minimum use of materials. Among the various forms of steel–concrete composite construction in practice, concrete–filled tube (CFT) and specifically concrete–filled steel tube (CFST) is a well-received system. Concrete–filled steel tube (CFST) system comprises of an infill concrete core that withstands loading and prevents local buckling and steel at the outer circumference to effectively resist bending. Owing to the benefits of CFST in buildings viz., strength, ductility, constructability, and aesthetics, its usage has been extended to bridges in recent years. One such adaptation is CFST truss girders, where the concrete infill increases the compressive strength of the top chord and the tensile strength of the bottom chord preventing buckling and pinching action respectively. Since design methods for CFST composite girders are not yet established in detail, the use of CFSTs in girder bridge systems is limited. So far, the responses of this system have been studied under static and dynamic loading both experimentally and analytically. This paper collectively presents the behavior of such CFST truss girders with special emphasis on truss bridge girders based on the extensive research activities carried out in the last two decades. Potential areas of research in the future are also identified and summarized.
Rabies in a postpandemic world: resilient reservoirs, redoubtable riposte, recurrent roadblocks, and resolute recidivism
Authors: Rupprecht Charles E. , Mshelbwala Philip P. , Reeves R. Guy , Kuzmin Ivan V.
Published: May 2023

Rabies is an ancient disease. Two centuries since Pasteur, fundamental progress occurred in virology, vaccinology, and diagnostics—and an understanding of pathobiology and epizootiology of rabies in testament to One Health—before common terminological coinage. Prevention, control, selective elimination, and even the unthinkable—occasional treatment—of this zoonosis dawned by the twenty-first century. However, in contrast to smallpox and rinderpest, eradication is a wishful misnomer applied to rabies, particularly post-COVID-19 pandemic. Reasons are minion. Polyhostality encompasses bats and mesocarnivores, but other mammals represent a diverse spectrum of potential hosts. While rabies virus is the classical member of the genus, other species of lyssaviruses also cause the disease. Some reservoirs remain cryptic. Although global, this viral encephalitis is untreatable and often ignored. As with other neglected diseases, laboratory-based surveillance falls short of the notifiable ideal, especially in lower- and middle-income countries. Calculation of actual burden defaults to a flux within broad health economic models. Competing priorities, lack of defined, long-term international donors, and shrinking local champions challenge human prophylaxis and mass dog vaccination toward targets of 2030 for even canine rabies impacts. For prevention, all licensed vaccines are delivered to the individual, whether parenteral or oral–essentially ‘one and done’. Exploiting mammalian social behaviors, future ‘spreadable vaccines’ might increase the proportion of immunized hosts per unit effort. However, the release of replication-competent, genetically modified organisms selectively engineered to spread intentionally throughout a population raises significant biological, ethical, and regulatory issues in need of broader, transdisciplinary discourse. How this rather curious idea will evolve toward actual unconventional prevention, control, or elimination in the near term remains debatable. In the interim, more precise terminology and realistic expectations serve as the norm for diverse, collective constituents to maintain progress in the field.
Genetic and Genomic Testing for Prostate Cancer: Beyond DNA Repair
Authors: Herberts Cameron , Wyatt Alexander W. , Nguyen Paul L. , Cheng Heather H.
Published: May 2023

Significant progress has been made in genetic and genomic testing for prostate cancer across the disease spectrum. Molecular profiling is increasingly relevant for routine clinical management, fueled in part by advancements in testing technology and integration of biomarkers into clinical trials. In metastatic prostate cancer, defects in DNA damage response genes are now established predictors of benefit to US Food and Drug Administration–approved poly (ADP-ribose) polymerase inhibitors and immune checkpoint inhibitors, and trials are actively investigating these and other targeted treatment strategies in earlier disease states. Excitingly, opportunities for molecularly informed management beyond DNA damage response genes are also maturing. Germline genetic variants (eg, BRCA2 or MSH2/6) and polygenic germline risk scores are being investigated to inform cancer screening and active surveillance in at-risk carriers. RNA expression tests have recently gained traction in localized prostate cancer, enabling patient risk stratification and tailored treatment intensification via radiotherapy and/or androgen deprivation therapy for localized or salvage treatment. Finally, emerging minimally invasive circulating tumor DNA technology promises to enhance biomarker testing in advanced disease pending additional methodological and clinical validation. Collectively, genetic and genomic tests are rapidly becoming indispensable tools for informing the optimal clinical management of prostate cancer.
Management of Prostate Cancer in Older Adults
Authors: Graham Laura S. , Lin John K. , Lage Daniel E. , Kessler Elizabeth R. , Parikh Ravi B. , Morgans Alicia K.
Published: May 2023

The majority of men with prostate cancer are diagnosed when they are older than 65 years; however, clinical trial participants are disproportionately younger and more fit than the real-world population treated in typical clinical practices. It is, therefore, unknown whether the optimal approach to prostate cancer treatment is the same for older men as it is for younger and/or more fit men. Short screening tools can be used to efficiently assess frailty, functional status, life expectancy, and treatment toxicity risk. These risk assessment tools allow for targeted interventions to increase a patient's reserve and improve treatment tolerance, potentially allowing more men to experience the benefit of the significant recent treatment advances in prostate cancer. Treatment plans should also take into consideration each patient's individual goals and values considered within their overall health and social context to reduce barriers to care. In this review, we will discuss evidence-based risk assessment and decision tools for older men with prostate cancer, highlight intervention strategies to improve treatment tolerance, and contextualize these tools within the current treatment landscape for prostate cancer.
Deep time-recurrence features
Authors: Pham Tuan D.
Published: May 2023

In this study, the notion of recurrence in chaos and nonlinear dynamics is formulated as a new method for deep feature extraction from complex data. This feature type can enhance the learning power of a state-of-the-art approach in artificial intelligence using time series or sequential data. The deep time-recurrence features are derived using the fuzzy recurrence algorithm and the iterative procedure of convolution, non-linear transformation, and down-sampling. Experimental results obtained from using a public database of healthy and pathological voice signals show that the proposed features can significantly improve the classification performance of long short-term memory networks.
Autoimmune Diabetes From Childhood to Adulthood: The Role of Pancreatic Autoantibodies and HLA-DRB1 Genotype
Authors: Urrutia Inés , Martínez Rosa , Calvo Begona , Saso-Jiménez Laura , González Pedro , Fernández-Rubio Elsa , Martín-Nieto Alicia , Aguayo Anibal , Rica Itxaso , Gaztambide Sonia , Castano Luis
Published: May 2023

Context

Autoimmune diabetes can develop at any age, but unlike early-onset diabetes, adult onset is less well documented. We aimed to compare, over a wide age range, the most reliable predictive biomarkers for this pathology: pancreatic-autoantibodies and HLA-DRB1 genotype.

Methods

A retrospective study of 802 patients with diabetes (aged 11 months to 66 years) was conducted. Pancreatic autoantibodies at diagnosis: insulin autoantibodies (IAA), glutamate decarboxylase autoantibodies (GADA), islet tyrosine phosphatase 2 autoantibodies (IA2A), and zinc transporter-8 autoantibodies (ZnT8A) and HLA-DRB1 genotype were analyzed.

Results

Compared with early-onset patients, adults had a lower frequency of multiple autoantibodies, with GADA being the most common. At early onset, IAA was the most frequent in those younger than 6 years and correlated inversely with age; GADA and ZnT8A correlated directly and IA2A remained stable.

The absence of HLA-DRB1 risk genotype was associated with higher age at diabetes onset (27.5 years; interquartile range [IQR], 14.3-35.7), whereas the high-risk HLA-DR3/DR4 was significantly more common at lower age (11.9 years; IQR, 7.1-21.6). ZnT8A was associated with DR4/non-DR3 (odds ratio [OR], 1.91; 95% CI, 1.15-3.17), GADA with DR3/non-DR4 (OR, 2.97; 95% CI, 1.55-5.71), and IA2A with DR4/non-DR3 and DR3/DR4 (OR, 3.89; 95% CI, 2.28-6.64, and OR, 3.08; 95% CI, 1.83-5.18, respectively). No association of IAA with HLA-DRB1 was found.

Conclusion

Autoimmunity and HLA-DRB1 genotype are age-dependent biomarkers. Adult-onset autoimmune diabetes is associated with lower genetic risk and lower immune response to pancreatic islet cells compared with early-onset diabetes.
New-Onset Diabetes After COVID-19
Authors: Kim Sun H , Arora Ipsa , Hsia Daniel S , Knowler William C , LeBlanc Erin , Mylonakis Eleftherios , Pratley Richard , Pittas Anastassios G
Published: May 2023

There is evidence suggesting that infection with SARS-CoV-2 can lead to several long-term sequelae including diabetes. This mini-review examines the rapidly evolving and conflicting literature on new-onset diabetes after COVID-19, which we term NODAC. We searched PubMed, MEDLINE, and medRxiv from inception until December 1, 2022, using Medical Subject Headings (MeSH) terms and free text words including “COVID-19,” “SARS-CoV-2,” “diabetes,” “hyperglycemia,” “insulin resistance,” and “pancreatic β-cell.” We also supplemented searches by examining reference lists from retrieved articles. Current evidence suggests that COVID-19 increases the risk of developing diabetes, but the attributable risk is uncertain because of limitations of study designs and the evolving nature of the pandemic, including new variants, widespread population exposure to the virus, diagnostic options for COVID-19, and vaccination status. The etiology of diabetes after COVID-19 is likely multifactorial and includes factors associated with host characteristics (eg, age), social determinants of health (eg, deprivation index), and pandemic-related effects both at the personal (eg, psychosocial stress) and the societal-community level (eg, containment measures). COVID-19 may have direct and indirect effects on pancreatic β-cell function and insulin sensitivity related to the acute infection and its treatment (eg, glucocorticoids); autoimmunity; persistent viral residency in multiple organs including adipose tissue; endothelial dysfunction; and hyperinflammatory state. While our understanding of NODAC continues to evolve, consideration should be given for diabetes to be classified as a post-COVID syndrome, in addition to traditional classifications of diabetes (eg, type 1 or type 2), so that the pathophysiology, natural history, and optimal management can be studied.
Estrogen and the Vascular Endothelium: The Unanswered Questions
Authors: SenthilKumar Gopika , Katunaric Boran , Bordas-Murphy Henry , Sarvaideo Jenna , Freed Julie K
Published: May 2023

Premenopausal women have a lower incidence of cardiovascular disease (CVD) compared with their age-matched male counterparts; however, this discrepancy is abolished following the transition to menopause or during low estrogen states. This, combined with a large amount of basic and preclinical data indicating that estrogen is vasculoprotective, supports the concept that hormone therapy could improve cardiovascular health. However, clinical outcomes in individuals undergoing estrogen treatment have been highly variable, challenging the current paradigm regarding the role of estrogen in the fight against heart disease. Increased risk for CVD correlates with long-term oral contraceptive use, hormone replacement therapy in older, postmenopausal cisgender females, and gender affirmation treatment for transgender females. Vascular endothelial dysfunction serves as a nidus for the development of many cardiovascular diseases and is highly predictive of future CVD risk. Despite preclinical studies indicating that estrogen promotes a quiescent, functional endothelium, it still remains unclear why these observations do not translate to improved CVD outcomes. The goal of this review is to explore our current understanding of the effect of estrogen on the vasculature, with a focus on endothelial health. Following a discussion regarding the influence of estrogen on large and small artery function, critical knowledge gaps are identified. Finally, novel mechanisms and hypotheses are presented that may explain the lack of cardiovascular benefit in unique patient populations.
Current and Future Advances in Surgical Therapy for Pituitary Adenoma
Authors: Khan Danyal Z , Hanrahan John G , Baldeweg Stephanie E , Dorward Neil L , Stoyanov Danail , Marcus Hani J
Published: May 2023

The vital physiological role of the pituitary gland, alongside its proximity to critical neurovascular structures, means that pituitary adenomas can cause significant morbidity or mortality. While enormous advancements have been made in the surgical care of pituitary adenomas, numerous challenges remain, such as treatment failure and recurrence. To meet these clinical challenges, there has been an enormous expansion of novel medical technologies (eg, endoscopy, advanced imaging, artificial intelligence). These innovations have the potential to benefit each step of the patient’s journey, and ultimately, drive improved outcomes.

Earlier and more accurate diagnosis addresses this in part. Analysis of novel patient data sets, such as automated facial analysis or natural language processing of medical records holds potential in achieving an earlier diagnosis. After diagnosis, treatment decision-making and planning will benefit from radiomics and multimodal machine learning models. Surgical safety and effectiveness will be transformed by smart simulation methods for trainees. Next-generation imaging techniques and augmented reality will enhance surgical planning and intraoperative navigation. Similarly, surgical abilities will be augmented by the future operative armamentarium, including advanced optical devices, smart instruments, and surgical robotics. Intraoperative support to surgical team members will benefit from a data science approach, utilizing machine learning analysis of operative videos to improve patient safety and orientate team members to a common workflow. Postoperatively, neural networks leveraging multimodal datasets will allow early detection of individuals at risk of complications and assist in the prediction of treatment failure, thus supporting patient-specific discharge and monitoring protocols.

While these advancements in pituitary surgery hold promise to enhance the quality of care, clinicians must be the gatekeepers of the translation of such technologies, ensuring systematic assessment of risk and benefit prior to clinical implementation. In doing so, the synergy between these innovations can be leveraged to drive improved outcomes for patients of the future.
Current Evidence and Rationale to Guide Perioperative Management, Including Transfusion Decisions, in Patients With Sickle Cell Disease
Authors: Azbell Roberta C. G. , Lanzkron Sophie M. , Desai Payal C.
Published: May 2023

Sickle cell disease (SCD) is a collection of inherited hemoglobin disorders that results in chronic hemolytic anemia, vaso-occlusion, pain, and end organ damage. Surgery in the SCD population requires careful planning, as perioperative stressors can lead to increased sickling and risk of inducing or further exacerbating vaso-occlusive episodes (VOEs). Additionally, the underlying hypercoagulability and immunocompromised state due to SCD places patients at increased risk of both venous thromboembolism and infection. Judicious fluid administration, temperature regulation, thorough preoperative and postoperative analgesic planning, and preoperative transfusion are all crucial components of decreasing risks of surgery in patients with SCD.
Literature as Medium: The Development and Cultural Space of New Worker Literature
Authors: Picerni Federico
Published: May 2023

Over the past few years, China's cultural landscape has seen the emergence of several authors from among its migrant laborers, or “new workers.” Fan Yusu and Xu Lizhi are the most representative. Their literary production, which draws on their personal experiences and tells their workplace stories, is an artistic configuration entirely different from both mass culture and high literature. This article analyzes the significance of this new worker literature from three perspectives. First, since the 1990s, new workers have been using the traditional medium of literature to speak with their own voices, which is particularly remarkable in the age of the internet. Second, workers’ culture spaces like the Picun Literature Group, from which Fan Yusu emerged, not only support ordinary laborers’ active interest in writing but also represent a specific cultural practice that has come into being in the post-Mao era. Third, the fact that a large number of new worker writers are “borrowing” from the language and style of 1980s literature generates a productive relation between the critical spirit of that literature and the alienating conditions under which the new workers labor. Although seen as marginal by many, new worker literature is of great cultural value for contemporary China.
Cik1 and Vik1 accessory proteins confer distinct functions to the kinesin-14 Kar3
Authors: Bergman Zane J. , Wong Jonathan J. , Drubin David G. , Barnes Georjana
Published: May 2023

The budding yeast Saccharomyces cerevisiae has a closed mitosis in which the mitotic spindle and the cytoplasmic microtubules (MTs), both of which generate forces to faithfully segregate chromosomes, remain separated by the nuclear envelope throughout the cell cycle. Kar3, the yeast kinesin-14, has distinct functions on MTs in each compartment. Here, we show that two proteins, Cik1 and Vik1, which form heterodimers with Kar3, regulate its localization and function within the cell, and along MTs in a cell cycle-dependent manner. Using a yeast MT dynamics reconstitution assay in lysates from cell cycle-synchronized cells, we found that Kar3-Vik1 induces MT catastrophes in S phase and metaphase, and limits MT polymerization in G1 and anaphase. In contrast, Kar3-Cik1 promotes catastrophes and pauses in G1, while increasing catastrophes in metaphase and anaphase. Adapting this assay to track MT motor protein motility, we observed that Cik1 is necessary for Kar3 to track MT plus-ends in S phase and metaphase but, surprisingly, not during anaphase. These experiments demonstrate how the binding partners of Kar3 modulate its diverse functions both spatially and temporally.
Divergence in cell cycle progression is associated with shifted phenology in a multivoltine moth: the European corn borer, Ostrinia nubilalis
Authors: Xia Qinwen , Chen Chao , Dopman Erik B. , Hahn Daniel A.
Published: May 2023

Evolutionary change in diapause timing can be an adaptive response to changing seasonality, and even result in ecological speciation. However, the molecular and cellular mechanisms regulating shifts in diapause timing remain poorly understood. One of the hallmarks of diapause is a massive slowdown in the cell cycle of target organs such as the brain and primordial imaginal structures, and resumption of cell cycle proliferation is an indication of diapause termination and resumption of development. Characterizing cell cycle parameters between lineages differing in diapause life history timing may help identify molecular mechanisms associated with alterations of diapause timing. We tested the extent to which progression of the cell cycle differs across diapause between two genetically distinct European corn borer strains that differ in their seasonal diapause timing. We show the cell cycle slows down during larval diapause with a significant decrease in the proportion of cells in S phase. Brain–subesophageal complex cells slow primarily in G0/G1 phase whereas most wing disc cells are in G2 phase. Diapausing larvae of the earlier emerging, bivoltine E-strain (BE) suppressed cell cycle progression less than the later emerging, univoltine Z-strain (UZ) individuals, with a greater proportion of cells in S phase across both tissues during diapause. Additionally, resumption of cell cycle proliferation occurred earlier in the BE strain than in the UZ strain after exposure to diapause-terminating conditions. We propose that regulation of cell cycle progression rates ultimately drives differences in larval diapause termination, and adult emergence timing, between early- and late-emerging European corn borer strains.
Biceps Femoris Fascicle Behavior during Submaximal and Maximal Slow Speed Contractions
Authors: BRUSCO CLARISSA M. , PINTO RONEI S. , BLAZEVICH ANTHONY J.
Published: May 2023

Purpose

The present study compared the effects of contraction intensity (submaximal vs maximal) and mode (concentric vs eccentric) on biceps femoris long head (BFlh) fascicle lengthening, rotation, and architectural gear ratio at long and short muscle lengths.

Methods

Data were captured from 18 healthy adults (10 men and 8 women) without history of right hamstring strain injury. BFlh fascicle length (L
f), fascicle angle (FA), and muscle thickness (MT) were assessed in real time using two serially aligned ultrasound devices while submaximal and maximal concentric and eccentric isokinetic knee flexions were performed at 30°·s−1. Ultrasound videos were exported and edited to create a single, synchronized video, and three fascicles were analyzed through the range of motion (10° to 80°). Changes (Δ) in L
f, FA, MT, and muscle gear at long (60° to 80° knee angle; 0° = full knee extension) and short (10° to 30°) muscle lengths and across the full knee flexion range were measured and compared.

Results

Greater ΔL
f was observed at long muscle length (P < 0.001) during both submaximal and maximal eccentric and concentric contractions. When the full length range was analyzed, a slightly greater ΔMT was observed in concentric contractions (P = 0.03). No significant differences between submaximal and maximal contractions were observed for ΔL
f, ΔFA, or ΔMT. No changes were detected in the calculated muscle gear between muscle lengths, intensities, or conditions (P > 0.05).

Conclusions

Although gear ratio ranged ~1.0 to 1.1 under most conditions, the increased fascicle lengthening observed at long muscle lengths might influence acute myofiber damage risk but also speculatively play a role in chronic hypertrophic responses to training.
Ventilatory Threshold Related to V̇O2reserve, Heart Rate Reserve, and Rating of Perceived Exertion in a Large Varied Sample
Authors: GASKILL STEVEN E. , SKINNER JAMES S. , QUINDRY JOHN
Published: May 2023

Purpose

ACSM guidelines state that aerobic exercise intensity should be 30%/40% to 89% V̇O2reserve (V̇O2R) or heart rate reserve (HRR). Determining the proper intensity within this range is the “art” of exercise prescription, often relying on rating of perceived exertion (RPE) as the adjunctive intensity modulator. Current guidelines do not consider the use of ventilatory threshold (VT) due to the need for specialized equipment and methodological issues. The purpose of this investigation was to evaluate VT related to V̇O2peak, V̇O2R, HRR, and RPE across the full spectrum of very low to very high V̇O2peak values.

Methods

Eight hundred and sixty-three records of exercise tests were retrospectively examined. Data were stratified for V̇O2peak, activity level, age, test modality, and sex.

Results

When stratified for V̇O2peak, V̇O2 at VT (V̇O2vt) had a lower mean value of ~14 mL·kg−1·min−1 in the lowest fit, rose gradually until median V̇O2peak, and rose steeply thereafter. When graphed relative to V̇O2peak, V̇O2vt as a percentage of V̇O2R (VT%V̇O2R) resembled a U-shaped curve, with a nadir ~43% V̇O2R at V̇O2peak ~40 mL·kg−1·min−1. Average VT%V̇O2R increased to ~75% in groups with the lowest or highest V̇O2peak. There was a large variance in the value of VT at all V̇O2peak levels. Mean RPE at VT was 12.5 ± 0.93, regardless of V̇O2peak.

Conclusions

Given the relationship of VT as the transition from moderate- to higher-intensity exercise, these data may help the understanding of aerobic exercise prescription in persons across the spectrum of V̇O2peak values.